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\ 



MONOGRAPHS ON BIOCHEMISTRY 

EDITED BY 
R. H. A. PLIMMER, D.Sc. 

AND 

F. G. HOPKINS, M.A., M.B., D.Sc, F.R.S. 



MONOGRAPHS ON BIOCHEMISTRY 

Royal 8vo. 

THE NATURE OF ENZYME ACTION. By 
W. M. Bayliss, M.A., D.Sc, F.R.S. 

THE CHEMICAL CONSTITUTION OF THE 
'PROTEINS. By R. H. A. Plimmbr, D.Sc. 

Part I. — ^Analysis. 

Part II. — Synthesis, etc. 

THE VEGETABLE PROTEINS. By Thomas B. 
Osborne, Ph.D. 

THE SlilPLE CARBOHYDRATES AND THE 
GLUCOSIDES. By E. Frankland Armstrong, 
D.Sc, Ph.D. 

ALCOHOLIC FERMENTATION. By A. Harden, 
Ph.D., D.Sc, F.R.S. 

SOIL CONDITIONS AND PLANT GROWTH. 
By E. j. Russell, D.Sc, F.R.S. 

THE SIMPLER NATURAL BASES. ByG. Barger, 
M.A., D.Sc 

NUCLEIC ACIDS. THEIR CHEMICAL PRO- 
PERTIES AND PHYSIOLOGICAL CON- 
DUCT. By WalI^er Jones, Ph.D. 

THE RESPIRATORY EXCHANGE OF ANIMALS 
AND MAN. By August Kroqh, Ph.D. 

LECITHIN AND ALLIED SUBSTANCES. THE 
LIPINS. By Hugh Maclean, M.D., D.Sc 



LONGMANS, GREEN AND CO., 

LONDON, NEW YORK, BOMBAY, CALCUTTA, AND MADRAS. 



I 

\ 



il 



THE 

-SIMPLE CARBOHYDRATES 

AND 

THE GLUCOSIDES 



E. FRANKLAND AliMSTRONG, D.Sc, PuD., F.I.C. 

rELLOW OF THE CITT AND GUILDS Of LONDON INSTITUTE 



THIRD EDITION 



LONGMANS, GREEN AND CO. 

39 PATERNOSTER ROW, LONDON 

FOURTH AVENUE ft 30th STREET. NEW YORK 

BOMBAY, CALCUTTA, AND MADRAS 

1919 






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S, » V 



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-7 



3 



I I 



GENERAL PREFACE. 

The subject of Physiological Chemistry, or Biochemistry, is 
enlarging its borders to such an extent at the present time, 
that no ^ngle textbook upon the subject, without being 
cumbrous, can adequately deal with it as a whole, so as to 
give both a general and a detailed account of its present 
position. It is, moreover, difficult in the case of the larger 
textbooks to keep abreast of so rapidly growing a science 
by means of new editions, and such volumes are therefore 
issued when much of their contents has become obsolete. 

For this reason an attempt is being made to place this 
branch of science in a more accessible position by issuing 
a series of monographs upon the various chapters of the 
subject, each independent of and yet dependent upon the 
others, so that from time to time, as new material and 
the demand therefor necessitate, a new edition of each mono- 
graph can be issued without re-issuing the whole series. • In 
this way, both the expenses of publication and the expense 
to the purchaser will be diminished, and by a moderate 
outlay it will be possible to obtain a full account of any 
particular subject as nearly current as possible. 

The editors of these monographs have kept two objects 
in view : firstly, that each author should be himself working 
at the subject with which he deals ; and, secondly, that a 
Bibliographyy as complete as possible, should be included, 
in order to avoid cross references, which are apt to be 
wrongly cited, and in order that each monograph may yield 
full and independent information of the work which has been 
done upon the subject. 

It has been decided as a general scheme that the volumes 
first issued shall deal with the pure chemistry of physiological 
products and with certain general aspects of the subject. 
Subsequent monographs will be devoted to such questions 
as the chemistry of special tissues and particular aspects of 
metabolism. So the series, if continued, will proceed from 
Physiological Chemistry to what may be now more properly 
termed Chemical Physiology. This will depend upon the 
success which the first series achieves, and upon the divisions 
of the subject which may be of interest at the time. 

R, H. A, P. 

45273-3 ^- ^- "■ 



/ 



PREFACE. 

Twenty-eight years ago the late Sir John Burdon Sanderson 
described one of the aims of Physiology as the acquirement 
of an exact knowledge of the chemical and physical processes 
of animal life. The recent history of physiological progress 
shows that investigations confined to the study of physical 
and chemical processes have been the most fruitful source of 
physiological advance, and it is principally the exact chemical 
study of the substances found in animals and plants which has 
enabled the physiologist to make this advance. 

The last decade has seen very material progress in our 
knowledge of the carbohydrates, more particularly with regard 
to their inner structure, biochemical properties, and the mechan- 
ism of their metabolism. In consequence, many problems 
of the greatest fascination for the biochemist have presented 
themselves for solution. 

This monograph aims at giving a summary of the present 
position of the chemistry of the carbohydrates. The reader is 
assumed to be already acquainted with the subject so far as 
it is dealt with in the ordinary textbooks. The available 
information is, however, so widely scattered in the various 
scientific periodicals that it is impossible for any one approach- 
ing the subject to inform himself rapidly of what has been done. 
It is to meet such needs that this monograph is primarily 
intended. 

A bibliography is appended, which contains references, 
classified under appropriate headings, to most of the recent 
works on the subject and to the more important of the older 
papers. It makes no claim to be exhaustive but serves to 
indicate how much is at present being done in this field. 

E. F. A. 



VI 



i 



PREFACE TO THE SECOND EDITION. 

Our interest in the carbohydrates has been again aroused by 
the return of Emil Fischer to the subject. He has announced 
his acceptance of the y-oxide formula of glucose which was 
used in the First Edition of the Monograph to explain all the 
properties of this carbohydrate. In continuation of his work 
on the acyl derivatives of glucose he has been able to show the 
probable composition of the tannins : he seems to think that 
compounds of this type may be widely distributed in animals 
and plants and may account for some of the peculiar properties 
of carbohydrates known to biologists. 

It has been found advisable to modify the arrangement of 
Chapter I. The treatment of the rarer carbohydrates has been 
extended and, wherever possible, their relation to enzymes has 
been demonstrated. The chapter on the glucosides has been 
considerably enlarged and a new chapter, dealing with the 
significance of the carbohydrates in plant physiology, has been 
added. The monograph should therefore appeal more generally 
to those interested in the subject from the botanical and agricul- 
tural sides. These problems are some of the most fascinating 
of those now under investigation, and their study must add to 
our conceptions of vital change. 

It is a pleasant duty to express my thanks to Mr. F. W. 
Jackson, B.Sc, A.C.G.I., for his help in the revision of the 
proofs. 

E. F. A. 



vu 



PREFACE TO THE THIRD EDITION. 

Since the Second Edition of this Monograph was completed 
the chemistry of the carbohydrates has developed on two main 
lines, 1both of which now receive special recognition. The 
discovery of a third isomeric form of glucose differing from the 
pentaphane ring forms in structure — probably containing a 
three-membered (triphane) ring — opens up ways to much future 
work and in particular has served to elucidate that very vexed 
problem the structure of sucrose. The discovery of this new 
glucose derivative also affords an example of the temporary 
nature of the doctrines of chemical structure : if the arguments 
for the acceptance of what was known as the y-oxide formula of 
glucose had been too rigidly construed there would have been 
no possibility of a third isomeride. Chemical formulae are of 
service so long as they serve to express known facts and 
stimulate further investigation ; they cease to be of value when 
used to give expression to observations with which they are not 
in harmony. We owe the recognition of the new form both to 
Emil Fischer and to J. C. Irvine, particularly to the latter and 
his students. The very patient and brilliant work of Irvine on 
the substituted methyl derivatives of the carbohydrates has done 
much to increase our knowledge of their structure. 

The relationship of optical rotatory power to structure in 
the case of the carbohydrates has long been a source of specu- 
lation, but, because of the indifferent manner in which many of 
the carbohydrate derivatives had been characterised, nothing 
definite had been achieved until recently. Owing to the 
painstaking work of Hudson and his school in America, we 
are noy in possession of many of the necessary data, and the 



VIU 



PREFACE TO THE THIRD EDITION ix 

generalisations of this chemist have given a new and most 
promising aspect to this field. 

Some of the rarer sugars have been made more available, 
thus stimulating inquiry ; indeed, as the methods of investigation 
improve and more attention is paid to the composition of plant 
products, the occurrence of the scarcer sugars is found to be 
far more general than had been anticipated, and it may be 
prophesied that future researches in this direction will be very 
fruitful. In particular much progress has been made in estab- 
lishing the structural formulae of the disaccharides. References 
to new work have been introduced where appropriate. 

Probably in no other branch of chemistry, at all events in 
that of the aliphatic compounds, is so great an opportunity 
afforded for the study in detail of the influence of structure on 
the properties of the molecule. Much has already been done 
in this direction but we are as yet only on the threshold of the 
inquiry. 

During the past few years most chemists in the allied 
countries have had to follow more urgent national calls than 
those of the research laboratory. The British and American 
nations have, however, learnt to appreciate more fully the need 
of scientific research, and it is to be expected that in the near 
future the chemistry of the carbohydrates will be a subject that 
will attract the attention of workers. 

It would have been very difficult for the writer to prepare 
this edition without the great assistance which he has so freely 
received from Dr. T. P. Hilditch. 

E. F. A. 



CONTENTS. 

* 

CHAPTER PAGE ] 

Introduction - - - - i 

I. Glucose -- 6 

II. The Chemical Properties of Glucose and the Hexoses 44 

III. The Hexoses, Pentoses and the Carbohydrate Alcohols 70 

IV. The Disaccharides - 96 

V. The Relation Between Configuration and Properties - 114 

VL Hydrolysis and Synthesis 129 

VII. The Natural Glucosides - - - - - - 149 

VIII. The Synthetic Glucosides - - - - - - 180 

IX. The Function of Carbohydrates and Glucosides in 

Plants 187 

Bibliography 201 

Index - - - 235 



I 



1 



» • • • 

.• • •• 

• • • 



: ". !. 



• :••••. :** •• • • • 

•••• ••••••• •• 

• • ••» »• •••• 



INTRODUCTION. 

The carbohydrates, together with the proteins, rank first in importance 
among organic compounds on account of the part they play, both in 
plants and animals, as structural elements and in the maintenance of 
the functional activity of the organism. 

The interest attaching to the group may be said to centre around 
glucose, t his carbohydrate being the first to arise in the plant and the 
unit group from which substances such as cane sugar, maltose, starch 
and cellulose are derived ; it is also of primary importance in animal 
metabolism, as the main bulk of the carbohydrate in our food materials 
enters into circulation in the form of glucose. 

Under natural conditions the higher carbohydrates are resolved into 
the simpler by the hydrolytic agency of enzymes, but these also exer- 
cise synthetic functions ; the simpler carbohydrates are further resolved 
by processes which are undoubtedly akin to that of ordinary alcoholic 
fermentation. The carbohydrates are, therefore, of primary importance 
as furnishing material for the study of the processes of digestion and 
assimilation. 

The carbohydrates are all remarkable on account of their optical 
characters ; it is possible to correlate these with their structure. Of 
the large number of possible isomeric forms of the gluco-aldohexose, 
CgHigOg, sixteen in all, of which glucose is one, only three are met 
with in nature, although fourteen have already been prepared by arti- 
ficial means ; this natural limitation of the number produced in the 
plant and utilised by it and by the animal is a fact of great significance 
and clear proof of the manifestation of a selective process at some 
period in the evolution of life. The elucidation of these peculiarities 
invests the inquiry into the nature and functions of the carbohydrates 
with particular interest and significance. 

The simple carbohydrates are all of the empirical composition cor- 
responding with the formula CHoO^t he most important being those 
containing five or six atoms of carbon. The members of the sugar 
group are usually distinguished by names having the suffix ose. 

The simplest carbohydrate, CHgO, formaldehyde or formal, is in 
3,11 probability the first product of vital activity in the plant, the carbon 

X 



• •••'•• • 

• • • • • • 



- • • ,• ,•• .•• '•• • • 
• • ••,•••" •••• • ' 
•• • • .•••••,•• • • 



th'e'sTmpLe carbohydrates and glucosides 

dioxide absorbed from the air being converted into this substance by 
the combined influence of sunlight and chlorophyll. The conversion 
of formaldehyde into glucose has been accomplished in the laboratory, 
but the transformation takes place in such a way that a variety of pro- 
ducts is obtained which are optically inactive ; there is reason to sup- 
pose that but the single substance dextro-glucose is formed in the plant 
and that this is almost immediately converted into starch ; in other 
words, the vital process is in some way a directed change. The record 
of the synthetic production of glucose and of the discovery of methods 
of producing the isomeric hexoses, as well as of determining the structure 
of the several isomerides, is one of the most fascinating chapters in the 
history of modern organic chemistry. 

A short outline of the ground covered by the complete carbohydrate 
group may be of value to some readers and will be given before the 
subject is developed in detail. 

The numerical relation existing between the proportions of 
"carbon" and of "water" in a carbohydrate molecule, C«(H20)„, is 
the basis of general classification. 

The simplest sugars are those in which m and n are equal and 
range in value from 2 upwards ; these are known as monosacc harides y 
and include such carbohydrates as arabinose, CgHj^Og, and glucose, 



le next, more complex, type of carbohydrate may be regarded, 
for the moment, as derived either from two molecules of a mono- 
saccharide or from two different monosaccharides, by elimination of a 
molecule of water, and will have the general formula ^^J^%^\m-\ \ 
these are the disaccharides^ of which can^e sugar or sucrose is the most 
familiar. 

Similarly, by elimination of two molecules of water from three 
of monosaccharide, or of three molecules of water from four of 
monosaccharide, we arrive at the empirical formulae for the trU or the 
tetra-saccharideSy which are also found in nature. 

Important exceptions to this numerical classification are the 
starches, gums, and celluloses of the general formula {(Z^yfi^x \ these 
have, of course, little resemblance to the saccharide group beyond 
their empirical composition ; they are of far greater molecular com- 
plexity than the sugars, and do not fall within the scope of this work. 

The distinctive feature of saccharides other than the monosac- 
charides is their ready conversion into a mixture of the latter com- 
pounds by hydrolytic agency ; in other reactions they show the same 
behaviour as the monosaccharides, 'if he basis of all carbohydrates is 



\ 



INTRODUCTION 3 

thus the class of monosaccharides, which are systematised according 
to the number of carbon atoms they contain. 

In passing it may be said that the simplest member of the series, 
CHgO, formaldehyde, is not a true carbohydrate, since it possesses 
neither the physical characteristics (a sweet syrup or solid material) 
nor the chemical (alcoholic) functions of the rest of the sugars. 

The compound, CHgCOH) . CHO, glycollic aldehyde, however, is a 
sweet-tasting crystalline substance readily soluble in water and posses- 
sing all the general properties of the carbohydrates. The next term of 
the series, C3(H20)3, includes glycerose, CHgCOH). CH(OH). CHO, 
and dioxyacetone, CHaCOH) . CO . CH2(0H), and here a further dis- 
tinction appears, for glycerose is an aldehyde and dioxyacetone a 
ketone. Moreover, a compound, CH3 . CH(OH) . CH(OH) . CHO, has 
been prepared to which the name methylglycerose is given ; this sub- 
stance possesses the general properties of a sugar, and analogous com- 
pounds such as rhamnbse, CH8[CH(OH)]4. CHO, occur in nature. 

The monosaccharides are therefore classified as dioseSj^rjgges, etc, 
by the number of carbon atoms in the molecule, whilst each class may 
be subdivided according as , it possesses an aldehydic , ketonic or 
f p f>fh y L radicle. So, whilst glucose is an aldohexose, and fructose a 
ketohexose, rhamnose is a methylaldopentose: 

A carbon atom which has four different groups attached to it is 
known as asymmetric. These groups can obviously be written in 
order either clockwise : — 

a 

d b 

c 
or counter clockwise : — 

a 

h d 

\ /^ 

c 

Two different forms of the substance are therefore possible, related 
as object to image, and they are termed stereoisomerides. 

Nearly all the carbohydrates contain asymmetric carbon atoms 
and display optical activity, and the number of possible stereoiso- 
merides is in many cases very large. Of the monosaccharides the 
diose, glycollic aldehyde, contains no asymmetric centres and only 
exists in one form, but in the triose, glyceric aldehyde, there are 
already possibilities of a dextro- and a laevo-rotatory form, with, of 

course, the corresponding racemic compound : — 

I* 



4 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 



CHaCOH) 
H . C . OH 
CHO 



and 



CHa(OH) 
HO . C . H 
CHO 



Similarly in the tetroses there are four possible active forms : — 



CHa(OH) 
H.C.OH 
H . C. OH 

CHO 



CH2(0H) 
H.C.OH 
HO . C . H 
CHO 



CHj(OH) 
HO . C . H 
H . C . OH 
CHO 



CH,(OH) 
HO . C . H 
HO . C . H 

CHO 



In general, as van't Hdff has pointed out, the total number of 
i active forms of sugars of the same structural formula containing n 
\ asymmetric carbon atoms is^. 

On mild oxidation of the aldehydic group of the aldoses, optically 
active hydroxy-monocarboxylic acids corresponding to each active 
form are produced, but if by further oxidation the terminal primary 
alcoholic group is also converted to an acid, or if the original mono- 
saccharide is reduced to a polyhydric -alcohol, the number of possible 
forms of the respective dibasic acids or polyhydric alcohols is some- 
what lessened. Thus, referring again to the tetroses, the dibasic acids 
formed by oxidation are : — 

COOH 
H.C.OH 
H.C.OH 

COOH 

(a) 

Of these, only {V) and {c) are optimally active, and are, in fact, the 
d and / forms of tartaric acid, whilst {a) and (4) are identical and re- 
present the " internally compensated " or mesoA.'axXzxiQ. acid. So that 
there are only three stereoisomeric dibasic acids (and also tetrahydric 
alcohols) derived from the four tetroses, and of these only two are 
optically active. 

Some of the possible stereoisomerides in the simpler aldomono- 
saccharides, with their related dibasic acids or polyhydric alcohols, 
are in number as follows : — 



COOH 


COOH 


COOH 


H . C . OH 


HO . C . H 


HO.C.H 


HO . C . H 


H . C . OH 


HO . C . H 


COOH 


COOH 


COOH 


(M 


W 


{d) 



Aldoses. 


Number of 

Asymmetric 

Atoms. 


Number of 

Stereo- 
isomerides. 


Corresponding Stereoisomeric Alcohols or ; 
Dibasic Acids. 

! 


Total No. 


Optically Active. 


Meso-compounds. 


Diose 
Trioses 
Tetroses . 
Pentoses . 
Hexoses . 
Heptoses . 


O 

I 

2 

3 
4 
5 


I 
2 

4 
8 

i6 ^ 
32 


I 
I 

3 

4 

lO 

i6 


p 
o 
2 
2 

8 

12 


o 
o 

I 

2 
2 

4 



Comparatively few of these sugars are found in nature, but tetroses, 
pentoses and all the hexoj5.es except two are now known in active 



INTRODUCTION 5 

forms corresponding to those predicted by stereochemical theory ; 
those not occurring naturally have been produced synthetically, to- 
gether with their reduction and oxidation products, by methods which 
will receive attention later in this monograph. 

It would be impossible within the limits of a brief monograph to 
deal at length with the carbohydrates generally. In the following ac- 
count, glucose will be taken as a typical sugar, and its properties and 
inter-relationships will be considered more particularly with reference 
to their biochemical importance. The disaccharides and glucosides 
will be dealt with in a similar manner. Those who desire fuller in- 
formation should consult the comprehensive works compiled by Lipp- 
mann and by Maquenne. 

In discussing the various problems associated with the carbohydrates, 
the writer will strive to indicate the alternative views which have been 
advanced. He will, however, endeavour to develop the subject as far 
as possible as a logical whole, rather than leave the reader undecided 
at every turn. Such a method of treatment is more likely to stimulate 
inquiry by giving a picture of the present attitude of workers towards 
the various problems which the carbohydrates present. 



^ -« r^ 



^«. . — 








CHAPTER I. 

GLUCOSE (DEXTRO-GLUCOSE OR DEXTROSE). 

It has been customary to speak of this sugar as grape sugar to 
distinguish it from cane sugar and on account of its occurrence in the 
juice of the grape and of other ripening fruits in association with fructose 
(laevulose). The two hexoses are probably derived from pre-exTstent 
cane sugar, as the three sugars are nearly always found together and as 
cane sugar is easily resolved into glucose and fructose by hydrolysis : — 

Cane Sugar. Glucose. Fructose. 

Glucose is also formed from other more complex sugars when these 
are broken down by hydrolysis with the assistance of the appropriate 
enzymes or of acids — for example, from milk sugar or lactose, malt 
sugar or maltose, starch and cellulose. It is easily prepared from 
starch by the action of diluted sulphuric acid and is therefore to be 
purchased at small cost. It separates from an aqueous solution with 
a molecule of water of crystallisation, but this is held only loosely, 
as the anhydrous substance may be crystallised from dilute alcohol. 
Unlike cane sugar, it never separates in well-defined clear crystals from 
either water or alcohol, but is usually met with as a crystalline powder. 

Constitution. 

Glucose is represented by the molecular formula CgHjgO^,. Five 
of the six atoms of oxygen are to be regarded as present in the 
alcoholic form, as hydroxyl (OH) ; the sixth under certain conditions 
manifests aldehydic functions.' Thus, when acted upon by metallic 
hydroxides, glucose forms compounds which resemble the "alcoho- 
lates " ; and it is converted by acids, acid anhydrides and chlorides, 
into ethereal salts or esters such as the following : — 

CeH^OiNOJj CeH^OCO . CO . CHJg CgH^OCO . CO . CgH^JB 

Glucose pentanitrate. Glucose pentacetate. Glucose pentabenzoate. 

On reduction, it takes up two atoms of hydrogen and is converted 

into a hexahydric alcohol ; on oxidation, it yields the monobasic acid, 

gluconic acid, C5H^(OH)5 . CO . OH ; when heated with a concentrated 

6 



-^ 



GLUCOSE (DEXTRO-GLUCOSE OR DEXTROSE) 7 

solution of hydrogen iodide, it loses the whole of its oxygen and is 
converted into an iodohexane, QH13I, which itself is a derivative of / 
normal hexane, CHg . CH2 . CHg . CHg . CH2 . CH3. 

On account of the stability of glucose, it is to be assumed that each 
hydroxyl group is associated with a different carbon atom ; as glucose 
is a derivative of normal hexane, the constitutional formula of the 
aldehydic form may be written in the following manner : — 

CHa(OH) . CH(OH) . CH(OH) . CH(OH) . CH(OH) . CHO 

But it was long a matter of remark that glucose, as a rule, is far 
less active than was to be expected, assuming it to be an hydroxyalde- 
hyde. The difficulty was removed when Tollens, in xi883, proposed to 
represent it by a formula in which four of the carbon atoms are included 
in a ring, together with a single oxygen atom. 

If the regular tetrahedron be adopted as the model of the carbon 
atom and it be supposed that the four affinities are directed towards 
its four solid angles from the centre of a sphere within which the tetra- 
hedron is inscribed, the direction of the affinities is such (109° 24') that 
on uniting four such tetrahedra together and interposing as representa- 
tive of the oxygen atom a ball with two affinities arranged in about the 
same directions as the two carbon affinities, a closed system or ring is 
formed almost naturally, in which there is no strain, the internal angles 
being practically those in a regular pentagon, thus : — 



H H 

Hv /-OH H0\ 





CH . CH(OH) . CHa(OH) 



This symbol has been very widely adopted, as it is in general 
accordance with the interactions of glucose: Fischer has stated 
his acceptance of it in preference to the aldehyde formula. It is 
the representation in a plane surface of a solid model of glucose made 
by combining tetrahedra in the conventional manner. The reader is 
advised strongly to construct such a model himself to enable him to 
follow the argument developed in this chapter. The behaviour of 
glucose as an aldehyde is accounted for if it be assumed that, when the 
ring is ruptured by hydrolysis, the closed-chain form passes into an 
aldehydrol and this in turn into the aldehydic form in the following 
manner : — 



8 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 



H OH H OH 

c c 



H OH H OH 

c c 



HO 




+ H2O 
CH . CH(OH) . CH2(OH) 



H 



HO 



> 



/ \ 



CH.CH(OH).CH,(OH) 



H OH H OH 

\/ V 

c c 



OH . HO 

Aldefiydrol. 

H OH H OH 

\/ '\/ 
C C 



H 



HO 



\ 



/ 



CH . CH(OH) . CH2(OH) 



H 



O 



> 



\ 



+ H,0 
CH . CH(OH) . CHgpH) 



OH HO 
Aldehydrol. 



HO 

Aldehyde. 



This action being reversible, it is to be supposed that when an 
agent such as phenylhydrazine/ which will act upon an aldehyde, is 
added to the aqueous solution, the small amount of aldehydrol present 
is attacked and removed ; the equilibrium is thereby disturbed, but is 
rapidly restored by the formation of a fresh quantity of the aldehydrol, 
which in turn disappears but only to have its place taken by a further 
quantity. Ultimately the whole becomes converted into the aldehydic 
derivative. 

On reference to the closed-chain formula of glucose, it will be seen 
that the potentially aldehydic carbon atom (printed in clarendon type), 
as well as the three other carbon atoms in the ring, and also the atom 
which is immediately contiguous to the ring^on-^the" right-hand side 
, oCthe formula (page 7), are all asymmetric^ in the sense that each of 
them is associated with four different radicles, or, in other words, a fifth 
asymmetric carbon atom has arisen in this formula. Consequently the 
closed-chain form of glucose m.ay be written in either of two ways^ de- 
pending on the arrangement of the groups around this atom, printed 
here in clarendon, thus :— 



^ See Chapter H., page 49. It is quite possible that the closed-ring form of glucose 
will interact directly with phenylhydrazine without the butylene oxide ring becoming opened. 
In such case it is unnecessary to assume the presence of any aldehydrol at all in solution. 



GLUCOSE (DEXTRO-GLUCOSE OR DEXTROSE) 

HO C H H C OH 



HCOH 

HOCH 

\. 
HC 



'O 



HCOH 

H CH.OH 



i 



HjOH CHjOH 




a-Glueose. i8-Glucose. 

This conclusion, though in general agreement with the behaviour 
of glucose, does not embrace all the known facts which, as indicated 
on page 13, go to show that glucose may react in yet other isomeric 
forms owing to the presence of other cyclic systems containing only 
two or three carbon atoms united with the oxygen atom. 

The two methyl glucosides are to be regarded as the methyl 
derivatives of these two stereoisomer ic forms of glucose. 

Nomenclature. 

Carbon Atoms. Alcohols. 

I 



2 a Secondary 

3 /3 Secondary 

4 7 — 

5 $ Secondary 

6 € Primary 

In order to avoid confusion it is necessary to be clear as to the 
nomenclature adopted. Two systems are in use: the carbon atoms 
may be numbered commencing with the terminal, potentially aldehydic, 
active carbon atom, and the formula is usually written with this 
upwards. Alternatively they may be designated by means of Grreek 
prefixes in the manner customary for aliphatic acids so that the carbon 
atom next the potentially aldehydic atom becomes a and carbon 
number 4 is 7. The prefixes a^,^^ etc., are also commonly used by 
chemists to distinguish isomerides, the modifications being usually 
named in the order of their discovery. In the sugar group the prefixes 
a and /8 have come to acquire a special meaning as indicating the 
configuration of derivatives attached to carbon .1 : accordingly, their 
use in the more general sense will be restricted as much as possible. 

It is a characteristic property of y-hydroxyacids to lose water very 
readily, forming ring compounds containing four atoms of carbon and 




10 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

one of oxygen : these are termed 7-lactones as the 7-carbon atom is 
concerned in their formation. Thus — 

CH2(0H) . CHj . CH3 . COaH = HjO + CH,. CHj . CH, . CO 
7-Hydroxybutyric acid. 7-Butyrolactone. 

Similarly, four carbon-oxygen ring compounds, when derived from 7- 
hydroxy compounds other than acids, are named 7-oxides. The ring is 
termed a pentaphane ring. 

It is, however,^referable again to avoid the use of the Greek pre- 
fix and to denote the character of the ring structure by the terms, 
ethylene, propylene, or butylene oxide instead of as a-, )8- or 7-oxides, 
as was done in the former edition. 

An alternative, advocated by Hudson, is the use of the word ** cyclo " 
with a Greek prefix to show the nature of the ring, e.g. methyl-a-cyclo- 
glucose or methyl-7-cyclo-glucose. Acree has suggested the term 
lactonyl to indicate an aldehyde group that has formed a lactone-like 
ring, and Hudson uses the symbol < to denote this. This symbol is 
useful in expressing the structure of the disaccharides. 

The carbon atom and the attached H and OH radicles are often 
referred to collectively as primary or secondary alcohol groups. 
J The» prefix epi is used to denote the new carbohydrate formed by 
the interchange ^£the H and OH groups on the o-carbon atom ; thus 
mannose becomes epiglucose, ribose becomes epiarabinose. The 
change is spoken of as epimerism, and the isomeric pair as epimerides. 

The Methyl Glucosides. 

In considering the structure of glucose, the compounds which 
deserve attention in the first place are the two isomeric methyl gluco- 
; sides (a and /8), which are formed by the interaction of glucose and 
methylic alcohol under the influence of hydrogen chloride. These 
compounds are the prototypes of the natural glucosides. They were 
discovered by Emil Fischer in 1893. He prepared them by dis- 
solving glucose in cold methylic alcohol saturated with dry hydrogen 
chloride gas. After several hours, when it had lost all cupric reducing 
power, the mixture was neutralised with lead carbonate. Crystals of 
the a-compound were obtained on concentrating the solution ; the 
)8-compound was isolated later from the mother liquor, and was first 
obtained crystalline by Van Ekenstein. 
/ The methyl glucosides differ considerably from glucose, more par- 
I ticularly in never behaving as aldehydes ; and their rotatory power in 
. solution is the same in a freshly-prepared solution as it is in one which 



GLUCOSE (DEXTRO-GLUCOSE OR DEXTROSE) ii 

has been kept for some time, which is not the case with glucose. They 
are undoubtedly formed by the introduction of methyl, in place of an 
atom of hydrogen, in the hydroxyl group attached to the carbon atom 
which exercises aldehydic functions in the open-chain form of glucose. 
It is to be noted that the introduction of methyl in this position has 
the effect of rendering the ring far more stable than it is in glucose, as 
it is to be supposed that compounds such as phenylhydrazine, and 
\ oxidi^g agents such as Fehling's solution, are without action because 
the gliicosides do not undergo hydrolysis in solution in the way that 
glucose does. 

The two glucosides are distinguished by the arbitrary prefixes a, 
and /8, their physical properties being as follows : — 

Melting-point. Rotatory Power. 
a-Methyl glucoside .... 165° + 157° 

/3-Methyl glucoside .... 104° - 33° 

They are both colourless crystalline substances, the a-isomeride 
crystallising usually in long needles, the )8-isomeride in rectangular 
prisms. c v j * • ^ 

When hydrolysed by acids they yield methyl alcohol and glucose. 
At ordinary temperatures hydrolysis, even by moderately strong mineral 
acids, proceeds but slowly ; and if it be desired to study the course of 
hydrolysis it is advisable to work at elevated temperatures, say 70° to 
80° C. As in other chemical reactions, the hydrolytic power of acids 
towards glucosides increases as the temperature is raised. A conven- 
ient method of experimenting consists in mixing acid and glucoside in 
a closed flask immersed in a thermostat so as to maintain the required 
temperature. Samples of the liquid are withdrawn at stated intervals 
of time, rapidly c6oled by immersion in ice water to check hydrolysis, 
and the amount of glucose formed estimated either gravimetrically or 
with the polarimeter. To prevent evaporation it is advisable to add 
a little paraffin wax to the mixture of glucoside and acid. Measure- 
ments made in this way show that a definite fraction of the glucoside 
present is hydrolysed in each unit of time, the course of change follow- 
ing what is known as the logarithmic curve. The ,^comj)ound is at- 
tacked more rapidly than the a. This point will be referred to again 
in Chapter VI. 

The methyl glucosides are also hydrolysed by enzymes, but both 
isbmerides are not hydrolysed by the same enzyme. In fact, the action 
of enzymes towards the glucosides is specific, and each form requires 
its own particular enzyme : a-methyl glucoside is hydrolysed by 
maltase : )8-methyl glucoside by emulsin. The enzymes act at 



12 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

ordinary temperatures, preferably not above 37° C, and are far more 
active as hydrolytic agents than acids. 

Returning to the preparation of the glucosides just described 
it will be noted that both forms are produced simultaneously, the 
o-isomeride predominating. When solid anhydrous glucose (o-glucose) 
is dissolved in dry methyl alcohol containing dry hydrogen chloride, 
the first change is its rapid conversion into a mixture of a- and yS- 
, glucose in nearly equal parts. Each of these then undergoes etherifi- 
. cation, the primary result being a mixture of a- and /8-methyl gluco- 
sides, in which the latter is slightly in excess. On standing, slow 
conversion of the /8-methyl glucoside into the more stable a-isomeride 
, takes place. The equilibrated mixture of the glucosides contains yj 
per cent of the a- and 23 per cent of the /8-isomeride. If, however, 
the solution be neutralised as soon as etherification is complete and 
before the isomeric changes take place, and the solvent be removed, a 
mixture of the two glucosides in approximately equal quantities is ob- 
tained. These may be separated by fractional crystallisation. 

Such a process is somewhat tedious when /8-methyl glucoside is the 
object of the preparation, and it is more convenient to make use of 
biological methods. On treatment with yeast, which contains the 
enzyme maltase, the a-methyl glucoside is hydrolysed to glucose and 
methyl alcohol, and the glucose is removed by fermentation, so that 
/8-methyl glucose, which is not attacked by yeast, alone remains, and 
( can be isolated and purified. 

When, on the other hand, a-methyl glucoside is desired, the action 
of the acid is allowed to continue until equilibrium is attained, and, 
after crystallisation of some quantity of the a-methyl glucoside, the 
mother liquors are again heated with a little acid. This has the effect 
of causing the /8-glucoside present to be converted into a-glucoside 
until equilibrium is again reached, when yy per cent, of the total solid 
present is a-glucoside, and in consequence a further quantity of a-glu- 
coside crystallises on removal of the solvent 

Fischer employs an alternative method, which consists in heating 
the alcoholic glucose solution with very little acid in an autoclave. It 
is then not necessary to neutralise before crystallisation of the a-gluco- 
side. 

Maquenne has prepared yS-methyl glucoside by the action of methyl 
sulphate and sodium hydroxide on glucose dissolved in water. It is 
stated that the /8-isomeride alone is formed under these conditions, 
but the quantity obtained is not large. 

The two methyl glucosides are regarded as stereoisomeric 7 or 
butylene oxides, and have the following structural formulae : — 



•N. 



GLUCOSE (DEXTRO-GLUCOSE OR DEXTROSE) 13 



I 



OHgO— C— H 





CHaOH CHjOH 

a-Methyl glucoside. iS-Methyl glucoside. 

In practically every respect the above formulae may be regarded 
as satisfactory and consistent with the properties of the isomeric glyco- 
sides, their different solubilities, rotations, rates of hydrolysis, and 
their behaviour towards enzymes. Considering the cyclic structures 
possible in glucose it is obvious that the ring forming oxygen can 
occupy other positions than the 7 or butylene oxide position so far 
assumed. 

The alternatives are : — 

/CH.OMe /CH.OMe /CH.OMe /CH.OMe 

^1^ 






H . OH], 
CH, . OH 






OH 



Ethylene Propylene Butylene Amylene 

oxide. oxide. oxide. oxide. 

The remarkable ease with which fructosides are hydrolysed suggests 
that these compounds are constituted on a plan different from that of 
the glucosides, and careful experimental work has indeed shown that 
further isomerides, both of the methyl glucosides and other derivatives 
of glucose and similar sugars, exist although these are somewhat in- 
definitely characterised. Fischer originally showed that the reaction 
between glucose and methyl alcohol containing i per cent of hydrogen 
chloride yields, in addition to the two crystalline methyl glucosides, a 
considerable amount of a syrup which has hitherto not been purified 
and has been regarded as glucose dimethylacetal, CgHigO^, i.e. 

CH,(OH) . [CH . 0H]4 . CH<^ 

or as an uncrystallisable mixture of the a- and /8-methyl glucosides. 
He found in 19 14 that the syrup distils without decomposition in a 
high vacuum, and has the composition, C^Hj^O^, of a methyl glucoside. 
It IS stable to alkalis, Fehling's solution and hot water, is hydrolysed 



14 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

by acids but scarcely attack^ A)y emulsin or by maltase. It is 
obviously a third isomeric methyl glucoside. 

Irvine, Fyfe and Hogg have shown that this methyl glucoside is a 
mixture of isomerides derived from an entirely new variety of glucose. 
The new methyl glucoside is characterised by the remarkable ease with 
which it enters into condensation with acetone, the remarkable capacity 
to reduce alkaline potassium permanganate solutions, the tendency to 
unite with one atomic proportion of "oxygen to give a neutral product, 
and the ready auto-condensation of this oxy-compound to give a product 
allied to the disaccharides. 

When methylated by the silver oxide method a new tetramethyl- 
methylglucoside is formed which behaves as a mixture of isomerides. 
When hydrolysed a new liquid, tetramethylglucose, is obtained which 
is laevo-rotatory and behaves as a derivative of a much more reactive 
, form of glucose than the a or ^ variety. It fails to form a phenyl- 
losazone, being resinified by phenylhydrazine and acetic acid. The 
Optical properties of the tetramethyl hexitol formed from the sugar by 
reduction indicate that it is represented by the formulae : — 

CH2(0Me) . [CH . OMelj . CH(OH) . CHa(OH) 

On this basis an ethylene oxide structure must be assigned to the new 
tetramethylglucose, and the new methyl glucoside is a mixture of 
stereoisomerides, having the formulae : — 



CHoO— C— H H— C— OCH 



3 



[CH . OHjj [CH . OH], 

CHg . OH CH2OH 

The new glucose itself has not yet been isolated in the free state 
but it is evident that its reactivity far exceeds that of a- or /8-glucose. 

Nef, as the result of his investigations on the /8 and 7 lactones of 
the sugar acids, considers that the isomerism of the methyl glucosides 
does not depend on the position of the methyl group. He formulates 
the a-glucoside with a butylene oxide ring and the /8-glucoside with a 
propylene Pxide ring. 



1 
( 

I 



GLUCOSE (DEXTRO-GLUCOSE OR DEXTROSE) 15 

Mutarotation— The Isomeric Forms of Glucose. 

The hypothesis that there are two stereoisomeric forms of glucose 
is the only one hitherto proposed which affords a satisfactory explana- 
tion of a peculiar property, characteristic of glucose and other sugars 
manifesting aldehydic functions, now known as mutarotation or multi- 
ro tation (but formally termed birotation) ; namely, the optical rotatory 
power of the freshly dissolved substance changes gradually, sometimes 
increasing, but more usually falling, until a constant value is reached. 
The term birotation was introduced because the rotatory power of glu- 
cose in solution is about twice as great when it is freshly dissolved as 
that which it eventually assumes. The change takes place very slowly 
when highly purified materials are used, but almost immediately if 
a small quantity of alkali be added. The phenomenon was first ob- 
served by Dubrunfaut in 1 846 and ascribed by him to purely physical 
causes. The subject has of recent years caused a good deal of dis- 
cussion, and it is simplest to deal with the views that have been 
advanced in historical sequence. 

E. Fischer, in 1890, noticed that the optical rotatory power of 
certain lactones closely related to the sugars underwent change in 
solution as the lactone became hydrolysed to the corresponding acid. 
He therefore ascribed the change which occurs with glucose to a like 
addition of a water molecule, and assumed that the glucose (aldehyde) 
underwent conversion into a heptahydric alcohol (aldehydrol) of lower 
rotatory power : — 

CHO CH(OH), 

CH(OH) C] 



:H(0H) CH(OH) 

CH(OH) + HjG -> CH(OH) 

CH(OH) CH(OH) 

CH(OH) CH(OH) 

CHj(OH) CHa(OH) 

Glucose (aldehyde). Alcohol (aldehydrol). 

The subject assumed a new aspect when it was shown by Tanret, 
in 1896, that besides the anhydrous and hydrated forms of glucose 
other isomeric anhydrous modifications could be obtained. He 
described an a-glucose (Mo + 110°). the initial rotatory power of 
which fell gradually to [ajo + 52*5° ; further, a /8-glucose^ of low initial 

^ Tanret actually termed the substance represented above as /S-glucose 7-gIuco8e and 
designated y-glucose as iS-glucose. The terms have been altered^^ring them into agree- 
ment with the nomenclature adopted. 



i6 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

rotatory power ([a]o + 19°), increasing to [a% + 52*5'* in solution ; and, 
lastly, a 7-glucose ([a^ + 52*5'^ of unalterable rotatory power in solu« 
tioa The three supposed isotnerides were isolated by allowing glucose 
solutions to crystallise under different conditions — a-glucose separated 
at ordinary temperatures from solutions in 70 per cent alcohol, and 
/8-glucose from aqueous solutions at temperatures above 98*^ C. ; 
• 7-glucose was obtained by precipitating a concentrated aqueous 
solution of glucose with alcohol. a-Glucose hydrate crystallises from 
aqueous solutions at the ordinary temperature. When powdered 
anhydrous glucose is added to water, it immediately undergoes hy- 
dration before passing into solution. 

The behaviour of these isomeric forms does not fit in with the 
theory that the mutarotation is due to the conversion of an aldehyde 
into an aldehydrol ; moreover, the increase in rotatory power from 
/8- to 7-glucose has also to be explained 

Tanret, Lippmann and others suggested that some forms of glucose 
have a closed-ring structure, as proposed by ToUens, and that in solu- 
tion these are completely converted into the isomeric aldehyde. 

A more fruitful suggestion was made by Simon who drew atten- 
tion to the optical behaviour of a- and /S-glucose in relation to that 
of the isomeric methyl glucosides of which the structure was known : — 

[o]d [o]d 

o-Methyl gluooside + 157° o-Glucose + 105°^ 

jS- Methyl glucoside - 33° i3-Glucose + 22® 

He suggested that the a- and /9-glucoses are homologues of the a- and 
/8-methyl glucosides, and that do^A contain a closed oxygenated ring. 
Direct proof of the glucosidic structure of a- and /9-glucose was 
afforded by their preparation from the corresponding glucosides effected 
by the writer. Both glucosides are resolved into methyl alcohol and 
glucose by appropriate enzymes, and as the enzymes condition the 
hydrolysis more quickly than the glucose which is formed can undergo 
isomeric change, it is possible to determine the nature of the sugar 
which is formed initially. In practice, this is done by preparing a 
clear solution of glucoside and enzyme, allowing hydrolysis to proceed 
for a short time and then observing the optical rotatory power of the 
solution before and after the addition of a drop of ammonia, which 
hastens the rate of the isomeric change, and therefore has the effect 
of establishing equilibrium almost immediately. As a glucose of high 
initial rotatory power was obtained from a-methyl glucoside, and one 

^ The numerical values are Simon's, 



GLUCOSE (DEXTRO-GLUCOSE OR DEXTROSE) 17 

of low initial rotatory power from the /S-glucoside, it is clear that 
Or- and )3-glucose correspond respectively to the a- and /8-glucoside. 

It remains to establish the nature of Tanret's 7-glucose, which he, 
as well as Simon and Lippmann, regarded as a third isomeride, ascrib- 
ing the mutarotation of a- and /S-glucose to their complete conversion 
into the isomeric aldehyde. 

The change in rotatory power of glucose was shown to be a process 
of reversible isomeric change by Lowry in 1 899. Lowry subsequently 
(1903) concluded that not only are a- and )8-glucose isodynamic com- 
pounds, but that Tanrefs 7-glucose is a mixture in whiqh these two 
compounds are present in equilibrium. 

On concentration of the solution of such an equilibrated mixture, 
a point is reached when one of the constituents crystallises out froizi 
the saturated liquid. The mixture in solution is consequently thrown 
out of equilibrium ; but as this happens a change takes place spon- 
taneously to restore the equilibrium — /9 passing into a, or vice versd. 
A solution of glucose containing a and /9 forms can therefore be made 
to yield wholly a- or wholly /9-glucose on concentration, according to 
the temperature at which crystallisation takes place. The a form, 
which is then the less soluble, is that obtained at lower temperatures ; 
■ but above 98°, the ^ form, being the less soluble at the higher tem- 
perature, alone separates. Were the change into aldehyde complete, 
as Simon and Lippmann suggest, it would be impossible by mere 
crystallisation to convert this into a-glucose. 

Tanret (1905) has accepted the conclusion that there are but two 
isomerides of glucose, corresponding to the a- and /S-methyl glucosides, 
and that his supposed third modification is an equilibrated mixture of 
these two forms. He has calculated from the rotatory power [ajo + 110° 
of the pure a and [a]i, + 19° of the pure/8 form that the proportion in 
which these are in equilibrium is a = 37 per cent, )8 = 63 per cent in a 
10 per cent solution, and a = 40, /9 = 60 per cent in a concentrated 
aqueous solution. 

By means of solubility determinations Lowry finds 52 per cent, of 
the a form to be present in saturated solutions of glucose in methyl 
alcohol : the proportion of a decreases as the amount of water increases, 
amounting to 40 per cent in the mixture MeOH + HgO. He does 
not, however, interpret the remaining 60 per cent of sugar present in 
solution as )8-glucose, but considers that some quantity of the alde- 
hyde form is also present 

Conclusive proof that the mutarotation is caused by a balanced 

reaction between the a and ^ forms of the sugar is afforded by the 

2 






1 8 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

I numerical equality of the velocity coefficients of their mutarotation 
which have been determined over a range of temperature from o° to 40°. 

Behrend finds that a-glucose can exist in contact with boiling 

ethyl or isobutyl alcoholic solutions, or as the monohydrate in contact 

with aqueous solutions. From the solution in boiling pyridine a 

'^ r monopyridine salt of )8-glucose separates, which on exposure rapidly 

I loses pyridine. This forms a convenient method of preparing 

i I /8-glucose, which, according to Behrend, has m.p. 148°-! 50"*, [a]^ + 207°. 

Glucose as purified by crystallisation from dilute methyl alcohol is 
almost invariably a mixture of the different forms. To obtain a 
homogeneous substance the solid is soaked during several days or 
weeks with the solvent, at a constant temperature, until the whole of 
the )8-sugar present has been converted into the a-isomeride (Lowry). 

According to Hudson and Dale, acetic acid of various concentra- 
tions is the most suitable solvent for the recrystallisation of a- and 
)8-glucose. To obtain a-glucose 2 parts of the sugar are dissolved 
in I part of water and mixed with 4 parts of glacial acetic acid ; 
crystallisation is allowed to take place at the ordinary temperature. 
The best method of preparing /8-glucose is as follows: 10 parts of 
glucose are dissolved in i part of water on a water bath and 1 2 parts 
' of glacial acetic acid heated to 100° are added The whole is well 
mixed and removed from the water bath, when crystallisation at once 
commences. After four such crystallisations pure )8-glucose is 
obtained. 

Hudson gives [a]p + 110'' for a-glucose and + 19° for ^-glucose. 

When the mixture of alcohol and water is sufficiently dilute glucose 
crystallises as hydrate, the transformation from anhydrous glucose to 
hydrate being clearly visible to the eye as the sugar changes from a 
fine powder to a hard cake of glistening crystals. Glucose hydrate 
undoubtedly has the structure of the oxonium hydroxide : — 

It is characteristic of the carbohydrates that their optical rotatory 
power is altered, in some cases very considerably, by changes of con- 
centration of the sugar. On the hypothesis that actually there is 
present in solution a mixture of two isomerides in equilibrium, it is 
obvious that the change in question will disturb the equilibrium in one 
or the other direction. In the case of glucose temperature has hardly 
any influence, but the rotation is greater in more concentrated solutions. 
When these are diluted the rotatory power returns to the lower value 
only slowly, corresponding with the gradual establishment of the new 



GLUCOSE (DEXTRO-GLUCOSE OR DEXTROSE) 19 

equilibrium. The rotation of fructose is very greatly influenced by 
change of temperature. The effect of salts in altering the rotatory 
power is also in part due to their concentration effect tending to alter 
the position of the equilibrium. 

The knowledge of the mutarotation of glucose and fructose, par- 
ticularly when liberated from sucrose, has been materially advanced by 
Hudson in a series of papers commenced in 1908, some years subse- 
quent to the definite proof of the nature of mutarotation by Armstrong 
and Lowry. 

Hudson draws attention to the recognition by O' Sullivan and 
Tompson in 1890 that the earlier polarimetric measurements of the 
inversion of sucrose by invertase were vitiated by a systematic error 
due to the fact that the glucose formed is initially in a mutarotatory 
condition. The optical rotation only gives a true measure of the 
amount of inversion after the addition of a drop of alkali. 

The conductivity of a-glucose in presence of boric acid decreases 
during mutarotation, whilst in the case of the /8 form the reverse is 
the case. Boeseken, in the light of his experience with polyhydroxy 
alcohols, interprets this fact as a proof that in a-glucose the hydroxyl 
radicles attached to carbons i and 2 are on the same side of the 
molecule and assigns a configuration to a-glucose which is the reverse 
of that pictured on page 9. In drawing this conclusion he has over- 
looked the conditions developed when water is added to the oxygen 
atom of the ring— 

I. H— C— OH 

2. 




6. CHoOH 



From the formula above it will be seen that the pair of hydroxyls 
I , 7 may be responsible for the change in conductivity just as much 
as the pair i , 2. 

The question has been settled by Irvine and Steele from the study 
of the mutarotation and conductivity of tetramethylglucose. Proof is 
afforded that when dissolved in water this exists in the first place as 
a monohydric alcohol. The marked increase in conductivity in the 
presence of boric acid, observed as mutarotation proceeds, shows that 
an additional hydroxyl group becomes attached to the sugar, and this 

2* 



20 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

can only take place at the oxygen atom of the ring (position 7). The 
subsequent elimination of water may take place in either of two ways 
to generate the a or /8-sugars. The final equilibrium is : — 

a form ^ oxonium hydrate ^ fi form. 
It follows that Boeseken's deductions cannot be accepted as proof of 
the structure of a and )8-glucose. 



1 



Isomeric Change. — a ^ )3-Glucose. 

It remains to discuss the mechanism of the isomeric change 
a ^ )8-glucose. Two rival explanations have been advanced which 
differ really only in one respect : Lowry considers the formation of 
the aldehyde or its hydrate, which involves the opening of the ring, 
to be an intermediate stage in the process ; E. F. Armstrong, how- 
ever, has formulated the change as taking place without any dis- 
ruption of the 7-oxide ring. 

According to Lowry's view, the change is represented by the 

scheme of equilibrium : — 
c 



HO— c— H 




CH(OH)s 



H— C— on 



CH.OH 



#0'^ 



CH.OH 



CH.OH 



CH.OH 



CH, . OH 
a-Glucose. 



i 

I 



H.OH 




CHa.OH 
iS-Glucose. 



CHa . OH 
Aldehyde hydrate. 

This scheme is intermediate in character between Fischer's former 
view (p. IS), that mutarotation is due to hydration and the more recent 
view that mutarotation is due to isomeric change. 

In anhydrous alcohol (which, however, contains traces of water) the 
velocity of the isomeric change a !^ y8-glucose is small, but it increases 
as water is added and the opportunity for hydration is increased. 
Lowry takes the view that an aqueous solution of glucose contains a 
considerable proportion of aldehyde (open-chain form), in addition to 
a- and fl-glucose (closed-ring forms), whereas in alcoholic solution 
there is little or no aldehyde. 

E. F. Armstrong considers the first stage in the process to be the 
formation, by the addition of water, of the oxonium hydrate, from 
which, by the elimination of water in another manner, an unsaturated 
compound results. This is illustrated in the following scheme, in 
which only the carbon skeleton of the pentaphane ring is indicated : — 



GLUCOSE (DEXTRO-GLUCOSE OR DEXTROSE) 21 

Q Q 

I I .OH (+ Hfi) 

c— c— c c( ^ C— C 

\/ \h 
o 




^ 



QH OH 

rr ■ 



Glucose. Oxonium hydrate. Unsaturated compound. 

It is possible to add the elements of water to this unsaturated 
bond in either of two ways, giving rise to the a- and )8-glucoses re- 
spectively, or their oxonium hydrates. If this stereoisomerism is 
pictured in plane projection in the conventional manner with reference 
to the terminal carbon atom^ (in Clarendon type in the preceding 
diagram), the simultaneous formation of both isomerides according 
as the hydroxyl group re-enters into combination with the terminal 
carbon atom at the respective valency points marked (a) and (j3) in 
the unsaturated oxonium compound is evident : — 



HO H / \ H OH 





\o/^'' 




C OH 

/ Unsaturated / 

1st position = a-Glucose. oxonium 2nd position = jS-Glucose. 

compound. 






Lowry's view that an aldehydrol is the intermediate compound is 
not consistent with the increase in conductivity during mutarotation 
and may therefore be dismissed, and the evidence in favour of the 
oxonium theory may now be regarded as conclusive. 

The mechanism of mutarotation probably varies with the particular 
solvent employed, but it depends essentially on combination between 

^ The asymmetric carbon atom in Clarendon type has attached to it the four radicles — 
(i) hydrogen, (2) hydroxyl, (3) the pentaphane oxygen, (4) a carbon atom of the ring. The 
stereoisomerism of a- and )3-glucose is explained above as due to the interchange in the 
relative positions of the hydrogen and the pentaphane oxygen. This relationship is 
awkward to picture in plane formulae; it is therefore more convenient to represent the 
stereoisomerism as due to the interchange in the relative positions of the hydrogen and 
hydroxyl radicles, as is done for example in the formula on previous pages. Reference 
to a solid model will show that this comes to exactly the same in the end, as the carbon 
atom in engaging with the pentaphane oxygen in its a or jS position is necessarily rotated, 
so that a projection of the solid tetrahedron viewed in plan will show hydrogen alternately 
on the right and left of hydroxyl. It is almost essential to consult a model if a full under- 
standing of the difference between a* and jS-glucose and also between glucose and galactose 
is desired. 



22 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

s olvent^ and solute followed by decomposition of the complex in two 
directions. 

X Tetramethyl glucose shows mutarotation in water, in dehydrated 
organk solvents, in hydrocarbons and in halogen compounds. Irvine 
has obrkmed-pofarimetric evidence in some of these cases that com- 
plexes of the oxQnium type are formed. Whereas in aqueous solutions 
the change is prombted by ^alkaline catalysts, in acetone an add 
catalyst appears necessary before the change takes place, probably 
because change is only promoted when the solvent is partly enolised 
and may thus combine with the sugar. Examples of this are afforded 
by dimethyl-)8-glucose (Irvine and Scott) and by the anilides of 
alkylated sugars (Irvine and McNicoll). 

No doubt the same explanation — combination with the enolised 
solvent — will be found to apply to the mutarotation in anhydrous 
formamide solution studied by Mackenzie and Gosh. 

The formation of a definite compound of pyridine with glucose 
(Behrend and Roth) affords further confirmation of this view. 

This explanation of the isomeric change has the advantage that it 
is equally applicable to the analogous interconversion of the a- and 
^ /8-acetochloro glucoses and of the a- and )8-pentacetyl glucoses, neither 
of which can be explained on the aldehyde hydrate hypothesis ; and 
it also applies to the interconversion of the cu- and )8-methyl glucosides. 
In this last case Fischer has assumed that an intermediate compound 
of the acetal type is produced and the pentaphane ring is opened — a 
scheme identical with that just described as subsequently advocated 
by Lowry. The first product of the action of dry methyl alcohol 
containing i per cent, of hydrogen chloride on glucose at the ordinary 
temperature is a s^rup differing from either glucoside. This could 
npt be analysed, but was regarded by Fischer as glucose dimethyl- 
' acetal. It has now been shown to be probably the ethylene oxide 
form of methyl glucoside. 

Measurements of the velocity of their transformation made by 
Jungius led him to the conclusion that the two glucosides are directly 
convertible into each other and that it is very improbable that an 
acetal is formed. Further, the reversible conversion of the a- and 
/8-tetramethyl methyl glucosides takes place at temperatures of 
iio°-iSO° independently of the nature of the solvent used: a result 
which excludes the intermediate formation of a compound of an 
acetal type. 

The isomeric change of one series of glucose derivatives into the 
other has been formulated in the foregoing on the hypothesis that 



GLUCOSE (DEXTRO-GLUCOSE OR DEXTROSE) 23 

additive oxonium compounds are formed in which the lactonic Qxygen 
displays quadrivalency. Indeed no other explanation is applicable to 
alTtEe transformations observed in the glucose series. Such additive 
oxonium compounds are well known to be formed in other cases, such 
as dimethylpyrone (Collie and Tickle). Irvine and Moodie have 
brought forward evidence to show that tetragaethyl glucose forms 
an oxonium derivative with isopropyl iodidj?. The presence of the 
etheric groups in the alkylated sugar apparently increases the basicity 
of the butylene-oxidic oxygen atom, and so makes the identification 
of the oxonium compound possible. 

From the biological point of view, the fact that glucose exists in 
solution not as a single substance but as an equilibrated mixture of 
stereo isomeric butylene oxide forms, readily convertible into one 
another, is of fundamental and far-reacTiing importance. If one of the 
stereoisomerides is preferentially metabolised in the plant or animal, 
in the course of either synthetic or analytic processes, the possibility 
of controlling the equilibrium in the one or other direction, so as to 
increase or limit the supply of this form, places a very delicate directive 
mechanism at the disposal of the organism. This question is un- 
doubtedly one which demands the close attention of physiologists. 

The speeds of mutarotation of most of the sugars are indicated in 
the following table, given by Hudson : — 

TABLE I. — The Velocity-Coefficients of the Mutarotation of the Sugars in 

Water at 20°. 

sug«. *'+*« = 7 '»«'f^ 

(Minutes and Decimal Logarithms). 

Fructose 0*082 

Ljrxose 0*065 

Rhamnose 0*039 

Arabinose 0*031 

Fucose o*o22 

Xylose o*02i 

Mannose o'oigo 

a-Glucoheptose 0*0122 

Galactose 0*0102 

Melibiose . . . . 0*0088 ' 

Maltose 0*0072 

Glucose 0*0065 

Cellose 0*0047 

Lactose 0*0046 

The initial and final solubilities of most of the crystalline sugars are 
summarised in the following table likewise due to Hudson : — 



24 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

TABLE 11, — Solubilities of Suoars at 20°. 











Gi*m(ot 

SuguiDioo 


sfiss. 


Sucu. 




Pannaliu 


Solvcol. 






iDltSd. 


FiMlSoL 


a-ArabinOM: 


. C 




Sopercentalcoho 


074 


1-94 


fl-CelioM . . 


. C 




20 „ „ 


3-a 


47 


^-Fructose . 


. c 




80 


^3;j 


27-4 




. c 




95 




4'2 




. c 




Methyl alcohol 


5-a 




a- Galactose 


. c 




6d pet cent, alcohol 




3'* 




. c 




Bo „ 


0-27 


0-6S 


8,a-Glucobeptosc 


. c 






4-0 


4'5 


^-Glucose . . 


. c 




So ., 




4'5 




. c 




Methyl alcohol 


0-85 


1-6 


B- " hydrate 


. c 


H,0 


Bo per cent, alcohol 


1-3 


3-0 


B- „ . . 


. c 




Bo „ 


4'9 


9-1 


a-LactOM hydrate 


. c 


.H,0 


40 




2-4 


a-LyxoBe , 
jS-Ha1(0Be hydrate 


. c 
. c 


.H,0 


90 

60 


5-4 
3-0 


7-9 
475 


jS-Mannose 


. c 




80 




iS^o 




. c, 




Methyl alcohol 


078 


4'4 




. c 


.aH,0 


So per cent alcohol 


0-76 


1-3 




. c 


H,0 


Absolute alcohol 


8-6 


9'5 




. c. 


H.'0 


70 pet cent, alcohol 


8-a 


9-6 


»-Xyloae . 


. c 




80 „ 


27 


6-2 


Sucrose . 


. c 




80 


37 


37 




. c: 


.3H,0 


70 


1-8 


1-8 




e . C 


.5H,0 


S° 


"■4 


1-4 



The More Important Derivatives of Glucose. 

The experimental work of the last ten years has shown that most of 
the derivatives of glucose likewise exist in two or more forms differing 
in physical properties, more particularly crystalline form, optical rota- 
tory power and melting-point The chemical behaviour of all these 
substances is such that it must be assumed that the aidehydic function 
has disappeared, giving rise' to the closed-ring structure already 
formulated. 

Glucose Pentacetates. 

Under proper experimental conditions, all five hydroxyl groups 
in glucose become acetylated, the a- or ^-pentacetate predominat- 
ing in the product according to the method adopted. As these 
compounds form the starting-point for a number of syntheses, it is 
important to understand fully the methods of preparing them. 



GLUCOSE (DEXTRO-GLUCOSE OR DEXTROSE) 25 



They have the fdllowing formulae : — 

AcO— CH 
HCOAc 



AcO 




HC— OAc 

/ 
HCOAc' 



AcO 



[Ac = C^HjO] 




HC 



HC.OAc 



OAc 
a-Glucose pentacetate. 



i, 



;h, . OAc 

jS-Qlucose pentacetate. 



To obtain the g-pentacetate it is necessary to acetylate glucose 
instantly before isomeric change can take place, since the presence of 
acid greatly accelerates the isomeric change from a- to )8-glucose. This 
is done by adding anhydrous a-glucose to boiling acetic anhydride con- 
taining a small quantity of zinc chloride as catalyst. A violent action 
ensues, and the sugar passes into solution. The product is poured into 
water, which is changed from time to time to remove the acetic acid ; 
finally the a-glucose pentacetate solidifies. The crude product contains 
both isomerides : it is purified by crystallisation from alcohol. The 
a-pentacetate predominates^sQ when glucose is acetylated in pyri - ^ 
^ dine solution at 0°. 

To obtain the j8:pentacfitate, glucose is mixed with acetic anhydride 
and sodium acetate, and heated for some time at the temperature of 
the water bath. As the change from a- to /9-glucose in this case pre- 
cedes acetylation, )8-glucose pentacetate predominates in the final 
product, and may be separated by fractional crystallisation. 

The pentacetates are colourless crystalline compounds, insoluble 
in water and readily hydrolysed by alkaline hydroxides. When heated 
with acetic anhydride either form is partially converted into the other 
until equilibrium is attained when 90 per cent, of the a and 10 per 
cent, of the /9 form are present. Jungius has shown that this change 
may also be effected by adding a small amount of sulphur trioxide to 
a solution of the acetate in chloroform. 

In the case of galactose no less than four pentacetates have been 
isolated. 

The )8-butylene-oxide form was first prepared by Erwig and 
Koenigs by acetylating galactose with acetic anhydride and sodium 
acetate. Hudson and Parker find that when this form is boiled with 
acetic anhydride and a little zinc chloride the o-butylene oxide isomer- 
ide is obtained to the extent of about 70 per cent, of the original 



26 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

material. The usual method of separating the /8-pentacetate is to 
pour the acetylation product into cold water. Hudson finds that the 
chloroform extract of this water after filtering off the /8-pentacetate 
contains a third isomeride, and this on treatment with zinc oxide in the 
manner described is converted into a fourth isomeride in small quanti- 
ties — only about lo per cent, of the original. The isomerides have the 
following physical constants : — 



TABLE III. 



No. 


Structure. 


Melting-point. 


Wd- 


I 

2 

3 
4 


3-Butylene oxide 

a- II II • • 

jS-Ethylene oxide . 

O- II II • . 


142 

95*5 
98 

87 


+ 7*5° 
+ io6-o° 

-42° 



Hudson regards his new isomerides as possessing an oxide structure 
other than a butylene oxide, and in the light of the foregoing pages 
the ethylene oxide structure may provisionally be assigned to them. 

Acetochloroy Acetonitro Glucoses, — In either isomeride, one of the 
acetyl groups — that attached to the terminal carbon atom (in Clarendon 
type) linked to the pentaphane oxygen atom — is jar_jnQi:eactive than 
the rest. When subjected to the action of anhydrous liquid hydro- 
gen bromide or hydrogen chloride in sealed tubes at the ordinary 
temperature, this acetyl group alone is displaced by halogen. In this 
way a-pentacetyl glucose gives a-acetochloro glucose, j8-pentacetyl 
glucose the corresponding ^-acetochloro glucose — both beautifully 
crystalline colourless substances. Nitric acid acts in a similar manner, 
causing the formation of crystalline a- and /S-acetonitro glucoses : — 



HC . NO3 

/ 
HC . OAc' 



HC . OAc 

HC . OAc^ 



AcO . CH 
HC 



° JE^*) AcO.L 



HC.OAc 



,1. 

CHo. 




(HCl) 



HC . OAc 



OAc 



i 



Ho . OAc 




H, . OAc 



jS-Acetonitro glucose. jS-Glucose pentacetate. j3-Acetochloro glucose. 

Physical measurements also indicate that one of the acetyl groups 
is more easily detached than the others. This is proved by the fact 
that the rate at which the acetyl groups are removed by hydrolysis 
with alkali from the glucose pentacetates decreases as change pro- 



GLUCOSE (DEXTRO-GLUCOSE OR DEXTROSE) 27 

ceeds ; yet the tetra-acetyl methyl glucosides, which contain four simi- 
larly placed acetyl groups but lack the one contiguous to the pentaphane 
oxygen, are hydrolysed by alkali at a rate which is constant throughout 
the whole change. 

Hudson in a similar manner has obtained a new acetochloro galac- 
tose from his third /8-ethylene oxide pentacetate, and it is obviously 
possible to obtain a whole series of ethylene oxide derivatives of 
galactose in this manner. 

The chloro-, bromo- and nitro- groups are even more reactive than 
the acetyl group, and are easily displaced — for example, by methoxyl 
\ t — on shaking a solution of the compound in anhydrous methyl alcohol 
]\ with silver carbonate. The isomeric tetra-acetyl me thyl glucosid es 
thus obtained are converted, when hydrolysed by an alkali, into the 
corresponding isomeric methyl glucosides. These syntheses make it 
possible to pass from )8-glucose to /9-methyl glucoside through a series 
of )8 compounds and to correlate all these compounds with y8-glucose. 

Acetochloro and acetobromo glucose have been rendered easily 
accessible by a more convenient method of preparation : powdered 
crystalline anhydrous glucose, dissolved in about five times its weight 
of acetic anhydride, is boiled with half its weight of anhydrous sodium 
acetate fo r two or t hreejiours. The product is poured into a large 
volume of ice-water and the crude )8-glucose pentacetate is freed as 
much as possible from acetic anhydride by pulverisation under water 
and then crystallised from 96 per cent, alcohol, when it is obtained in 
74 per cent, yield. 

One part of the pentacetate is left with two parts of the commercial ,. . 
solution of hydrobromic acid in acetic acid, for two hours at the ordi- j ' ^ 
nary temperature. Four parts of chloroform are added and the mixture 
shaken with twice its weight of ice-water ; the chloroform extract is 
run off and the residue again shaken with a little x;hloroform, after 
which the united chloroform solutions are washed with water, dried 
over calcium chloride, and the chloroform removed under a vacuum. 
The oily residue is triturated with light petroleum until crystallisation 
sets in and subsequently the collected crystals are rapidly recrystallised 
from a little amyl alcohol, washed with light petroleum, and stored in 
a vacuum over soda-lime. 

Irvine considers that Hudson's method of simultaneous bromina- 
tion and acetylation by a solution of hydrobromic acid in acetic anhy- 
dride is superior in many ways to the above. 

Acetoiodo glucose has also been prepared. In all cases, by this 
method only the )8 derivatives are obtained. Apparently rearrange- 
ment takes place very readily during the preparation of a acetochloro 



28 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

glucose by means of anhydrous hydrogen chloride and the a derivatives 
are not always obtainable ; indeed, Fischer has cast some doubt on 
their existence. 

Mono-, di-, tri-, tetra- and two isomeric pentabenzoyl derivatives of 
glucose have been prepared. The most interesting of these is 6-mono- 
benzoyl glucose which proves to be identical with the natural com- 
pound vacciniin isolated by Griebel from the whortleberry. 

When )8-acetobromoglucose is shaken in ethereal solution with 
silver carbonate and a little water tetra-acetyl glucose is obtained ; 
this, like tetra-methyl glucose, exhibits mutarotation and exists in two 
forms. It yields a phenylhydrazone. 

Hudson has isolated a /9-tetra-acetyl galactose having the ethylene 
oxide structure which shows mutarotation with increasing dextro rota- 
tion. Acetobromo glucose also interacts with pyridine, forming tetra- 
acetyl glucose {jyridinium bromide. 

Anhydroglucose. 

When the action of anhydrous hydrogen bromide on glucose pent- 
acetate is prolonged dibromo-triacetyl glucose, 

O- 



II 

CHaPr . CH(OAc) . CH . (CH . OAc)a . CHBr, 

is obtained. One of the bromine atoms can be displaced by methoxyl 
with the formation of triacetyl methyl glucoside bromohydrin. This 
compound has served as the starting-point for the preparation of a new 
isomeride of glucosamine (p. 64). When it is heated with barium 
hydroxide hydrogen bromide is eliminated, and anhydromethyl gluco- 
side, C7H12O5, is formed ; this when hydrolysed by dilute acids yields 
anhydroglucose, a well-characterised crystalline substance. It forms 
a phenylhydrazone and phenylosazone, both containing one molecule 
of water less than the corresponding glucose compounds. On the 
assumption of a butylene-oxide ring structure for the new anhydride, 
anhydro glucose will have the attached formula. This is fully in har- 

HCOH 

/ 

a HCOH 

fi CH 




GLUCOSE (DEXTRO-GLUCOSE OR DEXTROSE) 29 

mony with the deductions possible from the solid model of glucose. 
The €-carbon being free to rotate can take up the position indicated, 
which is favourable for the formation of a butylene-oxide ring, linking it 
with the ^-carbon atom through oxygen. The second bromine atom 
in triacetyl-dibromo glucose is in the e-position, as proved by the 
reduction to a methylpentose (page 84). 

Anhydromenthol glucoside has been obtained in a similar manner 
to anhydromethyl glucoside ; it is of interest that emulsin is without 
action on either compound, though it readily hydrolyses the normal 
glucosides. 

It would appear that the possibility of the existence in nature of 
anhydrides of glucose and of glucosides is not excluded, since the 
reduction product of anhydroglucose, anhydrosorbitol, is an isomeride 
of naturally occurring styracitol. 

Glucal. 

When )8-acetobromoglucose is reduced by zinc dust and acetic 
acid, a peculiar compound, to which Fischer has given the name of 
glucal, is produced (after removal of the acetyl groups). It is a slightly 
sweet, soluble, viscid syrup of aldehydic properties, forming oily hydra- 
zones but no osazones, and evidently possesses ethylenic unsaturation, 
since it decolorises bromine water. Fischer's later formula for glucal 
is : — 

CHa(OH) . CH . CHj . CH(OH) . C : CH(OH). 
I ^O -J 

When it is hydrogenated in presence of palladium, hydroglucal is 
formed, the double bond disappearing ; the same product is obtained 
when acetylglucal is hydrogenated in similar manner and then hydro- 
lysed. 

The evidence for the formula does not seem entirely conclusive, 
and it is conceivable that an explanation on the basis of the ethylene 
oxide isomerides of the sugars may later serve to explain the abnormal 
reducing powers of the compound ; the formation of a butylene-oxide 
ring between the second and fifth carbon atoms of the chain appears 
unusual. 

Methyl Glucoses. 

The properties of the hydroxyl groups in glucose can be masked 
by their replacement by acetyl or benzoyl groups. The ethers so 
formed crystallise well, but the acid groups render these compounds 
resistant to the action of enzymes ; they are, moreover, too easily re- 
moved in subsequent interactions. The substitution of methoxyl for 



30 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 



/ 



hydroxyl has a less disturbing influence ; indeed, methylation has little 
effect on the characteristic chemical reactions of reducing sugars except 
in increasing stability. The reducing sugars themselves cannot be 
directly methylated by any of the ordinary methods ; but, as Purdie 
and Irvine have shown, it is possible to methylate the methyl glucosides 
by exhaustive treatment with methyl iodide^nd silver oxide. The 
products are purified by distillation in vacuum and subsequently ob- 
tained crystalline. 

This method has proved of the greatest value, since it has been 
found that during the reaction stereochemical changes such as racemisa- 
tion, the Walden inversion, or interconversion of glucosides, do not 
take place. On the other hand, it is expensive, for very large excesses 
of the costly methyl iodide and silver oxide are necessary, and the 
recent work of Haworth, who has succeeded in determining the con- 
ditions under which commercial sodium hydroxide and methyl sulphate 
in aqueous solution may be employed without detriment to the optical 
purity of the products, is a welcome improvement. 

Briefly, the sugar, dissolved in the least quantity of water, is stirred 
at a constant temperature of 70°, and in the course of an hour three 
times the theoretical amount of the new alkjdating reagents are 
simultaneously added from two separate funnels ; subsequently the 
temperature is raised to 100° for half an hour. A slight alkalinity 
must be maintained throughout, for even the transitory local existence 
of an acid system tends to induce hydrolytic changes, whilst, of course, 
excessive alkalinity causes enolisation, resinification, etc., to set in. 

Sometimes, by this method, the last hydroxyl group to be attacked 
is left wholly or incompletely methylated owing to diminishing solu- 
bility of the products in the medium, and in these cases it is well to have 
recourse to the former method for the final stages of the methylation. 

The isomeric a- and ^-pentamethyl glucoses (e.g. tetramethyl- 
methyl glucosides), when hydrolysed by acids, are converted into tetra- 
methyl glucoses : — 



MeOC— H 




CHaOMe 



a-Pentamethyl glucose. 



HOC— H 



HCOMe 

I 
MeOCH 



HC' 



i 



HCOMe 



i 



HgOMe 
a-Tetramethyl glucose. 



GLUCOSE (DEXTRO-GLUCOSE OR DEXTROSE) 31 

Both compounds yield finally the same tetramethyl glucose of 
constant rotatory power, but initially a- and ^-tetramethyl glucoses are 
obtained from them, which exhibit mutarotation and slowly change in 
solution into the equilibrated mixture. Tetramethyl glucose is con- 
verted by Fischer's method of etherification into a mixture of a- and 
/8-tetramethyl-methyl glucosides. 

Tetramethyl glucose is not fermentable, but tetramethyl ^-methyl 
glucoside is hydrolysed by emulsin, a fact which indicates that the 
introduction of the methyl groups into a glucoside does not put the 
resulting compounds out of harmony with enzymes. 

A number of other sugars have been fully alkylated in like manner. 

The partially methylated derivatives of the sugar group possess 
a special interest, as their study has already afforded a clue to many 
of the vexed questions in carbohydrate chemistry. Definite mono-, 
di- and trimethylated hexoses have been prepared by Irvine, and 
their investigation has already assisted materially in the character- 
isation of the new ethylene oxide forms of glucose which have been 
described on page 13. The methods employed in their preparation 
consist in subjecting to methylation by the silver iodide method 
hexose derivatives in which certain of the hydroxyl groups a re shiel ded 
from attack ; for instance, the terminal (aldehydic) hydroxyl may be 
transformed to niethyl glucoside before the operation^or other of the 
hydroxyl groups may be temporarily occupied in condensation com- 
plexes with compounds such as_benzaldehyde or acetone. The partially 
methylated glucoses are obtained on submitting these compounds to 
hydrolysfer / 

Thus, glucose diacetone forms only a monomethyl derivative, from 
which on hydrolysis 6-monomethylglucose, 



7 



CHaCOMe) . CH(OH) . CH . [CH(OH)]a . CH(OH), 

I O I ' / 

is obtained. It is of interest that above about 35° C. the acetone 
groups are removed simultaneously and at the same rate. 

Both ja and j8 forms of the monomethyl glucose have been ob- 
tained crystalline and optically pure. The new compound forms a 
monomethyl glucosazone, identical with that obtained from 6-mono- 
methyl fructo se, in which the methoxyl group has been proved to occupy 
the terminal position, since it yields dihydroxymethoxybutyric acid on 
oxidation which is incapable of forming a lactone. Neither form of 
monomethyl glucose is attacked by yeast ferments. 

To prepare dimethyl glucose (probably the 2, 3- compound), benzyl- 
idene a-methyl glucoside is methylated and the product hydrolysed. 



32 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

first the benzylidene group and then the glucoside group being elimin- 
ated. Both a- and ^-isomerides of the compound have been prepared ; 
it has the constitution — 

CH,(OH) . CH(OH) . CH . [CH(OMe)]j . CH(OH) 

I O 1 

It yields a crystalline phenylhydrazone, but, as would be expected, 
no phenylosazone, since number 2 hydroxyl is not available ; its be- 
haviour to enzymes does not seem yet to have been studied. 

When methyl glucoside is methylated in methyl alcoholic solution 
a trimethylglucose methylglucoside is the main product from which 
2-, 3-, 5-trimethyl glucose is obtained on hydrolysis : — 

CH,(OH) . CH(OMe) . CH . [CH{OMe)i • CH(OH) 

' O 1 

When glucose diacetone, referred to above, is hydrolysed for several 
hours at about 30° C, only one acetone group is removed, and when 
the product, glucose monoacetone, is alkylated a trimethyl derivative 
is formed which gives 3-, 5-, 6-trimethylglucose on hydrolysis : — 

CH(OMe) . CH(OMe) . CH . CH(OMe) . CH(OH) . CH(OH) 

I O ! 

Probably two forms of this carbohydrate exist, but they have been 
obtained so far only in the equilibrated mixture, the optical behaviour 
of which appears to be abnormal and requires investigation. 

Denham and Woodhouse have isolated a crystalline trimethyl- 
glucose from cellulose and show that it is probably 'the 2-, 3-, 6-isomer- 
ide :--r 

CHa(OMe) . CH(OH) . CH . [CH{0Me)]2 . CH(OH) 

J O ^ 

Thio-derivatives. — Glucose interacts with two molecules of a thio- 
alcohol forming well-characterised crystalline mercaptals : — 

/SEt 

CHj(OH) . (CH . OH)4 . CH<; 

\SEt 

The amyl mercaptal is sparingly soluble and ^amylmercaptan 
has been used by Votocek for resolving racemic aldoses, e.g. 
arabinose. 

Thio-derivatives of glucose are also obtained when a pyridine 
solution of the sugar is saturated with hydrogen sulphide. The silver 
salt of these closely resembles that of thioglucose obtained by Schneider 
from thiourethane glucosides and sinigrin. He considers it to be a 
mixture of the salts A and B, in the proportion 2:1. 



O 



Iv - " ' 



CHj(OH) . CH(OH) . CH . (CH . OH), . CH . SAg ... A 



.CH.(CH.OH)o.CH. 



CHj(0H).CH(0H).CH.(CH.0H)2.CH.SAg , . . B 



GLUCOSE (DEXTRO-GLUCOSE OR DEXTROSE) 33 

Anilides^ Hydrazones^ Oximes. — The interactions involved in the 
formation of anilides, hydrazones and oximes of glucose are most 
simply explained, on the assumption that the sugar is participating in 
a typical aldehyde reaction. None the less the occurrence of more 
than one form of all these derivatives forces the adoption of the closed- 
ring formula in such cases. Skraup early showed that a second phenyl- 
hydrazone of glucose could be isolated, isomeric with that described 
originally by Fischer. Isomeric benzyl phenylhydrazones have also 
been obtained. The rotatory power of hydrazones changes in solution. 
It would go too far to discuss the nature of the isomerism here, nor is 
it yet satisfactorily established, but it may be pointed out that glucose 
phenylhydrazone may be formulated in syn- and anti-forms of the 
true aldehydic derivative, or as a- and )8-hydrazides of butylene-oxide 
structure, nor does this exhaust the possible isomerides. 

Irvine and Moody have shown in the case of tetramethyl glucose 
that both the oximes and anilides possess the butylene-oxide ring in 
the hexose residue, and are thus to be regarded as derived from the 
a- or )8- form of glucose, and not from an aldehydic isomeride. Their 
conclusions may reasonably be extended to the oximes and anilides 
of glucose, the latter of which Irvine and Gilmore have shown to exist 
in two modifications. The same authors failed to alkylate glucose 
phenylhydrazone or tetramethyl glucose phenylhydrazone, and con- 
sider it still an open question whether these derivatives belong to the 
butylene-oxide type. 

The properties of a number of these derivatives are summarised in 
the following table : — 

TABLE IV. 





A-Series. 


jS-Series. 


Glucose Derivative. 














M.'pt. 


[«3d. 


M..pt. 


Wp. 


Penta-acetate 




112° 


+ 100° 


134° 


+ 3° 


Acetochloro 




63° (?) 


— 


73° 


+ 165° 


Acetobromo 




79° (? 


— 


88° 


+ 198° 


Acetonitro . . 




92- 


+ 1*5° 


150° 


+ 149° 


Tetra-acetylmethyl 




100° 


+ 137° 


105° 


- 23° 


Methyl glucoside 




165° 


+ 157° 


104° 


- K 


6-Monomethyl glucose 




157° 


+ 96° 


130° 


+ 32 


2 : 3-Dimethyl glucose 




85° 


+ 82° 


108° 


+ 6° 


2:3: 5-Trimethyl glucose . 




— 




— 


— 


2:3:6- „ „ 




— ^ 


— — 


-^— 


— - 


3:516- „ „ . 




— 


— 




■— 


2:3:5: 6-Tetramethyl glucose . 


— 


101° 


— 


+ 73° 


Pentamethyl glucose . 


" 


154° 




- »7° 



34 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

Stereoisomerism of the Aldohexoses. 

A compound represented by the empirical formula, 

CHj(OH) . CH(OH) . CH(OH) . CH{OH) . CH(OH) . CHO, 

containing four asymmetric carbon atoms, should, according to the 
Le Bel-van't Hoff hypothesis, be capable of existing in sixteen stereo- 
isomeric forms, eight of which would be mirror images of the other 
eight and of equal but opposite rotatory power. 

Thus, corresponding to ordinary dextro-glucose (d^glucose), there 
should be a laevo-rotatory isomeride (/-glucose) of equal and opposite 
rotatory power, of like configuration but having the dissimilar radicles 
in reversed order.^ In point of fact, when glucose is prepared by arti- 
ficial means from optically inactive material, a mixture in equal pro- 
portions of d and / forms is actually obtained. Such a mixture is 
optically inactive — whether the two forms actually combine or merely 
neutralise one another in optical effect is unknown. 

Although only three aldohexoses occur naturally (glucose, man- 
nose, galactose), fourteen of the sixteen possible isomerides are now 
known. Emil Fischer, to whom we owe the discovery of this remark- 
able series, has not only shown how they may be prepared, but has 
made them in such ways that their structural relationship may be 
regarded as established. His results are summarised in the following 
table : — 

^ The fonnulae assigned to d- and /-glucose are chosen arbitrarily ; that is to say, it 
is assumed that in the d form the groups occupy a certain position, whence it follows that 
in the stereoisomeride they are present in the reversed position. For the original proof of 
the validity of the formulae and the arguments by which they are deduced, the reader is 
referred to Fischer's summary in the Berichte der deutschen chemischen Gesellscha/t for 
1894 (p. 3189). A further convention is to indicate as belonging to the d- series all com- 
pounds derived from dextro-glucose by simple reactions which leave the stereochemical 
structure of the molecule unchaf%ed. In many instances, as for example ^/-fructose and 
^-arabinose, the new compound rotates polarised light to the left, so that the prefix does 
not give a correct indication of the sense of the rotation. Similarly all compounds derived 
from laevo-glucose are designated as of the / series though they may be dextro-rotatory. It 
has been possible to connect the amino acids, hydroxy acids and some other optically active 
substances with dextro-glucose, so that the prefix d has a very definite significance in these 
cases, the number of which is likely to increase. Unfortunately, in other cases the prefix 
merely denotes the sign of the rotation, so that <i-mandelic acid, for example, which is 
dextro-rotatory, forms a laevo-rotatory nitrile, which is therefore termed /-mandelo nitrile. 
A new symbol other than 4 to connote relationship to <^glucose appears highly desirable. 



GLUCOSE (DEXTRO-GLUCOSE OR DEXTROSE) 35 



CHO 



H— 
H- 
HO- 



HO- 



— OH 
—OH 



-H 
-H 



CH3OH 
/-Mannose. 



TABLE V. 



ALDOHEXOSES. 



CHO 



HO— 

HO— 

H- 



— H 
— H 
-OH 



H OH 

CHjOH 
<{- Mannose. 



CHO 



HO— 

H— 

HO- 



HO- 



— H 
—OH 
— H 
— H 



CHjOH 
/-Glucose. 



CHO 



H 
HO 



-OH 



— H 

H OH 

H OH 

CHjOH 
d-G\ucose, 



CHO 



HO— 
H- 



HO— 
H— 



— H 
-OH 



— H 
-OH 



CH2OH 
/-Idose. 



CHO 



HO— 

H— 



H— 
HO— 



— H 
-OH 



—OH 
— H 
CH2OH 



/-Galactose. 



CHO 



H- 



HO— 

H— 

HO— 



-OH 



— H 
—OH 
— H 



CH,OH 
<{-Idose. 



CHO 



H— 
HO— 
HO- 

H- 



— OH 
— H 
— H 
—OH 



CHjOH 
^/-Galactose. 



CHO 



H- 

H- 
HO- 



H— 



-OH 
-OH 



H 



—OH 



CHjOH 
/-Gulose. 



CHO 



H- 
H- 
H- 



HO— 



-OH 



-OH 



OH 



— H 



CHjOH 
/-Talose. 



CHO 



HO— 
HO- 



H— 
HO— 



— H 
-H 



—OH 

— H 

CHjOH 
<i-Gulose. 



CHO 



HO- 



HO— 

HO— 

H— 



-H 

-H 
— H 
—OH 



CH2OH 
</-Talo8e. 



HO- 



HO- 



CHO 
-H 
-H 



CHO 



CHO 



CHO 



HO— 
HO- 



— H 
— H 



CHjOH 

/-Allose 
unknown. 



H— 
H— 
H- 
H- 



— OH 
—OH 
—OH 
—OH 



CHjOH 
^/-Allose. 



H— 
HO— 
HO- 



HO— 



—OH 
— H 
— H 
— H 



CHjOH 

/-Altrose 
unknown. 



HO- 
H— 
H— 
H— 



— H 
—OH 
-OH 
—OH 



CHaOH 

<f- Altrose. 



As two closed-chain butylene oxide as well as two closed-chain 
ethylene oxide forms should exist corresponding to each of the open 
chain aldehydic forms, no less a number of isomeric ** glucoses " is 
foreseen by theory than 16 + 32 +32 = 80. 

The last four aldohexoses in the table remained unknown to 
Fischer, though he pointed out that they were to be derived theoreti- 
cally from the isomeric riboses, only one of which had at that time been 

3* 



36 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 



prepared. The discovery by Levene and Jacobs that rf-ribose is a 
constituent of nucleic acids, from which it can be obtained in quantity, 
has enabled two of the missing aldoses to be prepared. By the 
application of the cyanohydrin synthesis (p. 58) to rf-ribose, ^-allose 
and rf-altrose were obtained as syrups both yielding the same phenyl- 
osazone. Their behaviour on oxidation is in agreement with the 
structural formulae assigned to them. 

It is desirable to indicate briefly the manner in which the configura- 
tion of the sugars has been determined, as the same methods serve in 
the case of new compounds which may be found to occur naturally. 

The most straightforward method of procedure is to determine first 
the structure of the pentoses and from them that of hexoses. 



H— 
H— 
H— 



CHO 
-OH 



—OH 

—OH 

CHjOH 

I. 



CHO 

HO— tr-H 

H__i^OH 
H— ^OH 
CH,0H 

2. 



H- 



HO— 
H— 



CHO 
—OH 
— H 
—OH 

CH2OH 



CHO 



HO— 
HO- 



H- 



— H 
— H 



—OH 
CH2OH 



There are eight possible aldopentoses, that is four pairs of optical 
antipodes, and considering only the d forms there are four alternative 
formulae. 

The relevant facts are : — 

(i) Arabinose and ribose give the same osazone, hence their con- 
figuration must be identical except as regards the a-carbon atom. 
And arabinose and ribose must be (i and 2) or (3 and 4). 

(2) On oxidation arabinose gives an optically active dibasic acid ; 
ribose and xylose give optically inactive dibasic acids. Pentoses 2 
and 4 will give an optically active dibasic acid, from i and 3 the acids 
will be optically inactive. 

Hence arabinose is either 2 or 4, ribose and xylose are I and 3, 
lyxose is either 4 or 2. 

(3) When HCN is added to the pentose and a new asymmetric 
carbon atom introduced, and the compound is subsequently oxidised 
to a dibasic acid it is found that arabinose gives a mixture of two acids 
both of which are optically active, whereas lyxose gives a mixture of 
two acids, one active and one inactive. 

This can only happen in the case of 4 : — 



COOH 



COOH 



HO— 

HO— 

H— 



CHO 
-H 
H 



—OH 
CH2OH 



H— 

HO— 

~HO— 

H— 



—OH 
— H_ 
— H 
—OH 
COOH 

in Active. 



and 



HO— 

HO— 

HO— 

H— 



— H 

— H 

— H 

—OH 

COOH 

4l^active. 



GLUCOSE (DEXTRO-GLUCOSE OR DEXTROSE) 37 



Accordingly lyxose has the constitution 4 so that arabinose is 2, 
ribose i, and by elimination xylose is 3. 

Proceeding from the pentoses to establish the formula of the 
hexoses we have : — 

(i) Arabinose gives rise by Kiliani's reaction (addition of HCN) to 
two hexoses, glucose and mannose : — 

CHO CHO 



CHO 



HO— 
H— 
H— 



— H 

—OH 

—OH 



H— 

HO— 

H— 

H— 



—OH 
— H 
—OH 
-OH 



and 



HO— 

HO— 

H— 

H— 



— H 
— H 
—OH 
—OH 
CHjOH 

6. 



CHaOH CH2OH 

2. 5. 

Hence glucose must be either 5 or 6. 

(2) The same dibasic acid is produced on oxidation of glucose as 
from another hexose (gulose), viz. saccharic acid This means that the 
configuration of each of the four asymmetric carbon atoms is the same 
and that, therefore^ the difference between the two sugars is that their 
primary alcohol (CHgOH) and aldehydic groups are interchanged. 



CHO 



COoH 



H— 

HO— 

H— 

H— 



—OH 

— H 

—OH 

-OH 

CHjOH 

5. 



H— 

HO— 

H— 

H— 



—OH 
— H 
—OH 
—OH 



H- 

HO- 

H- 



CHgOH 

-OH 

-H 



CHO 



H— 



COjH 
2. 



—OH 
—OH 
CHO 



I.e. 



HO— 

HO— 

H— 



— H 
— H 
—OH 
— H 



CHmOH 



In the case of 5 a new sugar 7 is formed by this process of inter- 
change : — 



CHO 



HO- 
HO— 

H— 
H— 



— H 
— H 

OH 
—OH 
CHjOH 

6. 



HO- 



COjH 
-H 



HO— 
H— 

H— 



— H 

—OH 

—OH 



HO— 
HO— 
H— 
H- 



CHjOH 



CHO 



COjH 



— H 
— H 



—OH 
OH 
CHO 



I.e. 



HO— 

HO— 

H— 

H— 



H 

H 

—OH 

—OH 

CH3OH 



8. 



In the case of 6 the same sugar 8 is formed by interchanging the groups. 

Accordingly, glucose is represented by formula 5, mannose by 
formula 6, and gulose by formula 7. An extension of the reasoning 
leads to the formulae for the other hexoses. 

A useful suggestion for the simplification of the symbols showing 
the sterical relationships of the sugars has been made by Wohl. In- 
stead of ^^riting the whole formula vertically attention is confined to 
the H anc^ OH groups on one side of the molecule (the right) only, and 
these are written down in order. If it is agreed to consider the alde- 
hyde group as being to the right of the formula when written horizon- 
tally, rf-gjicose is OH OH H OH. 

The following table shows all the possible tetrose, pentose, and 
hexose sugars derived from rf-glucose, i.e. THE SUGARS OF THE d 
SERIES, according to Wohl's symbols : — 



38 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 



TABLE VI. 



Triose. 


Tetroses. 


Pentoses. 


Hezoses. 






rOH OH OH 


/OH OH OH OH <i-aUose 
\OHOHOH H rf-altrose 




r OH OH 


^-ribose 




d-etythiose 


' OH OH H 


/OH OH H OH rf-glucose 
\0H OH H H rf-mannose 


OH 




,^-arabinose 


4-glycerose 


- 


rOH H OH 


/OH H OH OH /.gulose 
\0H H OH H /-idose 




OH H 


J /-xylose 




v^threose 


lOH H H 


/OH H H OH rf-galactose 
\OH H H H rf-talose 






V <i-lyxose 



The optical antipodes of these sugars — the /-series — are derived 
from /-glycerose or /-glucose and can be incorporated in a similar table. 

Wohrs work on glycerose has fortunately established that the 
nomenclature of the sugars as d and /, based originally by Fischer on 
their derivation from rf-glucose, is equally the same when based on 
rf-glycerose. Consequently, in the above table the / symbols of threose, 
xylose, gulose and idose should properly become d. It is therefore 
proposed for the sake of uniformity to make the alteration in this edition, 

rf-Glycerose is happily both dextro-rotatory and genetically related 
to rf-glucose. Since in it the only hydroxyl is to the right of the 

molecule, Wohl suggests the symbol ^for this position of the hydroxyl. 

Accordingly, glucose is ddld aldohexose, and symbols can be given to 

the sugars which avoid the use of H and OH. Fischer originally used 

+ and - to denote the position of these groups and his nomenclature 

seems less likely to lead to confusion than the use of d and /. 

As the final result of the above considerations it can be stated that 
the rfand /nomenclature of the sugars is based on their relationship to 
d and / glycerose, that is on the configuration of the fifth carbon'^atom, 
and is irrespective of the direction of their optical rotatory powen 



Rotatory Powers of the a and ^ forms of Sugars. 

Relation between Rotation and Configuration. 

Most of the carbohydrates exist in more than one form and show 
mutarotation. Before dealing with their numeric relationships a word 
is required as to the nomenclature of the derivatives of sugars of the 
dextro and laevo series. As proposed by Hudson in the case of a 
dextro sugar the a form is that which is most dextro-rotatory whereas 
for a laevo sugar the reverse is the case, the more laevo-rotatory (i.e. less 
dextro-rotatory) modification being regarded as the a form. On this 
basis a-rf-glucose becomes the optical antipode of a-/-glucose. 



GLUCOSE (DEXTRO-GLUCOSE OR DEXTROSE) 30 

Ordinary crystalline maltose is thus a )8-sugar ; crystalline fructose 
IS a )8-sugar and not a-fructose as previously supposed. Natural xylose 
is considered to be genetically related to rf-glucose and not to /-glucose, 
as supposed by Fischer. 

According to van't HofTs principle of optical superposition, as 
applied by Hudson, the molecular rotation of a sugar is essentially 
dependent on two factors: (i) the optical effect of the asymmetric 
system containing the reducing group, and (2) the rotatory power of 
the remaining asymmetric system. If these factors are represented by 
A and B respectively : — 

a-glucose (M)d = 20,340 = + A + B, 
/3-glucose (M)d = 3»420 = - A + B, 

whence by subtraction 2 A = 16,900 and by addition 2B = 23,760. 

It is shown from the available data, firstly that the difference be- 
tween the molecular rotations of the a and ^ forms of the aldehyde 
sugars and their derivatives (^A) is a nearly constant quantity, and 
secondly that the a and ^ forms of those derivatives of any aldose sugar 
in which only the end carbon atom is affected have molecular rotations, 
the sum of which (2B) is equal to the sum for the a and ^ forms of 
the aldoses. 

This method enables the calculation of the rotation of the unknown 
isomerides of many of the sugars and their derivatives and is proving 
of the utmost value in elucidating questions as to their structure, as 
will be illustrated hereinafter. 

Hudson has further shown that the mutarotating sugars have as a 
•comftion property a measurable maximum rate of solution, which is 
caused by the slow establishment in solution of the equilibrium between 
the a and 13 forms of the sugar ; those sugars, such as sucrose, trehalose, 
raffinose, which do not reduce Fehling's solution or show mutarotation, 
do not exhibit this maximum rate of solution. 

Experimental evidence of the rotatory powers of those sugars for 
which both modifications have not yet been crystallised and measured 
directly has been obtained by measuring the maximum rate of solution, 
or the initial and final solubilities — e.g. for xylose, arabinose, lyxose, 
ribose, mannose, fructose, gluco-heptose, maltose, cellose. 



\ 

V 








^' 



l^r-?*. 



46 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 
The results are summarised in the following table : — 

TABLE VII. — Rotatory Powbrs of tbb Hutarotatino Suoahs. 



Sugu. 


M. W. 


Foraul.. 


Sp«i 


cRotUiODiD 


W...r. 


Moleciilu 














■ Form. 


Conit. Rot. 


flPorm. 


DJSmo^ 




180 


c , 


+ I13'4 


+ Sa"2 


+ 19 


+ 16,900 


d-GalactoBc 




180 


c , 


+ l44'o 


+ 80-5 


+ 53 


+ 16,600 


<MiIuino8e 




180 


c , 


+ 34 


+ 14*6 


- ^7 


+ 9,180 


d-FruclOBe 




180 


c , 


-31 




- ■33'5 




d-Xyiose . 




ISO 


c , 


+ 92 


+ 19 


~h 


+ 16,800 


d-LyxoK . 




ISO 


c , 


+ 5'5 


- 14 


- 36 


+ 5,a2o 


d-Atabiaose 




IJO 


c , 


~5i 


- 105 


- 175 


+ 18,100 


i-Rhamnose 




164 


c , 


- 77 


+ 8-g 


+ 54 


- 10,000 


o-Glncoheptose 






c 


+ 45 


- M-4 


- a8-4 


+ 15.300 


Lac'toee . 




342 


C t„ 


+ 90-0 


+ 55'3 


+ 35 ■ 


+ 18,800 


MaltoM . 




342 


C l„ 


+ 168 


+ 136 


+ n8 


+ 17.100 


Melibiose . 




34a 


C 1,, 


+ 179 


+ r42'5 


+ 134 


+ 18.800 


CelloM . 




342 


C_ .. 'u 


+ 72 


+ 35 


+ 16 


+ 19,200 






Calculated valuci in italics. 







In the last column are recorded the differences between the molecular 
rotations of the respective alpha and beta forms of each aldose. If the 
rotatory power of the end asymmetric carbon atom in these aldoses has 
the value + A for the a-sugar and - A for the fi form, and the rotation of 
the remainder of the structure is B, the molecular rotation of an a-sugar 
is A + B, and of its ^ form - A + B, and the difference of these values is 
2 A. It is to be expected, on the view that the value of A is not influenced 
by changes in the configuration of the remainder of the molecule, that this 
difference 2A is a constant for all the aldoses. The last column shows 
that the theory is fairly well borne out except in the case of mannose, 
lyxose and rhamnose. Fructose is not considered, since it is a ketose and 
does not apply in the theory. The negative sign for the difference in the 
case of rhamnose is the result of the system of nomenclature for the 
a and /3 forms and is due to the fact that rhamnose is an /-series sugar. 
Now the configurations of i^mannose, i^lyxose and /-rhamnose are 
H OH H OH OH H 



[CH 

iCH 6 



HCOH 
O HCOH 



HCOH 
HjCOH 
<j- Mannose. 



CHs 



d- Lyxose. i- Rhamnose. 

and it will be observed that these configurations are identical (or anti- 
podal) from the 7-carbon atom upward. It appears probable, therefore, 
that the exceptional value of the difference for these sugars may be de- 
pendent upon this type of conf^ration. Since, however, a^lucoheptose 



GLUCOSE (DEXTRO-GLUCOSE OR DEXTROSE) 41 



has the same configuration from the 7-carbon upward, and nevertheless 
shows a molecular difference nearer, though not equal, to the average 
value for most of the aldoses, this possible connection between structure 
and exceptional rotation remains in some doubt. In the case of closely 
related sugars, such as the four disaccharides, the agreement between 
theory and experiment is very good when it is recalled that it has been 
possible to make the measurements only by an indirect procedure. 

A comparison of the formulae of glucose, mannose, xylose, lyxose, 
which differ only in the configuration of the a-carbon atom and their 
molecular rotations has enabled Hudson to deduce the value of the 
molecular rotation of this carbon as + 4, 500 for glucose and xylose 
and - 4,500 for mannose and lyxose. 

The glycol glucosides may be quoted as examples of Hudson's 
second rule : — 

(M}d. 
a-Glucose 20,340 = A + B 
/3-Glucose 3,420 = -A + B 

Sum 23,760 = 2B 

Glycol-a-glucoside 30,347 = A' + B 
Glycol-/8-gluco8ide 6,843 = - A' + B 

Sum 23,504 =: 2B 

whilst the monomethylglucoses afford a further example of the first 
rule : — 

Monomethyl-a-glucose 20,874 = A + B' 
Monomethyl-iS-glucose 4.733 = -A + B' 

Difference 16,141 = 2 A 

For glucose the difference is 16,900. 

The relative ease with which the isomeric fully acetylated deriva- 
tives are prepared and purified makes them especially suitable for 
testing the relation of rotation and constitution. The difference in 
the molecular rotations of the a- and ^-sugars should be a constant as 
is evidenced by the following figures : — 

TABLE VIII. 



Substance. 


Molecular Rotation 
of a form. 


Molecular Rotation 
of /3 form. 


Difference. 


<f-Glucose pentacetate . 
^-Lactose octacetate 
£^- Maltose octacetate 
d-CeXlose octacetate 
^-Glucosamine pentacetate 
^^-Chondrosamine pentacetate 
</-Gentiobiose octacetate 
i-a-Glucoheptose hexacetate . 
<f-Mannose pentacetate . 
d'GaXzctose pentacetate . 
<f-Xylose tetracetate 
/-Arabinose tetracetate . 




+ 39,600 

+ 36.500 
+ 83,000 

+ 27,800 
+ 36,400 
+ 39.500 
+ 35.500 
+ 40,200 
+ 21,400 
+ 41,600 
+ 28,300 
+ 13.400 


+ 1,500 

- 2,goo 
+ 42,500 

- 10,200 

+ 470 
+ 4,100 

- 3.600 
+ 2,200 

- 9,800 
+ 8,900 

- 7.900 
+ 46,800 


+ 38,100 
+ 39,400 
+ 40,500 
+ 38,000 

+ 35,930 
+ 35,400 
+ 39.100 
+ 38,000 
+ 31,200 
+ 32,700 
+ 36,200 
- 33,400 



42 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

The sign and magnitude of the optical rotatory power enable a 
considerable insight to be gained into the structure of the molecule. 
For example, it is established in the case of twenty-four lactones of 
the monobasic sugar acids and eleven lactones of the saccharinic acids 
that polarised light is rotated to the right or to the left according as 
the butylene oxide ring on the 7-carbon is on the right or left of the 
configuration (when the formula is written with the acid group on top, 
as on p. 54). Accordingly, the configuration of the 7-carbon atom of 
any new lactone can at once be determined from its rotation. 

Similar deductions as to the configuration of the a-carbon atom 
may be made from the direction of rotation of the phenylhydrazide of 
the acid. If the phenylhydrazide rotates to the right the hydroxyl on 
the a-carbon atom is on the right, and vice versa. 

In gluconic acid, for example, there are four asymmetric carbon 

atoms, a, ^, 7, S, and the molecular rotation may be expressed as 

+ a, -^, +7, +S, the + value indicating an hydroxyl on the right. 



a HO 

$ HOCH 

,i 

HC( 

A 



COOH 

:oH 

J, 

HCOH 

:oH 

I 
JHaOH 

Hudson has deduced values for a, ^, 7 and S, by solving the four 
equations for the phenylhydrazides of gluconic, gulonic, idonic and 
galactonic acids, for which the rotations have been measured by Nef. 
He finds the comparative values ( x 10^) are — 

a + 37*3°, 3 + 3*9°, 7 + i-4°» « - 0'6°» 

showing that the value of a, the rotation of the a-carbon atom is so 
very much larger than the values of the rotagtions of the other three 
carbons that its sign determines the direction of the rotation. 

The same rule holds good in the case of the amides of these acids, 
of which Weerman has measured the rotatory power. The specific 
rotations are small so that the calculation is only approximate, but it 
yields the following figures — 

a + 32°» 3 - 10°, Y - i^ 5 - 7«, 

which show once again that the direction of rotation is influenced by 
the a-carbon atom. 

Levene finds for the salts of the monobasic acids that the con- 



GLUCOSE (DEXTRO-GLIICOSE OR DEXTROSE) 43 

figuration of the a-carbon atom has a strong influence on the rotation. 
The values calculated from his observations are — 

a + 22°, 3 + 13°, y + 12°, 8 - 4^ 

These are quite different from those found for the phenylhydrazides 
and amides, owing perhaps to the salts being largely dissociated. It 
is evident further that the influence of the a-carbon is less than that 
of the sum of the other three carbons. 

Lastly, it may be mentioned that the benzylphenylhydrazones of 
the sugars rotate to the left when the asymmetric a-carbon atom of 
the configuration has its hydroxyl to the right, and vice versa. 

Enough has been said to show the large amount of certainty with 
which a part of the configuration formula of a sugar may be deduced 
from the optical rotation of its derivatives, and it is to be expected 
that the extension of these methods of investigation will go far to 
clear up the outstanding problems of structure both for the carbo- 
hydrates and other aliphatic hydroxy compounds. 



CHAPTER II. 

THE CHEMICAL PROPERTIES OF GLUCOSE AND THE HEXOSES. 

Glucose, the other aldoses and the ketoses in gfeneral show a great 
tendency to become further oxidised ; this is evidenced by their activity 
as reducing agents. They reduce alkaline copper solutions on warming, 
forming red cuprous oxide, likewise ammoniacal silver solutions forming 
a metallic mirror. When heated with alkali, a sugar solution colours 
at first yellow, subsequently brown and finally decomposes ; a variety 
of substances, including lactic acid and other hydroxy acids, are formed. 
Valuable analytical methods for the estimation of glucose are bas^ on 
the reaction with copper salts in alkaline solution, but the precise changes 
which the sugar undergoes under these conditions are not completely 
understood. 

When carbohydrates are kept with alkali hydroxide at 37° the 
optical rotation of the solution decreases and the acidity increases. 
Sodium hydroxide exerts the greatest action, sodium carbonate being 
considerably weaker ; ammonia of the same strength is almost without 
action. 

The ketose sugars without exception are decomposed when their 
aqueous solutions are exposed in quartz tubes to sunlight Carbon 
monoxide is evolved and the corresponding alcohol containing one 
carbon atom less is formed. The aldose sugars are practically un- 
affected under these conditions. Exposure of the ketoses to the ultra 
violet light from a mercury lamp brings about the same decomposition, 
but other actions also take place involving the formation of hydrogen, 
methane, formaldehyde and non-volatile acids. The aldoses are de- 
composed in a similar manner to the ketoses by ultra violet rays but 
are less susceptible to attack. 



44 



"n 



PROPERTIES O F GLU COSE AND THE HEXOSES 45 

Interconverrflhi cflT CrHRftse, Fructose and Mannose. 

Glucose, fructose and mannose pass over into one another in aqueous 
solution in presence of alkalis. This most important transformation was 
first observed by Lobry de Bruyn and Van Ekenstein ; it takes place 
slowly at ordinary temperatures, quickly and with much decomposition 
at higher temperatures. Starting from glucose, the optical rotation is 
observed to fall to about 0° ; considerably more fructose than mannose 
is formed in the final product. The change was rightly explained by 
Wohl as due to conversion^ into, the enpjic (unsaturated) form common 
to all three tarbohydratdg^.-^ • » - **** " 



CHO 

HCOH 

I 
HOCH 



CHO 



Hi 
,i 



HCOH 



HOCH 

,i, 

HC( 



HOCH 

:oH 

HCOH 



CHa(OH) 

CO 

>CH 



i 



:H2(0H) 
Glucose. 



CH2(0H) 
Mannose. 



HO 

;0H 
HCOH 

i 



CH(OH) 

II 
C.OH 

>CH 



CH(OH) 

l\o 

HC/" 



Ha 



H0( 
HCOH 



HOCH 



A 



HCOH 



OH 



OH 



Ha(OH) 
Fructose. 



J, 



IHa(OH) 
Enolic form. 



„i 

Hi 

CHj(OH) 

Ethylene 
oxide form. 



The sugar originally present is slowly transformed into enol ; this 
is reconverted into all three of the possible hexoses. It is to be sup- 
posed that the formation of enol from each one of the hexoses and the 
reverse changes all take place with different velocities ; the interchange 
is further complicated by secondary effects. 

For example, fructose can give rise to a second enolic form, and 
this will occasion the formation of other isomerides, e.g. glutose : — 



CHaCOH) 

io 
in 

i, 

HC( 



CHa(OH) 

i, 



HO 

HCOH 

JOH 

CH(OH) 
FructOT^e. 



:oH 



COH 

I 
HCOH 






CH2(0H) 

CH(OH) 

I 
CO 

I 

HCOH 
toH 



HC( 



tH2(0H) 
Second Enolic form. 



CH,( 



.(OH) 

Glutose. 



which Lobry de Bruyn has isolated as a regular product of the trans- 
formation of glucose. The change is obviously exceedingly complicated. 
Prolonged action of the alkali or action at a high temperature leads to 
the formation of hydroxy acids. . In pure aqueous solution glucose can 



46 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 



be kept for years without alteration. This proves that there can be 
no enolic form present in the equilibratea miiture'of a- and )8-glucose 
as is sometimes suggested. It is highly probable that the ethylene 
oxide form, rather than the unsaturated enolic form, is actually pre- 
sent in solution. 

The guanidine compounds of glucose, fructose and mannose show 
changes of rotatory power in aqueous solution due to the interconver- 
sion of the three hexoses brought about by the guanidine. The 
changes are very similar to those caused by alkalis, but fewer second- 
ary changes take place in the case of guanidine. 

Action of Alkalis. 

A very elaborate study of the action of alkalis on carbohydrates 
extending over ten years has been made by Nef. In consequence, a 
complete and relatively simple explanation can now be given of the 
behaviour of any carbohydrate in aqueous alkali hydroxides towards 
oxidising agents such as air, hydrogen peroxide or the oxides of mer- 
cury, silver and copper. In the course of this work a number of the 
sugar acids and their lactones, salts, etc., have been fully characterized. 

According to Nef any carbohydrate in weak alkaline solution 
undergoes profound change but is eventually transformed into an equili- 
brated mixture in which no less than one hundred and sixteen substances 
can in theory take part. These are the thirty-two aldoses with one to 
six carbon atoms, the thirty-two corresponding methylenols, the twenty- 
six ketoses with three to six carbon atoms in an unbranched chain 
and the twenty-six dienols. Actually in practice only ninety-three 
different substances are formed, and in the absence of an oxidising 
agent the different sugars are converted into saccharinic acids. 

In the presence of air or other oxidising agents the oxidation of the 
sugars results in the formation of carbon dioxide, formic, glycollic, 
oxalic and ^/-glyceric acids, four trihydroxy butyric acids, eight tetra- 
hydroxy valeric acids, and eight tetrahydroxyhexoic acids, all of which 
have been isolated and identified. 

The unsaturated enols first formed show a tendency to undergo 
fission at the double bond, and by the spontaneous decomposition of 
the a/3-, fiy- and 7S-dienols, any hexose may yield {a) formaldehyde 
and aldopentoses, (b) diose and aldotetroses, and (r) dZ-glyceraldehyde. 

Taking glucose as a type the following products result : — 

(a) From glucose a)3-dienol -> formaldehyde and arabinose, 
(h) From glucose /3y-dienol -> diose and triose. 
(c) From glucose T^-dienol -> glyceraldehyde. 



PROPERTIES OF GLUCOSE AND THE HEXOSES 47 

An example of transformation (a) which has been the most difficult 
to verify experimentally, is furnished by the formation of ^-arabonic 
acid on oxidation of glucose in weak alkaline solution by air. 

When galactose is oxidised by a stream of air at 30^-40° in presence 
of six equivalents of sodium hydroxide the products from 50 grammes 
of sugar were 1*27 grammes of carbon dioxide, 12*8 grammes of formic 
acid and 41 grammes of non-volatile hydroxy acids. When hydrogen 
peroxide is the oxidising agent the quantity of the C5 acids is less but 
still exceeds the amount of the Q acids, whereas with Fehling's solu- 
tion the reverse is the case. A resin is formed in varying amounts 
during oxidation ; it is considered that this is the explanation why 
the different sugars do not give exactly the same results by titration 
with Fehling's solution. 

When the amount of sodium hydroxide is diminished to 0*5 
equivalent or less the number of substances in the system after equili- 
brium has been attained is much smaller — thus only the six isomeric 
active sugars of the corresponding series are formed, from glucose. 
The equilibrium is limited and the various dienols do not decompose 
under these conditions into aldoses according to fission (a) above. 

The relative quantities of the sugars obtained are strikingly 
different, whilst ketoses are only enolised in quite definite directions, 
i.e. only certain preferred olefine dienols are formed and not all those 
theoretically possible. For example, from glucose and ^ equivalent 
of calcium hydroxide, aldoses and ketoses are formed in approximately 
equal quantities, whilst the aldoses consist of glucose and mannose in 
the ratio of 5 : 1. In the case of galactose only the a/3- and )87-dienols 
are formed and galactose comprises 90 per cent, of the aldoses. 
Arabinose or xylose yield the corresponding three active pentoses. 

In the case of all carbohydrates salt formation with the alkali 
hydroxide takes place at the carbon atom next the carbonyl group 
CH(OH) . CH(OM) . CO. The methylene derivative CH(OH) . C . CO 
forms first glycide and then ortAo-osonQ, CH2 . CO . CO, from which by 
the benzilic acid transformation saccharinic acids are formed. In the 
presence of an oxidising agent the i : 2 osone, CH(OH) . CO . CO, is 
formed. To avoid further changes ortho-oson^ formation must be 
effected in neutral or faintly acid solution, the best reagent being lead 
hydroxide or chloride or basic acetate. 

Both resins and polysaccharides are formed when a sugar solution 
is kept or warmed in contact with very dilute alkali hydroxide or 
carbonate. The polysaccharides synthesized belong to two classes 
according to the ease with which they are hydrolysed by acids. 



J^ 



^ t ^ 



^ 7 ^ ^ 



/ 



. M 4 ^ '^ 



48 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

Nef s investigations give an explanation of the quantitative diflFer- 
ences in the behaviour of the various sugars towards Fehling's solution. 

Saccharinic Acids. 

The saccharinic acids are formed from the hexoses by the action 
of concentrated alkali hydroxide. Twenty-four isomeric acids with 
six carbon atoms are theoretically possible, viz. : — 

(i) Eight stereoisomeric metasaccharinic acids, - 

CH3(0H) . CH(OH) . CH(OH) . CHj . CH(OH) 

derived from the sixteen aldohexoses. 

(2) Four isosaccharinic acids derived from tM||0[it ketoses, 

,C0, 



CHa(OH) . CH(OH) . CHj . C(OH) 



/ 




\ 



CHjOH 



(3) Eight saccharinic acids — 

.CO,H 
CHa(OH) . CH(OH) . CH(OH) . C(OH)<^ 

(4) Four parasaccharinic acids — 

/COaH 
CHa(OH) . CH(OH) . C(OH)<; 

\CH2.CHj(0H) 

The lactones of these acids are termed saccharins. Nef has very 
carefully studied these substances : their fuller treatment lies outside 
the scope of this monograph. 

Since lactic acid and various hydroxy acids result from the action 
of alkalis on glucose, the action of ammonia might cause the formation 
of alanine or other amino acids. Windaus and Knoop, in investigat- 
ing this point, find that the strongly dissociated zinc hydroxide ammonia 
acts on glucose even in the cold, producing methyl glyoxaline, a closed- 
ring compound containing nitrogen. Amino acids are not formed. To 
explain this transformation, it is assumed that glyceric aldehyde is 
first formed, which passes into methyl glyoxal ; this in its turn is acted 
upon by ammonia and formaldehyde to give methyl glyoxaline : — 

CHj . C . NHv 
CH3 . CO . CHO + 2NH3 + HCHO = II ' \CH 

Windaus finds that the reaction is not confined to glucose, but that the 
same methyl glyoxaline is yielded by mannose, fructose, sorbose, 
arabinose, xylose and rhamnose, or by the disaccharide lactose. 

The formation of the glyoxaline nucleus from the sugars is of con- 
siderable interest in view of the important place this holds among 
natural products. Thus it is present in ergot, in pilocarpine and in 



PROPERTIES OF GLUCOSE AND THE HEXOSES 49 

the purines. Further, by condensation of methylglyoxaline with 
glycine and simultaneous oxidation, histidine is formed. 



Interaction with Phenyl Hydrazine. 

Particularly characteristic is the behaviour of the sugars with ex- 
cess of phenyl hydrazine on heating in dilute acetic acid solution. An 
orange-yellow insoluble phenyl osazone is formed, which serves to 
characterise glucose even when present only in very small quantities, 
though not to distinguish it from some of the isomeric hexoses which 
give the same or closely related phenyl osazones. The use of phenyl 
hydrazine possesses further a historical interest, as in the hands of 
Emil Fischer it served as one of the chief aids in the elucidation of the 
chemistry of the carbohydrates. 

Glucose and phenyl hydrazine interact in acid solution, acetic acid 
being usually employed, in two stages. In the first, which takes place 
in cold solution, a phenyl hydrazone is formed : — 

^Hr^Oj + C^Hj . NH . NrfD= CjHnO. . CH : N . NH . Cfl^ + HjO 

This is a colourless compound, soluble in water, existing in two 
modifications, one or other of which is obtained according to the method 
of preparation. 

Skraup's )8-phenyl hydrazone, formed by shaking glucose with 
phenyl hydrazine in alcoholic solution, crystallises in needles, m.p. 
1 06*'- 1 07°, and has an optical rotation in aqueous solution of [aj^ - 2** 
changing to - 50°. Fischer's a-isomeride, formed in alcoholic acetic 
acid solution, crystallises in leaflets, m.p. 15 9°- 160*', [a]^ - 70** changing 
to - 50°. Behrend has shown Skraup's )8-isomeride to be in reality a 
compound of phenyl hydrazine (i mol.) with 2 molecules of the /8- 
hydrazone. This hydrazone also forms an additive compound with 
pyridine which, on treatment with alcohol, yields glucose fi-phenyl hy- 
drazone, m.p. 140°-! 41°, [ajo - 5 "5*. Behrend has advanced evidence to 
show that this is a true hydrazone, 

CHalOH) . [CH(0H)]4 . CH : N . NHPh, 

whereas Fischer's glucose a-phenyl hydrazone is a hydrazide : — 



O 



CHj(OH) . CH(OH) . CH . [CH(OH)]a . CH . NH . NHPh 

It should be capable of existing in two stereoisomeric forms (cp. p. 33). 

The phenyl hydrazones of glucose and most of the other sugars, 

being easily soluble, are not adapted for characterising the parent sugars. 

An exception is afforded by mannose, which forms an almost insoluble 

4 



50 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 



phenyl hydrazone and can thus be very readily detected. This com- 
pound affords a striking illustration of the influence exercised by the 
configuration of the molecule on its physical properties. Sparingly 
soluble phenyl hydrazones are also formed by the methyl pentoses. 

Asymmetrically disubstituted hydrazines of the type, NHj . NR . 
C^Hg, such as methylghenyl, benzylphenyl or diphenyl hydrazines, also 
react with the sugars, and some of these hydrazones are spa^ingtjr^oluble 
and are characteristic of a particular sugar. Many of them are in- 
cluded in the following Table IX. In some instances two forms of the 
hydrazone have been described. 

Thus the methylphenyl hydrazone is characteristic of galactose and 
the diphenyl hydrazone of arabinose. The influence of the position of 
the OH groups on the physical properties is even more marked in the 
case of the dihydrazones formed with diphenylmethane dimethyl dihy- 
drazine, CH2[CcH4NMe. NH2I (Braun). Hydrazones are only pro- 
duced when at least two or three of the hydroxy! groups attached to 
the carbon atoms immediately adjacent to the aldehydic group have 
the same spatial configuration. Thus, rhodeose, fucose, mannose, 
galactose, ribose, lyxose, arabinose, and rhamnose give hydrazones 
with this reagent, whilst isorhodeose, glucose, and xylose do not. It 
is suggested that the reagent may be useful in deciding questions of 
configuration of the aldoses in view of this peculiarity. 



TABLE IX. — Melting-points 


OF Sugar Hydrazones and Osazones 


• 




Arabinose. 


Glacose. 


Mannose. 


Galactose. 


Maltose. 


Lactose. 


Hydrazones, 














Phenyl hydrazone 


I5i°-i53° 


/ii5°-ii6°\ 
\i44°-i46°/ 


ise'-iss" 


158° 




— 


^-Bromophenyl hydrazone . 


150° 


147" 


mS'-sio" 


168° 


— 




o-Methylphenyl hydrazone . 


161° 


130° 


178° 


180° 


— 


— 


a-£thylphenyl hydrazone . 


153° 


— 


159° 


169*' 




— 


a-Amylphenyl hydrazone . 


120° 


128° 


^K 


H6° 




123° 


o-AUylphenyl hydrazone . 


'< 


'55! 


142° 


'57: 




132° 


a-Benzoylphenyl hydrazone 


170° 


165° 


'^5! 


154° 




I28« 


Diphenyl hydrazone • 


218° 


161°' 


155° 


157° 




— 


/B-Naphthyl hydrazone 


141° 


• 


157° 


167° 


176° 


203*^ 


Osazones, 














Phenyl osazone . 


160° 


208° 


208° 


193'' 


206° 


200** 


^-Bromophenyl osazone 


196^-200° 


222° 


— 


— 


198° 


— 


/-Nitrophenyl osazone 




257° 


~ 




261° 


258^ 



To prepare the phenyl osazone, glucose is heated with a considerable 
excess of phenyl hydrazine ^ (3-4 mols.) and acetic acid, the vessel being 

^ It is important that the phenyl hydrazine should be almost colourless and free from 
oxidation products. 



PROPERTIES OF GLUCOSE AND THE HEXOSES 51 

immersed in rapidly boiling water for an hour or more, when the in- 
soluble osazone separates : it is best purified by crystallisation from a 
dilute solution of pyridine. The excess of phenyl hydrazine acts as 
an oxidising agent towards the phenyl hydrazone, converting the 
penultimate - CH(OH) group into - CO and being itself reduced to 
aniline and ammonia. The CO group so formed interacts with a 
further molecule of phenyl hydrazine to form the osazone : — 



CHO 
CH(OH) 
H(OH) 
CH(OH) 



d 



d 



H(OH) 



CH2(0H) 
Aldose 



CH : N . NHPh 
CH(OH) 
CH(OH) 
CH(OH) 

i 

CH2(0H) 
Hydrazone 



H(OH) 



CH : N . NHPh 

do 

CH(OH) 

i, 

CH(OH) 

CHa(OH) 
Oxidation product 



CHrN.NHPh 
. C:N. 



NHPh 



iH(OH) 



I 



H(OH) 
H(OH) 



CH(OH) 

CH2(OH) 
Osazone 



Glucose, mannose and fructose yield the same phenyl osazone, 
since the asymmetry of the ancarbon atom is destroyed in its formation. 
The osazones of the different sugars are as a class very similar in pro- 
perties, those formed by the disaccharides being distinguished by their 
greater solubility in boiling water. The melting-points of the osazones 
depend very largely on the rate of heating and on the method of puri- 
fication adopted, and too much dependence is not to be placed on them 
in identifying unknown sugars. Fischer, for example, states that care- 
fully purified glucosazone heated rapidly in a narrow capillary tube be- 
gins to melt at 208° (corrected), and completely melts at this temperature 
with decomposition if the source of heat be withdrawn. When heating 
is continued at the same rate the thermometer rises to 213° before the 
• glucosazone completely melts. When the heating is slower the sub- 
stance begins to sinter and melt at 195°. In the case of the disacchar- 
ides, where the purification of the osazone is more difficult, the 
determination of the exact melting-point is even less reliable. 

The asymmetrically disubstituted hydrazines do not form osazones 
with glucose on account of their being unable to act as oxidising agents. 
Fructose is more easily attacked by them, probably in consequence of 
the presence of the CHgCOH). CO group, and yields a methylphenyl 
osazone. 

It is often a matter of considerable difficulty to obtain a carbohyd- 
rate in a pure state from solutions which may also contain inorganic 
salts or nitrogenous substances. One of the methods adopted is to 
isolate the phenyl hydrazone, purify this by crystallisation, and decom- 
pose it into sugar and phenyl hydrazine. Fischer originally used fuming 



\ 



52 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

» 

hydrochloric acid to effect the decomposition. Benzaldehyde was sub- 
stituted for this by Herzfeld ; the phenyl hydrazone is boiled in water 
with a slight excess of benzaldehyde, and the phenyl hydrazine removed 
from solution as insoluble benzaldehyde phenyl hydrazone, 

CeHiaOj : N . NHPh + CgH, . CHO = C^ti^fif^ + CjHjCH : N . NHPh. 

This method was repeatedly adopted with success by Fischer, but it 
gives less satisfactory results with the disubstituted hydrazones, in which 
case formaldehyde may with advantage be substituted for benzaldehyde, 
as suggested by Ruff and Ollendorf. The hydrazone is dissolved in 
dilute formaldehyde and heated at the temperature of the water bath, 
QHiA : N . NRR' + HCHO = QHiA + H . CH : N . NRR'. The 
excess of formaldehyde is removed and the pure sugar solution concen- 
trated in a vacuum. 

Fuming hydrochloric acid acts on the osazone in the same manner 
as it does on the hydrazone, eliminating in this instance both hydrazine 
groups to form an osone : — 

CH:N.NHPh HCl, HoO CHO HCl.HjN.NHPh 

CrN.NHPh HCl, HjO CO HCl. HaN. NHPh 

CnrOH) CI 



:H(0H) CH(OH) 

CH(OH) C 

i 



H(OH) CH(OH) 

H(OH) CH(OH) 



)Ha(OH) CH,(OH) 

Phenyl osazone. Osone. 

Glucose, mannose and fructose, which form the same phenyl osazone, 
likewise form the same osone. These osones are colourless syrups ; 
they act as strong reducing agents, and combine directly with phenyl 
hydrazine or with disubstituted phenyl hydrazines forming osazones. 
The osones combine also with (?-phenylene diamine. They are not 
fermentable. On reduction glucosone is converted into fructose. This 
is the only method available of regenerating a sugar from the phenyl 
osazone. When the sugar originally used was an aldose the correspond- 
ing ketose results. The method is of great historical interest, as by its 
aid Fischer established the nature of the synthetical a-acrose. The 
osazones of the disaccharides are hydrolysed by acids to hexose, 
hexosone and phenylhydrazine — 

CjHuG, . O . CjHio04(NjHPh)a + 2HCI + sHjO 
= C«HuOj + CjHioOj + 2NHj . NHPh . HCl 
Hexose. Hexosone. 

— and Fischer's hydrochloric acid method is thus not available for the 
conversion into osone. Since, however, the osazones of the disac- 



PROPERTIES OF GLUCOSE AND THE HEXOSES 53 

charides are soluble in boiling water, it is possible to remove the phenyl 
hydrazine residues by means of benzaldehyde (Fischer and Armstrong), 
and so obtain the osones — 

CgHjiOff . O . CHa . [CH . OH], . CO . CHO 

These osones are similar to glucosone in properties : they are hydro- 
lysed by enzymes in the same way as the parent disaccharides. 

Reduction. 

When reduced with sodium amalgam, glucose and its isomerides 
form the corresponding hexahydric alcohols, two hydrogen atoms 
being added to the hexose. Sorbitol is formed from glucose, mannitol 
from mannose, and dulcitol from galactose. Fructose yields a mixture 
of the two alcohols, sorbitol and mannitol, since a new asymmetric 
carbon atom is formed from the ketonic radicle. These alcohols 
have the following configuration formulae : — 

CH2.OH CH..OH CH-.OH 

I I I 

HC.OH HO.CH HC.OH 

HO . CH HO . CH HO . CH 

HC.OH HC.OH HO.CH 

HC .OH HC . OH HC . OH 

CHj . OH CH2 . OH CH, . OH 

Sorbitol. Mannitol. Dulcitol. 

All three alcohols occur in plants, mannitol being widely distributed. 
In the fungi and some other orders mannitol exceeds glucose in quan- 
tity, or even replaces it None of the alcohols are fermented by 
yeasts ; mannitol, however, is a product of some bacterial fermenta- 
tions, and is attacked by many moulds and bacteria. Dulcitol, no 
doubt on account of the difference in configuration, is in general far 
more resistant to bacterial attack. 

All these alcohols are sweet, well-crystallised compounds quite 
soluble in water and alcohol. They form hexacetyl, hexabenzoyl^ 
and explosive hexanitro derivatives, also compounds with acetone 
and benzaldehyde. 

Their configuration is discussed in detail in the next chapter. 



54 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 



Oxidation. 

Glucose on oxidation gives rise to three acids containing the same 
number of carbon atoms ; two of these acids are monobasic, the third 
is dibasic. Their structure is as follows : — 



CHO 


CO,H 


CHO 


CO3H 


(CH . OH)^ 
CHaOH 

Glucose. 


(CH . OH)^ 
CHjOH 
Gluconic acid. 


(CH . OH)^ 
COjH 
Glucuronic acid. 


(CH . OH)4 
COaH 
Saccharic acid. 



In g^luconic acid the aldehyde group of glucose is oxidised to carboxyl : 
it is conveniently prepared by the action of bromine on glucose. 
Gluconic acid in solution very readily passes over into a 7-lactone, the 
change, which is accompanied by an alteration in rotatory power, being 
a reversible one. The reaction is not compile, but continues until an 
equilibrium between acid and lactone is reached. Mannose and other 
aldoses form mannonic acid and similar acids corresponding to gluconic 
acid. 

As pointed out by Hudson these 7-lactones, like the aldose sugars 
and their gliicosidic derivatives, all of which have a butylene-oxide 
structure, exhibit strong optical rotatory power, whereas the corres- 
ponding alcohols and acids, which are open-chain compounds, are but 
slightly active. The rotatory power is evidently connected with the 
butylene-oxide constitution, and the sign of the rotation must depend 
on the position of the ring, which is in turn dependent on the position 
of the hydroxyl group attached to the <y-carbon atom before the ring 
was produced. ^According to Hudson the dextro-rotatory lactones 
have the ring on one side of the structure, whilst the laevo-rotatory 
lactones have rings on the other side as is illustrated by the lactones 
of gluconic and galactonic acids. 

CO CO 





Gluconic lactone. 
[o]d + 68°. 



OH 

,0H 

Galactonic lactone. 
Wd - 7*07°. 



The theory has been extended to the determination of the constitu- 
tion of lactones of unknown structure. It does not apply to the aldoses 
themselves or to the glucosides. 



PROPERTIES OF GLUCOSE AND THE HEXOSES 55 

Whereas most of the monobasic sugar acids form ry-lactones, 
rf-mannonic acid is remarkable in that when liberated from its salts 
at the ordinary temperature it changes almost entirely into a P^ 
lactone. 

CHa(OH) . (CH . OH)^ . CH . CH(OH) . CO 

To obtain the 7-lactone it is necessary to evaporate a solution of 
the acid or of the )3-lactone to dryness, preferably in presence of a 
little hydrochloric acid. The )ff-lactone rapidly undergoes spontaneous 
conversion into the parent acid in aqueous solution and is much less 
stable than the 7-lactone. Similarly, gluconic acid yields both a ^- and 
a 7.1actone, and Nef claims that bimolecular a-lactones are also formed 
by the hydroxy acids. 

The behaviour of the methylated mannonic acids lends no support 
to the idea that a-lactones are readily formed. Thus Irvine and 
Paterson have shown that the acid 

CHa(OMe) . CH(OMe) . CH(OH) . [CH . OMe]j . COjH 

forms a lactone whereas 

CH2(0Me) . (CH . OMe)g . CH(OH) . COgH 

could not be converted into any such derivative. 

The rate of action of bromine water on the aldoses is influenced 
considerably by their configuration : galactose, for example, is much 
more rapidly oxidised than glucose. (Votocek and N^mecek.) 

An important property of gluconic and similar acids, and one which 
has been of the utmost value in effecting the synthesis of the sugars, 
is their behaviour on heating with quinoline or pyridine. It is well 
known that in most substances containing an asymmetric carbon atom, 
rearrangement takes place, when they are 'heated, so as to form the 
corresponding antimere mixed with the original substance. When 
gluconic acid is heated with quinoline or pyridine at 130°-! 50° it is 
partially converted into mannonic acid The rearrangement is appar- 
ently restricted to the groups attached to the a-carbon atom, as is the 
case in the transformation of glucose to mannose by alkalis. It is 
reversible, mannonic acid being converted into gluconic acid : — 

CO3H COjjH 

H . C . OH > HO . C . H 

(CH . 0H)8 ^ (CH . 0H)3 

CH2OH CHgOH 

d-Gluconic acid. c^Mannonic acid. 

Similarly, rf-galactonic and rf-talonic acid are mutually interconvertible. 

Saccharic acid is formed by the action of nitric acid on glucose ; 

it forms a sparingly soluble acid potassium salt, -which serves as a 



56 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

test for glucose. Saccharic acid is also produced from sucrose, raffinose, 
trehalose, dextrin and starch, all of which contain glucose. On the 
other hand, mucic acid — the corresponding oxidation product of 
galactose — is produced by the action of nitrig acid on galactose, 
dulcitol, lactose, melibiose and the gums. 

Free saccharic acid is crystalline; in solution it passes into the 
monobasic 7-lactonic acid until equilibrium is attained, (he rotatory 
power rising from 97" to 22*5°. The lactone crystallises in leaflets : 
in solution the rotation falls from 38° to 22** as it is converted into the 
free acid. 

Mucic acid has a sandy crystalline structure and is optically in- 
active. When distilled alone pyromucic acid (furfurane-a-carboxylic 
acid) is formed. Heating with hydrobromic acid converts it into de- 
hydromucic acid (furfurane-oa-di-carboxylic acid). 

Glucuronic Acid/ — Physiologically the most interesting oxidation 
product of glucose is glucuronic acid, which is frequently found in the 
urine, combined with a variety of substances, forming compounds of 
glucosidic nature. Normally glucose is rapidly oxidised in the animal 
organism to carbon dioxide and water. When certain substances, 
such as chloral or camphor, which are oxidised in the body only with 
difficulty, are brought into the system, the organism has the power of 
combining them with glucose to form glucosides. In such compounds 
one end of the glucose molecule is shielded from attack, but oxidation 
takes place at the other extremity of the molecule, and a glucuronic 
acid derivative is formed. They are excreted in the urine. The 
faculty of removing injurious substances from circulation in combination 
with glucose seems to be common to both the animal and the v^etable 
kingdom, and the glucosides in the plant may be compared to the 
glucuronic acid derivatives in the animal. The glucuronates behave 
like glucosides, and form glucuronic acid when hydrolysed by mineral 
acids. The glucuronate most commonly employed for the preparation 
of the acid is euxanthic acid, a substance obtained in India from the 
urine of cows which have been fed with mango leaves. Euxanthic 
acid is very readily hydrolysed by dilute acids and breaks down into 
euxanthon, i.e. 2 : 8-hydroxyxanthone and glucuronic acid — 

CijHigOii = CijHgO* + CjHjoG^ 

A vast number of substances when introduced into the organism 
are excreted in the urine as " paired ** glucuronic acid compounds. 
Almost every organic group yields an example. The most important 
are included in the following list : — 

^ Also written Gtycuronic acid. 



chloral 


benzene 


turpentine oil 


butylchloral 


nitrobenzene 


camphor 


bromal 


aniline 


borneol 


dichloracetone 


phenol 


menthol 




resorcinol 


pinene 




th3rmol 


antipyrine 




a- and /3-naphthol 


etc. 



PROPERTIES OF GLUCOSE AND THE HEXOSES 57 

isopropyl alcohol 
methylpropyl carbinol 
methylhexyl carbinol 
tertiary butyl alcohol 
tertiary amyl alcohol 
pinacone 

As the formula indicates, glucuronic acid is the first reduction product 
of saccharic acid, and it was obtained in this way by Fischer and Piloty 
from saccharic acid lactone. Glucuronic acid forms a lactone which 
crystallises well. The paired acids are laevo-rotatory. 

Since aniline dyes have almost entirely displaced euxanthic acid 
from the market the latter has begome very scarce. A convenient 
source of glucuronic acid has been found in the menthol compound 
obtained in the urine of rabbits after administration of menthol. The 
urine is extracted with ether and ammonia added, when the ammonium 
salt separates (Neuberg). 

According to Neuberg glucuronic acid or an isomeride is produced 
in small quantity when glucose is oxidised by nitric acid for the pre- 
paration of saccharic acid. 

An interesting derivative of glucuronic acid is produced according 
to Sieburg on the administration of nitroso-phenylhydroxylamine to a 
dog. The new crystalline compound is decomposed by emulsin into 
its two components and is considered to be the lactam of /-amino- 
phenolglucuronic acid. 

The administration of chloralose leads to the excretion of a paired 
chloralose glucuronic acid from which chloralose and glucuronic acid 
were the only products obtained on hydrolysis (Tiffeneau). 

Galacturonic Acid. 

Saurez has isolated an isomeric form of glucuronic acid from lemon 
pulp. It gives many of the reactions of glucuronic acid but does not 
form a/-bromophenylhydrazone nor yield glucuronic anhydride ; on 
oxidation it gives mucic acid. 

A similar galacturonic acid has been discovered by Ehrlich in the 
pectin substances from the sugar beet. On heating pectic acid with 
I per cent, of oxalic acid, galactose galacturonic acid is obtained. 
Treatment of pectic acid with alkali leads to the formation of an 
amorphous white powder (a)D = + 270"*, 02^11^02^9 which Ehrlich 
regards as a tetragalacturonic acid, viz. 4CjHi^07 - sHgO. 

This gives all the reactions of the pentoses and of glucuronic acid 
except that on oxidation it forms mucic acid ; ^-galacturonic acid is a 
feebly dextro-rotatory syrup, reducing Fehling's solution in the cold, 



^ i 



.-/."A'/ ^ iJ^<^^^ - "- \*itu'u 



^' )[^i- //^^^v^ //VWw 



/ 

58 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

giving furfural with hydrochloric acid and readily undergoing oxida- 
tion to mucic acid. 

Pectin substances obtained from a large number of plants and 
vegetables have all been shown to be derivatives of this acid, and it 
must be regarded as playing an important part in the structure of 
plant material. The presence of galactose in this oxidised form in 
plants is of the greatest interest. Glucuronic acid is said to have 
been found in the sugar beet, but in view of the above it was probably 
mistaken for galacturonic acid. 

Synthesis and Degradation. 

The methods devised in the laboratory for the formation of carbo- 
hydrates containing a greater or lesser number of carbbn atoms than 
six in the chain are of interest 

The aldoses combine directly with hydrogen cyanide forming 
nitriles ; these, when hydrolysed, give rise to acids containing one, 
carbon atom more than the original carbohydrate. 

C.HnOg . CHO + HCN = CjHi.05 . CH(OH) . CN -*► 
C5H11O5 . CH(OH) . COaH "» CgH^iG^. CH(OH) . CHO 

The lactones of these acids, when reduced with sodium amalgam, 
yield the corresponding aldoses with one carbon atom more than the 
original carbohydrate. 

In this manner glucose can be obtained from arabinose, glucohep- 
tose from glucose. The process has been continued by Fischer as far 
as the aldononoses in the case of glucose and mannose ; Philippe has 
prepared glucodecose. It would be possible by such a method to 
advance step by step from formaldehyde to the highest sugars, but the 
operation would demand the expenditure of very large quantities of 
material. 

The cyanohydrin synthesis, however, is not in reality so simple 
as just pictured, inasmuch as usually two stereoisomeric nitriles are 
formed simultaneously. Arabinose gives both glucose and mannose ; 
glucose yields two glucoheptoses. On the basis of the aldehydic 
formula for glucose a new asymmetric carbon atom is created in the 
nitrile, and, according to the ordinary rules, two forms will be pro- 
duced unless the synthesis is asymmetric in character. Mannose and 
fructose afford the only instances at present recorded in which only 
one nitrile is formed. 

An alternative view of the synthesis, based on the closed-ring 
formula, considers the two nitriles as formed simultaneously from a- 
and /3-glucoses by a process involving first the rupture of the butylene* 



PROPERTIES OF GLUCOSE AND THE HEXOSES 59 



oxide ring, and secondly the addition of hydrogen cyanide. The 
presence of a- and /3-glucose in unequal proportions and the probable 
difference in the rate of formation of the addition product in the two 
cases will explain the formation of the isomeric nitriles in unequal 
proportions. Arabinose gives rise to a preponderance of laevo-rotatory 
mannonic acid, whereas from xylose and lyxose the predominating 
acids are laevo-rotatory. The various stages of the operation are 
formulated below in the case of the a-derivative — 

COjH 




HO— G-H 

/ 
HCOH 



H = 



HO 



HC 
HC.OH 



in 

HC 



OH 



Hydrolysis 



HOCH 

/ 
HCOH 



HOCH 



HC.OH 



I 



Ha. OH 



a-Glucose 



L 
t 



\ 

HCOH 



,i 



HCOH 



IHj.OH 
a-Glucose nitrile 



HC.OH 




CHaOH 
> a-Glucoheptonic acid. 

CHO 



HO.CH 



OH 



Reduction 
> 



HO 



OH 



OH 



OH 



i, 

HC. 

.CH 

HC.OH 

HC.OH 

CHa . OH 
a-Glucoheptose, aldehyde formula. 



Lactone of a-Glucoheptonic acid. 

The degradation of a sugar, i.e. the conversion into one with fewer 
carbon atoms, has been studied by four experimental methods. In 
that of Wohl the oxime of glucose is heated with concentrated sodium 
hydroxide and converted into the nitrile of gluconic acid, from which, 
on further heating, hydrogen cyanide is eliminated and a pentose — d- 
arabinose — formed. The following scheme shows the changes : — 



CHO 

i 



I 



H(OH) 



CH(OH) 

CH(OH) 

CH(OH) 

CHa(OH) 
Qlucbse. 



CH : N . OH 

CH(OH) 

CH(OH) 

CH(OH) 

CH(OH) 

CHa(OH) 
Oxime, 



CN + HaO 
CH(OH) 
CH(OH) 
CH(OH) 

C 



HCN 
CHO 
CH(OH) 
CH(OH) 



H{OH) 



c! 



H5,{0H) 
Nitrile. 



H(OH) 



CH,{OH) 
Arabinose. 



6o THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 



In practice it is preferable to heat the oxime with acetic anhydride 
and a grain of zinc chloride : a vigorous reaction ensues, and the pent- 
acetate of gluconic acid nitrile is formed from which hydrogen cyanide 
is eliminated by treatment with ammoniacal silver oxide. 

The alternative method due to Ruff makes use of Fenton's mode 
of oxidation with hydrogen peroxide and ferrous salts. The aldose 
is first converted into aldonic acid, the calcium salt of which is sub- 
jected to oxidation, with the result that the carboxyl group is eliminated 
and the pentose formed. 



CHO 

CH(OH) 

CH{OH) 

ciH{OH) 

CH(OH) 

CHj(OH) 
Aldohexose. 



COjH 



CH(OH) 
CH(OH) 
CH{OH) 
CH{OH) 
CHa(OH) 



CO, + H,0 

CHO 

CH(OH) 

CH(OH) 

CH(OH) 

CHa(OH) 
Aldopentose. 



Aldonic acid. 

Neuberg has made use of an electrolytic method : the aldose is 
converted into the corresponding acid, the copper salt of which is then 
electrolysed between platinum electrodes. Gluconic acid is in this 
manner converted into ^arabinose and all the steps in the complete 
degradation to formaldehyde may be traversed. The process has been 
carried out with a number of sugars, including melibiose, from which 
a sugar with eleven carbon atoms has been obtained. 

Either of these methods is equally applicable to the conversion of 
a pentose into a tetrose, and by them it would be possible to pass 
from glucose to formaldehyde. 

According to Guebert, mercuric gluconate when heated undergoes 
intramolecular oxidation, forming ^-arabinose in satisfactory quantity. 
Tollens and Boddener find, however, that this method is not applicable 
to the degradation of arabinose. 

Weerman has contributed a new and apparently very useful 
method of degradation of the monosaccharides. Taking glucose- 
arabinose as a case in point, ^gluconamide is produced by saturating 
an alcoholic solution of gluconolactone with ammonia, and this is 
treated with hypochlorous acid, when the following change occurs 
(analogous to the Hofmann reaction with hypobromite) : — 

R . CH{OH) . CO. NHj -> R. CH(OH) . N :C : O -> R.CHO 

In this way a 50 per cent, yield of ^-arabinose was obtained. 

The method has also been applied successfully to the transforma- 
tion of ^galactose to ^lyxose, /-mannose to /-arabinose, and /-arabi- 
nose to /-erythrose. 



PROPERTIES OF GLUCOSE AND THE HEXOSES 6i 

The Aminohexoses. 

Four isomeric aminoglucoses are known, viz. : — 

glucosamine = 2-aminoglucose 
glucosimine = i-aminoglucose 
isoglucosamine = i-aminofructose 
€-glucosamine = 6-aminoglucose 
In addition, the corresponding 2-amino derivatives of other hexoses 
have been synthesised from the pentoses, and one of these, chondros- 
amine, occurs naturally. 

Chitosamine (^-Glucosamine). 

Glucosamine, or aminoglucose, is of interest as being the first 
weH-defined carbohydrate compound isolated from an animal tissue 
(Ledderhose, 1 878). It is obtained by boiling the shells of lobsters, 
particularly the claws, with concentrated hydrochloric acid. The 
glucosamine hydrochloride so formed is a colourless crystalline com- 
pound. Lobster shell consists of carbonate of lime and a substance 
termed chitin, which yields acetic acid and glucosamine on hydrolysis. 
Chitin is stated by Offer to be a monacetyl diglucosamine ; more 
recently Irvine has established the identity of the chitins derived from 
various invertebrate animal structures. He considers chitin to con- 
tain acetylamino-glucose and amino-glucose residues in the proportion 
of three to one, in agreement with the formula (CgoHgoOi^NJ^. 

Glucosamine was obtained by Winterstein from fungus cellulose ; 
indeed chitin seems to be the most important cell-wall material of the 
fungL 
^<^ The glucosamine in Boletus edulis is considered by Ross to pre- 
exist as a glucoprotein and not as a glucoside. Two glucosamine 
residues are said to be present in lycoperdin isolated from the fungus 
Lycoperdum gemmatum. Glucosamine is a constituent of the mucins 
and mucoids. 

Irvine considers that it is still an open question whether glucosamine 
is derived from glucose or mannose, though he inclines to glucose. 
Levene's work on the synthetic amino-sugars makes the mannose for- 
mula much more probable. As aminoglucose it has the formula : — 

H H OHH 
CHaOH. C . C . C . C . CHO 
OH OH H NHg 

which is more properly written in the pentaphane ring form, 

CHj(OH) . CH(OH) . CH . CH(OH) . CH(NHa) . CH(OH) 

I O 1 



62 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

Glucosamine is prepared from the hydrochloride by decomposing 
it with diethylamine (Breuer) or sodium methoxide (Lobry de Bruyn). 
It derives special interest from the fact that it may be regarded as a 
link between the carbohydrates and £r-hydroxyamino acids. The 
synthesis of glucosamine, by Fischer and Leuchs, which at the same 
time established its constitution, thus becomes of enhanced import- 
ance. By the combination of ^arabinose and ammonium cyanide, 
or of rf-arabinoseimine with hydrogen cyanide, ^glucosamic acid, 
CHjCOH) . [CH . OHjj . CH(NH2) . CO2H, was obtained and its lactone 
reduced to glucosamine. Glucosamine forms a penta-acetyl derivative 
and also an oxime, semi-carbazone and phenyl hydrazone, but it cannot 
be converted into glucose, though it gives glucose phenyl osazone 
when heated with phenyl hydrazine. Nitrous acid converts it into a 
compound (QHi^^Og) formerly regarded as a sugar and termed chitose ; 
this forms chitonic acid when oxidised. Glucosamine is often regarded 
as a derivative of chitose, and termed chitosamine. It is perhaps 
desirable to retain this name until its identity as glucosamine or 
mannoseamine has been established. 

Chitose was claimed by Fischer and Andreae to be a hydrated fur- 
furane derivative rather than a true sugar, formed by simultaneous 
elimination of the amino group and anhydride formation. It has the 
formula — 

HO . CH— CH . OH 
(CH,OH).CH CH.CHO 

o 

Irvine and Hynd formulate chitose (anhydro-glucose) with the 
aldehydic radicle present, as in the hexoses, in the butylene oxide 
form — 



o 



CHj(OH) . CH . CH . CH(OH) . CH . CH(OH) 

I o ! 

whereas Levene and La Forge consider it to be a-S-anhydromannose. 
Accordingly, chitonic acid is a-S-anhydromannonic acid whilst the 
isomeric chitaric acid formed by the action of nitrous acid on glucos- 
amic acid is considered to be a-S-anhydrogluconic acid. 

Irvine has prepared an amino methyl glucoside from glucosamine 
and converted it into glucose, thus establishing the relationship between 
glucose and glucosamine. The conversion takes place through the 
following reactions : ^/-glucosamine hydrochloride->bromotriacetyl 
glucosamine hydrobromide->triacetyl amino methyl glucoside hydro- 
bromide->amino methyl glucoside hydrochloride. 



PROPERTIES OE GLUCOSE AND THE HEXOSES 63 

This last compound, like other derivatives of glucosamine, reacts 
abnormally with nitrous acid and does not yield methyl glucoside, 
On methylation by the silver oxide method dimethyl amino methyl 
glucoside is obtained, from which the substituted amino group is expelled 
by heating with barium hydroxide. The product is further methylated 
and converted into tetramethyl methyl glucoside, from which ^-glucose 
results on removal of the methyl groups. 

Irvine and Hynd have also converted glucosamine into ^-mannose 
in almost quantitative yield by the following sequence of reactions : — 

^Glucosamine hydrochloride-^methylglucosamine hydrochloride-^ 
benzylidene methylglucosamine hydrochloride->a benzylidene hexose-> 
^-mannose. A Walden inversion might take place during the course 
of these changes, and probably in the formation of the benzylidene 
hexose, which is effected by the action of sodium nitrite upon the 
preceding amino-compound. 

Glucoseimine^ first obtained by Lobry de Bruyn, is prepared by 
the action of ammonia on glucose dissolved in methyl alcohol. It 
has been held at various times to be an iminoglucose or a nitrogen 
ring compound, but the bulk of the evidence available points to it being 
a i-amino-glucose — 

CHa(OH) . CH(OH) . CH . (CH . OH), . CH . NH„ 

' O ^1 

and isomeric with glucosamine (2-aminoglucose). 

A similar crystalline ethylaminoglucose which exhibits mutarotation 
is formed from glucose and ethylamine. In these compounds hydro- 
lysis with acids takes place so readily that definite salts cannot be 
isolated : this appears to be due to the nitrogen group occupying the 
reducing position on carbon i. 

Isoglucosamine was obtained by Fischer by reducing phenylglucos- 
azone with zinc dust and acetic acid. It forms salts and shows precisely 
similar reactions to those given by glucosamine. It is i-aminofructose, 
with the formula — 

CHa(OH) . (CH . OH), . CO . CHj . NH, 

The reaction is a general one and can be extended to other sugars. 

Lobry de Bruyn has shown that glucosamine in aqueous solution 
changes to a substance which can be obtained more readily by the 
action of alcoholic ammonia on fructose. This substance yields a 
pyrazine derivative on oxidation (Stolte), and its formation from 
glucosamine would appear to take place according to the equation — 

sCeHiaOjN + O = Q^-^^O^^ + sHjO 

The product has been shown to be 2, 5-ditetrahydroxy butylpyrazine. 



64 THE SIMPLE CARBOHYDRATES AND GLUCOSlDES 

A second product — QH^04N — is also formed during this reaction. 
It is converted into glucosephenylosazone without difficulty and is 
produced also by the action of ammonia in methylalcoholic solution on 
glucosone. It is stable towards acids but the nitrogen is easily ex- 
pelled as ammonia by alkalis. Irvine terms it fructoseazine and 
assigns to it the formula — 

I °^i 

CHj(OH) . CH . [CH . OH], . C CH 

\^ 

N 

deriving it from the unknown fructoseimine by the elimination of 
water. 

An isomeride of glucosamine has been obtained by Fischer by the 
following series of operations : )8-pentacetyl glucose, when treated 
with anhydrous liquid hydrogen bromide, forms dibromo-triacetyl 
glucose which reacts with methyl alcohol to give triacetyl )8-methyl 
glucoside bromohydrin. This is converted by ammonia at the ordinary 
temperature into amino )8-methyl glucoside from which the amino 
sugar is obtained on hydrolysis. The new compound reduces Fehling's 
solution but differs from glucosamine in a number of ways, the osazone 
which it yields with phenyl-hydrazine being different from phenyl- 
glucosazone ; it is also less stable to acids. Judging from the produc- 
tion of an anhydro glucose from dibromo-triacetyl glucose (p. 28) the 
amino group in the new isomeride is attached to the carbon atom in 
the terminal position thus : — 

H H OH H 
CH-NHo . C . C . C . C . CHO 
OH OH H OH 

Irvine and Hynd have obtained synthetic aminoglucosides by 
condensing bromo-triacetylglucosamine hydrobromide with an hy- 
droxy compound in presence of a base ; glucosides of two types are 

produced : — 

— o 



(A) CH2(0H) . CH(OH) . CH . CH(OH) . CH . CH OR 

NHj . HCl 

y ° ' 

(B) CH2(0H) . CH(OH) . CH . CH(OH) . CH . CH 

N 

/l\ 
H H R 

When the group condensed with the glucosamine residue consists 
of a short open chain the product possesses properties similar to those 
of o-aminomethylglucoside and thus belongs to type B, which includes 



PROPERTIES OF GLUCOSE AND THE HEXOSES 65 

a modified betaine ring in the molecule. Derivatives which contain a 
benzene nucleus in the glucosidic position behave as true glucosides 
and behave as type A. 

Compounds of type B are remarkably stable towards the hydro- 
lytic action of acids, they are not hydrolysed by emulsin. The normal 
aminoglucosides are easily hydrolysed by acids and both aminosalicin 
and aminohelicin are hydrolysed by emulsin. 

The wide distribution of betaines in nature makes the synthetic 
aminoglucosides of type B of special interest, the more so as they may 
be closely related to glucoproteins. Irvine regards these last as 
glucosamine derivatives in which aminoacyl residues, i.e. short poly- 
peptide chains (Ri, Rg, R3, etc.), occupy the amino position and possibly 
all the hydroxyl positions with the exception of the glucosidic group. 

O 



CH2(0Rg) . CH(ORJ . CH . CH(OR3) . CH — CH 



N- 



i 



R2 Rj G 

Much of the behaviour of the mucins is in agreement with this 
hypothesis. 

Irvine's observations receive support from the fact that when 
glucosamic acid, the oxidation product of glucosamine, is methylated 
by means of methylsulphate and barium hydroxide the molecule under- 
goes fission, the products, according to Pringsheim, being betaine and 
an uncrystallisable solid, consisting probably of a methylated tetrose. 
This observation is of interest in view of the possible connection of such 
an action with the occurrence of betaine and of proteins in the sugar 
beet. 

Chondrosamine. 

Cartilage (nasal septa) contains a substance, chondroitin sulphuric 
acid ; this is a tetrasaccharide consisting of two glucuronic acids and 
two chondrosamine units, in which the amino groups are acetylated. 
Chondrosamine has been the subject of an extensive investigation by 
Levene and La Forge. It was at first described as glucosamine but 
proved to be an isomeride of this and was considered to be /-allosamine 
or /-altrosamine owing to the supposed similarity between the osazones 
of chondrosamine and these hexoses. The osazone was subsequently 
identified as galactosazone, and chondrosamine shown to be identical 
with the synthetic lyxohexosamine, both amino sugars yielding anhy- 
dromucic acid on oxidation and forming identical derivatives. It is 
thus either 2-amino-galactose or 2-amino-talose, probably the latter. 

5 



66 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

H OH OH NHj 
CHj(OH) . C . C . C . C . CHO 
OH H H H 

The aminohexoses are synthesised from the pentoses by the follow- 
ing series of operations. By means of methylalcoholic ammonia the 
imine (i-aminopentose) is formed which is left with hydrocyanic acid 
and the product hydrolysed with hydrochloric acid at o** C. A mixture 
of the two epimeric hexosamic acids is obtained in this manner and 
oxidation with nitric acid converts these into the corresponding tetra- 
hydroxyadipic acids. The epimeric acids can be converted into one 
another by heating with pyridine in the usual manner. 

The two ^arabinohexosamic acids correspond to chitosamic acid 

(from glucosamine) [a]^ - 15° and the epimeride [a]^ - 10°. From 

dAyxose the acids obtained are chondrosamic [a]jy - 17° and the 

epimeride [aj^ + 8^ The acids from xylose have [ajo + 14° and 

- 11° respectively. 

As already indicated on page 59 arabinose yields a preponderance 
of the laevo-rotatory mannonic acid when coupled with hydrogen 
cyanide, whereas lyxose and xylose yield mainly dextro-rotatory 
hexonic acids. Similarly, i-aminoarabinose yields a larger proportion 
of a laevo-rotatory hexosamic acid (identical with glucosamic acid), 
whereas dextro-rotatory hexosamic acids preponderate from amino- 
lyxose and aminoxylose. Levene considers the analogy to justify 
the regarding of the acid from arabinose as mannosamic acid. 

The configuration of these synthetic a-hexosamic acids is also 
indicated by optical considerations. In each pair of hexonic acids 
the member which has the same configuration of the a-carbon atoms 
as ^-gluconic acid possesses either a higher dextro-rotation or a lower 
laevo-rotation than the epimeride. By heating the acid with pyridine 
an increase in rotation occurred with each of the acids excepting 
lyxohexosamic acid Hence chitosamic acid (from glucosamine) has 
the configuration of mannosamic acid, xylohexosamic acid that of 
idosamic acid, chondrosamic acid that of talosamic acid, and ^-lyxo- 
hexosamic acid that of galactosamic acid. The value of the a-carbon 
atom in each pair of epimeric acids is found by experiment to be 12*5°. 

Levene and La Forge consider chondroitin to be a tetrasaccharide 
consisting of two glucuronic acids and two chondrosamine units. The 
amino groups are acetylated and the primary alcohol groups esterified 
with sulphuric acid. On hydrolysis the sulphuric and acetic acids are 
split off and the molecule ruptured between the two glucuronic acid 
molecules forming chondrosin. Levene has obtained mucoitin 
sulphuric acid from a number of mucins and mucoids. This differs 



PROPERTIES OF GLUCOSE AND THE HEXOSES 67 

from chondroitin since on hydrolysis it yields a disaccharide composed 
of glucuronic acid and glucosamine which is termed mucosin : — 

C12H21O11N 

Hudson has isolated the a- and )8-pentacetates of glucosamine 
and chondrosamine and contrasted their molecular rotations with those 
of the glucose pentacetates. The end asymmetric carbon has the 
same configuration in all though it is reversed in chondrosamine, which 
is a derivative of an /-sugar, and, as the table on p. 41 shows, the values 
of 2 A for the amino-sugars agree closely. The agreement is not quite 
so good with the glucose pentacetates which may indicate that the 
nature of the groups on the chain have in this case a definite though 
small influence upon the rotation of the end asymmetrical carbon 
atom. 

Phosphoric Esters. 

The discovery of the r61e played by hexose phosphate in fermenta- 
tion lends considerable interest to the phosphoric esters of carbohydrates. 

The hexose phosphate CjHi^04(P04H2)2 from glucose, mannose or 
fructose (see p. 116) is not precipitated by ammoniacal magnesium 
citrate mixture, but the lead salt is precipitated by lead acetate. It 
can be purified by decomposition by hydrogen sulphide and reprecipita- 
tion. With phenyl hydrazine an osazone is formed, one molecule of ' 
phosphoric acid being eliminated, which has the composition — 

The sodium, phenyl hydrazine and aniline salts have been characterised. 

Hexose phosphoric acid contains an active carbonyl group and two 
phosphoric acid groups, one of the latter being probably attached to 
the carbon atom adjacent to the carbonyl group since it is split off in 
the formation of the osazone. 

Neuberg has described phosphoric esters of glucose and sucrose 
prepared by the action of phosphorus oxychloride on the carbohydrates 
in presence of calcium carbonate or hydroxide. These have the com- 
position C^HiiOg . O . POgCa and C^gHgiOio . O . POgCa. Neither of 
them is fermented by yeast. On the other hand, the corresponding 
calcium fructose phosphate obtained by partly hydrolysing sucrose 
phosphate with dilute hydrochloric acid is stated to be readily fermented 
by yeast It reduces Fehling's solution. 

Phosphoric acid esters of the carbohydrates play an important 
part in the structure of the nucleic acids. Thus inosinic acid when 

5* 



68 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

hydrolysed in acid solution yields a purine base and rf-ribose phos- 
phoric acid. The position where pentose and acid are attached is not 
known. Yeast nucleic acid contains this grouping four times, whilst 
in thymus nucleic acid the sugar is a hexose. 

Tannins. 

The tannins have long been regarded as glucosides, Strecker in 
1852 being the first to show that they contained glucose. His formula, 
CgTHgjOii, for tannin corresponded with three molecules of gallic acid 
to one of glucose. Other observers have disputed the presence of 
glucose in tannin, which often figures simply as digallic acid in the 
older textbooks. Statements as to the amount of glucose obtained 
from tannin on hydrolysis vary very widely : this is due to the great 
difficulty experienced both in purifying the tannin and in separating 
the glucose formed Fischer and Freudenberg ( 1 9 1 2) showed that care- 
fully purified tannin yields somewhat more than 8 per cent, of glucose 
on hydrolysis. This proportion is too small for tannin to be a glucoside 
of the ordinary type, but it is suggested by Fischer and Freudenberg 
that it is an acyl derivative of glucose analogous to pentacetylglucose 
or pentabenzoylglucose. A pentadigalloylglucose, 

CH2(0X) . CH(OX) . CH . CH(OX) . CH(OX) . CH(OX) 

I o ^1 

where 

X = - CO . C8H2(OH)a . O . CO . CeHjCOH), 

should contain io*6 percent of glucose. It has the high molecular 
weight 1700. This formula is in agreement with what is known as 
to the composition, optical activity, small acidity and the behaviour of 
tannin on hydrolysis. 

Proof of the correctness of this hypothesis is afforded by the syn- 
thesis by Fischer and Freudenberg of acyl derivatives of glucose closely 
analogous to natural tannin. On shaking glucose with a chloroform 
solution of trimethylcarbonato galloylchloride in presence of quinoline 
an acyl derivative is formed from which, on cautious hydrolysis with 
alkali, the methylcarbonato groups can be removed so that penta- 
galloylglucose is formed. The synthetic compound has all the pro- 
perties of the tannins. Other phenolcarboxylic acids may be used 
for the condensation, and methyl-glucoside or glycerol may be sub- 
stituted for glucose. The way is thus opened for the synthesis of a 
variety of products of high molecular weight, amounting in the ex- 
treme case of derivatives of the disaccharides to several thousands. 
It is quite possible that such compounds may be present in animals. 



PROPERTIES OF GLUCOSE AND THE HEXOSES 69 

Fischer and Bergmann have succeeded in synthesising penta- 
(»/- and /-digalloyl)-^-glucoses, the former of which is remarkably 
similar to Chinese tannin, the only point of difference noted being the 
specific rotation, which is of minor importance in colloid substances of 
such complexity. 

Glucose in combination with gallic acid has been shown by Feist 
to be associated naturally with tannin. The natural compound differs 
from the ^-glucosidogallic acid, CgHnOg . O . CcH2(OH)2 . CO2H, 
prepared by Fischer and Strauss in which the coupling of the hexose 
and the aromatic residue involves a phenolic group, as is confirmed by 
its conversion into glucosyringic acid. It is suggested that in the 
natural compound the carboxyl group is involved — 

C«HiA . O . CO . C,H2(OH)3, 

and this has been confirmed by the preparation of a i-galloylglucose 
having the above structure by Fischer and Bergmann which is in all 
respects identical with the natural glucogallin isolated by Gilson from 
Chinese rhubarb, though it is said to be quite distinct from Feist's 
glucogallic acid. 



CHAPTER III. 

THE HEXOSES, PENTOSES AND CARBOHYDRATE ALCOHOLS. 

The general properties of the monosaccharides have been fully dealt 
with in the foregoing and exemplified in the case of glucose. In 
dealing with the remaining hexoses it is only necessary to recapitulate 
briefly their more important properties and any salient points of 
difference from glucose. Most of the synthetic sugars are not referred 
to in detail as they are not of biochemical interest. 

Glucose and fructose are the only two of the monosaccharides which 
occur naturally as such. The others are found in nature as poly- 
merides, as glucosides, or in the form of alcohols, and are prepared 
by hydrolysis or oxidation. 

Fructose and sorbose are types of the ketohexoses, a group which 
has been much less investigated than the aldohexoses. Both fructose 
and sorbose have the ketonic oxygen attached to the a-carbon atom, 
but a number of other isomerides are possible in which the keto group 
is situated elsewhere in the molecule. The ketohexoses do not yield 
acids containing the same number of carbon atoms on oxidation, but 
the molecule breaks into two at the ketonic group. 

TABLE X. — Thb Monosaccharides. 

Diose. Triases. Tetroses, 

GlycoUic aldehyde. d- and /-Gljrcerose. d- and Z-Erythrose. 

Dihydroxyacetone. d- and /-Threose. 

Methylglycerose. Erythrulose. 

Pentoses. Methylpentoses. 

d- and Z-Arabinose. Z-Rhamnose. 

d- and /-Xylose. d- and Z-Isorhamnose. 

d~ and /-Ribose. Fucose, Rhodeose. 

d' and l-Lyxose. Epiihodeose. 

Aldohexoses. Ketohexoses. 

d' and Z-Glucose. d- and /-Fructose. 

d' and /-Mannose. d- and /-Sorbose. 

d- and /-Gulose. Tagatose. 

d' and /-Idose. 

d' and /-Galactose. 

d- and /-Talose. 

iZ-Altrose. 

<i-Allose. 

70 



HEXOSES, PENTOSES, CARBOHYDRATE ALCOHOLS 71 

TABLE X. — The Monosaccharides — continued. 

Hej^toses, Octoses, Nonoses, Decose, 

Mannoheptose. Manno-octose. Mannononose. Glucodecose. 

Glucoheptose. Gluco-octose. Glucononose. 

Galactoheptose. Galacto-octose. 

Mannoketoheptose. 

Perseulose. 

Sedoheptose. 

Mannose. 

^Mannose is widely distributed in nature in the form of an- 
hydride-like condensation products termed mannosans which are con- 
verted into mannose when hydrolysed by acids ; it does not occur in 
more simple form. A convenient source for its preparation is the 
vegetable ivory nut. This is the endosperm of the seed of the tagua 
palm Phytelephas macrocarpa. A method of obtaining as much as 
4 per cent, of the weight of the vegetable ivory in the form of pure 
crystalline mannose has been worked out in detail by Hudson. The 
meal is hydrolysed by 75 per cent, sulphuric acid, the acid removed 
by means of calcium hydroxide, and after purification the colourless 
solution is evaporated to a thick syrup and this mixed with an equal 
volume of glacial acetic acid. This method makes a great advance on 
the original practice of Fischer and Hirschberger of isolating the 
phenyl-hydrazone and decomposing this to the sugar, and makes the 
sugar available for the further study of its properties. 

Mannose forms rhombic crystals and has initially a sweet taste 
followed immediately by a distinctly bitter one. This bitterness is 
quite characteristic and of interest, in view of the pure sweetness of 
the closely related isomerides glucose and fructose, the latter being 
the sweetest sugar known. 

Crystalline mannose is the fi form having \a\o - 17°. The rotation 
of the a form is calculated by Hudson to be + 34° and that of the 
equilibrated mixture is + 14*6°. •■- 

Mannose is the true aldehyde of mannitol, and may be obtained 
from it by oxidation, or converted into it by reduction. It is of in- 
terest that it was first prepared by Fischer and Hirschberger in this 
manner, and only subsequently identified as a natural product. It is 
very similar to ^-glucose in its general properties, exhibits muta- 
rotation, and forms the same phenyl osazone as glucose and fructose. 
Mannose is altogether remarkable in forming a sparingly soluble 
phenyl hydrazone which enables it to be very easily identified. This 
hydrazone is precipitated within a few minutes when phenyl hydrazine 
is added to a solution of mannose. 



72 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

Nitric acid oxidises mannose to ^mannosaccharic acid, which 
readily forms a double lactone : — 

I ° — J 

CO . CH(OH) . CH . CH . CH(OH) . CO 

I o 1 

Mannose forms an additive compound with hydrogen cyanide, 
which, on hydrolysis, yields mannoheptonic acid. Apparently one 
only of the two possible isomerides is formed. The mannoheptose 
obtained from this is very similar to mannose, and forms a sparingly 
soluble phenyl hydrazone. On reduction it yields the alcohol C7Hi(j07 
identical with the natural perseitol. 

Galactose. 

^Galactose occurs as a constituent of milk sugar and raffinose, 
also in many gums and seaweeds as the polymeric form galactan ; its 
presence in the form of a galactoside is rare, being confined to the 
saponins, xanthorhamnin, and a few other natural glucosides. Lipp- 
mann records the apjjearance oXgg^lactQsg ^ a crys tallin^^ fflorescence 
r esembling hoar fro st o n ivy berries following a sharp frost, the fir st 
after a late dry autumn . Both isomeric forms of galactose occur 
naturally: Winterstein found ^/-galactose in Chagnal gum, Tollens 
obtained it from Japanese Nori. 

The galactans are widely distributed in the form of gums, muci- 
lages, pectins. Galactose is usually associated in them with arabinose 
or xylose. The pectins, which are of importance in the jam industry, 
are hydrolysed by acids to galactose and arabinose and by an venzyme 
pectase into pectic acids. It resembles glucose in properties ; char- 
acteristic is the formation of mucic acid on oxidation with nitric acid, 
and this may be used for its identification. On reduction with sodium 
amalgam the corresponding alcohol, dulcitol, is formed ; this is found 
naturally. By the action of alkalis it is transformed into ^-talose and 
rf-tagatose. It is fermented by some yeasts, but not by all those 
which ferment glucose ; a fact which has been taken as indicating that 
a special galacto-zymase is required for the fermentation. 

Ordinary galactose is the a form [a]^ + 1 44° ; it crystallises in 
anhydrous leaflets or from water as the hydrate in large prisms. The 
)8 form has +52° and the equilibrium mixture + 80°. a-Methyl- 
galactoside is not hydrolysed by enzymes ; )8-methylgalactoside is 
attacked, like milk sugar, by the lactase of kephir, by the lactase 
present in some yeasts, and by a lactase present in an aqueous ex- 
tract of almonds (see Chapter V.). 



HEXOSES, PENTOSES, CARBOHYDRATE ALCOHOLS 73 

The 7 form of methylgalactoside has recently been isolated and 
corresponds in general behaviour to the ethylene oxide form of methyl- 
glucoside ; it is of interest that its tetramethyl derivative, after re- 
moval of the glucosidic methyl group by gentle hydrolysis, undergoes 
auto-condensation to an octamethyldigalactose. 

Under abnormal conditions galactose is formed in the sugar beet, 
and appears in combination with sucrose as the trisaccharide, raffinose. 
The quantity of raffinose is increased abnormally by disturbances of 
growth, such as those occasioned by sudden frost. Under these con- 
ditions the galactans are supposed to undergo hydrolysis and form 
galactose. Apparently the plant, when confronted with galactose, 
utilises it first to form a disaccharide, melibiose, composed of glucose 
and galactose, and then makes use of the glucose half in this di- 
saccharide, according to its fixed habit, by combining it with fructose, 
with the result that a compound carbohydrate containing all three 
simple hexoses is formed. 

Galactose is the sugar of the brain whence it was isolated and 
described under the name cerebrose by Thudichum. It is a constitu- 
ent of the cerebrosides known as phrenosin and kerasin. 

These compounds on hydrolysis furnish galactose, a base sphingo- 
sine and a fatty acid ; that in phrenosin being phrenosinic acid, 
C25H50O3, and that in kerasin being lignoceric acid, C24H48O2. They 
are both optically active and have the property of forming liquid 
crystals. (For further details see the monograph by Maclean in this 
series.) 

Fructose. 

^-Fructose or laevulose, discovered by Dubrunfaut in 1 847, occurs 
together with glucose in the juices of fruits, etc., the mixture being 
often termed fruit sugar or invert sugar. It is present in chicory and 
especially the Jerusalem artichoke. Combined with glucose it occurs 
as cane sugar, raffinose, etc. It is a constituent of alliin, the gluco- 
side of garlic and of some saponins. The polysaccharide inulin yields 
fructose alone when hydrolysed. 

To prepare it from invert sugar or hydrolysed inulin it is best to 
form the crystalline calcium laevulosate and decompose this with 
carbon dioxide. 

Fructose is a ketohexose having the following alternative consti- 
tution : — 



74 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

CH, . OH CH,(OH) . [CH(OH)]j . CH . C{OH) . CHa(OH) 

i \/ 

CO o 

iEthylene-oxide formula. 
H 



HC( 



HCOH HOC CH 

:0H I H HO I 

I CHj(OH)— C CH . CHj(OH) 

CHjOH /' 

Ketonic formula. HO 




O 

' Butylene-oxide formula. 

Fructose crystallises less easily than glucose, and its derivatives 
are also difficult to crystallise. It is much sweeter than glucose. It 
exhibits mutarotation, and, like glucose, exists in solution presum- 
ably as an equilibrated mixture of several stereoisomeric forms. It is 
remarkable for the very large change produced in the specific rotatory 
power by changes of temperature. The rotatory power becomes less 
negative as the temperature is increased, and at 87*3° C. it is equal 
and opposite to that of glucose. 

The recent work of Irvine and his school has afforded evidence 
that fructose is much more prone than is glucose to react in the 
ethylene oxide form. Pure solid fructose which has been dissolved 
in water is quite stable to permanganate and represents the butylene- 
oxide form, but if the solution is made acid, kept for an hour and 
neutralised, permanganate is decolorised within a few minutes, show- 
ing that the ethylene-oxide form of fructose has been formed. Ethyl- 
ene-oxide itself in solution behaves similarly towards permanganate. 
Fructose thus reacts either as — 

(i) A compound containing the butylene-oxide ring and existing 
in a and fi modifications. Ordinary fructose, the /3 modification, 
forms rhombic crystals, [ajo - 133 '5° falling to -92° in solution. 
The calculated rotation of the a form is - 2I^ 

This type of fructose is not attacked by permanganate, does not 
combine readily with acetone and forms stable fructosides and acetyl 
derivatives, e.g. a pentacetate and tetracetyl /3-methyl fructoside, also 
a crystalline tetramethyl-fructose \a\^ - 125°. 

(2) A more active compound probably containing an ethylene- 
oxide ring and likewise capable of existing in interconvertible a and 
/3 modifications having lower specific rotations. The derivatives of 
this form are highly reactive, combine readily with acetone, and re- 
duce permanganate. The fructosides are very easily hydrolysed 



HEXOSES, PENTOSES, CARBOHYDRATE ALCOHOLS 75 

by acids and resemble sucrose, which is perhaps a derivative of 
the ethylene-oxide fructose. The tetramethyl derivative is a liquid 
having [a]^ + 29/3°. 

When submitted to the action of ultra-violet rays, solutions of 
fructose are transformed into carbon monoxide and dioxide, formal- 
dehyde, methyl alcohol, and aldehydic and acidic substances ; this is 
said to be the first degradation of fructose which has been effected by 
other than purely chemical or biochemical agency. 

Fructose shows a number of characteristic reactions. Hydrogen 
bromide interacts with fructose in ethereal solution to form bromo- 

CH : C(CH2Br)v 

methylfurfuraldehyde | >0, a substance which crystallises in 

CH : C(CHO) / 

golden yellow rhombic prisms; the ethereal liquid is coloured an 
intense purple-red (Fenton and Gostling). A yS-oxy-y-methylfurfural- 
dehyde is produced on heating concentrated solutions of fructose under 
pressure, preferably with oxalic acid. 

On prolonged boiling with dilute mineral acids, laevulinic acid, 
CHj . CO . CHg. CHg. CO2H, is formed together with formic acid and 
humus substances. 

; ' .,When oxidised by means of mercuric oxide fructose forms 
l^lycollic acid, CH2(0H) . CO2H, and trihydroxybutyric acid, 
CH2OH . (CH . 0H)2 . CO2H. It is not acted upon by bromine water 
of low concentration : aldoses can be distinguished from ketoses by 
means of this test. Mannitol and sorbitol are formed on reduction 
with sodium amalgam. 

By the action of methyl alcohol and hydrogen chloride on fructose 
a syrup is obtained which probably represents a mixture of methyl 
fructosides, in which undoubtedly both a and )8 modifications of the 
ethylene and butylene-oxide forms are present On methylation and 
hydrolysis a mixture of tetramethylfructoses is obtained, which has 
been separated into the syrupy, ethylene-oxide and the crystalline, 
butylene-oxide forms. The original syrupy mixture could not be 
obtained crystalline. 

This syrup is partially hydrolysed by yeast extract, but, inasmuch 
as Pottevin has shown that it is not hydrolysed by 5. octosporus^ Mucor 
mucedo and other ferments which attack cane sugar and maltose, the 
hydrolysis is presumably caused by an enzyme other than invertase 
or maltase, neither of which should act on these fructosides (see 
Chapter IV.). 

Crystalline yS-methylfructoside, [ajo - 172°, was obtained by Hud- 
son by methylation of tetra-acetyl fructose and subsequent hydrolysis. 



76 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

It is not hydrolysed by the enzymes of yeast nor by emulsin and 
does not show mutarotation. It undoubtedly has the butylene-oxide 
structure. 

Fructose, like glucose, forms an additive compound with hydrogen 
cyanide which yields fructose carboxylic acid on hydrolysis ; this, when 
boiled with hydriodic acid, is converted into methyl butylacetic acid, 
C4HJ . CHMe . COgH. This reaction and the behaviour on oxidation 
establish the formula of fructose. 

Fructose forms the same osazone as glucose; it also forms 
osazones with some disubstituted phenyl hydrazines, the primary 
CHaCOH) group being more easily oxidised by these than the 
secondary CH(OH) group in glucose. The methyl phenylosazone is 
characteristic of fructose. 

Glucose and its isomerides combine with acetone in presence of 
hydrogen chloride forming mono- and diacetone derivatives of a gluco- 
sidic nature since they no longer reduce Fehling's solution. Enzymes 
are entirely without action on them. The acetone compounds of 
fructose have been investigated by Irvine who has proved the existence 
of two isomeric fructose monacetones— ^ 





CHjOH CHjOH 

A B 

having probably the formulae A and B, each of which will exist in a and 
/8 forms. From A a diacetone is formed, but B is not prone to further 

condensation : this is consistent with the view that the acetoney CMeg 

residue displaces the hydrogen atom of two adjacent hydroxyl groups 
which need not, however, be on the same side of the formula as re- 
presented on a plane surface. 

The expressions cis and trans are used by Irvine to distinguish be- 
tween the linkage between hydroxyl groups on the same or on opposite 
sides of the molecule. In fructose diacetone both types are present 



HEXOSES, PENTOSES, CARBOHYDRATE ALCOHOLS 77 



CH,OH . CH 



It is not therefore surprising that the two acetone groups are 
eliminated at different rates on hydrolysis, fructose cis monoacetone 
being formed as an intermediate product. In triacetone mannitol there 
is evidence that the acetone groups are in order trans^ trans^ cis^ and di- 
and monoacetone compounds are formed in turn on cautious hydrolysis. 
The most stable acetone residue is attached to a terminal primary 
alcohol group. 

It is probable that glucose and fructose play distinct parts in meta- 
bolism. Brown and Morris have shown that glucose is mainly con- 
cerned in respiration ; fructose appears to take part more particularly 
in the elaboration of tissue since it is far less stable than glucose. 

In this connection the experiments of Lindet are of particular in- 
terest. Dealing more particularly with yeasts and moulds he adduces 
experimental evidence to prove that fructose is specially concerned in 
tissue formation, glucose being more readily used for fermentation and 
respiration. Yeasts and moulds, for equal weights of sugar consumed, 
show greater growth in fructose and they consume glucose preferen- 
tially from invert sugar. 

It is stated also that fructose is sometimes found to be assimilated 
by diabetics when glucose is inadmissible. 

Sorbose. 

Sorbose was discovered by Pelouze in 1852 and was isolated from 
the juice of mountain ash berries which had been exposed to the air for 
many months. These berries contain the alcohol sorbitol, which, under 
the influence of an oxidising organism, shown by Emmerling to be 
identical with the bacterium xylinum of Adrian Brown, is oxidised to 
sorbose. The brilliant researches of Bertrand have given a complete 
explanation of the transformation, and have rendered the preparation 
of sorbose a relatively simple matter. Sorbose is a ketose having the 
formula — 



78 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

CHjOH 

CO 
HOCH 

HCOH 
HOCH 

CHjOH 

It has a marked crystallising power, is not fermentable, and generally 
behaves as fructose ; on reduction it yields sorbitol. Lobry de Bruyn 
has shown that under the influence of alkali sorbose is converted 
into /-gulose, /-idose and ^galactose, and so affords a connecting link 
between hexoses of the mannitol and dulcitol series. This result is 
of importance, as the direct synthesis of a hexose of the dulcitol series 
has not been achieved. 

Fischer originally designated it as rf-sorbose because on reduction 
it yields the same sorbitol as rf-glucose. Both Rosanoff and Hudson 
suggest the name /-sorbose on account of the structural relationship 
to /-glycerose and /-glucose : their contention is undoubtedly correct. 

a-Methyl-/-sorboside, [aj^ - 88°, obtained by the action of methyl 
alcohol and hydrochloric acid on /-sorbose, is so named by Hudson to 
fit in with his contention that the a-isomeride of a laevo sugar is the 
more laevo-rotatory. 

The antipode rf-sorbose has been prepared by Lobry de Bruyn 
and van Ekenstein by the partial transformation of rf-galactose under 
the influence of dilute alkalis. It has [a]o + 42*9°. 

The Pentoses CgHjoOs. 

Two pentoses, /-arabinose and rf-xylose,^ are widely distributed in the 
vegetable kingdom as polysaccharides of high molecular weight, the so- 
called pentosans ; they also occur in complex glucosides, but are never 
found as the simple sugars. Xylose is found in straw, oat hulls and in 
most woods ; arabinose in gums, being conveniently prepared from 
cherry gum or gum-arabic. The ^isomeride of arabinose can be 
obtained synthetically from rf-glucose by the degradation methods 
indicated in the previous chapter. Recently it has been found 
naturally as a constituent of the glucoside barbaloin, and described 
under the name aloinose (L6ger). 

In the animal kingdom a pentose is a constituent of the nucleopro- 
teins and nucleic acids. The nature of this pentose has been a sub- 
ject of controversy ; it is now regarded as rf-ribose and identical with 

^ Hitherto known as /-xylose. 



HEXOSES, PENTOSES, CARBOHYDRATE ALCOHOLS 79 

the carnose of Levene and Jacobs. The nucleic acids consist of a 
carbohydrate, phosphoric acid, two purine bases and two pyrimidine 
bases. In plant nucleic acids the carbohydrate is rf-ribose and this is 
also the only pentose of the animal body. Such nucleotides as guanylic 
or inosinic acids consist of phosphoric acids and a purine base united 
by ribose, and they form the corresponding nucleosides consisting of 
ribose and purine base when submitted to neutral hydrolysis at 175° 
under pressure. The nucleosides are glucosides (pentosides) and are 
decomposed by boiling mineral acids. Similar compounds of the 
pyrimidine bases exist. (For further details see the monograph by 
Walter Jones in this series.) 

The carbohydrate group obtained from thymus nucleic acid is 
generally regarded as laevulinic acid, which can be formed by beating 
hexoses with sulphuric acid. It is regarded as of secondary origin 
from a hexose group. Laevulinic acid is obtained uniformly from 
animal nucleic acids but never from plant nucleic acids. The recent 
work of Feulgen makes it very probable that the carbohydrate group 
consists of glucal, CgHj^^O^, 

As described later glucosides of carbohydrate and purine have been 
prepared synthetically. 

A pentose appears as an abnormal product in urine in the rare dis- 
ease pentosuria — according to Neuberg this is inactive rf/-arabinose 
(see Garrod, ** Inborn Errors of Metabolism "y 

But little is known of the mechanism of the formation of pentoses 
in plants ; they maybe formed in the same manner as the hexoses, but 
independently of these, or they may be degradation products of the 
hexoses (cp. p. 46). Xylose and arabinose serve as nutrient to 
yeast and bacteria, but higher plants have no power of utilising them. 

The pentosans are resistant towards alkali and require prolonged 
heating with mineral acids to effect hydrolysis. They are comparable 
with starch and cellulose and contain as a rule both Cg and C^ carbo- 
hydrates. No enzymes are known as yet which hydrolyse them ; in- 
asmuch as they are present essentially as skeletal, and not as food 
products in the plants, it is to be expected that they will be outside 
the range of the ordinary plant enzymes. 

Their origin and function in plants has been studied recently by 
Ravenna, who concludes that the simple sugars more than the complex 
carbohydrates exert a preponderating influence on their formation. 
They can act as a reserve material when the plant has exhausted the 
more readily utilisable food-stuffs. In leaves the pentosans increase 

' But Zerner regards it as /-lyxose or the corresponding xylo-ketose. 



8o THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

in amount during the day, decrease during the night. They increase 
when the leaves are supplied with glucose, diminish when the action 
of the chlorophyll is prevented and carbohydrate nutriment is 
absent 

The eight possible aldopentoses are given in the following table, 
together with their configuration formulae. The table also contains 
the configuration formulae of the remaining lower members of the 
group of monosaccharides, viz. 4 tetroses and 2 trioses : — 



CHO 
HOH 
HOH 
HOH 

CHjOH 
/-Ribose. 



H 

HO 

HO 



CHO 
OH 
H 
H 



CHjOH 
/-Arabinose. 



CHO 
HOH 
HOH 

CH2OH 
/-Erythrose. 



TABLE XI. 



Aldopentoses. 



CHO 



^ 



CHO 



H 
H 
H 



OH 
OH 
OH 



H 

HO 

H 



CHjOH 
^-Ribose. 



OH 
H 
OH 
CHaOH 

^-Xylose. 



H 
H 
HO 



CHO 
OH 
OH 
H 



"^ 



CHaOH 

/-Lyxose. 



CHO 



CHO 
HO H 
H OH 
H lOH 

CHjOH 
^-Arabinose. 



Aldotetroses. 



HOH 
HOH 
CHaOH 

d-Erythrose. 



CHO 
H OH 
HO H 

CHjOH 

/-Threose 
Unknown. 



CHO 



HO 

H 

HO 



H 
OH 
H 
CH2OH 
/-Xylose. 



\ CHO 



J 



HO 
HO 
H 



H 

H 

OH 



CHgOH 
d-Lyxose. 



CHO 
HO H 
H OH 

CHjOH 
i- Threose. 



Aldotrioses. 



CHO 
H|OH 

CH2OH 
d-Glycerose. 



CHO 
HOIH 
CHjOH 



/-Glycerose. 

The optically active glyceroses (glyceraldehydes) have been syn- 
thesised by Wohl. The dextro-rotatory form has ap + 13° to 14°. 
By the hydrogen cyanide synthesis it is converted into a trihydroxy- 
butyric acid which yields /-tartaric acid on oxidation. 





CN 


COjH 


COaH 


CHO 
HOH 
CH2OH 
<i-Glycerose. 


CH(OH) 
HOH 
CHaOH 


CH(OH) 
HIOH 

CHaOH 
Trihydroxy 
butyric acid. 


HO 

H 

C 

/-Ta 

3H 


H 

OH 

JOjH 

irtaric 

cid. 



Hence the spatial formula of rf-glycerose is established. 
Since /-tartaric acid is the dicarboxylic acid of rf-threose the spatial 
relationship of the dextro-rotatory glycerose to rf-glucose is also proven. 



HEXOSES, PENTOSES, CARBOHYDRATE ALCOHOLS 8i 



Fortunately, as pointed out on page 38, the designation of " ^gly- 

cerose " expresses both its optical activity and spatial relationship to 

rf-glucose. 

It remains to convert rf-glycerose into the corresponding monocar- 

boxylic acid by methods which eliminate all possibility of a Walden 

rearrangement. The formulae— 

HO 

CHa(OH) . C . COaH 
H 

at present ascribed to dextro-rotatory glyceric acid would indicate it is 
derived from /-glycerose. This configuration is based on its prepara- 
tion from malic acid by Freudenberg, but the reactions may well have 
involved a Walden rearrangement. It is supported also by the fact 
established by Frankland, Wharton and Aston that the calcium salt 
and amide of the acid are laevo-rotatory, indicating by Hudson's rule 
that the hydroxyl is on the left of the formula, i.e. above the chain 
of carbon atoms. 

The natural pentoses are in reality closely related to the natural 
hexoses. As the formulae below show, the arrangement of the groups 
on the upper four carbon atoms is the same in each case in galactose 
and arabinose, and the same also in glucose as it is in xylose : — 

CHO 



HCOH 



HOCH 



i, 



i 



HCOH 



CHjOH 



CHO 


CHO 
HCOH 
HOCH 
HOCH 
CHjOH 


CHO 
HCOH 
HOCH 
HOCH 
HCOH 
CH2OH 


HCOH 
[OCH 
HCOH 
HCOH 
CH2OH 


^-Glucose. 


/-Arabinose. 


(f-Galactose. 



<f-Xylose. 

In this connection, it is not without interest that some polysaccharides 

yield both xylose and glucose on hydrolysis, whilst arabinose and 

galactose occur together in many gums. 

When the cyanohydrin synthesis is applied to natural /-arabinose a 

mixture of two nitriles is obtained, and the corresponding acids, when 

reduced, give rise to /-glucose and /-mannose ; similarly, ^xylose can 

be converted into rf-gulose and rf-idose. rf-Glucose, when degraded by 

the methods of Ruff or Wohl, gives rf-arabinose ; <i^galactose forms 

dAyxose. The carbon atom which requires to be eliminated in order 

that ^glucose may give rise to the natural ^xylose, a transformation 

which there is reason to think may take place in the plant, is not the 

one effected by the processes described, but is situated at the extreme 

6 



c 



82 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

end of the chain. No chemical means of effecting this change has as 
yet been discovered. 

Arabinose and xylose show the usual aldose reactions. They are 
not fermented by yeasts. Arabinose forms a characteristic, almost 
insoluble, diphenyl hydrazone. Xylose is best recognised by conver- 
sion into xylonic acid, and isolation of this as the cadmium bromide 
double salt. 

Pentoses are determined quantitatively by distillation with hydro- 
chloric acid when furfuraldehyde is formed. This is coupled with phloro- 
gluclnol, and the condensation product isolated and weighed. The 
colour reactions obtained on heating with orcinol or phloroglucinol and 
hydrochloric acid are very characteristic, and frequently used for de- 
tecting the pentoses. 

Hudson finds that xylose can be very readily prepared from 
cotton-seed hulls with a yield of 8-12 per cent The hulls are ex- 
tracted first with 2 per cent, ammonia and then hydrolysed by boiling 
with 7 per cent, sulphuric acid. The filtrate is carefully neutralised 
with calcium hydroxide, made just acid with phosphoric acid and con- 
centrated. The remaining calcium sulphate is precipitated on the 
addition of alcohol and the solution evaporated to a syrup under re- 
duced pressure. This is mixed with alcohol and crystallisation soon 
takes place. 

The Methyl Pentoses. 

Several representatives of this class of carbohydrates have been 
discovered latterly in plants. In them, one of the hydrogen groups of 
the primary alcohol is replaced by methyl. They show most of the 
reactions characteristic of the pentoses, but form methyl furfuraldehyde 
on distillation with acids. 

Their biochemical significance is not yet understood ; they are not 
fermented by yeasts. The configuration of most of them has been 
established by the ordinary methods with the exception of the relative 
positions of the groups attached to the methylated carbon atom which 
remain uncertain in some of them, though for rhamnose and isorham- 
nose this is now established. 

The configuration formulae of the methyl pentoses, so far as at 
present known, are given in the following table: — "t!^ v- 



HEXOSES, PENTOSES, CARBOHYDRATE ALCOHOLS 83 









TABLE XII. 








CHO 


CHO 


CHO 


CHO 


H 


OH 


HO 


H 


HO 


H 


H 


OH 


H 


OH 


HO 


H 


H 


OH 


HO 


H 


HO 


H 


H 


OH 


HO 


H 


H 


OH 


HO 


H 


H 


OH 


HO 


H 


H 


OH 


( 


^Hj 


CHs 




^Ho 


CHj 


/-Rhamnose. 


Unknown. 


/-Isorhamnose. 


^-Isorhamnose 


CHO 


CHO 


CHO 


CHO 


HO 


H 


H OH 


HO 


H 


H 


OH 


H 


OH 


HO 


H 


HO 


H 


H 


OH 


H 


OH 


HO 


H 


HO 


H 


H 


OH 


( 


CH.OH 


CH.OH 


CH.OH 


CH.OH 


CHg 


CHj 


CHs 


CHs 


Fu 


cose. 


Rhodeose. 


Epirhodeose. 


Unknown. 



RhamnosCy CeHjaOs, is a constituent of many glucosides, the best 
known of which are quercitrin and xanthorhamnin, the colouring 
matter of Persian berries. It occurs particularly in combination with 
flavone derivatives. 

Rhamnose crystallises with a molecule of water the hydrate having 
the composition CgHi^Og ; in consequence it was regarded at one time 
as belonging to the hexahydric alcohols and termed " isodulcitol ". 

Rhamnose forms a phenyl osazone and other derivatives similar to 
those of glucose. It exists in a and yS forms which exhibit mutarota- 
tion. By the cyanohydrin reaction two rhamnohexonic acids are 
formed, one of which yields mucic acid when oxidised. The synthesis 
has been extended to the preparation of rhamnohexose and rhamno- 
heptose. Methyl rhatonoside is not hydrolysed by enzymes. 

In view of the relatio'n^hip in configuration of rhamnose to /-man- 
nose or /-gulose it must be regarded as /-rhamnose ; it is the methyl 
derivative of the unknown /-lyxose. 

Vlsorhamnose was obtained by Fischer by heating rhamnonic acid 
with pyridine and reduction of the isorhamnonic acid with sodium 
amalgam. It is the optical antipode of rf-isorhamnose {isorhodeose\ 
one of the products of hydrolysis of purgic acid, the amorphous con- 
stituent of the glucoside convolvulin (Votocek). The crystalline con- 
stituent of this glucoside, convolvulinic acid, is hydrolysed to glucose, 
rhamnose and rhodeose. This latter is the optical antipode oifucose^ 
which as the polymeride fucosan is a component of the cell-wall of 
many seaweeds^^^^o^ek has converted rhodeose into epirhodeose in 
the orditBH5)*Tffimnerr These compounds and their derivatives have 
been fully described. The configuration of quinovose, known only in 
the glucoside quinovin, has not yet been established ; other methyl 
pentoses have been obtained by the hydrolysis. of glucosides, which 
may prove to be new compounds. 



84 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

Fischer and Zach have established the configuration of these methyl 
pentoses beyond doubt by the conversion of dT-glucose into ^isorham- 
nose. Starting from triacetyl methylglucoside bromohydrin, prepared 
from acetodibromoglucose by substitution of methyl for one bromine 
atom (page 28), the bromine atom was reduced by means of zinc dust 
and acetic acid. The triacetyl derivative obtained yielded a glucoside 
on alkaline hydrolysis from which the methylpentose was finally ob- 
tained on acid hydrolysis. Since no optical inversion can have taken 
place during the transformation, in which no asymmetric carbon atom 
was concerned, ^isorhamnose must have the same configuration as 
glucose and it is possible to deduce from it the configuration of Arham- 
nose as that given on the previous page. 

Heptoses. 

Sugars with seven carbon atoms have now been found to occur 
naturally so that added interest attaches to the synthetic members of 
this group. 

Mannoketoheptose has been isolated by La Forge from the Avocado 
pear (Persea gratissima). It crystallises in six-sided prisms [aju + 29°. 
It is not fermentable by yeast and does not show mutarotation. The 
phenylosazone is identical with that of rf-mannoaldoheptose. On re- 
duction with sodium amalgam ^-perseitol and rf-/8-mannoheptitol are 
formed. 

The following formula is therefore assigned to mannoketoheptose : — 

H H OH OH 
CH„(0H) . C . C . C . C . CO. CH2(0H) 
OH OH H H 

Perseulose. — The natural alcohol, perseitol, which is also obtained 
on reduction of mannoheptose is converted on oxidation by B. xylinum 
to a crystalline ketose having a sweet taste and [a]D - 81''. It exhibits 
mutarotation (Bertrand). On reduction with sodium amalgam two 
alcohols are formed, perseitol and perseulitol. 

La Forge considers perseulose to be /-galactoheptose with the 
structural formula — 

H OH OH H 
CHj(OH) . C . C . C . C.CO.CHa(OH) 
OH H H OH 

obviously both mannoketoheptose and perseulose would give rise to 
the alcohol — 

H H OH OH H 
CHoOH. C . C . C . C . C.CHa(OH) 
OH OH H H OH 

which is therefore the formula of perseitol. 



HEXOSES, PENTOSES, CARBOHYDRATE ALCOHOLS 85 

The configuration of the heptoses derived from galactose and man- 
nose has been studied by Pierce. Mannoheptitol and galactoheptitol 
are optical antipodes, each having the structure of perseitol. 

The second mannoheptitol derived from /8-mannoheptose has three 
hydroxyl groups on the same side of the chain attached to contiguous 
carbon atoms, whereas perseulitol has the constitution — 



H 


OH 


OH H 


OH 


C . 


. C . 


C . C 


. C 


OH 


H 


H OH 


H 



CHgCOH) . C . C . C . C . C . CHa(OH) 
OH H H OH H 

corresponding to the yS-galactoheptitol from /8-galactoheptose. 

The structural formula of the two ketoheptoses, of a- and yS-galac- 
toheptose, and of a- and yS-mannoheptose are thus all established. 

Sedoheptose was obtained by La Forge and Hudson from a common 
stonecrop — Sedum spectabile — as a syrup. It is non-fermentable, re- 
duces Fehling's solution and gives a phenyl osazone. It is probably 
a ketose. When it is heated with dilute acid anhydrosedoheptose, 
CyHjgO^, is produced. This forms crystals, has a sweet taste, has [ajo 
- 146° without mutarotation ; in boiling dilute acid solution an equili- 
brium mixture containing 20 per cent, of sedoheptose is formed. 

On reduction with sodium amalgam two sedoheptitols are obtained. 

The one a-sedoheptitol has m.p. 151°, [ajo + 2*2° in water and + 22 '1° 

in borax solution : it would thus appear to be identical with the natural 

alcohol volemitol, m.p. 149°-! 51°, [aj^ + i'9° and + 2-6° in water and 

+ 20 -8° in borax solution. 

However, the benzylidene derivatives differ ; that from sedoheptitol 
having m.p. 200° and that from volemitol m.p. 90°, so that the identity 
of the two alcohols is still an open question. yS-Sedoheptitol crystal- 
lises in short thick prisms, m.p. I27°-I28°, and is optically inactive; 
the benzylidene derivative has m.p. 272°. 

Volemitol, which occurs naturally, is oxidised by B, xylinum to a 
ketoheptose, volemnose, which gives the same phenyl osazone as the 
reducing sugar obtained by chemical oxidation of the alcohol. 



86 THE SIMPLE CARBOHYDRATES ANJD GLUCOSIDES 

Other Monosaccharides. 

Apiose. 

Mention may be made of an altogether abnormal sugar, termed 
apiose, on account of its presence in the glucoside apiin. This con- 
tains a branched chain of carbon atoms, having the formula — 

CHjOHv 

>C(OH) . CH(OH) . CHO 
CHjOH/ 

It is not fermentable, bromine oxidises it to apionic acid. When 
reduced by hydrogen iodide and phosphorus, tr^valeric acid is obtained. 
Apiin contains the disaccharide glucoapiose; when hydrolysed by 
dilute mineral acids apiose and glucoapigenin are formed. 



Cymarose, Di^talose, Di^toxose. 

These rare sugars are obtained on hydrolysis of the glucosides 
cymarin (from the root of apocyanum) and digitalin and digitoxin, two 
of the glucosides of digitalis. 

Digitoxose, C^jHjgO^, crystallises in prisms [aj^ + 46°. Kiliani 
has shown it to be a reduced methyl pentose having the following 
formula : — 

CH3 . CH(OH) . CH(OH) . CH(OH) . CH, . CHO 

Cymarose, C^H^^O^, closely resembles digitoxose in behaviour and 
is considered by Windaus and Hermanns to be a methylether of 
digitoxose. 

Digitalose, CyHj^Og, gives the reactions of an aldose sugar : it is 
perhaps a reduced methylhexose. All three compounds require further 
investigation. 

The Carbohydrate Alcohols. 

Several of the carbohydrate alcohols are widely distributed in plants. 
They crystallise well and are soluble in water. On cautious oxidation 
they give in turn a reducing sugar, monobasic acid and dibasic acid 
They are not fermentable though attacked by a variety of bacteria and 
moulds. 

OH OH 
Erythrttol—CYl^(pii).C -C . CHgCOH)— is found in many 

H H 
algae and mosses, particularly Roccella tinctoria^ where it is present as 
erythrin, CgoHjgOjQ, a diorsellinate of erythritol. 

It has a sweet taste and is optically inactive, being the tneso or 



HEXOSES, PENTOSES, CARBOHYDRATE ALCOHOLS 87 

internally compensated variety. It has been synthesised from buta- 

diene-7-S-oxide 

Cri2 I CH . Cxi . Cri2 

o 

by Pariselle. 

The two optically active varieties [a]o ± 4° have been obtained by 

alkaline reduction of /-threose and rf-erythrulose. 

OH OH OH 
Adani^l—CH^iOH) . C . C . C . CHaCOH)— corresponds to 

H H H 

/-ribose, from which it is obtained on reduction ; it is the only naturally 

occurring pentose alcohol, and is found in Adonis vernalis. 

Theoretically four pentose alcohols are possible : two meso forms, 
viz. adonitol and xylitol ; and d- and /-arabitol, obtainable by reduction 
old- and /-arabinose or /- and rf-lyxose. 

There are ten possible stereoisomeric modifications of the hexose 
alcohols but three only are of interest. The others are obtainable by 
alkaline reduction of the appropriate aldo- or keto-hexoses. 

OHH H OH OH OH 
d-Mannitol — HC — C — C — C — C — CH has been found in manna, 

HOHOH H H H 

in the sap of the larch, etc., in leaves, in fruits, and particularly in 

fungi where it exceeds glucose in quantity or even replaces it. A 

glucoside, clavicepsin, present in the ergot of rye, yields glucose and 

mannitol when hydrolysed (Marino-Zirco and Pasquero). 

Mannitol seems in many cases to be a fermentation product derived 
from trehalose so that its formation may be avoided by preserving 
plant extracts under sterilised conditions. Irvine has noted specimens 
of sea-weed (Laminarid) which had become encrusted with mannitol 
after the cessation of active bacterial action on the surface of the 
thallus. 

Mannitol is optically inactive in water, but becomes dextro-rotatory 
on the addition of borax, if the mixture be acid. In alkaline solution 
it becomes laevo-rotatory. 

d'Sorbitol is present in ripe mountain ash berries, from which it 
can be prepared without difficulty, and in the fruits of most of the 
RosacecB ; it is probably also present ifi the leaves. It has been found 
as a crystalline efflorescence on the heads of a fungus {Boletus 
bovinus), 

d-Iditol is also present in mountain ash berries. 

\-Dulcitol occurs particularly among the Scrophulariacece. 



88 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 



Two heptose alcohols, C2Hi^07, are known, eg. perseitol, occurring 
in Persea gratissima, and volemitol, discovered in Lactarius volemus^ 
and since identified in the rhizomes of some species of primula. Per- 
seitol is the alcohol corresponding to mannoheptose. 

An octitol has been isolated from the mother liquors of the sorbitol 
preparation from the fruit of some of the Rosacea. 

These alcohols are similar in properties to mannitol. Their 
physical constants are collected below : — 

TABLE XIII. 



Alcohol. 


Mdtinir-point. 


Optical 
Rotatory Power 


Erythritol .... 
Adonitol .... 
Mannitol .... 
Dulcitol .... 
Sorbitol .... 
Perseitol .... 
Volemitol .... 


126° 
102° 
168° 
188° 

110° 

180° 
154^ 


inactive 
>> 

+ 22-5'' 

inactive 
+ 12-3'' 

- 1*3° 
+ 1-9° 



Starting from glucose, Philippe has synthesised the higher alcohols 
of this series, obtaining them by reduction of the corresponding aldoses. 
a-Glucoheptitol is optically inactive and therefore symmetrically con- 
structed. /8-Glucoheptitol has slight optical activity, the same applies 
to (aa)-gluco-octitol, to (aaa)-glucononitol and to (aaaa)-glucodecitol, 
which are therefore all asymmetric in configuration. They are 
crystalline substances resembling mannitol in their properties. 

The polyhydroxy compounds can be coupled with acetone or 
benzylidene residues : fortunately these substances can be methylated 
by methyliodide in presence of silver oxide without decomposition, 
and it has thus been possible to study the influence of the position of 
the hydroxyl groups : — 

TABLE XIV. 



Alcohol. 


Number of Hydroxyl 
Groups Present. 


Number of Hydroxyl Groups 
which React with 


Acetone. 


Benzaldehyde. 


Erythritol 

Arabitol .... 

Dulcitol .... 

Sorbitol .... 

Mannitol 

Glucoheptitol . 


4 
5 
6 

6 
6 

7 


4 

4 

4 
6 

6 

6 


4 
2 

4 

4 
6 

2 



HEXOSES, PENTOSES, CARBOHYDRATE ALCOHOLS 89 

The series of reactions summarised above shows that the relation- 
ship between configuration and condensation is very complex, and 
that the action of acetone is less irregular than that of benzaldehyde. 

Two types of condensation are possible, depending on whether the 
hydroxyl groups concerned are on the same side or on opposite sides 
of the carbon chain : — 



O— C— H 



H—C— O I 

I NcMe^ """ / 

H— C— 0/ H— C— O^ 



~ CMe, 



ffs-conaensation. ^raMs-condensation. 

It is generally accepted that the ketonic residues are coupled as 
five-membered rings. 

The study of mannitoltriacetone by Irvine and Patterson has 
shown that it is hydrolysed in stages, both diacetone and monoacetone 
being formed in turn. The three ketonic residues are symmetrically 
attached to a-carbon atoms, and this difference in stability indicates 
that the substituents possess the trans-y ^r^i:«j-aj-arrangement. 

The formula of triacetonemannitol is thus — 

— O A, 



CHa 



/ \ 
H H O O O 

C C L.Z C CHj 

I /A, I I 

O-^ H . H 



O 



According to this the terminal alcohol groups in mannitol, though 
unconnected directly with an asymmetric carbon atom, assume pre- 
ferentially different positions in virtue of the attractive and repulsive 
forces exercised by the remaining hydroxyl groups. 

This fact explains the resistance of mannitol to complete alkyla- 
tion, one of the terminal primary hydroxyl groups remaining unat- 
tacked although the other offers no such resistance. The constitution 
of pentamethylmannitol is — 

OMe H H OMe OMe OH 

tHj C C C C CH„ 

I'll 
OMe OMe H H 

6 54321 

Complete methylation would thus involve the substitution of three 
adjacent hydroxyl groups on the same side of the carbon chain ; such 
a process would naturally present difficulties which would not arise 
were the terminal carbon atom able to take up either position. 



90 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

According to the older views a di- derivative of mannitol involving 
groups I and 2 would be identical with one in which 5 and 6 were 
similarly substituted. On the basis of the new formula this would not 
be the case, but Irvine and Steel have been able to demonstrate for the 
methyl derivatives that though mannitol contains six reactive hydroxyl 
groups numbers i and 2 are unique, and principally responsible for 
the increase in conductivity of mannitol in presence of boric acid.^ 

oo-Diaryl derivatives of the alcohols have been obtained by Paal 
by the application of the Grignard reaction to fully acetylated gluco- 
nolactone. Diphenyl, ditolyl and dibenzyl sorbitol and dulcitol are 
thus prepared. The dulcitol compound on warming readily forms an 
internal anhydride, probably — 



o 




Mannitol has been converted into methyl-a-pyrone, 

^CH . CHMe. 

cuf^ ^0,by treatment with formic acid. The diformate of 

\CH : CH^^ 

the mannitan, CgH^gOg, decomposes into carbon dioxide and the 
pyrone and also into carbon monoxide and isomannide (Windaus and 
Tomich). 

The Inositols or Cycloses. 

The molecular formula CjHjjOg is common not only to the im- 
portant classes of aldohexoses and ketohexoses, but is shared by certain 
cyclic polyalcohols such as the hexahydrocyclohexanes. These sub- 
stances, a number of which are found in nature generally associated 
with true sugars, contain no carbonyl group and are therefore not, 
strictly speaking, members of the carbohydrates. On the other hand, 
they are not only isomeric with the latter but possess a sweet taste, 
are high-melting crystalline compounds, generally soluble in water, 
and exist in various stereoisomeric modifications, some of which are 
optically active ; so that the superficial resemblance to the true hexoses 
is close and justifies their inclusion in a work dealing with natural 
carbohydrates. 

^ Many sugar and other polyhydroxyl alcohols have their specific rotation increased in 
the presence of boric acid. Boeseken has shown that such increase is always accompanied 
by a notable increase in conductivity, and further that this double effect only takes place in 
compounds in which two hydroxyl groups are attached to neighbouring carbon atoms on 
the same side of the chain. 



HEXOSES, PENTOSES, CARBOHYDRATE ALCOHOLS 91 

Moreover, a perhaps fanciful analogy may be drawn between the 
hexoses C^H^O^ the methylpentoses C^HigOj, and the methyltetrose 
digitoxose C^H^^O^ on the one hand, and the following series of 
natural cycloses in which the number of hydroxyl groups are simi- 
larly decreased : — 

CeHjjOg the inositols, 
CeHigOg the quercitols, 
and CeHj204 of which quintc acid, CeH7(OH)4 . COOH, is a carboxylic acid 

derivative. 

If the series is extended to the members C^Hj^O,, CgHjjOj and 
CgHijO, it becomes clear that these compounds are simply hydro- 
genated phenols ; the less oxygenated members of the group have not 
been found in nature, but hexahydrophenol, CjHn(OH), quinitol or 
hexahydroquinol, CgHi^(0H)2, and phloroglucitol (hexahydrophloro- 
glucinol), C(5H9(OH)3, have been prepared synthetically by the Sabatier 
method of hydrogenation of the respective phenols over reduced nickel, 
whilst quinitol was first synthesised by Baeyer by alkaline reduction 
of /-diketohexamethylene, and phloroglucitol had been similarly pre- 
pared from phloroglucinol and sodium amalgam. 

It is of interest that just as glycollic aldehyde is the first sweet 
tasting sugar in the monosaccharides, so quinitol possesses a sweetish 
taste, although hexahydrophenol does not ; as usual, the presence in 
close contiguity in the molecule of more than one hydroxy! group 
appears necessary for the development of this property, at all events 
in the case of simple compounds of carbon, hydrogen and oxygen. 

The stereoisomerism of the cycloses demands some explanation, since 
it is not due to the simple "atomic" asymmetry of the carbon atoms 
as in the simple sugars. Thus, in the case of the inositols CjHg(OH)j 
there are no "asymmetric carbon atoms" of the conventional type, 
but both dextro- and laevo-rotatory forms of the substance are known ; 
if, however, the steric formula be examined it will be seen that the 
hydroxyl groups may lie on either side of the plane of the carbon 
ring-system. 

For example we may have : — 



H 


H 


OH 


OH 




H 


H 


H/OH 
OH\P 


OH\H 

H /OH 

C^ 


H/H 
O^OH 


h\ 

OH . 
— C^ 


OH 
^H 


oh/oh 

andC<: 

h\ h 


oh\oh 

H/OH 


OH 


OH 


H 


H 




OH 


OH 




(i) 


^ 


(ii) 




(iii) 





92 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

(i) is a syrametrically arranged molecule identical with its mirror 
image, but (ii) and (iii) are mirror-images of each other and non-super- 
posable, although it is difficult to show this clearly in a plane illus- 
tration. The total number of possible optical isomerides of the inosi- 
tols may be arrived at by considering the possible number of hydroxyl 
groups on the "upper" side of the carbon-ring plane in formulas of 
of the above type : — 





No. of 










Hvdrozyl 
Groups. 






No. of Forms. 










a) 


o 


I 


optically 


inactive. 




I 


I 


» 


active. 


2 


3 


t> 


inactive. 


3 


3 


ft 


ft 


(e) 


4 


3 


*> 


„ (identical with {c)). 


(/) 


5 


I 


ff 


active (the optical antipode of (b)). 


(g^) 


6 


I 


f* 


inactive (identical with (a)). 



Of these seven distinct possibilities of optically inactive (meso) 
forms, and two possible enantiomorphic optically active forms, the d- 
and /- forms of inositol correspond to configurations Q\) and (iii) in the 
diagram and to {b) and (/) in the table, but it is not known to which of 
the classes (^), {c) or (^, the four inactive or meso varieties so far identi- 
fied, belong. 

Similarly, there are ten possible distinct configurations of quercitol, 
CgH7(OH)6, eight optically active and two unresolvable inactive 
(meso) modifications, but only two are known, a dextro-rotatory 
variety and a laevo-rotatory variety which is not the optical antipode 
of the former. 

The cyclose group may possibly be produced in nature by the 
union of the ends of the six-carbon hexose chain, but such a trans- 
formation has not hitherto been effected in the laboratory. 

The only instance of a complex organic compound being obtained 
from both the ordinary carbohydrates and from the inositols is the 
formation of furfural when meso-inositol is distilled with phosphoric 
anhydride in a copper vessel (Neuberg). 

Inositols^ CgHg(OH)g. 

Six of the nine inositols predicted by theory have been described, 
namely, the natural optically active forms of d- and /-inositol, two 
naturally occurring meso forms, /-inositol and scyllitol, and two other 
meso forms obtained by Hugo MUUer by chemical treatment of /-inosi- 
tol and named /j(7-inositol and -^inositol. 

No precise configuration is yet attached to any of the inactive 
forms. 



HEXOSES, PENTOSES, CARBOHYDRATE ALCOHOLS 93 

A-Inositol IS prepared by boiling its naturally-occurring monomethyl 
ether, pinitpl^ C7H14OJ, with concentrated hydriodic acid ; it crystal- 
lises in anhydrous prisms which melt at 247''-248'' C, and have 
Md + 65° ; it does not show mutarotation. 

Pinitoly also known as matezite or sennitey was discovered in 1856 
by Berthelot in the resin of the Californian pine, Pinus lambertiana 
(Dougl). It also occurs in the residues from the manufacture of 
coniferin in senna leaves and in Madagascar rubber. Its structure was 
established by Maquenne. 

VInositol was obtained by Tanret by demethylation of quebrachitol 
in 1889. It crystallises in needles which melt at 247°, [a]D - 65°. 
The monomethyl ether quebrachitol is found in quebrache bark. 

The racemic inositol, composed of equimolecular proportions of 
the rf- and /-isomerides, may be prepared by crystallisation of a 
mixture of the latter in equal quantities, and melts at 253° C. It was 
found, with /-inositol, in the fresh ripe berries of mistletoe by Tanret 
in 1907. 

Meso- or /-inositol {dambose^ nudte) is widely distributed in plants 
and animals ; it is found in the muscles and various organs of oxen 
and horses and in the urine in Bright's disease. In the vegetable 
world it occurs in the Leguminosae, in the leaves of asparagus, the 
oak, ash and walnut, and in all parts of the grape vine, and also in 
many fungi. Its chief sources of extraction are walnut leaves and 
mistletoe. It crystallises in bunches of needles and melts at 225°. 
It does not reduce Fehling's solution and is not fermented by yeast, 
but is attacked by certain fungi. The hexacetate forms monoclinic 
plates and melts at 2 1 2° C. 

When /-inositol is evaporated almost to dryness with nitric aci^ and 
then again carefully evaporated with calcium chloride solution a rose- 
red solution is obtained ; if ammoniacal strontium acetate is substituted 
for the calcium salt a violet tint is produced (Scherer's reaction). Both 
these colour tests are excessively delicate, especially the latter. 

H. Miiller found that treatment of /-inositol with a solution of 
hydrochloric or hydriodic acid in acetic acid transformed it partially 
into two other meso forms : — 

iso-Inositol^ crystals melting at 246^-250°, readily soluble in water, 
insoluble in alcohol, but soluble in boiling 50 per cent alcohol, and 
tasting faintly sweet ; and 

'^'Inositol^ an amorphous or microcrystalline compound, very 
soluble in water, but very sparingly so in alcohol. 



94 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

The monomethyl ether of /-inositol, Bornesitol, occurs in Borneo 
rubber, and the dimethyl ether, Dambonitoly in Gabon rubber. 

Phytifiy a compound of /-inositol and phosphoric acid, is an im- 
portant derivative of /-inositol found in the seeds of many plants. It 
was isolated from rice bran as inositol phosphoric acid by Winter- 
stein and from maize meal by Vorbrodt It is stable at 115° C, but 
in presence of water at 155** C is resolved into phosphoric acid and 
inositol. 

Contardi synthesised an inositol hexaphosphate in 191 2 by the 
action of phosphoric acid on inositol at 120**- 130° C. in the absence of 
air, and considered it to be probably identical with the phytin in 
seeds. 

Anderson at about the same period recorded unsuccessful attempts 
to obtain the hexaphosphate synthetically, obtaining only tetraphos- 
phates of the formula C6H,(OH)204[PO(OH)2]4, and inositol derivatives 
of pyrophosphoric acid. 

Scyllitoly the other natural inactive form of inositol, was formerly 
known by the three names of scyllitol, cocositol and quercine, but 
H. Miiller showed in 191 2 that all three were identical. 

Scyllitol was discovered by Staedeler and Friedrichs in 1858 in 
various organs of the spur dog-fish {Plagiostomt). H. Miiller found 
it in 1907 in the leaves of Cocos nudfera (Linn.) and Cocos plumosa 
(Hook), assigning to it at that time the name "cocositol". It also 
occurs in acorns. 

The formation of the same complex organic product in such different 
organisms as those of the cocoa-nut palm and oak on the one hand, 
and the spur dog-fish on the other is very remarkable. 

Scyllitol is optically inactive, forms hard lustrous monoclinic 
prisms which melt at 349°-3So'* C, is sparingly soluble in water, gives 
Scherer's colour reaction and yields the customary acetyl, benzoyl, 
etc, esters. 

Quercitolsy QH7(OH)5. 

As previously mentioned, two optically active forms of the quercitols 
are found in plants. 

A'Quercitol occurs in acorns and in small quantities in the cork 
and bark of oak. H. Miiller also obtained^t from the leaves of 
ChanuBTops humilis (Linn.), the only European representative of the 
palm-family, which was formerly used like esparto for paper-making. 
The leaves contain 1*35 per cent of quercitol. 

rf-Quercitol crystallises in prisms and melts at 234"* C. ; its rotatory 



HEXOSES, PENTOSES, CARBOHYDRATE ALCOHOLS 95 

power IS [a]o + 20°. It is not fermentable. It gives pentacetates 
and similar esters, thus possessing five hydroxyl groups in the mole- 
cule. Oxidation with permanganate leads to the formation of malonic 
acid and other products which confirm its structural formula as penta- 
hyd roxycy clohexane. 

I'Queratol wdiS obtained by Power and Tutin in 1904 from the 
leaves of Gymnema sylvestre (R.Br.). It crystallises in prisms from 
water and in needles from alcohol and melts at 174° C, having 
[«]d ~ 74°« It gives penta-acetyl and penta-benzoyl compounds, and 
yields with sodium hypobromite a diketotrihydroxycyclohexane, 
CeH,02(OH)8. 

d' and /-Quercitol are not optical antipodes. 

Quinic Acid, C^HyCOHXCOOH. 

Qutntc acid IS a carboxylic derivative of a tetrahydroxycyclohexane 
occurring in cinchona bark, coffee beans, bilberries and other plants. 
It melts at 162° and is optically active. When it is submitted to dry 
distillation, phenol, quinol, benzoic acid and salicylaldehyde are pro- 
duced. Oxidising agents convert it into a variety of common aromatic 
compounds, notably quinone and hydroquinone. Certain ferments 
attack it, producing a mixture of the lower fatty acids in absence of 
air, whilst in presence of air protocatechuic acid is formed. 

Quinide, CyHjoOs, melting at 198°, an optically inactive lactone of 
quinic acid, is produced by heating the natural acid at 220°-240° C, 
and when this compound is hydrolysed with milk of lime an optically 
inactive form of quinic acid is produced, 

Shikimic Acid, CjH8(OH)8COOH. 

The only natural representative of the trihydroxycyclohexanes at 
present known is shikimic acid, which is found in the fruit of Illicium 
religiosum, and is an analogue of quinic acid. 



CHAPTER IV. 

THE DISACCHARIDES. 

The disaccharides or compound sugars are carbohydrates containing 
twelve carbon atoms and consist of two simple six-carbon atom 
residues united through an oxygen atom. They are thus analogous to 
the simple glucosides, and when acted upon by hydrolytic agents — 
acid or enzymes — they break down by combining with a molecule of 
water into their constituent simpler hexoses, which may be either 
aldoses or ketoses : — 

One of the constituent hexoses functions in the same manner as 
glucose does in the methyl glucosides : the aldehydic or ketonic group 
of the second hexose may remain functional or it may disappear. In 
the former case the disaccharide reduces cupric salts, forms an osazone, 
and exhibits mutarotation behaving just as glucose does ; in the latter 
all these properties are absent. Accordingly, the disaccharides are 
classified under two types. 

The table on opposite page contains the better-known disaccha- 
rides with their component hexoses and optical rotatory power. 
Some trisaccharides are also included ; also the tetrasaccharide, 
stachyose. 

The disaccharides of type i form sparingly soluble phenyl osazones, 
which are difficult to purify, similar to one another and do not show 
sharp melting-points as they decompose at the melting-point ; more- 
over, both melting-point and crystalline form are greatly altered by 
small quantities of impurities. The hydrazones, even those prepared 
from asymmetrically disubstituted phenyl hydrazines, are too soluble, 
as a rule, to be used for the isolation of disaccharides from aqueous 
solutions. 

The difficulty attending research in this group lies in the fact that 

no really characteristic derivatives of the disaccharides, by means of 

which they can be isolated and identified with certainty, are known, 

and partly for this reason but little progress has been made in the 

direction of their synthesis. 

96 



THE DISACCHARIDES 



97 



TABLE XV. 



Sugar. 


Components. 


Rotatory Power. 




DiSACCHARIDBS. 




Type I. — Aldehyde Group Potentially Functional, 




Maltose 

Isomaltose 

Gentiobiose 

Cellose 

Lactose 

Isolactose 

Melibiose 

Turanose 


Glucose-a-glucoside 

Glucose-^-glucoside 

Glucose-^-glucoside 

Glucose-j3-glucoside 

Glucose-^-galactoside 

Glucose-gsdactoside 

Glucose-galactoside 

Glucose and fructose 

Type 2. — No Reducing Properties, 


+ 138° 

+ 84-4° 
+ 9-6** 

+ 34-6° 

+ S^'S"" 

? 

+ 143° 


Sucrose 

Trehalose 

Isotrehalose 


(Uucose and fructose 
Glucose and glucose 
Glucose and glucose 

Trisaccharidbs. 


+ 66-5° 

+ 197° 
- 58° 






Type I. 
Mannotriose 
Rhamninose 


Glucose + galactose + galactose 
Glucose + rhamnose + rhamnose 


+ 167° 
- 41" 


Type 2, 
Rafiinose 
Gentianose 
Melicitose 


Galactose + glucose + fructose 
Glucose + glucose + fructose 
Glucose + glucose + fructose 

Tetrasaccharide. 


+ 123^ 

+ 31° 
+ 88-5<» 


Type 2. 
Stachyose 


Fructose + glucose + galactose + galactose 


+ 148° 



Maltose, lactose and melibiose, which reduce Fehling*s solution, 
form hydrazones and osazones with phenyl hydrazine and combine 
with hydrogen cyanide, contain, like glucose, an aldehyde group or its 
equivalent. Since they all show mutarotation, and exist in two 
modifications, there is no doubt that, like glucose, they possess a 
closed-ring structure rather than a free aldehyde group. In solution 
they exist as an equilibrated mixture of dynamic isomerides. Both 
halves of the molecules thus possess a butylene-oxidic structure, one 
section only retaining the aldehyde group potentially functional. 

Interest in the configuration of the disaccharides centres round 
three main points : — 

(i) The nature of the component hexoses. 

(2) Whether they represent a- or ^-glucosides. 

(3) Which hydroxyl group is concerned in the attachment of the 

two hexose residues ? 
The solution of the first of these problems is a simple matter. The 
second question has been answered in two ways : firstly, by studying 

7 



98 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

the behaviour of the sugar towards the enzymes, maltase and emulsin 
— if hydrolysed by the former it is an a-glucoside, if by the latter a 
/J-glucoside ; secondly, by studying the optical behaviour of the glucose 
immediately produced, on hydrolysing the sugar with an enzyme, 
towards a drop of alkali — downward mutarotation classes it as an 
a-glucose, upward mutarotation indicates the presence of y3-glucose. 
The third question has begun to be solved satisfactorily ; and it has 
been possible to show for maltose, lactose, melibiose and sucrose which 
groups are concerned in the junction. 

Assuming the primary alcohol group to be concerned in the attach- 
ment of the two hexose residues four isomeric diglucoses with reducing 
properties are possible. The attachment of the two glucoses may be 
either a or P, and the free aldose group will exist in a and fi modifi- 
cations. Maltose or lactose in solution represents, like glucose, an 
equilibrated mixture of two isomerides : the solid disaccharides corre- 
spond to more or less pure single substances. 

Considerations based on the numerical relations among the rotatory 
powers of the disaccharides make it probable that the left-hand glucose 
residues in lactose and cellose have identical structures, whereas maltose 
and gentiobiose do not agree with either melibiose or lactose as re- 
gards the structure of this glucose molecule. 

Three isomerides are conceivable of the non-reducing diglucose 
according as two a^lucoses, two /J-glucoses or an a- and a y3-glucose 
are linked together. These three disaccharides will be single substances 
either as solid or in solution and they should crystallise more freely 
than maltose. 

The compound sugars of type 2 which contain fructose are re- 
garded as members of the sucrose group since they all contain the 
sucrose union and are hydrolysed by invertase. Hudson has established 
that for sugars of this group, which yield fructose and an aldose on 
hydrolysis, the molecular rotation of the aldose is less than that of its 
parent sugar by 2340 for its alpha form and 19,300 for its beta form. 
The specific rotation of the a and ff forms of melibiose, gentiobiose 
and mannotriose calculated in this manner agree with those deduced 
by other methods. 

In the following pages the individual disaccharides are briefly dealt 
with. The problems connected with their hydrolysis and synthesis 
are deferred to Chapter VI. 



THE DISACCHARIDES 99 

Sucrose. 

Sucrose or cane sugar, industrially the most important of the 
sugars, is widely distributed in the vegetable kingdom, where it 
functions almost entirely as a reserve material. In contrast to most of 
the sugars, it crystallises exceedingly readily : this is almost certainly 
due to the fact that a single substance and not a mixture of isomerides 
is present in solution. It is very soluble in water, and has a much 
sweeter taste than glucose, but is not so sweet as invert sugar. 

Cane sugar does not reduce Fehling's solution nor exhibit muta- 
rotation, and it lacks both aldehydic and ketonic properties. Very 
characteristic is the behaviour towards mineral acids which hydrolyse 
it to glucose and fructose. Sucrose is dextro-rotatory, but, since 
fructose is more laevo-rotatory than glucose is dextro-rotatary, the 
products of hydrolysis rotate polarised light in the opposite sense to 
cane sugar. The change in rotation is from + 66*5° to - 20°: the 
process is hence termed inversion, and the product invert sugar. The 
like change is brought about by an enzyme present in yeasts, moulds, 
in many plants, also in bees and other animals, and termed invertase 
or sucrase. Cane sugar is fermented by yeasts only after previous 
inversion with the invertase of the yeast. Accordingly, it is not fer- 
mented by yeasts which do not contain invertase, eg. S. octosporus. 

Sucrose forms no compounds with phenyl hydrazine, and is stable 
towards alkali : this is in marked contrast to the behaviour of the 
aldoses and ketoses. Sucrose will withstand heating in alkaline 
solution at temperatures up to 1 30° without appreciable decomposition. 
It also does not give rise to glucosidic derivatives. It contains eight 
hydroxyl groups, as evidenced by the formation of an octa-acetate and 
an octa-methyl derivative, but gives rise to one form only of these 
derivatives. 

It forms saccharates, CigHgiOuM, with sodium and potassium 
hydroxides and more complex saccharates with lime, strontia and 
baryta. 

Until recently it was not possible to ascribe a constitutional 
formula to sucrose which was entirely satisfactory. It is at one and 
the san>it time a glucoside and a fructoside in which the hexose units 
are joined so as to destroy both aldehyde and ketone groups and give 
a neutral product. There is much evidence in favour of assigning a 
butylene-oxide structure to the glucose residue and an ethylene-oxide 
structure to the fructose residue so that it may be formulated as first 
proposed by Howarth and Law : — 

7* 



lOO THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 



o 



. CH . (CH . OH), . CH = 



CH3(0H) . CH(OH) . CH . (CH . 0H)3 . CH = glucose residue 



O 

/ 
CH,(OH) . CH(OH) . CH(OH) . CH . C . CH3(0H) = fructose residue 

\/ 
O 

In the older formula of Fischer, which in turn was a modification 
of the earlier one of Tollens, a butylene-oxide structure was assigned 
to both halves of the molecule. 

The behaviour of sucrose towards enzymes indicates that it is not 
a simple glucoside or fructoside ; it is not hydrolysed by maltase and 
the butylene-oxide ^-methyl fructoside is not hydrolysed by invertase. 
Invertase is remarkably active in hydrolysing sucrose, and its action 
seems to be controlled and inhibited by both glucose and fructose ; 
apparently the enzyme is so constituted that it can adapt itself to 
both sections of the disaccharide. The question is further discussed 
in Chapter VI. 

The extraordinary instability of sucrose in presence of acids also 
differs markedly from the behaviour of the simple glucosides, but it is 
in better agreement with the proposed formula containing an ethylene- 
oxide ring, as is indicated on page 133. 

According to Howartli and Law on hydrolysis of sucrose the 
following series of changes take place, the final products consisting of 
the equilibrium mixtures A and C together perhaps with a small pro- 
portion of B : — 

A B c 

Sucrose [-^j a-glucose + a-fructose [^] a-fructose 

t t t I t I 

^-glucose ^-fructose [Ij] ^-fructose 

(Butylene- (Ethylene- (Butylene- 

oxide oxide oxide 

forms). . forms). forms). 

The arrows in brackets represent changes involving structure ; the 
others indicate stereochemical intercon versions. 

The formula of Howarth and Law is based on the behaviour of 
octamethyl sucrose on hydrolysis. The optical change is small — from 
+ 667° to + 57° — whereas had the known butylene-oxide forms of 
tetramethyl glucose and fructose been obtained an end value of -18'' 
was to be expected. Actually an ethylene-oxide form of tetramethyl 
fructose having a rotatory power of + 29*3° is formed. The hydroly- 
sis may thus be formulated : — 



• • " J •' 
• • •• > 



9 rt ^. 



THE DISACCHARIDES loi 

Octamethyl sucrose [->] Tetramethyl + tetramethyl 

a-glucose a-fructose 

tetramethyl tetramethyl 
^-glucose ^-fructose 

(Butylene- (Ethylene- 

oxide formf). oxide forms). 

The Statement that a-glucose is a constituent of sucrose is based 
on the optical changes on hydrolysis of both sucrose and octamethyl- 
sucrose ; it still requires other confirmation. 

Trehalose. 

Trehalose, which occurs widely distributed in fungi, is composed 
of two glucose molecules fused together, so that both aldehydic groups 

have disappeared : — 

O 



I I 

CH,(OH) . CH(OH) . CH . CH(OH) . CH(OH) . CH\^ 
CHa(OH) . CH(OH) . CH . CH{OH) . CH(OH) . Ch/ 



-O— 



This structure is indicated by the fact that it does not reduce 
Fehling's solution or form a phenyl osazone or exhibit mutarotation. 
It is not affected by the enzymes maltase, invertase, emulsin or dia- 
stase, but is hydrolysed by a special enzyme named trehalase, which 
is contained in certain fungi and in many species of yeast Tre- 
halase is conveniently obtained from Aspergillus niger. According to 
Winterstein trehalose is only hydrolysed by acids with considerable 
difficulty, and contrasts markedly in this respect with sucrose. Pre- 
sumably the glucose molecules react in the butylene-oxide form. 

Trehalose crystallises in lustrous rhombic prisms \a\o + 197''« 
The best soured for its preparation is Selaginella lepidophylla (the 
resurrection plant) obtainable in large quantities in the arid South- 
west of America ; this contains 2 per cent, of the sugar which is 
readily crystallised (Ansel mino and Gilg). 

Trehalose is also a constituent of sea- weeds. Some of the Floridece 
contain up to lo per cent, of the dried material. It is absent from 
the FucoidecB where it is replaced by a laevo-rotatory disaccharide, 
termed laminareose, which has not beei\ isolated. Kylin finds that 
laminarin, the dextrin-like polysaccharide of these plants, consists of 
a series of closely related substances with a specific rotation varying 
from - 7" to - 32° as their molecular weight falls. It is hydrolysed by 
malt diastase to glucose and constitutes a reserve food-stuff analogous 



• » _• • > 

•• • • • 

• • * • • 



... *•:•;.. 



I02 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

to starch which is utilised by the sea- weed for growth and reproduction 
during the winter. 

Apparently trehalose replaces sucrose in those plants (fungi) which 
contain no chlorophyll and do not manufacture starch. The quantity 
of trehalose is a maximum just before the formation of spores. When 
the fungi are picked the trehalose is rapidly converted into mannitol, 
being hydrolysed by its enzyme to glucose, which is in some way 
then reduced. To obtain it, the fungi must be extracted with boiling 
solvents, so as to kill the enzyme, within two or three hours after 
gathering. 

As indicated on page 144 there are three possible combinations of 
the two glucose molecules in trehalose. Hudson has calculated the 
specific rotations of these forms to be aff + 70°, aa + 197°, /3^ - 58°, 
and thus identifies the natural sugar as the aa form. It is probable 
that the ^^ form is represented by /j(7-trehalose, which, in an amorphous 
impure state, had a^ - 39°. It was prepared by Fischer and Delbruck 
by saponification of the octacetate obtained on condensing two mole- 
cules of acetobromoglucose in presence of silver carbonate and is 
stated to be easily hydrolysed on warming with dilute acids. 

MALTOSE. 

Glucose-a-Glucoside. 

A sugar was first isolated from the products of hydrolysis of starch 
by De Saussure in 18 19, but it was not until 1847 that this new sugar 
was further examined by Dubrunfaut and named maltose. This dis- 
covery seems to have lapsed into comparative oblivion until the sugar 
was rediscovered by O'Sullivan in 1872. Maltose is prepared by the 
action of diastase on starch, the only other product of the change 
being dextrin. It crystallises in minute needles, has a high dextro- 
rotatory power and exhibits upward mutarotation, i.e. the rotatory 
power when the disaccharide is first dissolved is smaller than the 
equilibrium value. 

Maltose reduces Fehling's solution, forms a phenyl osazone, and 
shows many other of the properties of glucose. 

When hydrolysed by acids two molecules of glucose are formed. 
It is very much more resistant to acid hydrolysis than cane sugar. 

The enzymes diastase, invertase, lactase and emulsin are without 
action, maltase alone of all the known enzymes being able to effect 
hydrolysis. Maltose is fermented only by those yeasts which contain 
maltase, and then not until inversion has been brought about by the 



THE DISACCHARIDES 103 

enzyme. In view of the behaviour of maltose towards maltase, it is 
considered to be a glucose-a-glucoside, since it is only a-glucosides 
which are hydrolysed by maltase ; and in confirmation of this view 
a-glucose has been proved to be formed initially on hydrolysis. 

Maltose yields, on oxidation with bromine, an acid containing the 
same number of carbon atoms, which is termed maltobionic acid ; this 
is hydrolysed to glucose and gluconic acid by mineral acids. Maltose 
combines with hydrogen cyanide, forming a compound which, on 
hydrolysis, gives maltose carboxylic acid, and is hydrolysed by 
mineral acids to glucose and glucoheptonic acid. Maltose must con- 
tain eight hydroxyl groups, as it gives an octa-acetyl derivative when 
acctylated. The behaviour of maltose is in accord with the constitu- 
tional formulae below. As already stated, it is not known which 
carbon atom is concerned in the attachment of the two sugar residues. 
Provisionally, the terminal carbon atom is so represented (see Chapter 
VI.) :— 

CH2(0H) . CH(OH) . CH . [CH .GHJa . CH— O . CHa . CH(OH) . CH . [CH . OHJg . CH . OH 



/ \0-^ \0' 

Strong confirmation of this structure is afforded by the behaviour 
of maltose on oxidation with alkaline hydrogen peroxide, studied by 
Lewis and Buckborough. Relatively large amounts of glycollic acid 
glucoside are formed, showing that the primary alcohol carbon atom 
is concerned in the attachment. The participation of the first, second 
and third atoms from the free aldehyde group in the glucoside union 
is precluded by the formation of a- and ^- /j<;-saccharinic acids on 
oxidation, and the non-formation of glyceric acid glucoside excludes 
the fourth atom. 

Maltose forms a glucoside analogous to methyl glucoside, but the 
direct condensation with methyl alcohol in presence of acid is not 
possible, as the disaccharide becomes hydrolysed during the operation. 
^-Methyl maltoside has been prepared from acetochloro maltose, ob- 
tained by the action of hydrogen chloride on maltose octa-acetate. 
Acetochloro maltose interacts with methyl alcohol in presence of 
silver carbonate, forming hepta-acetyl methyl maltoside, which is con- 
verted into methyl maltoside on hydrolysis with baryta. The be- 
haviour of this maltoside towards enzymes is interesting. Maltase 
hydrolyses it at the a-junction, forming glucose and ^-methyl gluco- 
side ; emulsin attacks only the y8-junction, forming maltose and methyl 
alcohol. The maltoside is accordingly ^-methyl glucose-a-glucoside. 

The conversion of maltose octa-acetate into ^-methyl maltoside 



104 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

fixes it as a /9-derivative, and since this acetate is the main product of 
the acetylation of solid maltose it is probable that maltose belongs to 
the p series. The; rotatory power of crystalline maltose, unlike that 
of glucose, increases in solution. According to Hudson's rule maltose 
is a /9 compound. 

Isomaltose. 

Isomaltose is the name given by Fischer to the disaccharide ob- 
tained by him by the condensing action of strong acids on glucose. 
It was characterised only by means of the phenyl osazone and the fact 
that it is not fermented by yeast. Products similar to isomaltose have 
been repeatedly described as obtained in the hydrolysis of starch, e.g. 
gallisin, but, failing any characteristic derivative, definite proof of its 
presence in such cases is lacking. Isomaltose is probably identical 
with th^ disaccharide obtained by Croft Hill by the synthetic action 
of maltase on glucose (see Chapter VI.) which he has termed rever- 
tose. E. F. Armstrong has shown that isomaltose is hydrolysed by 
emulsin, but not by invertase or maltase, and considers the isomaltose 
obtained by means of acids or enzymes to be the same in each case. 
The behaviour towards emulsin and maltase suggests that it is prob- 
ably glucose-^-glucoside. 

A quantitative study of the action of hydrochloric acid of much 
lower strength (07 normal) than used by Fischer on glucose has been 
made by Harrison. He isolated unfermentable isomaltose, a^ + 84*4° 
and showed that in 52 per cent, glucose solution the final ratio of iso- 
maltose to glucose is 2:3. Davis finds that synthesis of isomaltose 
takes place in a i per cent, solution of glucose in fuming hydrochloric 
acid (40 per cent. acid). 

CELLOSE (CELLOBIOSE.) 

Glucose-^-glucoside. 

Cellulose (filter paper) when acetylated with acetic anhydride and 
a small amount of sulphuric acid forms a-cellose octacetate, among 
other products, from which the corresponding sugar, cellose, is ob- 
tained on hydrolysis with alcoholic potash. 

Cellose forms a fine crystalline powder, m.p. 225°, and has a faintly 
sweet taste ; it is much less soluble than sucrose. It exhibits muta- 
rotation, reduces Fehling's solution and forms a phenylosazone and 
osone. Acetochloro, acetobromo and other derivatives are known, 
cellose behaving exactly like maltose or lactose. 



THE DISACCHARIDES 105 

The a-octacetate prepared by acetylation of the sugar in presence 
of zinc chloride or sulphuric acid has m.p. 229**, [ajo +41°. The /3- 
octacetate is obtained on acetylation in presence of sodium acetate and 
has m.p. 202°, [ajo - 1 5°. It is readily transformed into the a-isomeride 
on heating with acetic anhydride in presence of sulphuric acid, so that 
the production of a-octacetate by the acetolysis of cellulose does not 
indicate whether cellulose is a condensation product of a- or ^-cellose. 
Klein has shown that it is possible to obtain 30 per cent, of the 
theoretical yield of cellose octacetate indicating that at least one-third 
of the monosaccharides in cellulose are united as in cellose. 

Cellose is not attacked by the p^rvyyrp^s nf y<i*a«^f (maltQCf*) It is 
hydrolysed by emulsin, and slowly by Kephir lactase and by Aspergillus 
niger, Fischer points out that inasmuch as emulsin is a mixture of 
enzymes it is not certain that the same enzyme which hydrolyses 
yS-methylglucoside also resolves cellose, gentiobiose and isomaltose. 
Bertrand and Compton have established the individuality of cellase, 
the enzyme acting on cellose, and shown that cellase and emulsin occur 
together in plants in variable proportions. There is, however, con- 
siderable similarity in the behaviour of lactose and cellose towards 
enzymes, and this analogy becomes all the more striking when Hud- 
son's proof that the glucose residues in these two sugars have similar 
structures is considered. 

When methylated cellulose is hydrolysed the most characteristic 
methylated glucose obtained is a crystalline trimethylglucose. Denham 
and Woodhouse have established the formula of this as : — 

CAa(OMe) . CH(OH) . CH . (CH . OMe).. . CH(OH) 

' -O ! 

It is definitely a butylene-oxide compound. 

Should the same trimethyl derivative be derived from cellose, and 
taking into account also the similarity between the glucose residues 
in cellose and lactose, it is possible to suggest the following structural 
formula for cellose : — 

CH2{0H) . CH{eH) . CH . [CH(0H)]2CH . = glucoside 

i \ residue 

T 




HO . CH . (CH , OH)j6ir CH . CH,(OH) = glucose 



o L-J 



residue 



io6 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

GENTIOBIOSE. 

Glucose-^-glucoside. 

Gentiobiose is closely allied to maltose, isomaltose and cellose, being 
composed of two glucose molecules. It is found in the form of a tri- 
saccharide, termed gentianose, present in the roots of various species 
of gentians ; when partially hydrolysed either by means of invertase 
or dilute acids this yields fructose and gentiobiose. The octacetate is 
conveniently obtained direct from powdered gentian root (Zemplen), 
and Hudson has obtained as much as lo grams per kilo of the dry 
root in this way. 

Grentiobiose shows mutarotation, the a and fi forms having rotation 
+ 39° and - ii"* respectively and the equilibrium mixture - 9*6°. 
It forms a phenylosazone, m,p. 1 60°- 170°: other derivatives are the 
a- and /3-octacetates and ^-methylgentiobioside which has [a]^ 36"*. 

It is hydrolysed by emulsin and is therefore a /3-glucoside. Bour- 
quelot has prepared and isolated it in a pure state by the action of 
emulsin on a concentrated solution of glucose, and his observations 
have been confirmed by Zemplen. It is concluded that gentiobiose 
and isomaltose are not identical, since whereas the octacetate of the 
former is readily isolated from very impure products an acetyl deriva- 
tive could not be obtained from isomaltose syrups. 

LACTOSR 

Glucose-^-Galactoside. 

Lactose or milk sugar, discovered in 161 5 by Fabriccio Bartoletti, 
in Bologna, occurs in the milk of all animals, but has not been en- 
countered in the vegetable kingdom. It is manufactured by evapora- 
tion of whey, purified by recrystallisation, and obtained in the form of 
a white crystalline powder. Mineral acids hydrolyse it to glucose and 
galactose ; it exhibits mutarotation, reduces Fehling's solution, and 
forms a phenyl osazone soluble in boiling water. Like glucose it gives 
rise to two series of isomeric derivatives, e.g. octacetates, acetochloro 
lactoses and methyl lactosides. Three isomeric modifications of the 
sugar itself have been described corresponding to the a- and /3-iso- 
merides and their equilibrated mixture. It is a glucose galactoside, 
since, on oxidation with bromine, lactobionic acid is formed, and this 
when hydrolysed by mineral acids gives gluconic acid and galactose, 
proving that the potential aldehyde group is in the glucose part of the 
molecule. 



THE DISACCHARIDES 107 

Adopting Fischer's glucoside formula for lactose, it is a question^ 
as previously indicated, whether the primary alcohol group or the 
S-secondary alcohol group of the glucose molecule takes part in the union 
with the galactose. The possibility of either the a- or 7-secondary 
alcohol groups being concerned is excluded by the facts that lactose 
forms a phenyl osazone, exhibits mutarotation, and gives rise to de- 
rivatives having a butylene-oxide structure. The ^-secondary alcohol 
group can also be excluded from consideration, as Ruff and Ollendorf 
have obtained, on oxidising the calcium salt of lactobionic acid by 
Fenton's method, a galactoarabinose sugar which forms a phenyl 
osazone in which this /3-alcohol group is involved. It must therefore 
be uncombined in the parent lactose. 

It remains therefore to decide in favour of the two remaining for- 
mulae. Here again as in the case of sucrose a study of the fully 
methylated lactose made by Howarth and Leitch enables a decision 
to be made. Heptamethyl methyl-lactoside, on hydrolysis at 80°, yields 
tetramethylgalactose and a trimethylglucose having the constitution : — 

CH,(OMe) . CH(OH) . CH . (CH . 0Me)2 . CH . OH 

I O ^1 

This affords definite proof that the secondary alcohol group of the 
fifth or 8-carbon atom of the glucose chain is concerned in the attach- 
ment of the two hexose sugars. 

Accordingly milk sugar has the constitution : — 

CHaCOH) . CH{OH) . CH . (CH . 0H)3 . CH . = /S-galactoside 

\ residue 

-O 




HO . CH . (CH . OH)o . CH . CH . CH2(0H) = glucose 

residue 

-0 



The isomeric a and ^ forms of milk sugar, originally described by 
Tanret and investigated subsequently by Hudson, differ only with 
respect to the relative positions of the hydrogen and hydroxyl radicles 
attached to the carbon atom printed in clarendon type in the glucose 
half of the molecule. Tanret's *7-lactose is an equilibrated mixture, 
a-lactose is properly a-glucose-^-galactoside, whereas ^-lactose is 
y8-glucose-^-galactoside. 

The milk sugar of commerce is a-lactose, [aj^ + 90°. The 13 form 
has +35° and the equilibrated mixture + 55*3°. 

Galactoarabinose is of interest as an example of a synthetical 
disaccharide containing both hexose and pentose sugars. It is 



io8 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

therefore akin to the natural sugar rhamninose. The formation of 
galactoarabinose affords additional proof that lactose is a galactoside. 

Lactose is hydrolysed by a specific enzyme lactase found in a few 
yeasts (or, more correctly, torulae), in some kefir preparations, and in 
the enzyme (crude emulsin) contained in an aqueous extract of almonds. 
It is believed that kefir lactase and almond lactase are not identical. 
Lactose is not hydrolysed by maltase, invertase, diastase, nor by any 
of the enzymes of dried brewers' yeast. Only those yeasts (torulae) 
which contain lactase are capable of fermenting milk sugar. Lactose 
is particularly prone to undergo lactic and butyric acid fermentations. 

Isolactose is the name given to a disaccharide obtained by Fischer 
and Armstrong by the synthetical action of the enzyme kefir lactase 
on a concentrated solution of equal parts of glucose and galactose, 
and isolated in the form of the phenyl osazone. It has not been 
further studied. 

MELIBIOSE. 

Glucose-^-Galactoside. 

Melibiose, together with fructose, is obtained from the trisaccharide 
raffinose by hydrolysis with dilute acids or certain yeasts (Scheibler 
and Mittelmeier). It crystallises with difficulty and it is advisable 
to remove the fructose from the products of hydrolysis of raffinose 
by fermentation with a top yeast before attempting to isolate it. 

Hudson obtains as much as 200 grammes from 500 grammes of 
raffinose by fermenting with baker's yeast in 10 per cent, solution for 
36-48 hours. The sugar separates with difficulty from a thick syrup 
to which ethyl alcohol has been added, in monoclinic prisms. It is 
very soluble in water. 

It exhibits mutarotation, the a form having + 197° the /3 form + 
125° and the equilibrium mixture + 143°. When hydrolysed with 
strong acids melibiose yields glucose and galactose. On reduction 
with sodium amalgam an alcohol, melibiitol, is formed. This, when 
hydrolysed, is converted into mannitol and galactose. Melibiose is 
thus a galactoside of glucose, i.e. very closely related to milk sugar. 

It forms a phenyl osazone, an osone, which latter decomposes to 
galactose and glucosone and a double series of derivatives in the same 
manner as lactose. 

Melibiose is slowly hydrolysed by emulsin, more rapidly by an 
enzyme contained in bottom fermentation, but not in top fermentation 
yeasts : this enzyme is appropriately termed melibiase. Melibiose is 



THE DISACCHARIDES 109 

not attacked by maltase, invertase or lactase. It affords a chemical 
means of distinguishing between top and bottom fermentation yeasts. 
It is apparently less easily hydrolysed by acids than is milk sugar. 

The difference between melibiose and milk sugar appears to depend 
upon which hydroxyl of the glucose molecule is united to the galacto- 
side (see types A and B, p. 132). 

In view of the proof of the structure of lactose afforded by Howarth 
and Leitch it is highly probable that in melibiose the glucose residue 
is attached to the galactoside through the terminal carbon of the 
chain : — 



O 



CH2(0H) . CH(OH) . CH . (CH . GHjg . CH = /3-galactoside residue 

> • 

CH(OH) . (CH . 0H)2 . CH . CH(OH) . CHa = glucose residue 
I JO ^1 

The possibility, however, is not altogether excluded that the third 
carbon atom from the left in the glucose molecule is concerned. 

Added interest attaches to melibiose in view of its being the first 
natural disaccharide obtained synthetically (Fischer and Armstrong, 
see p. 143): it was prepared from acetochlorogalactose and sodium 
glucosate. 

Melibiosone, which can be prepared from the osazone by heating 
with benzaldehyde, is hydrolysed by emulsin or by melibiase ta 
galactose and glucosone. 

Turanose. 

Turanose was discovered by Alechin in 1890 as a product, together 
with glucose, of the partial hydrolysis of a trisaccharide, melicitose, 
with weak acids. He stated that it yielded two molecules of glucose 
on further hydrolysis, but Tanret subsequently showed that an equi- 
molecular mixture of glucose and fructose is produced. Turanose is 
hydrolysed with such difficulty that much of the fructose liberated is 
destroyed by the strong acid solutions that must be used. Turanose 
is thus an isomeride of sucrose, but differs from this in containing a free 
aldehydic group, since it forms a phenyl osazone and reduces Fehling's 
solution. It is said not to exhibit mutarotation and crystallises in 
colourless rounded grains, [a]jy + 71 '8°. It is not at present known 
whether it is to be regarded as a fructoside or a glucoside. Invertase,. 
maltase, emulsin and diastase are without action. 



no THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

Vicianose. 

Vicianose was obtained by Bertrand from the seeds of a vetch ( Vicia 
angustifolicL) where it is present in the form of a glucoside, vicianin, 
allied to amygdalin. Vicianose is glucose-arabinoside, since on oxida- 
tion and subsequent hydrolysis gluconic acid and arabinose are formed. 
Accordingly, in the glucoside the glucose group is attached to the 
benzaldehyde cyanhydrin. 

Strophantobiose. 

Strophantobiose is a component of the glucoside strophantin. 
When this glucoside is hydrolysed by hydrogen chloride in methyl 
alcohol methyl strophantobioside is formed. This does not reduce 
Fehling*s solution and is hydrolysed by mineral acids to mannose, 
rhamnose and methyl alcohol. 

TRISACCHARIDES, Z^^Yi^^O^^. 
Mannotriose. 

Mannotriose, m.p. 150°, [ajo + 167°, a colourless faintly sweet 
crystalline substance, is obtained from stachyose by the action of in- 
vertase or of dilute acetic acid. It reduces Fehlings's solution and 
forms a phenyl osazone, m.p. I22°-I24° (Tanret). According to Bierry 
the compound, m.p. 193°-! 94°, described by Neuberg and Lachmann 
was impure. Mannotriose is hydrolysed by acids to glucose (one mole- 
cule) and galactose (two molecules). Bromine oxidises it to mannotri- 
onic acid which is hydrolysed by acids to gluconic acid and galactose, 
thus locating the glucose molecule at the end of the chain. The action 
of enzymes on mannotriose is still a matter of uncertainty. Bierry has 
shown that the intestinal juice of the snail probably first forms 
galactose and a disaccharide, glucose + galactose, which is subsequently 
hydrolysed. According to Neuberg and Lachmann glucose and a 
digalactose are formed by the action of almond emulsin. 

The constitution is probably 

CHO . C5Hio04-0-CeHio04-0-CeHn05 
Glucose Galactose Galactose 



^ V. 



Gluco-galactose. Digalactose. 



THE DISACCHARIDES in 



Rhamninose. 



Rhamninose, C^s^u^iv ^-P- ^35°-^40°, Md - 41°, is derived from 
the glucoside xanthorhamnin present in the Persian berry {Rhamnus in- 
fectoria). The berries also contain a specific enzyme, rhamninase, which 
resolves the glucoside into the trisaccharide and rhamnetin. The car- 
bohydrate forms colourless crystals which are somewhat sweet : it 
reduces Fehling's solution. On hydrolysis by mineral acids galactose 
and rhamnose (two molecules) are formed. The galactose is proved to 
be the terminal unit since the rhamninitol and rhamninonic acids, formed 
by reduction and oxidation respectively, are hydrolysed by acids to 
dulcitol or galactonic acid and rhamnose (two molecules). Rhamninose 
is not fermentable and the ordinary enzymes are without action. It ap- 
pears to be slowly hydrolysed by the intestinal juice of Helix. 

The formula may be written : — 

CHO . CsHjoO^— O— CeHiiG,— O— CgHiaO^ 
Galactose. Rhamnose. Rhamnose. 

Raffinose. 

Raffinose, m.p. iiS^-iig", [ajo + 104°. The best-known trisac- 
charide IS raffinose which is often found in considerable amount in the 
sugaf beet, and is present in other plants. The best source for the 
preparation of raffinose is cotton-seed meal which contains it to the 
extent of nearly 8 per cent. : this proportion of the weight of the 
cotton-seed cake that is produced annually in the United States amounts 
to 100,000 tons. The raffinose is extracted from the meal with water, 
and after purification by means of its barium salt, may be isolated from 
the latter by exact neutralisation of the barium with phosphoric acid. 
Strong mineral acids hydrolyse it completely to fructose, glucose and 
galactose in equal proportions. Dilute acids form melibiose and fructose. 
The action of enzymes on raffinose is more specialised ; invertase con- 
verts It into fructose and melibiose. Emulsin, however, hydrolyses it 
to sucrose and galactose. Bottom yeasts which contain both melibiase 
and invertase are able to ferment it completely. 

Raffinose has no reducing action and behaves chemically as cane 
sugar. The constitutional formula may be written : — 

CsHiiOj-O-CeHioO^-O-CeHiiOB 
Fructose Glucose Galactose 

Sucrose. Melibiose. 



112 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

Gentianose. 

Gentianose, m.p. 209°-2io°, [a]D + 3i'2°-33'4°, is obtained in faintly 
sweet colourless crystalline plates by extracting fresh gentian roots with 
95 per cent, alcohol. It is non-reducing and is hydrolysed by invertase 
or very dilute acids to fructose and gentiobiose. Some emulsin prepara- 
tions, in particular extracts of Aspergillus niger^ convert it into glucose 
and sucrose (Bourquelot). Stronger acids hydrolyse it to a mixture of 
fructose and two molecules of glucose having [ajo - 20*2°. Animal 
enzymes are without action, but those of molluscs and crustaceae, parti- 
cularly of the snail, act firstly to eliminate fructose and then hydrolyse 
the gentiobiose (Bierry). 

The constitutional formula is thus written : — 

CeHnOB-G— CgHioO^— O— CeH„05 
Fructose Glucose GIucobc 



Sucrose. Gentiobiose. 

Melicitose. 

Melicitose (Melezitose), m.p. 148°-! 50°, \a\^ + 88-5°, crystallises in 
rhombic prisms ; it is obtained from Briangon manna, the exudation 
from the young twigs of the larch. It does not reduce Fehling's 
solution, exhibit mutarotation, or form a phenyl osazone. Dilute acids, 
e.g. 20 per cent acetic acid, hydrolyse it to turanose and glucose, the 
rotation falling to + 63°. Living yeast and enzymes are without 
action. Stronger, acids give rise to fructose (one molecule) and glucose 
(two molecules). It forms a hendeca-acetate, m.p. 117°, [aj^ + 110°. 

Hudson has obtained it in quantity from the manna exuded by 
the Douglas fir tree, which contains as much as 75 per cent of the 
trisaccharide. He also found the sugar in comb honey which the bees 
had collected from pine trees. It is also present to the extent of 
30 per cent in Turkestan manna. 

The constitution may be represented provisionally by the alterna- 
tive formulae : — 

1. glucose + fructose + glucose. 

2. glucose + glucose + fructose. 

These would assign to turanose the structure alternatively of a glucoside 
or fructoside. 



THE DISACCHARIDES 113 

TETRASACCHARIDES, Ca^H^gOgi. 

Stachyose. 

Stachyose (Mannotetrose, Lupeose) is found in the tubers of 
Stachys tubifera^ in ash manna, in the twigs of white jasmine and in 
the subterranean parts of Lamium album. 

It is probably identical with lupeose obtained by Schulze from 
Lupinus luteus and Angustifolius, It forms lustrous colourless plates, 
m.p. 1 67°- 1 70°, [ajo + 148°, and tastes quite sweet. 

Fehling's solution and alkali are without action on it. Acetic 
acid and the invertase of yeast hydrolyse it into mannotriose and 
fructose. Sulphuric acid causes complete hydrolysis to hexoses. It 
is also hydrolysed by the intestinal juice of Helix pomatia which first 
eliminates fructose, then galactose, and finally resolves the gluco- 
galactoside remaining as described under mannotriose. Animal 
intestinal enzymes, though they hydrolyse sucrose, are without action 
on stachyose, the enzymes of molluscs and crustaceae are also without 
action. Vintilesco claims to have hydrolysed stachyose completely 
by the successive action of invertase and almond emulsin. On oxida- 
tion with nitric acid, mucic acid is formed. 

The formula may be expressed : — 

CjH„05— 0-CeH,oO,--0~CeHioO,— O-aHiiOg 
Fructose Glucose Galactose Galactose 



Mannotriose. 



It forms an insoluble compound with strontiurti hydroxide and is 
so easily separated Tanret has thus isolated it from haricot-beans 
and the seeds of a number of other leguminoseae. 

Crystalline polyamyloses have been obtained from potato starch 
paste by the action of Bacillus macerans, Tetra-amylose, (C^^JC^^^, 
or a-dextrin crystallises in colourless hexagonal plates, [a] + 128°, 
hexa-amylose or /3-dextrin forms rhombic crystals, [a] + 136°. On 
acetylation, hydrolysis of the dextrins takes place and from the acetyl 
derivatives formed diamylose and triamylose were obtained. These 
crystallise in needles and do not reduce Fehling's solution. Rice 
starch gives similar definite polyamyloses on degradation. 



8 



CHAPTER V. 

THE RELATION BETWEEN CONFIGURATION i AND BIOCHEMICAL 

PROPERTIES. 

Perhaps the most important, and at the same time the most interesting, 
chapter in the chemistry of the sugars is that dealing with the altera- 
tion in properties brought about by small changes in the stereo-chemical 
configuration of the carbohydrate molecule. Although the molecular 
weight and the gross structure of the molecule remain the same, the 
very slightest modification in the space arrangement of the groups 
attached to th|^Byi of carbon atoms is sufficient to affect the bio- 
chemical beha^^^Bn the most profound manner. How exactly 
structure is to o^P^^Iated with biological behaviour, and how little 
variation in stru^H^ is permissible, will be seen from the following 
examples. 

It has long been known that the optical antipodes of a substance 
containing an asymmetric carbon atom behave very differently towards 
biological agents, such as yeasts, moulds, enzymes, or bacteria. The 
celebrated researches of Pasteur showed, for example, that the green 
mould, Penicillium glaucum^ when allowed to grow in solutions of 
racemic acid, assimilated only ^-tartaric acid, leaving the /-tartaric acid 
untouched It was supposed at the time that the mould was unable 
to attack the /-tartaric acid ; later investigations suggest, however, 
that the mould ultimately destroys both antipodes, but attacks one at 
a very much greater rate than the other, and probably in a different 
manner. 

From a given racemic substance it is . possible to obtain sometimes 
the one and sometimes the other antipode by utilising appropriate, 
organisms. For example, an excess of rf-mandelic acid is obtained 
from ^/-mandelic acid on treatment with Penicillium glaucum, whereas 
when Saccharomyces ellipsoideus is used an excess of /-mandelic acid is 
obtained. 

■ 

^ By the term configuration is understood the positions of the hydroxyl groups relative 
to the skeleton chain of carbon atoms. Change involves transference from the right to left 
side of the chain as figured on the plane of the paper or vice versd from left to right. 

114 



CONFIGURATION AND BIOCHEMICAL PROPERTIES 115 

Fermentation. 

Yeasts only ferment one, the dextro, isomeride of glucose, convert- 
ing it into carbon dioxide and alcohol, and accordingly when yeasts are 
allowed to act on racemic glucose the laevo glucose remains unattacked. 
The same applies to the other fermentable hexoses ; in all cases only 
the dextro isomeride is attacked. 

The investigation of the behaviour of all the known hexoses, 
either found in nature or prepared in the laboratory, towards yeasts 
has shown that only four are fermented, viz. the ^-forms of glucose, 
mannose, galactose, and fructose, all of which are natural products. 

When the behaviour of different species of yeasts towards these 
natural hexoses is studied, it is found without a single exception that 
any species of yeast which ferments any one of the three hexoses — 
glucose, mannose, and fructose — likewise ferments all three of them, 
and with approximately the same readiness. The study of the kinetics 
of the three fermentation reactions confirms their similarity, and they 
have the same temperature coefficient (Slator). Everything, in fact, 
points to the mechanism involved in the fermentation of glucose, 
mannose, or fructose being the same in each instance. 

It has already been pointed out that the three hexoses in question 
are closely related in structure, so closely indeed as to be converted 
under the influence of alkalis into one another. An enolic or oxide 
form common to all three hexoses has been assumed to act as an inter- 
mediate substance in the transformation. The relationship will become 
clear when the formulae of these carbohydrates are consulted : — 



CHO 


CHO 


CH.OH 


CH2 . OH 


HCOH 


HOCH 


COH 


CO 


HOCH 


HOCH 


HOCH 


HOCH 


HCOH 


HCOH 


HCOH 


HCOH 


HCOH 


HCOH 


HCOH 


HCOH 


CHjGH 


CHjOH 


CHjOH 


CHj,0H 


Glucose. 


Mannose. 


Common enolic form. 


Fructose. 



It is clearer here to use the older open-chain formulae, but the reader 
is advised to study these formulae in the solid model in order to 
understand fully the stereoisomerism of these compounds. Represen- 
tations on a plane surface easily lead to confusion. 

On the basis of the closed-ring formula for glucose, enolisation 
involves in the first place rupture of the pentaphane ring and forma- 
tion of the aldehydrol ; secondly, water is eliminated between two 
contiguous carbon atoms to give the enol. Comparing the following 
scheme with that on p. 8, for the conversion of the aldehydrol into 

glucose, the difference is at once apparent : — 

8 ♦ 



ii6 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 




+ H,0 



HO/. CH 
H/COH O 



HO.CH 

\ 
HC.OH 



- H3O 



CH(OH) 
C.OH 

HO.CH 

\ 
HC.OH 



,i. 



HC.OH 



.2. OH 
Glucose. 



i, 



JHj . OH 
Aldehydrol. 



CHj. 



HC.OH 

OH 



EnoL 



According to the alternative formula the aldehyde forms aldehydrol 
and this enoL The change is a reversible one. 

The process of fermentation of a sugar is regarded as a series of 
consecutive changes each involving simplification of the sugar mole- 
cule till it breaks down into carbon dioxide and ethyl alcohol, com- 
pounds containing only one and two carbon atoms. Measurements 
of the rate of fermentation can be made by determining the rate of 
formation of either of these products — for example, the amount of 
CO2 formed after various intervals of time — but such measurements 
only apply to the slowest of these reactions. Similarly the quantita- 
tive effect produced by an increase of temperature in quickening the 
rate of fermentation in reality applies to the slowest reaction of the 
series. 

It has been suggested that the first process in fermentation is the 
conversion of the sugar into the enolic form by means of an enzyme 
contained in the yeast. The tfiree fermentable hexoses yield the same 
enolic form, but possibly it is formed at different rates according to 
the sugar ; and whether one and the same agency is operative in each 
case it is impossible to say. The subsequent simplification of the 
molecule is the same for each of the three hexoses, an hypothesis which 
is quite in agreement with the experimental observations. This sim- 
plification is also due to an enzyme or to several enzymes acting in 
turn. The breakdown of the molecule will thus commence at the 
double linkage between the two. terminal carbon atoms. 

This view is quite in harmony with the discovery by Harden and 
Young that the first stage in the fermentation of glucose by zymase 
is the formation of hexose phosphate CgHioO/HaPOJg. Glucose, 
mannose, and fructose give rise to the same hexose phosphate : when 
this is hydrolysed fructose is obtained. In other words, the hexose 
phosphate may be regarded as a compound of the enolic form of the 
three hexoses (cp. Dr. Harden's Monograph, p. 46). 



./ 



CONFIGURATION AND BIOCHEMICAL PROPERTIES 117 

Further support of this view of the fermentation process is afforded 
by the fact that substances so closely related to glucose as the methyl 
glucosides, glucosone, gluconic acid, ai;d ethyl gluconate are, without 
exception, unfermentable : in all these only the groups attached to 
the terminal carbon atom differ from those of glucose. EnoHsation in 
them, however, is impossible, and no action takes place since the for- 
mation of hexose phosphate is prevented. 

The behaviour of galactose is altogether different. It is fermented 
with much greater difficulty than glucose. Very many yeasts are 
quite without action on galactose. The temperature coefficient of the 
fermentation of galactose is different from the value found in the case 
of glucose. These facts suggest that galactose is fermented by a 
different mechanism, that a different enzyme is concerned perhaps in 
causing enolisation, which is less widely distributed in yeasts. None 
the less the two phenomena must be very closely allied. No yeast is 
known capable of fermenting galactose but not fermenting glucose. 

The change in configuration in passing from glucose to galactose, , 
though not sufficient to prevent fermentation altogether, causes the 
compound to be far more resistant to attack. It is not surprising, 
therefore, that any further change in configuration is sufficient to make 
the new hexose no longer fermentable. 

This is illustrated by the behaviour of galactose and its isomerides, 
talose and tagatose, which have an enolic form common to all three 
hexoses : — 



CHO 


CHO 


CHgOH 


CHOH 


HCOH 


HOCH 


CO 


COH 


HOCH 


HOCH 


HOCH 


HOCH 


HOCH 


HOCH 


HOCH 


HOCH 


HCOH 


HCOH 


HCOH 


HCOH 


CH2OH 


CH2OH 


CHjOH 


CHjOH 


Galactose. 


Talose. 


Tagatose. 


Enolic form. 



Neither talose nor tagatose is fermented- by any yeast whose 
action towards them has at present been investigated. Yet in talose 
the position of the two upper hydroxyl groups is the same as that in 
mannose, and the lower three hydroxyls occupy the same positions as 
they do in galactose. Obviously, for* it to be fermentable, the con- 
figuration of the hexose has to be correct as a whole, the fact that 
single hydroxyl groups occupy the same positions as they do in fer- 
mentable hexoses being of no moment. 

Presumably yeasts contain no enzymes compatible with talose or 
tagatose and able to convert them into the enolic form. 

The facts described can only be explained on the assumption that 
there is the very closest relationship between the configuration of a 



ii8 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

fermentable hexose and the enzymes which cause fermentation. This 
hypothesis receives confirmation which is little short of absolute when 
the behaviour of the sugars other than the hexoses is considered. No 
pentose, either natural or synthetical, is fermentable by yeast. None 
of the synthetic tetrose, heptose, or octose carbohydrates are fermentable. 

The only fermentable sugars, other than the four hexoses, are a 
nonose prepared by the cyanohydrin method from mannose and a 
ketotriose, dioxyacetone. The fermentability of **glycerose" — a mix- 
ture of glyceric aldehyde and dioxyacetone — was long a matter of 
controversy; Bertrand, however, showed tht pure dioxyacetone is 
fermented by very active yeasts and this has been repeatedly 
confirmed. 

A further illustration of the relation of configuration to fermenta- 
bility is afforded by the behaviour of that monomethylglucose in which 
the methoxyl group is attached to the carbon at the extreme end of 
the chain and therefore most remote from the part of the sugar mole- 
cule which is generally believed to have the most effect in controlling 
enzyme action — 

i ° — A 

MeO . CHa . CH(OH) . CH . [CH . OH]a . CH . OH 

Living top yeast and a maceration extract of dried bottom yeast were 
quite without action. The compound also resisted seven species of 
bacteria all of which acted on glucose. 

The identification of intermediate products in the fermentation of 
glucose has long been a matter of controversy. 

Buchner and his co-workers have suggested in turn lactic acid 
CH3 . CH(OH) . CO2H and dihydroxy acetone CHgOH . CO . CHgOH, 
but in both cases Slator has shown that these are fermented very much 
more slowly than glucose, an observation which renders Buchner' s 
, hypothesis untenable, and the same will probably apply to the latest 
suggestion that formic acid is an intermediate product. Bearing in 
mind Fischer's synthesis of acrose from dihydroxyacetone it appears 
probable that dihydroxyacetone is fermented by yeast only after it has 
been converted into hexose, and the same applies to glyceraldehyde. 
This hypothesis is greatly strengthened by Lebedeff's proof that the 
organic phosphate produced during the fermentation of dihydroxy- 
acetone is identical with the hexose phosphate obtained by Harden 
and Young from the fermentable hexoses. It is probable, therefore, 
that dihydroxyacetone is only fermented after conversion into hexose. 

Evidence is, however, accumulating that pyruvic acid — 

CHg . CO . CO2H 



CONFIGURATION AND BIOCHEMICAL PROPERTIES 119 

is a normal intermediary. When yeast is grown in sugar solutions in 
presence of sodium sulphite considerable quantities of acetaldehyde 
are formed. This fact is the basis of the suggestion by Neuberg that 
the sugar breaks down into two molecqles of pyruvic acid which are 
rapidly converted into aldehyde by the yeast carboxylase. The alde- 
hyde in turn acts as an acceptor of hydrogen and promotes the forma- 
tion of pyruvic acid from sugar under the influence of the yeast 
reductase, half the aldehyde being at once converted into alcohol. 
This subject is, however, more appropriately discussed in the mono- 
graph on fermentation. 

It is obvious how intimately the property of undei^oing fermen- 
tation is connected with the configuration of the sugar molecule. 
Lengthening or shortening the chain of carbons is sufficient to place 
the sugar molecule out of harmony with the yeast enzymes, and thus 
prevent its destruction by fermentation. The fact that triose, hexose, 
and nonose sugars are fermentable has led to the suggestion that the 
fermentable carbohydrates must contain a multiple of three carbon 
atoms : the fermentability of the nonose requires confirmation. 

Although hexosephosphate is formed under the influence of yeast 
juice living yeast cells do not ferment it, even when added coferment 
and artificial activators are supplied. Dried yeast or yeast juice 
esterifies phosphate almost quantitatively in presence of sugar whereas 
living yeast, even when toluene has been added, may esterify only 
some 8 per cent. ; the difference is probably a question of cell per- 
meability. It is further of interest that some yeasts, when weakened 
by nitrogen starvation, are able to esterify phosphates in presence of 
fructose but not with glucose. This is an indication that the proto- 
plasm can grip the ketose structure more readily than the aldose 
structure and that the preparatory process in fermentation may be 
concerned in the conversion of aldose into ketose, or far more probably 
into a common enolic or oxide form, which is more easily formed from 
fructose than from glucose. 

In this connection it is common knowledge that fructose is usually 
more easily or better utilised in the animal body than glucose, as, for 
example, under diabetic conditions. 



120 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

Glucoside Hydrolysis. 

The formation of stereoisomeric a- and ^-methyl glucosides by the 
interaction of glucose and methyl alcohol in presence of hydrogen 
chloride has already been discussed and their constitutional formulae 
established. These isomeric glucosides, though so alike in structure, 
behave very differently towards enzymes. 

o-Methyl glucoside is hydrolysed by the maltase (a-glucase ^) of 
yeast, ^-methyl glucoside by emulsin (/8-glucase) which is widely dis- 
tributed in plants. Emulsin is quite without action on the a-glucoside ; 
maltase has no effect on the ^-glucoside. 

CH.O.C.H H.C.OCH 



3W • X./ .XX *i . w . x^wAXj 





H 

HCOH 

jOH CH2OH 

a- Methyl glucoside /3-Methyl glucoside 

hydrolysed by Maltase hydrolysed by Emulsin 
(a-glucase). (/3-gIucase). 

Other alkyl derivatives of glucose behave in a similar manner. It 
may be stated as a general rule that ^-glucosides are hydrolysed by 
emulsin alone, a-glucosides are only attacked by maltase. Accordingly, 
compounds hydrolysed by emulsin are considered to be ^-glucosides. 
The corresponding derivatives of /-glucose are not affected in the 
slightest by either enzyme, a- and ^-methyl-/-glucosides represent the 
mirror images of the methyl-rf-glucosides and their behaviour is parallel 
to that of /-glucose towards living yeast. 

The glucosidic derivatives of mannose, viz. methyl-rf and /-manno- 
sides are also quite stable in presence of maltase or emulsin. Hence 
the change in position of a single hydroxyl (here that attached to the 
a-carbon atom) is sufficient to render the mannoside out of harmony 

^ Nomenclature of Enzymes. — The name of an enzyme is usually derived from that of 
the sugar which it hydrolyses by substituting the suffix -ase for -ose. Thus maltase 
hydrolyses maltose, lactase hydrolyses lactose. The enzyme which attacks glucosides 
may be termed glucose and is an a-glucase or /3-glucase accordingly as it hydrolyses the 
a- or /3-glucoside. 

Although it was at one time generally stated that maltase does not usually occur in 
plants W. A. Davis gives strong reasons for supposing that it is always present where 
starch degradation occurs. It is endocellular in origin and readily destroyed by tempera- 
tures above 50° : it has low solubility and low powers of diffusion. Daish has identified 
maltase in the crushed pulp of a number of leaves, all of which convert gelatinised starch 
into glucose. 



)Ei CONFIGURATION AND BIOCHEMICAL PROPERTIES 121 



tk 

it 
It 



of 



with these enzymes ; but, as has just been seen, the change in con- 
figuration is not sufficient to make mannose unfermentable by yeast 

a-Methyl-<3^galactoside is likewise not hydrolysed by maltase or 
emulsin. 

^-Methyl-rf-galactoside is hydrolysed by the crude emulsin prepara- 
tion obtained from almonds, but subsequent investigation has shown 
that this preparation contains a mixture of enzymes and that the 
hydrolysis of the y8-galactoside is due to a lactase (^-galactase) and 
not to the same enzyme which attacks y8-methyl glucoside. This 
behaviour shows that the alteration in the position of the hydroxyl 
attached to the 7-carbon atom in the glucoside molecule renders the 
galactosides out of harmony with maltase and emulsin. Any other 
alteration involving departure from the configuration of the glucose 
molecule or in the length of the chain of carbon atoms has the same 
effect on the behaviour towards enzymes. 

None of the knov^n glucosides ^ of the pentoses, methyl pentoses, 
heptoses, or other hexoses are hydrolysed by maltase or emulsin. 

This behaviour can only mean that the hydrolysing power of these 
two enzymes bears the very closest relationship to the configuration of 
the dextro-glucose molecule. 

Fischer has drawn particular attention to the behaviour of the a- 
and ^-methyl-rf-xylosides. These practically correspond to the corre- 
sponding glucosides with one asymmetric carbon atom removed : — 




H— C— OCH, 




H— C— OCH, 




CH2OH 
/3-Methyl-i-glucoside. 



CHoOH 



/3-M ethyl-<f-xyloside. 



HOCH 



HC 

HCOH 

CH, 
/3- Methyl-{/-isorhamnoside. 

Both xylosides are unaffected by either maltase or emulsin. In 
this instance, although the major part of the molecule is identically the 
same in each glucoside, the shortening of the chain is sufficient to 
destroy the close harmony with the enzyme. 

Fischer's latest investigations have shown that ^-methyl-rf-isorham- 
noside (see p. 121) is also hydrolysed by emulsin. This glucoside 
differs only from /8-methyl glucoside in that the terminal CH^OH 
group is reduced to CHg. Apparently such a difference is not enough 

^ The term glucoside is used generally for the corresponding derivatives of all the 
sugars and not restricted to the derivatives of glucose. 



122 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 



to put the enzyme out of action although, as just stated, the elimina- 
tion of this carbon atom prevents the enzyme from acting on the 
methoxyl group at the other end of the chain. 

Fischer's own attitude towards this question is expressed in the 
following extract from hts summary in 1898 : — 

" Die Indifferenz der Xyloside gegen Emulsin und Hefenenzyme 
zeigt mithin, welch feine Unterschiede fiir den Angriff dieser Stoffe 
massgebend sind, oder mit anderen Worten, wie grob die Vorstellungen 
noch sind, welche wir trotz aller Fortschrite der Struktur- und Stereo- 
chemie von dem Aufbau des chemischen Molekiils haben. Das weitere 
Studium der enzymatischen Prozesse scheint mir deshalb berufen zu 
sein, auch die Anschauungen iiber den molekularen Bau komplizierter 
KohlenstofFverbindungen zu vertiefen.'* 

The glucosides investigated by Fischer are summarised in Table 

XVI. in which + indicates hydrolysis, o denotes no action. 

TABLE XVI. 



Glucoside. 


Maltase 
(opGlucase). 


Emulsin 
(/3-Glucase). 


a-Methyl-<2-Glucoside 


+ 





jS-MethyW-Glucoside , 









+ 


a-Methyl-/-Glucoside 












i8-Methyl-/-Glucoside 












a- Ethyl-rf- Gl ucoside 






+ 





i8-Ethyl-d-Glucoside 









+ 


j3-Phenol-£f-Glucoside 









+ 


a-Methyl-{/-Galactoside . 












j3-Methyl-^-Galactoside . 












Methyl-rf-Mannoside , 












Methyl-Z-Mannoside . 












o-Methyl-rf-Xyloside 












)B- Methyl-rf-Xyloside 












Methyl-/- Arabinoside 












Methyl Rhamnoside 












Methyl Glucoheptosid 


e 










jB-Methyl-rf-iso-Rhamnoside . 


"■^^ 


+ 



The investigation of the rate of hydrolysis of maltose — an a-gluco- 
side — by maltase has shown that change takes place more slowly in the 
presence of glucose, indicating that this sugar has a definite retarding 
influence on the enzyme. Other sugars, e.g. mannose, fructose, galac- 
tose, arabinose, xylose are quite without influence on the rate of 
change, proving that the action of glucose is due not to any concentrat- 
ing effect but to the specific influence exerted by its configuration. 
The fact that /3-methyl glucoside also acts to retard the hydrolysis of 
the a-glucoside (maltose) affords the strongest confirmatory evidence 
of this specific hindrance. Part of the enzyme must combine with 



CONFIGURATION AND BIOCHEMICAL PROPERTIES 123 

the glucose and so be withdrawn from action. Maltase can apparently 
combine with yS-methyl glucoside though quite unable to hydro- 
lyse it. 

In an analogous manner the hydrolysis of ^-methyl glucoside by 
emulsin is controlled only by glucose and a-methyl glucoside, and by 
no other carbohydrate. 

These illustrations, selected from a number of carefully worked-out 
cases, suffice to show the very intimate relation which exists between 
enzyme and the substance upon which it acts. This can only be ex- 
plained by supposing some form of combination between the two. 
The enzyme, moreover, must fit the glucoside at every point along 
the chain of carbon atoms, thus : — 



y 



K 



•-^•4- 



RO 



The combination may perhaps be compared to the way in which 
the successive fingers of a glove fit on to a right hand : if the position 
of any finger be altered it is impossible to fit the glove ; further, the glove 
will not fit on the left hand Fischer's original simile compared the 
relationship of enzyme to hydrolyte to that existing between a key and 
the k>ck for which it is made, the shape of the key enabling it only 
to unfasten the particular lock to the arrangement of whose wards it 
corresponds. 

The enzymes themselves, if this hypothesis be accepted, must be 
closely related in configuration to the substances which they hydro lyse. 
From this point of view the presence of a carbohydrate in the molecule 
of invertase and some other enzymes is at least significant (see Mono- 
graph by Bayliss, p. 19). Salkowski states, however, that the carbohy- 
drate present in the yeast gum is precipitated with the enzyme, but 
that it is not a component of the purified enzyme. 

It is perhaps necessary to emphasise that the actual hydrolysis of 
the carbohydrate is due to the action of the water molecules. The 
enzymes may be conceived perhaps as acting as a vice in presenting 
in the appropriate manner the water molecule to the centre to be 
hydrolysed. 

Attachment of enzyme to hydrolyte takes place no doubt through 
the oxygen atoms of the hydroxyl groups. In these the oxygen atom 



124 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

possesses residual affinity, that is, is not fully saturated, and it is there- 
fore able to combine with appropriate elements of the molecule of the 
enzyme. 

The fact that tetramethyl-y8-methyl glucoside like /8-methyl 
glucoside itself is hydrolysed by emulsin is in full agreement with this 



view : — 




H . C . OMe 



MeOCH 



HC 

HCOMe 

CHj . OMe 
Tetramethyl-/3-methyl glucoside. 




JHa . OH 



/3-Methyl glucoside. 



Although in this compound the hydrogen in the hydroxyl groups of 
glucose has been replaced by methyl, this change is not sufficient either 
to destroy the residual affinity of the oxygen atoms or to mask them 
from the influence of the enzyme. 

Most of the natural and the synthetic /8-glucosides are hydrolysed 
by emulsin, the exceptions being usually cases where the non-sugar 
residue is sufficiently toxic to put the enzyme out of action. An 
interesting exception is afforded by the mandelamide glucosides, of 
which one only — the laevo form — is hydrolysed, whereas both d- and 
/-mandelonitrile glucosides are hydrolysed. 



Conversion of Galactose into Glucose. 

When the closed-ring formulae of the two hexoses, glucose and 
galactose, are considered side by side, it will be obvious that the differ- 
ence between them is confined to the relative positions of the groups 
attached to the 4th or 7-carbon atom, i.e. the oxygen atom of the 
pentaphane ring is attached to different sides of the molecule : — 



HCOH 



HCOH 




HC 

HCOH 

CHjOH 

Glucose. 



. a- Carbon . 

. i3-Carbon . 

. -y-Carbon . 

. S-Carbon . 




HCOH 



CH,OH 



Galactose. 



CONFIGURATION AND BIOCHEMICAL PROPERTIES 125 

The direct conversion of one sugar into the other involves the rupture 
of the ring at this point and its closure again in the opposite sense. 
The whole behaviour of glucose shows, however, that the pentaphane 
ring ruptures preferentially at the attachment of the oxygen to the 
first carbon atom. The conversion of glucose into galactose has been 
only^ indirectly effected by chemical means, but there is little doubt 
that it takes place in the organism, as it is only on this supposition 
that the formation of the galactoside, milk sugar, in large quantities ia 
mammals during lactation can be accounted for. 

Under normal conditions the blood transports glucose to the 
mammary glands, where, in the regular course of lactation, it is con- 
verted into the disaccharide, milk sugar, and excreted in the milk. 
Removal of the mammary gland results in an accumulation of glucose 
in the blood, from which it passes to the urine. Galactose is not 
found in the urine. Injection of glucose causes lactosuria when the 
mammary glands are in full activity, but produces glucosuria when the 
glands are less active. Nothing is known as to the mechanism by 
which the mammary glands are able to transform glucose into lactose,, 
but it is undoubtedly effected by means of enzymes. 

The enzyme lactase which hydrolyses ^-methyl galactoside, other 
yS-alkyl galactosides and milk sugar, is a specific enzyme for y8-galacto- 
sides, just as emulsin has been shown to be the specific enzyme for 
yS-glucosides. Lactase has its action controlled only by galactose and 
by no other sugar, and it is incapable of hydrolysing glucosides. The 
only enzyme at present known which can hydrolyse a-methyl galacto-^ 
side is the digestive juice of the Helix, which, according to Bierry, attacks 
both a- and y8-galactosides ; on the other hand, no compound of 
a-galactose is known in nature. Bierry states that the lactase ob- 
tained from the intestine of a dog hydrolyses lactose and not /3-methyl 
galactoside. 

Apparently two lactases exist, one form present in kephir being 
controlled by galactose, the other present in almond emulsin by glucose. 
The work of Miss Stephenson indicates that the lactase of the intestinal* 
mucous membrane of animals is a glucolactase. 



126 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

Oxidation. 

The influence of configfuration has been also studied in the case 
of the behaviour of carbohydrates towards oxidising bacteria. The 
bacterium xylinum (Adrian Brown), or sorbose bacterium, as it has 
been termed by Bertrand, oxidises aldoses to the corresponding mono- 
basic acids, and converts the alcohols into ketones, e.g. gluconic acid 
is formed from glucose, galactonic acid from galactose ; xylose and 
arabinose yield xylonic and arabonic acids. In all these cases the 

- CHO group is oxidised to - COgH by the agency of the bacterium. 

In the case of alcohols the sorbose bacteria oxidise - CH(OH) - 
to - CO - . Thus mannitol forms fructose ; sorbitol yields sorbose ; 
erythritol, arabitol and perseitol are oxidised to the corresponding 
ketones, and glycerol gives dihydroxyacetone. The bacterium has 
no action, however, on glycol, dulcitol, or xylitol. 

An examination of the formula of these alcohols shows that the 

- CH(OH) - group oxidised to - CO - is next to a - CHgCOH) 
group ; further, for action to take place, the hydroxyl group must not 
be adjacent to a hydrogen atom on the same side of the configuration 
formula ; in other words, the compound must contain the grouping — 

H H 

CHaCOH) . C . C— 
OH OH 

Consideration of the configuration formulae of mannitol and dulcitol 
will help to make this clear : — 

OHOH H H 
CHJOH) . C . C . C . C . CHj(OH) 
H H OHOH 

Mannitol — converted into Fructose. 

H OH OH H 

CHa(OH) . C . C . C . C . CHj(OH) 

OH H H OH 

Dulcitol — not attacked. 

Gluconic acid contains the sensitive grouping. Accordingly, it is 
further oxidised by the bacterium to a keto-gluconic acid : — 

OH H OH OH OH H OH 

COoH . C . C . C . C . CHJOH) -> CO-H . C . C . C . CO . CHj(OH) 
H OH H H H OH H 

Gluconic acid. Keto-gluconic acid. 

In contrast with the sucroclastic enzymes, which are apparently in 
harmony with the sugar molecule as a whole, these oxidising bacteria 
seem adapted to a section only of the molecule. Their action is none 
the less absolutely dependent on the presence of the requisite configura- 
tion in the molecule. 

Many bacteria act upon mannitol which are without action on 



CONFIGURATION AND BIOCHEMICAL PROPERTIES 127 

dulcitol. Harden found this to be true for Bacillus colt communis^ which 
is of interest also since it produces twice as much alcohol from mannitol 
as from glucose. This difference is ascribed to the presence of the 
group CHgCOH) . CH(OH) — which is contained once only in glucose 
but twice in mannitol. 

Only those bacteria which produce fermentation of glucose act on 
pyruvic acid, CHg . CO . COgH. 

According to Grey the fermentation of various carbohydrates and 
allied substances by bacteria is effected by a single set of enzymes the 
action of which is common to all such cases of fermentation. The 
first step in the alteration of a particular molecular structure may 
require a special enzyme to produce the common intermediate sub- 
stance but the subsequent changes are always similar, being due to 
the action of the standard series of bacterial enzymes. 

In animal tissues glucose is converted by oxidation into lactic 
acid with the intermediate formation of glyoxal. Glucosone, which 
may be regarded as a substituted glyoxal, remains unchanged, how- 
ever, in presence of a septic kidney tissue, proving that the enzyme 
can only effect the unchanged hexose (Levene). 

A further example of the influence of configuration on biochemical 
properties is afforded by the formation of the urease ferment by 
bacteria. Jacoby has shown that whilst rf-glucose, rf-galactose and 
^and /-arabinose contribute to the formation of the ferment, ^mannose 
and rhamnose are inactive. In the active sugars the configuration — 

OH H 
- C - C - CHO or its optical antipode 
H OH 

exists, whereas in the inactive sugars both hydroxyl groups are on the 
same side of the chain of carbon atoms. 

By floating detached leaves, which have been deprived of their 
starch by keeping them in the dark, on nutrient solution it is possible 
to determine which substances can occasion the formation of starch. 
The application of this method to the carbohydrate alcohols affords an 
excellent illustration of the influence of configuration on the biological 
properties. Plants which normally contain alcohols can utilise these 
and also glycerol to form starch ; thus the OleacecB utilise mannitol, 
Lingustrum and Chieranthus make use of dulcitol. Treboux has shown 
that the Rosacece^rt, able to produce starch from sorbitol, the production 
being more vigorous than from carbohydrates or from glycerol, but they 
are quite unable to utilise mannitol or dulcitol. The leaves of Adonis 
vernalis2x^ able to convert adonitol into starch but can make use of no 
other carbohydrate alcohols. 



128 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

The four polysaccharides, sucrose, gentianose,raffinose,and stachyose, 
may all be regarded as fructose derivatives of increasing complexity. 
The invertase of beer yeast eliminates fructose from all of them, the 
juice oi Helix pomatia or oiAstacus behaving similarly, though there is a 
difference in the degree of hydrolysis, sucrose being far the most readily 
attacked. The intestinal juice of the dog and that of other invertebrates 
acts only on sucrose (Bierry). 

The digestive juice of snails is remarkable in its activity towards 
substituted lactose derivatives. Thus it hydrolyses lactose-osazone, 
aminoguanidine, semi-carbazone, and carbamide to galactose and a de- 
rivative of glucose. In a similar manner it splits off galactose from 
derivatives of mannotriose (Bierry). 



CHAPTER VI. 

HYDROLYSIS AND SYNTHESIS. 

Hydrolysis of Disaccharides. 

DiSACCHARlDES are hydrolysed to monosaccharides by mineral and 
organic acids in accordance with the equation — 

Any acid will act on each sugar, though the intensity of the action 
differs more or less according to the acid or the disaccharide. 

The disaccharides are also hydrolysed by enzymes. The action 
of enzymes is essentially selective : each particular sugar is hydrolysed 
only by its appropriate enzyme and by no other. There is thus a 
sharp distinction between the two classes of hydrolysing agents. 

Great historical interest attaches to the phenomenon of the hydro- 
lysis of cane sugar by acids as it was one of the first chemical changes 
of which the course was followed by physical methods.^ The change 
in sign of the optical rotatory power on inversion was first announced 
byBiot in 1836. A few years later Wilhelmy (1850) showed that the 
amount of sugar changed in any given moment is a constant percent- 
age of the amount of unchanged sugar present. This is known as 
Wilhelmy's law, and put into mathematical form it is expressed by the 
equation : — 

— -- = K(a - x) I a = initial amount of sugar. 

where-! x = amount already inverted. 
ot K = -T^og^ -— . 1 1 = time which has elapsed since the reaction started. 

This law has been carefully verified experimentally : the above 
expression is the simplest type of mass action equation. The velocity 
constant K represents the rate at which the sugar is inverted. 

Cane sugar is hydrolysed at very different rates by different acids. 
If the acids are classified in order according to their power of hydro- 
lysing sucrose they will be found to be also arranged according to 

^ It is outside the limits of this monograph to do more than indicate the salient features 
of hydrolysis. A most valuable and complete summary of the literature beariig on the 
subject, with a bibliography complete up to 1906, is contained in a report presented by R. J. 
Caldwell to the British Association at York, igo6. 

129 9 



I30 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 



their electrical conductivity and power of hydrolysing methyl acetate. 
This fact was first recognised by Ostwald in 1884. Other disac- 
charides and the glucosides are also hydrolysed by acids in accordance 
with Wilhelmy's law, but hydrolysis takes place far more slowly than 
in the case of cane sugar. Indeed, whereas cane sugar is rapidly 
hydrolysed by normal sulphuric acid at 20°, milk sugar requires pro- 
longed heating at 80** to effect the same proportion of change. Arm- 
strong and Caldwell give the relative ease with which hydrolysis 
takes place as milk sugar i, maltose 1*27, cane sugar 1240. Other 
figures relating to the glucosides are given in Table XVII. : — 

TABLE xvn. 



Compound. 


Relative Rate of 
Hydrolysis. 


a-Methyl glucoside 
/3-Methyl glucoside 
a-Methyl galactoside , 
^•Methyl galactoside , 

Salicin 

Maltose . 

Milk sugar 




100 
179 

542 
884 

601 

740 

582 



The relative strength of acids as measured by their inverting power 
is dependent on the nature of the sugar by means of which the com- 
parison is made, and even with the same sugar the ratio is different at 
different temperatures. The following table, compiled by Caldwell, 
illustrates this point It would, however, lead too far to discuss the 
significance of these observations here : — 

TABLE xvin. 



Sugar Hydrolysed. 


Temp. 

1 


Relative Activities of the Acids. 


HCL 


H2SO4. 


H,Cs04. 


Camphor- 

Sulpbonie 

(Reychler). 


Sucrose • . . 
Salicin .... 
Maltose . • • . 
Lactose . . • . 
(Conductivity) . 


as* 
95' 
74° 

25» 


H H H H H 

88888 


537 

49*9 
40-5 

477 
6i*g 


i8-2 

23-3 
I4'i 

197 


89*8 
68*6 



The foregoing data (Table XVII.), though at present somewhat 
scanty, afford important material for the discussion of the nature of the 
hydrolytic process. Considering the hydrolysis of the glucosides two 
views are possible, either (i) that the compound behaves much as the 



HYDROLYSIS AND SYNTHESIS 131 

simple ether CH3 . O . CH3 would, and that the hydrolyst becomes as- 
sociated with the oxygen atom to which the CHg group is attached ; or 
(2) that the attachment is to the oxygen atom in the ring. On the 
former view the two isomeric a- and /8-glucosides should be hydrolysed 
with equal readiness, as the methoxyl groups are equally weighted in 
the a and /8 position. 

Actually in the case of both glucose and galactose the fi derivative 
is hydrolysed about 175 times as readily as the a derivative, and as 
there is every reason for thinking that the mechanism of change is the 
same in both cases, the difference in the rate of hydrolysis can only 
be due in main to the relative distances of the OCHg groups from the 
centre of the change. 

There is little doubt that the active system, within which change 
takes place, is formed by the association of acid-water molecules with 
the oxygen atom in the pentaphane ring. Oxonium compounds are 
formed of the type already discussed at length on pp. 18, 23. In 
other words, this oxygen is the centre from which attack proceeds. 

Reference to a solid model will readily show that a distinct differ- 
ence exists in the relative distances of the - OCH3 group, when in the 
a and ^ positions, from the oxygen atom in the ring : this is but im- 
perfectly rendered on a plane surface. 

\c . OCH, 




HO . CH ^ HO. CH 




HC.OH 

OH CH, . OH 

o-Methyl glucoside. /B-Methyl glucoside. 

The a-methyl glucoside, since it is the most stable form, may be 
assumed to be that in which the methoxyl (OCH3) group is furthest 
removed from the pentaphane oxygen as shown above : conversely, 
the /8-glucoside will be that in which the methoxyl is nearest the 
oxygen centre. 

Boeseken assigns exactly the opposite constitutions to a- and 
y8-glucose, basing his theory on the decrease in the conductivity of 
a-glucose, in presence of boric acid, during mutarotation and the 
increase in conductivity in the case of the fi form. 

As Irvine has shown, Boeseken, in making his deductions, ignores 

9* 



132 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

entirely the influence of the hydroxyl present as oxonium hydrate for 
which there is now ample evidence and they may be therefore regarded 
as invalid. This question has been fully dealt with under the heading 
Mutarotation on page 1 5. The same criticism applies to the formulae 
for the glucosides suggested by Michaelis based on their acid dissocia- 
tion constants. 

Apparently the rate of hydrolysis of a glucoside can be markedly 
affected by the nature of the non-sugar residue. In the case of the 
a- and )9-phenol glucosides Fischer states that under like conditions 68 
per cent, of the a- and 32 per cent, of the /8-glucoside were hydrolysed : 
the corresponding figure for a-methyl glucoside being 4*5 per cent. 
This is the reverse of what obtains with the methyl glucosides. With 
the menthyl glucosides however, the /9 form is somewhat more rapidly 
hydrolysed than the isomeride. 

The synthetic a- and /8-glucosides will afford valuable material for 
the complete investigation of these interesting differences. 

It must be assumed in the case of the galactosides, which are 
more readily hydrolysed than the glucosides, that the interchange in 
the position of the groups attached to the <y-carbon atom, which involves 
a shift in the position of the ring, brings the pentaphane oxygen 
nearer the methoxyl group (p. 13) and so facilitates action. It is im- 
possible to represent such a change on a plane surface, but it will be 
readily understood on reference to the model. 

The application of this line of argument to the disaccharides pro- 
mises most interesting results. 

As elsewhere pointed out (p. g^\ two types of reducing disac- 
charides may be formulated according to whether the primary or 
secondary alcohol group of one sugar is joined to the glucoside half 
of the molecule. These types may be formulated in skeleton thus : — 




Type A. — Secondary alcohol junction. 




Type B. — Primary alcohol junction. 



HYDROLYSIS AND SYNTHESIS 133 

In disaccharides of type A, attack will proceed from both penta- 
phane oxygen centres X and Y towards the centre marked Z, at which 
scission of the molecule occurs. Centre Y is further removed from 
exercising influence than centre X. 

In disaccharides of type B, centre Y is still further removed from 
centre Z, and its influence may be supposed to be correspondingly 
weakened. Carbohydrates of this type will be least easily hydrolysed. 

Differences introduced by the second hexose occupying the a or 
P positions will mainly affect the distance XZ in the formula, i.e. in 
practice they will increase or decrease the magnitude of the attack 
from the centre X, but they will also have an effect on the nearness of 
the centres Y and Z. As before mentioned, these reasonings are best 
followed with the aid of a solid model. 

It is possible on the basis of the foregoing argument to assign type 
formulae to many of the disaccharides ; for example, as lactose is more 
easily hydrolysed than melibiose it might be assigned to type A and 
melibiose to type B : other methods have proved this to be actually 
the case. It is best, however, to defer such speculations until the rates 
of hydrolysis of all the disaccharides have been compared under com- 
parable conditions, and it is to be hoped, now that many of these 
sugars are more easily available, that this work will be undertaken. 

In cane sugar the ethylene-oxide structure of the fructose residue 
brings centre Y into the closest possible contiguity with centre Z : — 



C.C 




x^ XY 

Glucose residue. Fructose residue. 

Everything is in favour of hydrolysis, which, accordingly, may be 
expected to take place with great rapidity. 

In turanose, which is hydrolysed with great difficulty, the centre Y is 
removed much further away from centre Z, and it may be further as- 
sumed that the fructose residue does not in this case possess an ethy- 
lene-oxide structure. Conditions are thus opposed to rapid hydrolysis. 




X-^ ^^--Y 

Glucose residue. Fructose residue. 



134 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

It is recorded that isotrehalose is more easily hydrolysed than 
trehalose: this is in full agreement with the structural formulae as- 
signed to them. 

The laws of hydrolysis by enzymes have been dealt with by 
Bayliss (Monograph on Enzyme Action), and the details of the selec- 
tive action towards the disaccharides will be found in Chapters IV. and 
V. of this monograph. 

Enzymes are far more active as hydrolysing agents than acids, 
a very minute quantity at the ordinary temperature being far more 
powerful than very strong acid at a high temperature. 

It is perhaps desirable here to lay emphasis on the difference 
noticeable in the behaviour of enzymes and acids respectively as 
hydrolytic agents. It is due mainly, if not wholly, (i) to the superior 
affinity of the enzymes for the carbohydrates ; (2) to the very different 
behaviour of the two classes of hydrolysts towards water — which is 
a consequence of the colloid nature of the one and the crystalloid 
nature of the other. In other words, whereas there is competition 
between the solvent water and the carbohydrate for the acid, water 
has very little attraction for the enzyme : in consequence, practically 
the whole of the enzyme present is taking part in the operation of 
hydrolysis. 

The Ssmthesis of Monosaccharides by Chemical Means. 

The synthetical preparation of natural dextro-glucose from its ele- 
ments may be justly claimed as one of the greatest achievements of 
the chemist, and it is enhanced in interest by the great biological im- 
portance of the carbohydrates. 

In the following section a brief outline is given of the operations 
performed in preparing glucose and fructose from their elements. 
Dealing first with the earlier work, the first attempt which was in any 
way successful was that made by Butlerow, who showed that when 
trioxymethylene is condensed by means of lime water a syrupy sub- 
stance is obtained which has the properties of a sugar. Subsequently 
Loew improved the technique of the method and named the product 
he obtained formose. Fischer and Tafel started with acrolein dibro- 
mide and effected condensation of this by means of baryta, the change 
being expressed by the equation : — 

2C8H40Bra + 2Ba(OH)2 = C^U^jO^ + 2BaBr2 

They showed that the syrupy product obtained contained two sugars 
distinguished as a- and ^-acrose. Subsequently glycerose was made 
the starting-point for the synthesis ; crude glycerose is a mixture of 



N 



HYDROLYSIS AND SYNTHESIS 135 

glyceric aldehyde, CH2(0H) . CH(OH) . CHO,and dihydroxyacetone, 
CHaCOH). CO. CHgCOH), and these two compounds can be formu- 
lated as undergoing the "aldol" condensation forming a ketone, 
CHaCOH). (CH. OH)8.CO . CHgCOH), which has the same compo- 
sition as fructose, a- and /S-acrose were obtained from this condensa- 
tion and characterised by means of the osazones they formed with 
phenylhydrazine. a-Acrosazone was found to possess a remarkable 
resemblance to glucosazone, differing only in being optically in- 
active. More recently Fenton has shown that glycollic aldehyde, 
CH2(OH) . CHO, may be used as the starting-point of the synthetical 
process ; three molecules of it condense to a-acrose. 

A product of synthesis by all these methods is a-acrose. Fischer 
converted this firstly into acrose phenyl osazone in order to isolate it 
from the mixture of substances and then into acrosone by treatment 
with hydrochloric acid as described in Chapter II. Acrosone, on re- 
duction, yielded firstly a sweet syrup having all the properties of fruc- 
tose, and secondly on further reduction an alcohol, a-acritol, very like 
mannitol but differing in being optically inactive. There was no doubt 
that a-acrose was inactive ^-fructose. The further problem was to 
obtain an optically active sugar from this. The product was partially 
fermented with yeast and a dextro-rotatory sugar, /-fructose, was ob- 
tained, but this biological method did not lead to the isolation of the 
natural sugar. Indeed, to obtain this a number of operations were 
necessary. ^-Fructose was reduced to ^-mannitol and the latter 
oxidised to the corresponding acid, ^^mannonic acid. (This acid 
forms a characteristic hydrazide from which it can be easily regene- 
rated.) The racemic acid gave crystalline alkaloid salts and these were 
separated by fractional crystallisation ; in this manner their resolution 
into the optically active forms was effected just as was done by 
Pasteur in the case of racemic tartaric acid, d- and /-mannonic acids 
were thus obtained by the crystallisation of the strychnine or morphine 
salt of the synthetical racemic acid : by reduction of their lactones 
they were converted into d- and /-mannose and the complete synthesis 
of these hexoses accomplished. To pass to ^fructose it only remained 
to reduce the mannosone (identical with glucosone) formed from d- 
mannose phenyl osazone in the manner already described (compare 
Chap. II.). 

The synthetical mannonic acids above mentioned are converted 
into the corresponding gluconic acids when heated with pyridine or 
quinoline (see p. 55), and it was only necessary to reduce these acids 
to obtain the corresponding glucoses. The stages of these syntheses 
are summarised in the chart on page 1 36. 



136 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 



Proceeding in this way Fischer effected the synthesis of the six 
hexoses derived from mannitol, and extended the methods to the 
synthesis of a number of isomeric hexoses which do not occur 
naturally. To-day, out of the sixteen possible isomeric aldohexoses, 
according to the Le Bel-van't Hoff theory, fourteen have been pre- 
pared synthetically. 

Theoretically a simpler method of passing from fructose (a-acrose) 
to glucose and man nose is afforded by warming with alkali, when the 
isomeric transformations observed by Lobry de Bruyn take place. 
These are of particular interest in the case of sorbose, which is con- 
verted into galactose and tagatose. Sorbose belongs to the mannitol 
series, galactose to the dulcitol series, so that this transformation 
connects the hexoses derived from the two alcohols and indirectly 
effects the complete synthesis of all the sugars derived from dulcitol. 

Before this transformation was discovered Fischer found it neces- 
sary to degrade gulonic acid to the pentose sugar xylose, transform 
this into the isomeric lyxose and combine lyxose with hydrogen 

Acroleindibromide Formaldehyde Glycerose GlycoIIic aldehyde 



a-Acrose 

I 

a-Acrosazone 

I 

a-Acro6one 
^/-Fructose 





I'Fructose 



<2/-Mannitol 
^/■Mannonic acid 




/-Mannonic acid 



</-Mannonic acid 



/•Gluconic acid 
l-Glucose 



l-Mannose 



d-Mannose 
<2-Glucosazone 

; 

<2-Glucosone 
d'Pruciose 



<2-Gluconic acid 
d'Glucosg 



HYDROLYSIS AND SYNTHESIS 137 

cyanide to give galactonic acid. It was only in this somewhat round- 
about fashion that the complete synthesis of galactose and other 
hexoses derived from dulcitol could be effected. 

Fischer regarded the other products of synthesis /3-acrose and 
formose as either allied to sorbose or containing a branched and not 
a straight chain of carbon atoms. Nef states that formose consists of 
hexoses and pentoses in equal proportions. 

By alkaline condensation of pure glyceraldehyde under conditions 
which would be unlikely to cause the aldose ij ketose conversion 
(presence of ci per cent excess of baryta at the ordinary temperature) 
Schmitz has obtained a solid crystalline mixture of inactive hexoses. 
Recrystallisation from hot methyl alcohol separated this into di- 
fructose (a-acrose),m. p. I29°-I30°, and<i/-sorbose, m.p. 1 62°-! 63°, which 
represents /8-acrose. The appearance of the ketonic group in the sugar 
synthesis must take place at the triose stage and therefore, strictly 
speaking, the reaction is condensation of glyceraldehyde with dihy- 
droxyacetone and not auto-condensation of glyceraldehyde : limita- 
tions are thus imposed on the number of hexoses which can theoretically 
be produced. The mechanism of acrose formation is thus established 
with a considerable degree of certainty. 

Both glycollic aldehyde and dioxyacetone are produced when form- 
aldehyde is condensed by means of calcium carbonate, and H. and A. 
Euler have shown that a pentose, ^-arabinoketose, is the main product 
of this polymerisation. It is derived from the condensation of gly- 
collic aldehyde and dihydroxyacetone. 

CHa(OH) . CHO + CO(CHa . OHJa = CHa(OH) . [CH . OH], . CO . CHa(OH). 

Arabinoketose has not yet been found among plant products. 

The Synthesis of Carbohydrates in the Plant.^ 

Though the primary facts of the photochemical assimilation by the 
green leaf may be r^arded as definitely established the full explanation 
of the process is still outstanding. Priestley (1771), Ingenhouse (1779) 
and Senebier (1788) established that green plants acquire their carbon 
from carbonic acid; De Saussure (1804), Boussingault (1861) showed 
that the volume of oxygen exhaled and that of carbon dioxide absorbed 
are approximately equal ; Sachs in 1862 proved that the first visible 
product of the process is starch. Brown and Morris (1893) showed 
that the first sugar which could be identified is sucrose, an observation 
confirmed by Parkin (191 i),'and Usher and Priestley (1906) found that 

^ A full account of the historical side of the question has been given by Meldola in a 
presidential address to the Chemical Society in 1906. 



138 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

formaldehyde is the first detectable compound of an aldehydic char- 
acter. Baeyer in 1870 advanced the hypothesis that formaldehyde 
formed by the reduction of carbon dioxide is the first product of as- 
similation : the aldehyde is considered to undergo polymerisation 
subsequently to carbohydrate. 

Although this hypothesis is generally accepted as a working basis 
two difficulties have always been experienced ; firstly all attempts to 
prove the presence of formaldehyde in the green parts of plants have 
led to inconclusive results, and secondly the experiments made to 
ascertain whether plants can utilise this aldehyde directly as a source 
of carbohydrates have indicated that it acts as a poison. 

However, more recent investigation now enables both questions 
to be answered in the affirmative. Usher and Priestley claim to have 
obtained from leaves, which had been killed by immersion in boiling 
water, after exposure to light, sufficient formaldehyde to be detected 
by the usual tests. Their work has been criticised by Ewart, Mameli 
and PoUacci, but it has been confirmed by Schryver, using Rimini's 
test for formaldehyde (the formation of a brilliant magenta colour with 
phenyl hydrazine hydrochloride, potassium ferricyanide and hydro- 
chloric acid). Schryver concludes that chlorophyll can form formal- 
dehyde directly, but that it rarely becomes sensible because it does not 
accumulate in the cell, since it is withdrawn to form sugars as fast as 
it is formed. 

Boussingault's experiments have been latterly repeated by Will- 
statter and Stoll in a trustworthy manner, eliminating respiratory 
effects. They find the **assimilatory quotient,'* that is the ratio of 
carbon dioxide absorbed to oxygen liberated, to be unity whether the 
temperature is 10° or 35° or whether the atmosphere is rich or deficient 
in carbon dioxide. 

Glycollic and glyceric aldehydes and dihydroxyacetone are all 
intermediate stages in the laboratory synthesis of fructose from form- 
aldehyde, but there is no evidence of these being found among normal 
plant products. They have so far only been encountered as down- 
grade products of the action of certain bacteria on mannitol or glucose. 
Attempts to imitate in the laboratory the formation of formaldehyde 
from carbon dioxide and water, HgCOj + 2H2O -> CHjO + 2H2O2, 
have been numerous, but, if some controversial and very doubtful experi- 
ments be excepted, formic acid has been in all cases the sole product 
of the reduction. However, definite proof of the formation of formal- 
dehyde has been given by Fenton (1907), who has shown that it is 
formed when carbon dioxide is reduced by means of metallic magnesium. 



HYDROLYSIS AND SYNTHESIS 139 

Brown and Morris, in 1893, working with the leaves of Tropaeolum, 
came to the unexpected conclusion that sucrose is the first sugar to 
be synthesised by the assimilatory processes. It functions in the first 
place as a temporary reserve material accumulating in the cell sap of 
the leaf parenchyma. As assimilation proceeds and the concentration 
of the cell sap exceeds a certain amount, which probably varies with 
the species of plant, starch is elaborated by the chloroplasts. This 
forms a more stable and permanent reserve material than the sucrose. 
Sucrose is translocated as glucose and fructose, starch as maltose, the 
latter process only taking place when the starvation of the cell has in- 
duced the dissolution of the starch by the leaf diastase. Fructose and 
glucose are the sugars which contribute most to the respiratory re- 
quirements of the leaf cell, glucose being more quickly used up than 
fructose. Probably a larger amount of fructose than of glucose passes 
out of the leaf into the stem in a given time. 

Parkin selected the leaves of the snowdrop {Galanthus nivalis) for 
investigation since this leaf does not form starch except in the guard 
cells of the stomata, though the bulb contains starch and inulin in 
abundance. Maltose was also proved to be absent from the leaf. 
His analyses confirm Brown and Morris that sucrose is the first sugar 
to appear and that the hexoses arise from it by inversion. Here again 
the quantity of fructose in the leaf is almost invariably in excess of that 
of glucose. The total quantity of the hexoses remains remarkably 
constant. 

Although the weight of evidence is strongly in favour of the view 
that sucrose is the first sugar formed in photosynthesis, some observers 
hold that hexoses are to be regarded as the primary products, sucrose 
being formed later by synthesis either in the leaf or in the root. 
Strakosch, for example, employing microchemical methods, concluded 
that glucose was the first sugar formed in the mesophyll of the leaf: 
his experimental work does not, however, carry conviction. In the 
previous edition of this book attention was directed to the work of 
Campbell but it has since been shown by Davis that in Campbell's 
analyses the cane sugar was greatly under-estimated, and his work 
must therefore be regarded as merely preliminary and his data and 
conclusions entirely withdrawn. 

A most careful study of the carbohydrates of the mangold leaf 
under actual normal conditions of growth has been made by Davis, 
Daish and Sawyer in 191 6, whose papers summarise the work in this 
very difficult field The facts they bring forward confirm the view of 
Brown and Morris that sucrose is the primary sugar formed in the 



I40 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

mesophyll of the leaf under the influence of the chlorophyll. It is 
transformed into hexoses in the veins, midribs and stalks, the pro- 
portion of hexoses increasing as the root is approached. It enters the 
root as hexose and is there reconverted into sucrose, remaining as such 
until required for the growth of the second seasoa Invertase is en- 
tirely absent from the root, so that it is highly improbable that the 
synthetic change is effected by this enzyme. 

Starch is entirely absent from the leaf after the very earliest stages 
of growth, and maltose is entirely absent at all stages and at all times. 
Pentoses only form a small proportion of the total sugars ; they are 
apparently formed from the hexoses and appear to be precursors of 
the pentosans. 

Davis shows that the determination of glucose and fructose separ- 
ately in leaf extracts is rendered difficult by the presence of optically 
active impurities not precipitated by basic lead acetate : it is therefore 
premature to draw any conclusions from the proportion of apparent 
glucose or fructose in plant tissue as to whether either of these sugars 
is better adapted than the other to tissue formation or to respiration. 
Davis, however, considers that the two hexoses exist in the leaves and 
stalks as invert sugar and travel in nearly, if not exactly, equal pro- 
portions to the root. 

Davis has studied in a similar manner the fluctuations in the carbo- 
hydrates in the potato leaf. Here also the first sugar to develop is 
sucrose : its amount increases from sunrise up to 2 P.M. and then falls. 
Up to 2 P.M. there is very little fluctuation in the amount of starch. 
At 2 P.M. the hexoses (derived from sucrose by hydrolysis) begin to 
increase, soluble starch appears for the first time and its amount in- 
creases regularly up to a maximum at 6 P.M. Between this hour and 
midnight the amount of starch falls so that finally only a very small 
proportion is left (o*2 per cent.). The starch is apparently converted 
directly into glucose, the amount of which increases in the leaf. 
Maltose is invariably absent from the potato leaf and also from the 
leaves of other plants which form much starch in the leaf; apparently 
the leaf enzymes are able to degrade starch completely to glucose. 
Glucose is certainly in excess in the stalks of the potato, and the starch 
in the tuber is built up from this hexose. 

Assuming that Baeyer's hypothesis is correct and that formaldehyde 
is the first product of the synthesis, two questions await an answer. 
Firstly, how is the condensation of the aldehyde caused ; secondly, 
through what intermediate stages do the compounds pass ? 

The vital synthesis differs essentially from that carried out in the 



HYDROLYSIS AND SYNTHESIS 141 

laboratory in affording optically active products. It might be sup- 
posed that the plant manufactures inactive racemic hexose and uses the 
t laevo-isomerides for purposes which are still unknown. In spite of 
ajc: frequent search, however, it has never been possible to detect /-glucose 
e:. or /-fructose in the leaves of plants, and the work of Brown and Morris 
i: leaves hardly any doubt that hexoses of the ^-series and their poly- 
saccharides are the only products of assimilation. 
(T^j The living organism is not satisfied with merely elaborating a par- 

r^ ticular sugar, but shapes it in a definite manner to a definite space con- 
£.: figuration. 

Fischer has pictured the carbon dioxide or formaldehyde as enter- 
ing into combination with the complicated optically active protoplasm 
3j of the chlorophyll granule, and being synthesised to optically active 
^ carbohydrates under the influence of the asymmetry of the protoplasm 

J, molecule. 

,; The formaldehyde elements are received one after the other, and 

j; superposed according to a definite plan until six are united, when the 
J, completed dextro-glucose or fructose molecule is split off and the pro- 

^ cess begins anew, only optically active substances being formed. 

Synthesis by laboratory methods leads to optically inactive forms, 
though apparently chemical synthesis does not take place entirely 
^ symmetrically when several asymmetric carbon atoms are present. 

It is now generally agreed that the protoplasm of the chlorophyll 
granule contains enzyme elements, and that it is these which occasion 
synthesis. The protoplasmic complex may be regarded as built up of 
a series of associated templates (enzymes) which serve as patterns for 
the maintenance of vital processes and of growth. The assimilated 
carbon dioxide, either before or after condensation to formaldehyde, is 
brought into contact with these templates in the protoplasm, and con- 
tiguous molecules are united to form the complete sugar, shaped 
according to the structure of the template. The enzyme specific for 
each particular hexose when incorporated in the protoplasmic complex 
may well serve as the template for its manufacture. Maltase, for ex- 
ample, might occasion the formation of a-glucose, emulsin that of 
/8-glucose, lactase that of galactose, and invertase, or some similar 
* enzyme, that of fructose. The existence of contiguous maltase and 
invertase^ branches in the protoplasmic complex might determine the 

^ Armstrong's recent researches suggest that invertase is compatible, at one and the 
same instant, with both glucose and fructose, so that its presence in the protoplasmic com- 
plex would, under suitable conditions, lead to the formation of cane sugar. It is probable 
that invertase is only compatible with the ethylene-oxide form of fructose and not with the 
butylene-oxide isomeride. 



142 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

formation of glucose and fructose in contiguity, and these might unite 
to cane sugar. Again, two glucose molecules in contiguity might unite 
to maltose, or a series formed in contiguity might remain potentially 
active so that a number would unite and give rise to a starch molecule. 
a- and /3-glucose would remain as such so long as they were incorpo- 
rated with the protoplasm ; when split off into the cell fluid they would 
no doubt tend to pass over in the equilibrated mixture. 

Certain claims have been made in reference to the synthesis of 
carbohydrates from simple substances by means of sunlight or ultra- 
violet light Thus glycerol in alkaline solution is partly converted 
into a-acrose (Bierry and Henri) after exposure to ultraviolet light ; 
after many months in sunlight sorbose has been obtained from a mix- 
ture of formaldehyde and oxalic acid (Inghilleri). 

The Sjrnthesis of Disaccharides. 

Although in the hands of Fischer the problem of the synthetical 
preparation of the natural simple carbohydrates — the monosaccharides 
— has been solved, the next step, the synthesis of the disaccharides, 
still awaits a satisfactory solution. 

The earliest synthetical disaccharide was obtained by Fischer by the 
action of cold concentrated hydrochloric acid on glucose. The com- 
pound obtained was termed isomaltose on account of the resemblance 
to maltose, from which it differed in being nonfermentable. The pro- 
cess had the disadvantage that it could not be controlled, so that only 
small quantities of disaccharide were formed together with considerable 
quantities of dextrin-like products. It was shown subsequently, as 
described later, that both maltose and isomaltose are formed by this 
process. A more hopeful method, based on Michael's glucoside syn- 
thesis, appeared to be the combination of acetochloro glucose with the 
sodium salt of a hexose. This method has been repeatedly used in 
attempting to synthesise cane sugar, and Marchlewski claimed to have 
been successful in artificially obtaining this sugar. Subsequent workers 
have found it impossible to confirm his results, and they are to be 
queried also for other reasons, chief of which is the observation of 
Fischer and Armstrong that a-compounds of glucose in presence of 
alkali undergo rearrangement to )8-compounds. These observers failed 
to prepare a-phenyl glucoside from a-acetochloro glucose and sodium 
phenolate, obtaining instead the /3-phenyl glucoside. Sucrose, a de- 
rivative of a-glucose, should not therefore be formed. The evidence 
brought forward by Marchlewski in proof of the formation of cane 
sugar was also very inadequate. There are thus no grounds for ac- 
cepting this synthesis. 



HYDROLYSIS AND SYNTHESIS 143 

By the interaction of acetochloro galactose with sodium glucosate 
or of acetochloro glucose with sodium galactosate, Fischer and Arm- 
strong obtained disaccharides of the type of maltose which they termed 
galactosido-glucose and glucosido-galactose. These sugars were suf- 
ficiently closely related to the natural products to be hydrolysed by 
enzyme3. Top yeast was without action, bottom yeast was able to 
ferment both disaccharides. They were hydrolysed by emulsin, but 
not affected by maltase or invertase. Both reduced Fehling's solution, 
formed phenyl osazones and osones, but could not be obtained in a 
crystalline state. The galactosido-glucose possessed very great simi- 
larity to the natural sugar melibiose both in structure, similarity of the 
phenyl and bromophenyl osazones and in physiological behaviour, and 
it is very probable that these disaccharides are identical. 

The galactosido-galactose obtained by the same method resisted 
the action of yeast but was hydrolysed by emulsin. It is of interest 
now that crystalline galactobioses have been synthesised by means of 
emulsin. 

Fischer and Delbriick have made use of )8-acetobromo glucose to 
effect the synthesis of disaccharides allied to trehalose. When aceto- 
bromo glucose is shaken in dry ethereal solution with silver carbonate 
and traces of water are added from time to time, bromine is eliminated 
and two molecules are joined through the intermediary of an oxygen 
atom to form an octacetyl disaccharide : — 

2C^^Hjfi^Bt + HjO = C28H38O19 + 2HBr 

This is obtained both crystalline and in an amorphous form, the latter 
being regarded as a mixture of isomerides. 

These acetyl compounds when hydrolysed by cold barium hydroxide 
solution are converted into disaccharides. That from the crystalline 
acetate, termed isotrehalose, differs from trehalose in optical rotatory 
power, [a]jy - 93*4°, but resembles it closely in chemical properties. It 
is a colourless amorphous powder, which does not reduce Fehling's 
solution and is easily hydrolysed to glucose when boiled with dilute 
mineral acids. The disaccharide from the amorphous acetate is re- 
garded as a mixture, it has [ajn about - 1*3°. It is remarkable in 
being partially hydrolysed both by yeast extract and by emulsin. 

Consideration of the constitutional formula of trehalose — 



CH,(OH) . CH(OH) . CH . CH(OH) . CH(OH) . CHv 

CH,(OH) . CH(OH) . CH . CH(OH) . CH(OH) . Ch/ 

I n ^1 



144 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

shows that three stereoisomerides are possible, as the two carbons in 
clarendon type are asymmetric. Using the prefixes a and p in the 
same sense as in the acetobromo glucoses, these isomerides may be 
described as aa, /3/3 or aff^ according as the constituent glucoses are 
present in the aor ff form. 

Hudson from optical considerations has identified natural trehalose 
as the €ui form and isotrehalose as the ffff form : — 

CHj(OH) . CH(OH) . CH . (CH . OH)^ . CH 

I O I" 

-o 




I • /. 

CHj(OH) . CH(OH) . CH . (CH . OH)^ . CH 

The same method has been extended by Fischer to the synthesis of 
non-reducing tetrasaccharides from acetobromo lactose and acetobromo 
cellobiose. In both cases the products were contaminated with re- 
ducing disaccharide and they could not be purified. 

The isotrehalose synthesis has beeh extended to the preparation 
of disaccharides containing sulphur and selenium (Schneider and 
Wrede). 

Treatment of )8-bromoacetylglucose with potassium hydrosulphide 
gave the octa-acetate of the thiodisaccharide Ci2H220iqS, which latter 
crystallises I in hexagonal leaflets, m.p. 174°, [aj^ - 85^ It is called 
thioisotrehalose from its apparent analogy with isotrehalose. It is 
remarkably resistant to hydrolytic reagents, warm aqueous alkalis 
and mineral acids. It is unattacked by emulsin, yeast enzyme, tre- 
halase and myrosin. It does not reduce Fehling's solution. 

Similarly, from /3-bromoacetylglucose and potassium selenide, an 
octa-acetate of selenoisotrehalose, Ci2H220iQSe, was obtained. The 
sugar closely resembles the thio-derivative, and melts at 193°, 
Wd - 84^ Both sugars are sweet, and when administered to dogs 
or guinea-pigs are excreted unchanged. 

The remarkable reactivity of the ethyl ene-oxide form of the hexose 
sugars is illustrated by their behaviour towards methyl alcohol con- 
taining 0*25 per cent, of hydrogen chloride, studied by Cunningham. 
In the case of galactose the active sugar condenses with the methyl- 
galactosides to form a methyldigalactoside having the structure : — 

MeO . CH . (CH . OH), . CH . CH(OH) . CH, . O. CH . CH . (CH . OH). . CH. . OH 

I o I \o/ 

This is an amorphous solid, [a]o + 101°, showing marked instability 
towards neutral potassium permanganate. It is of interest that no 
structural modification of the digalactoside can be obtained by varying 
the form of the methylgalactoside employed in its preparation. 



HYDROLYSIS AND SYNTHESIS 145 

The reaction cannot be readily controlled, and when a hexose is 
dissolved in the methyl alcohol reagent and the solution concentrated, 
products of greater complexity, viz. a methyltetragalactoside, containing 
three ethylene-oxide linkages, are obtained. Glucose and maltose 
behave similarly to galactose, but with fructose charring inevitably 
occurred on concentration. It is remarkable that lactose remained 
entirely unaffected by the reagent. 

Nef has effected the synthesis of polysaccharides from hexoses and 
pentoses. By keeping concentrated aqueous solutions at the ordinary 
temperature in the presence of i to 3 equivalents of calcium acetate 
bishexoses (CnH2nOn)2 are slowly formed. 

In the presence of metallic hydroxides these are converted into 
disaccharides (C12H22O11) by salt formation and subsequent loss of 
metallic hydroxide. The synthetic sugars have not been further 
characterised. 

Synthesis by Enzymes. 

Far more interesting than the above method of synthesis is that 
effected by means of enzymes. There can be no doubt that, in the 
plant, enzymes function as synthetical agents. 

The first to observe the synthetical or, as he termed it, reversible 
action of enzymes was Croft Hill. Hill proved that the hydrolysis 
of maltose by dried yeast extract in concentrated solutions was not 
complete, and that, starting from glucose alone in concentrated solu- 
tion, a disaccharide was produced by the action of maltase. This sugar 
he at first considered to be maltose, a conclusion controverted by Em- 
merling, who, repeating Croft Hill's experiments, considered the product 
to be £f(7maltose identical with that obtained by Fischer by the action 
of acid on glucose. Subsequently Croft Hill admitted the chief pro- 
duct to be an isomeride of maltose, but he regarded it as different from 
isomaltose and termed it revertose. He still claimed that maltose is 
also formed in small quantity. E. F. Armstrong considered that the 
product of the synthetical action of maltase on glucose was isomaltose 
identical with that produced by the action of hydrochloric acid on 
glucose, and showed that the two products agree in being hydrolysed 
by emulsin though not by maltase. They were accordingly regarded 
as having the structure of glucose ^S-glucosides. Croft Hill showed 
that his synthetical product was almost completely hydrolysed on 
dilution, indicating that the process is reversible, or that at all events 
the same mixture of enzymes which effects synthesis is able to hydro- 

lyse the synthetic product 

10 



146 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

A disaccharide is also formed when a mixture of glucose and 
galactose in concentrated solution is left in contact with lactase. This 
is undoubtedly isomeric with milk sugar but differs from it in being 
completely fermented by bottom yeast. 

The process by which a monosaccharide is converted into a disac- 
charide in presence of a synthetical catalyst must be regarded as pre- 
cisely similar to that by which a- and /3-glucoses are converted into 
the two methyl-glucosides. Glucose on condensation should give rise 
to both maltose and isomaltose synthesised from a- and )8-glucose 
respectively. The proportion of each ultimately present in equilibrium 
will depend to some extent on the proportions of the two glucoses in 
their equilibrated mixture and on their (possibly unequal) rates of 
condensation. This reasoning should apply so long as the condensa- 
tion is uncontrolled. Inasmuch as hydrolysis under the influence of 
enzymes is an absolutely selective process, as opposed to hydrolysis by 
acids which is general in character, it is to be supposed that synthesis 
under the influence of enzymes is likewise a controlled operation. 

The proof that hydrochloric acid forms both zsoma\tose and maltose 
from glucose was first given by E. F. Armstrong. The method of 
purification of the synthetical isomaltose mixture adopted by Fischer, 
viz. fermentation of the neutralised product with brewers' yeast, 
would have destroyed any maltose which had been formed Armstrong 
fermented a portion of the product with S. MarxianuSy a yeast which 
does not contain maltase and therefore is without action on maltose, 
in order to destroy the unchanged glucose. The resulting solution con- 
tained both maltose and /jf7maltose, and was partially hydrolysed by 
both maltase and emulsin. To remove the /jf7maltose it was submitted 
to the joint action of emulsin and S. Marxianus, It was not found 
possible to obtain the maltose in a crystalline condition from this 
solution, but the character of the osazone formed and the biological 
behaviour of the sugar leave little doubt of the presence of this sugar. 
Another portion of the original synthetical sugar was fermented with 
S, intermedianSy and so freed from glucose and maltose. The result- 
ing /j(?maltose solution behaved in all respects as described by 
Fischer. 

The manner of the synthesis by enzymes is still a matter of dispute. 
It is urged, on the one hand, that enzymes produce by synthesis the 
same bodies which they hydrolyse ; on the other hand, it is suggested 
that the action of the enzyme is restricted to the formation of a com- 
pound isomeric with that normally hydrolysed by the enzyme. A 
third view is that altogether distinct enzymes effect synthesis. 



HYDROLYSIS AND SYNTHESIS 147 

The arguments in favour of accepting the first view have been 
clearly put by Bayliss (see the Monograph on Enzyme Action in this 
series), and need not be repeated here. 

The question is complicated by the fact that the catalysts used are 
all mixtures of several enzymes. Yeast extract (maltase) contains at 
least five sucroclasts ; emulsin at least three. 

Armstrong has shown that the main product in the case of the 
action of yeast extract on glucose is isomaltose ; and contended that 
in the case of emulsin the main product is maltose. 

This contention can no longer be maintained in view of the proof 
given by Bourquelot and confirmed by Zemplen that gentiobiose is 
the product of the condensation of glucose in presence of emulsin. 
They have isolated the sugar in a crystalline state, and to Bourquelot 
belongs the credit of the first synthesis of a crystalline natural disac- 
charide. 

In all the above syntheses it cannot definitely be asserted that 
other isomerides are not also formed. When the complexity of the 
enzyme mixture, the number of reactive forms of the hexose and the 
variety of possible isomeric disaccharides are all taken into account 
the magnitude of the problem of their synthesis becomes apparent. It 
is to be hoped that it will be energetically attacked during the next 
decade. 

By the action of emulsin on a concentrated aqueous solution of 
galactose Bourquelot and Aubry have obtained two galactobioses. 
The one form was obtained in little spherical masses with a taste 
slightly sweeter than that of lactose. It had a^ + SS"" ^^^ showed 
mutarotation. The behaviour towards emulsin is not stated. The 
second modification crystallises in needles a + 35° showing mutarota- 
tion. It is hydrolysed by emulsin. The behaviour of this second 
isomeride is not unlike the galactosidogalactose synthesised by Fischer 
and Armstrong from /3-acetochlorogalactose. 

The formation of two isomerides in this manner is of the greatest 
interest and the further study of their relationship is of much import- 
ance. 

In the case of invertase the evidence is most definite that the 
enzyme from yeast accomplishes a complete hydrolysis of sucrose to 
glucose and fructose and that no synthesis takes place. This reaction 
does not establish an equilibrium and is not a reversible or balanced 
change. This problem was investigated with the greatest care by 
Armstrong in 1901 and by Hudson in 1914 with all the refinement 
which the modern methods of experiment permitted. 

10 * 



148 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

It is well known from the work of Pavy and Bywaters that living 
yeast forms glycogen when brought into excess of sugar solution. 
The enzymes involved in this synthesis are probably to some extent 
still present and active in yeast juice, as Cremer found that in yeast 
juice, free from glycogen, in presence of sugar, a substance was slowly 
formed which gave the characteristic glycogen reactions. Harden 
and Young find that one or more dextro-rotatory polysaccharides are 
produced during alcoholic fermentation by non-living yeast prepara- 
.tions. It is not settled whether these polysaccharides are formed 
from the glucose and fructose themselves or as the result of enzyme 
action on the products of hydrolysis of the hexose phosphate formed 
from them. 



CHAPTER VII. 

THE NATURAL GLUCOSIDES. 

The term glucoside is applied to a large number of bodies having the 
property in common of furnishing a ^glucose' and one or more other 
products when hydrolysed by acids. They are resolved with the 
addition of the elements of water into simpler compounds. Repre- 
sentatives of nearly every class of organic compound occur in plants, 
chiefly in the fruit, bark and roots, in combination with a sugar which 
is in most cases dextroglucose. These compounds are glucose ethers 
of alcohols, acids, phenols, etc ; they correspond in structure to the 
simple methyl glucosides, and the general formula of a glucoside is 
accordingly written : — 

CH,(OH) . CH(OH) . CH . [CH . OHJa . CH - O - R 

i O ' 

where R represents the organic radicle. It is noteworthy that the 
vegetable bases are only seldom found in the form of glucosides. 

The glucosides correspond to a certain extent to the paired glucu- 
ronic acid derivatives previously mentioned. In both instances more 
or less reactive specific substances are combined with the sugar residue 
to form indifferent and frequently more soluble substances. 

Glucosides are obtained by extraction of the plant substance with 
water or alcohol, an operation conveniently performed in a Soxhlet 
apparatus. It is necessary in the majority of cases first to destroy 
the accompanying enzyme when water is used as solvent. If this 
operation be omitted the glucoside is destroyed in the process of ex- 
traction. The purification of the extract is often a matter of difficulty 
owing to the scanty proportion of glucoside present. 

The glucosides as a class are generally colourless crystalline solids, 
having a bitter taste and laevo-rotatory optical power. Some of the , 
best-known glucosides are the amygdalin of the almond and other 
rosaceous plants, the salicin of the willow and the sinigrin of the 
cruciferae. 

The glucosides are all hydrolysed by heating with mineral acids to 

sugar and an organic residue. They are decomposed at very different 

149 



ISO THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

rates, some glucosides (e.g. gynocardin) being extremely resistant to 
acid hydrolysis. 

In the majority of cases the glucosides are bydrolysed by enzymes. 
The appropriate enzyme is contained in the same plant tissue, but in 
different cells, gaining access to the glucoside only when the tissue is 
destroyed. A great number of such enzymes exist, but it is too much 
to say that each glucoside has a special enzyme for its decomposition. 
The best-known glucoside-s putting enzymes are the emulsin of 
almonds and the rayrosin of black mustard seeds. Both these enzymes 
can effect hydrolysis of a number of glucosides. 

Emulsin is especially wide in its action. Since it is the specific 
enzyme for /3-alkyI glucosides, all glucosides hydrolysed by it are 
regarded as derivatives of /9-glucose, though the fact that emulsin is a 
mixture of enzymes must not be lost sight of. No glucoside deriva- 
tive of a-glucose has so far been isolated from plants. 

The hydrolysis of glucosides by myrosin is undoubtedly connected 
with their sulphur content. 

The majority of the glucosides are derived from dextro-glucose, but 
since more attention has been paid to the group, glucosides derived 
from a number of other carbohydrates have been discovered in plants, 
and there is little doubt that fresh investigation will extend their 
number. Glucosides are known which are derived from d- and /-ara- 
binose, (^xylose, i/-ribose, from rhamnose and other methyl pentoses, 
and from galactose, manno 
carbohydrates other than | 
their hydrolysis. 

Galactose has been ideni 
sapotoxin, solanin. Manno: 

Fructose is found in alii 
Sapindus rarak and Aesculu. 

Rhamnose is a constiti 
frangulin, fustin, glycyph) 
naringin, quercitrin, robinin, 
tin, trifolin, turpethein, xani 

Pentoses or methylpent 
barbaloin, convolvulin, genti 
vernin, vicianin. 

Some glucosides yield tw 
In such cases these are unitt 
priate enzymes, the sugar gi 
new glucosides are formed. 



THE NATURAL GLUCOSIDES 151 

residues, one of which is removed by an enzyme present in yeast and 
termed amygdalase. The new glucoside so formed was termed 
mandelonitrile glucoside : it has since been found in plants and named 
prunasin. 

Both on account of the very small quantity of a glucoside usually 
present in a plant, and the fact that glucosides do not as a rule form 
insoluble characteristic derivatives which allojv of their isolation, it is 
difficult to discover new glucosides and still more so to determine 
their nature. The introduction of biochemical methods has much 
facilitated work of this kind. Bourquelot's biological method has led 
to the discovery of several new glucosides, and ter Meulen has estab- 
lished the nature of the sugar component in several instances. Ter 
Meulen makes use of the fact (p. 122) that an enzyme is only com- 
patible with and therefore only enters into combination with that 
sugar, the simple glucosidic compounds of which it is able to hydrolyse. 
He has investigated the rate of hydrolysis of a glucoside by the 
appropriate enzyme in presence of a number of the simple sugars. 
Only one of these sugars retards the change ; the others are almost 
without influence. The glucoside in question is considered to be a 
derivative of that sugar which retarded the hydrolysis. 

For instance, rhamninose alone retards the hydrolysis of xantho- 
rhamnin ; glucose alone retards the decomposition of salicin or of 
amygdalin. In the case of glucosides of which the nature of the sugar 
component was not absolutely established, it was shown that aesculin, 
arbutin, coniferin, indican, sinigrin and several other glucosides con- 
taining mustard oils are derivatives of rf-glucose. 

Bourquelot's biological method of examining plants for glucosides 
consists in the addition of emulsin to an extract of the plant and the 
determination of the changes in optical rotation and cupric reducing 
power after a period of incubation. A change indicates the presence 
of /8-glucosides and its magnitude gives a rough indication of their 
quantity. 

In this manner taxicatin, CjjHggOy, has been discovered in Taxus 
baccata (Lefebvre) and the presence of aucubin demonstrated in a 
number of species of plantago (Bourdier). 

The use of invertase in the same manner affords a test for the 
presence of sucrose or raffinose. 

A number of the better-known glucosides are given in the follow- 
ing table which also shows the products of hydrolysis. They are 
classified under alcohols, phenols, aldehydes, etc., according to the 
nature of the non-sugar part of the molecule. 



153 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 



TABLE XIX. 
Natukal Glucosidss. 



GiBcoilde. 


M.p. 










Pkenoh. 


Aibutin . 


c„H„a, 


200" 


Glucose + hydioqainone 


Baptiein . . 




aio° 


RhamnoBc + baptigenin 


Glycyphyllin . 
HMperidin 




17S- 


Rhamnose + pblorelin 


C„H„0„ 


251° 




Iridin . . 


C„H,Ou 


808° 


Glucose + irigenin 


Methyl arbutin 


c^hX 


17S° 


Naringin . 




170° 


Rhamnose + glucose + nuigenin 


Phtoridzin . 


C„H„0„ 


.JO" 


Glucose + phloretin 

Akahols. 


Coniferin 


Ci,H„0, 


185" 


Glucose -f coniferyl alcohol 


PopuUn . . 


C^H^O 


180° 


Glucose + aaligenin + benzoic acid 


Salidn . . 


C„H„0, 


ZDI" 


Glucose + Baligenin 


Syringin 


c"h;:5: 


191" 


Glucose + syringenin 

Atdehydts. 


Amygdalin . 




200° 


2 Glucose -f d-mandelonitrile 


Dhurrin . 








Helicin . 






Glucose + salicylaldehyde 


Linamarin 






Glucose + acetonecyanhydrin 


Prulauraain . 




IM" 




PrunaBin 




147° 


Glucose + ((-mandelonitrile 


Salioigiin . 




195° 


Glucose + m-oxybenzaldehyde 






151 


Glucose + /-mandelonitrile 


VicUnin. . 




160° 


Acidi. 


Convolvulin . 


C„H„0„ 


'S°° 




Gaaltherin . 


CkH^O, 




Glucose + melhylsalicylate 


Jalapin . . 


c„Ko„ 


131° 


OrycumariH Derivatives. 


Aeseulin 


C„H„0, 


205° 


Glucose + lesculetin 


Daphnin 


C„H«0, 




Glucose -i- daphnetin 


Fraran , 


C,.H„0„ 


320° 


Glucose + fraxetin 


Scopslin 


c^hI^o;. 


siS" 


2 Glucose + acopoletin 


Skimmin 


C„H„0, 


210° 


Glucose + slcimmetin 


Frangolin . 


Cj,H„0, 


228° 




Polygonin . 


c^h;o„ 


202° 


Glucose -f emodin 




cLh^o" 


258° 


Glucose + alizarin 


Rubjadin 


C„H„0, 




Glucose + methylxanthofurfurin 
Oxyfiavme Derivatives. 


Apiin . . 


C^H„0,. 


238° 


Apiose + apigenin 


Campferitnn 








(RobLnin) . 


C»H,0„ 


201° 


Glucose + 3 rhamnose + campferol 


Euxanthic acid 








(magnesium salt 


c," 




Glucuronic acid + eujianihone 


Fuatin . . 


c^ 


aia- 


Rhamnose + fiselin 




c^ 




Glucose -1- Rossypetin 


Incanutiin , 


c. 


242° 


Glucose + quercetin 


Isoquercitrin . . 


c. 


217'' 


Glucose + queicetin x 


Lotusin . 


c^ 




2 Glucose + HCN + lotoflavin 


Quercimeriliin 


c. 


247'' 


Glucose + queicetin 



THE NATURAL GLUCOSIDES 



TABLE XIX. (conHtiiud}. 



Gl^ccid. 


M.p. 


ProdncbiofHydrolyBiiL 


Qaereitrin . . C„H„0„ 


183" 




Rutin . . .^hX 


i4° 




Seiotin . . . C„Ha„0„ 


245= 


Glucose + quercetin 


Sophorin . . C„H„0„ 




Rhamnose + glucose + aoplioretin 


Thujin . . . C„H„0„ 


183= 


Quercetin + traces of another glacoside 






Mustard Dili. 


Glucocheirolin C,,H„0„NS,K, HjO 


160= 


Glucose + cheirolin 




Glucose + benzyl isothiot^anate + KHSO^ 
Glucose + Binapin acid sulphate -1- acrinyl- 

isothiocyanate 
Glucose + ally! iMthiocyanate + KHSOj 


i^° 


Sinigrin . . C,oH„0,NS,K 


126° 






Anthocyans, 


Cyanin . . . C„H„0„ 


ao3° 


2 Glucose + cyanidin 


Delphinin . . C„H,,0„ 


200° 


2 Glucose + 2 f-oxybenioic add + del- 
phi ni din 
Galactose + cyanidin 


Idain . . . Cs,H„0„ 


_ 


Malvin . . . cJh"0 


165° 


2 Glucose -<- malvidin 


Myrtillin . . C^Ko'', 






Oenin . . CaH^O,, 




Glucose + oenidin 


Pelargonin . . Ci,H„0,, 


180° 


a Glucose + pelargonidin 

Digitalis Group. 


Cymarin. . . C„H«0, 


138° 


Cymarose (digitoxose methyl elher) + 

BUophanthidin 


Digitalin . . 


2.7° 


Glucose + digitalose + digitaligenin 


DLgLtonin . . 


2*5° 


Glucose + g^aclose + digitogenin 


DigitCBcin 


'45 


2 digitoxose + digitoxlgenin 


Gitalin . 


155 


Digitoxose + anhydrogiUligenin 


Gitin . . . 


.65: 




Giwnin . . 


272° 


3 Galactose + pentose + gitogenin 
Strophantibiose methyl ethei + stropluui- 


Strophanthin . 








Sapogtnins. 


AgtOBtemma sapotoxin (C„H„0,o)j 


— 


4 Sugars + C„H„0. 


Caulopbylloaaponin CnHu^Oi, 












Digitonfn ^ . . C„H„0„ 












Gypaophila (Levant 






aapotoxin) . {C„H„0,„,H,0), 
B-Hedeiin . . C,gHg,Oj] 




Glucose + galactose + CigH„0, 




Arabinose + rhamnose + o-hederogeniu 


Jegosaponin . . C,,HggOg, 


~ 


Glucose + glucuronic and tiglic acids + 


Parillin . . . 






PhytoBterolins 








— 




Quillaic acid . 


_ 




Qnillaja sapotoxin . 






Saporubrin . 




Several sugars + Ci,H„Oi 


Saiaasaponin . . fl 






Smilacin . . 


~ 





154 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 
TABLE XIX. {coHiiHutd). 



Glucd«d>. 


M.p. 


enimttotHyiniyOM. 






VariMi. 


AacutMH. 


_ 


Glucose + aucabigenin 


Barbaloin 












Datiscein . . 






Dibenioylslucoxylosc H,C 


.48" 


Glucbiylose + benzoic acid 




274= 


Glucose + jcylosc + gcntienin 


Gentiopicrin . 


.qi° 




Gynocaidin . 










Glucose + indoxyt 


Quinovin 




Quinovose + quinovaic acid 


Saponarin 




Glucose + saponaretin 




~ 


it-Ribose + guanine 



The better-known glucoside-splitting enzymes are grouped in Table 
XX. together with the glucosides they decompose. Emulsin from 
almonds hydrolyses aesculin, amygdalin, androsin, arbutin, aucubin, 
bankankosin, calmatambin, conferin, daphnin, dhurrin, gentiopicrin, 
helicin, incamatrin, indican, melatin, oleuropein, picein, prulaurasin, 
pninasin, salicin, sambunigrin, syringin, taxicatin, verbenalin, etc. 

TABLE XX. 
Glucosidoclastic Enzymhs, 



R.^. 




EmuUin .... 
Prunasc .... 

Amygdalaae. . . . 
Gaultheraae .... 

Linage 

MyroBin .... 


/Many natural glucosides 
\Synthe(ical ^glucosides 

Piunaein and many otber natural 
glucosides 

Amygdalin 

Gaulflierin 

Linamarin 

Xanthorhamnin 



The Principal Glucosides. 
A few only of the glucosides have been selected for detailed com- 
ment, more particularly for the purpose of showing the relationship 
between their structure and their distribution in plants. Such data, 
when more complete, will afford preliminary material for the differentia- 
tion of species upon a purely chemical basis, as has been indicated by 
Miss Wheldale. At present, since the knowledge of the glucosides is 
chiefly based on the investigation of substances used for medicinal 
purposes, only a b^inning has been made in this direction. 



THE NATURAL GLUCOSIDES 155 

Phenolglucosides. 

Arbutifty a colourless, bitter, crystalline substance, is obtained, 
together with methylarbutin, from the leaves of the bear berry, a small 
evergreen shrub {Arbutus uva ursi)^ and from many genera in the 
EricacecBy and yields hydroquinone and glucose when hydrolysed by 
means of emulsin or mineral acids : — 

Hydroquinone is a powerful antiseptic : hence the pharmacological 
value of arbutin, which has also a diuretic action. Methyl arbutin was 
one of the first glucosides to be artificially synthesised. Michael 
prepared it by the interaction of hydroquinone methyl ether and 
acetochloro glucose. 

Commercial arbutin contains methyl arbutin ; to purify it, it is dis- 
solved in alcohol, precipitated by potassium hydroxide and the pre- 
cipitate collected, washed and decomposed with calcium carbonate 
(H6rissey). 

Mannich states that a better, but still imperfect, method of separa- 
tion of pure arbutin from the mixture is to take advantage of the 
additive compound formed by arbutin and hexamethylene tetramine. 

When arbutin is hydrolysed by emulsin the quinol formed becomes 
slightly oxidised by the oxydase present in the enzyme and the solution 
darkens in colour. Methyl arbutin, which yields quinol methyl ether 
on hydrolysis, does not darken in solution. It is hydrolysed more 
rapidly than arbutin. 

Bourquelot and Fichtenholz have made an extensive study of the 
distribution of arbutin in the leaves of Pyrus species. Pear leaves 
{Pyrus communis) contain as much as 1*2 to 1*4 per cent of the 
glucoside, which can be extracted by ethyl acetate. None could be 
detected in Cydonia vulgaris^ Malus communis ^ Sorbus aucuparia, or 
S. torminaliSy all of which were at one time classed with Pyrus : the 
modem classification is thus justified on biochemical grounds. 

The leaves of certain varieties of Pyrus turn black when they fall ; 
these contain arbutin which is hydrolysed to quinol by the leaf enzyme, 
the quinol in turn being acted on by an oxydase to form the black 
substance. In other varieties a golden yellow tint first appears which 
then gives place to black. These varieties are shown to contain 
methyl arbutin ; they produce at first a yellow and not a black oxida- 
tion product. 

Phloridzin^ which is found in the bark of apple, pear, cherry, plum 
and other rosaceous trees, is remarkable for the property it possesses 
of causing glucosuria when taken internally. Emulsin is without 



156 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

action on it : mineral acids form glucose and phloretin, C^Hi^Og, which 
is a condensation product of /-oxyhydratropic acid and phloroglucinol. 
Phloridzin has the formula — 

(CeHuOj . 0)(OH),QH, . CO . CHMe . C,H4(0H) 

When phloridzin is treated with barium hydroxide it is hydrolysed 
to phloretic acid and phlorin (phloroglucinol glucoside) : — 

C.H,(OH), - O - C,HiiO„ 
which last is identical with the phloroglucinol glucoside synthesised 
by Fischer and Strauss. Phloretin is a component also of Glycyphylliity 
the glucoside of the leaves of Smilax glycyphylla^ where it is com- 
bined with rhamnose. 

The phloroglucinol complex is present in the aromatic part of a 
large number of glucosides. 

Salicin, a colourless, crystalline, bitter substance, is the active con- 
stituent of willow bark ; it has long been used as a remedy against 
fever' and in cases of acute rheumatism. It is hydrolysed by emulsin 
to glucose and saligenin (^-oxybenzyl alcohol), and has the formula 
QHi^Og . O . C^H^. CHjOH. Saligenin yields salicylic acid on oxi- 
dation, but has the advantage of being less irritant than this acid or its 
salts, and therefore does not produce digestive disturbances when 
administered medicinally. 

Salicin occurs in many but not all species of Salix^ also in poplars 
and in the flower buds of meadow-sweet, Spiraa ulmaria. In the 
willow it is found in the leaves and female flowers as well as in the 
bark ; the leaves and twigs of willows also contain a specific enzyme, 
salicase, which hydrolyses it (Sigmund). 

Salicin forms bromo and chloro derivatives which are hydrolysed 
by emulsin. 

When shaken with benzoyl chloride a monobenzoyl derivative is 
obtained in which the benzoyl group is in the sugar nucleus and not 
attached to the alcohol group of saligenin. This compound is identical 
with the natural glucoside populin found in the bark of a number of 
species of poplar {Populus), According to Weevers populin is hydro- 
lysed by an enzyme in Populus monilifera to salicin and benzoic acid. 
Emulsin is without action on populin. 

Helicin^ the glucoside of salicylic aldehyde, is obtained on oxidation 
of salicin with dilute nitric acid. It has not been found to occur 
naturally, but was synthesised by Michael from salicylaldehyde and 
acetochloro glucose. Emulsin hydrolyses helicin and also its hydrazone 
and oxime. Helicin was coupled by Fischer with hydrogen cyanide 
to yield a synthetic cyano-genetic glucoside from which a further series 
of glucosides were obtained. 



THE NATURAL GLUCOSIDES 157 

Salinigrifiy the glucoside of /^-hydroxy benzaldehyde, is isomeric 
with helicin. It was only found in one species {Salix discolor) out of 
thirty-three samples of willow and poplar examined by Jowett and 
Potter. 

Gaultherin, the glucoside of methyl salicylate, is widely distributed 
in plants. It is not hydrolysed by emulsin, but gaultherase, the enzyme 
of Gaultheria procumbens and other plants, and mineral acids decom- 
pose it into glucose and methyl salicylate. 

Coniferifty the glucoside of the fir-tree, is of importance as the start- 
ing-point for the synthesis of vanillin which is formed from it by oxi- 
dation with chromic acid 

It yields glucose and coniferyl alcohol when hydrolysed by emulsin, 
and has the formula : — 

(CjHuOg . O) . C6H8(OMe) . CH : CH . CHaOH 

By careful oxidation glucovanillin is formed, and this may be oxi- 
dised to glucovanilHc acid or reduced to glucovanillyl alcohol. All 
three glucosides are hydrolysed by emulsin. 

A methoxy coniferin is syringin^ the glucoside of the Syringa, which 
is likewise hydrolysed by, emulsin to syringenin (methoxy coniferyl 
alcohol). 

Coumarin Glucosides. — Coumarin is very widely distributed in 
plants : there can be little doubt that it is present in the form of a 
glucoside but this has not yet been isolated. Several glucosides con- 
taining hydroxycoumarins are known. 

Sktmminy CigHj^Og, a constituent of Skimmia japonica^ is the gluco- 
side of 4-hydroxycoumarin (skimmetin), which is isomeric if not identical 
with umbelliferone. 

Aescultfty CigHj^Og, found in horse-chestnut bark {Aesculus hippocas- 
tanum) and Daphnin, a constituent of several species of Daphne, are 
glucosides of isomeric dihydroxy coumarins named aesculetin and 
daphnetin respectively. 

Scopoliny present in Scopoliajaponica, is aesculin monomethyl ether. 
It is said to contain two molecules of glucose. 

Limettifiy the dimethyl ether of aesculin, is found in citrus. 

Fraxifiy Ci^HjgOio, found in the ash, in species of Aesculus and 
in Dienvillay is the glucoside of a monomethyl ether of trihydroxy- 
coumarin termed fraxetin. The position of the methyl group is un- 
certain. 

The following formulae show the relation of these glucosides : it 
is not known which hydroxyl is attached to the glucose residue : — 



IS8 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 




CH : CH . CO CH : CH . CO CH : CH . CO 

OHf |0 




u 



+ Me 



'OH OH 

OH on OH OH 

Skimmetin. '^Aesculetin. Daphnetin. Fraxetin. 

Madder. 

Madder, the ground root of Rubia tinctorum^ which was long con- 
sidered as the most important dye-stuff and has been cultivated from 
remote antiquity, consists of a number of glucosides of which the 
most important is ruberythric acid This is composed of two mole- 
cules of glucose and alizarin, Le. dihydroxyanthraquinone. The 
glucose molecules are probably united as a disaccharide since the 
glucoside is strongly acid and forms red coloured salts indicating the 
presence of a free hydroxyl group. Since its synthesis by Graebe 
and Liebermann alizarin has been manufactured entirely from anthra- 
quinone and the madder industry destroyed. 

The madder contains an enzyme, erythrozym, which hydrolyses 
the glucoside. 

Other glucosides present in madder are those o{ purpurin which is 
trihydroxyanthraquinone : xanthopurpurin which is a dihydroxyanthra- 
quinone isomeric with alizarin and ruBiadin, which is a methyl deriva- 
tive of xanthopurpurin united to one molecule of glucose. 

Hydroxyflavone or Anthoxanthinglucosides . 

The great majority of the soluble yellow plant pigments are 
glucosides derived from flavone or xanthone ; that is, they contain the 
benzopyrone nucleus : — 

^^ ^CH 

II 
CH 

CO 

In the pigments so far studied this nucleus contains one or more 
hydroxyl 'groups and is united to the simple aromatic compounds 
benzene, phenol, catechol, resorcinol or pyrogallol. The structure of 
the pigments has been deduced by the study of their decomposition 
products and in many instances confirmed by their synthesis : much 
of the progress in this group is due to the researches of A. G, Perkin. 
Syntheses of many of the hydroxyflavones have been accomplished by 
a method due to Kostanecki. 

The sugar residue may be either glucose or . rhamnose, or some 
other monosaccharide or even a disaccharide, the methylpentoses being 




THE NATURAL GLUCOSIDES 159 

common in this group. In addition to the differences in the non- 
sugar part of the molecule there are several isomerides possible accord- 
ing to which phenolic group is concerned in the attachment to the 
sugar. Such differences in constitution will correspond with differ- 
ences in the properties of the several glucosides, especially in their 
behaviour towards acids. 

The flavone glucosides are in general colourless or nearly so and 
it would appear probable that when a yellow tint is due to their 
agency it is to be traced, as in the case of the yellow cotton flower, to 
their presence as a potassium or other salt The sugar- free pigments, 
which occur also in the free state along with the glucosides, are yellow 
crystalline solids giving a number of characteristic colour reactions. 

The following hydroxyflavones or their glucosides have so far been 
isolated from plants : — 

The glucoside of chrysin (i : 3 -dihydroxy flavone) 

HO/^— O . C— CgHg 

Is^— CO . CH 
OH 

has not been itself isolated, but the flavone occurs in various species of 
poplar and mallows. 

Apiifty the glucoside present in the leaves of parsley, celery, etc, 
is hydrolysed to glucose, apiose (a sugar of abnormal structure with 
five carbon atoms) and apigenin (1:3: 4'-trihydroxy flavone) : — 

H0/\— O . C— CgH4(OH) 

X II 4' 

L J— CO . CH 

OH 

According to Perkin the sugar residue is united to the hydroxyl 
group marked x. Apigenin has been identified by Wheldale as the 
basis of the ivory white of antirrhinum flowers. 

The glucoside of luteolin (i : 3 : 3' : 4' : tetrahydroxy flavone), the 
colouring matter oi Reseda luteola and Genista tinctoria^ has likewise not 
been isolated : — 

HO/^— O . C— CeHs(0H)2 

II 3', 4' 

-CO . CH 

OH 

The glucoside of galangin (i : 3-dihydroxy flavonol) occurs in 
the root of Galanga : — 

HOf^^— O .C— CgHg 

'—CO . C . OH 
OH 




u 




i6o THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

Catnpferitrin (Robinin) is the glucoside of the white azalea 
{Robinia pseudacacia) and of Java indigo. It is composed of glucose, 
rhamnose (2 molecules) and campherol (1:3: 4'-trihydroxy flavonol) : — 

HO/^— O .C— C,H4(OH) 

II 4' 

Iv^— CO . C . OH 
OH 

Fustifty the glucoside of fustic {Rhus cotinus) and perhaps aiso of 
Quebracho Colorado^ is hydrolysed to rhamnose and 2 molecules of fisetin 
3:3': 4'-trihydroxyflavonol) : — 

HO/^— O .C— C,H,(OH), 
I ^ II 3', 4' 

Leo . C . OH 

Quercitrin is the glucoside of the oak bark. It is easily hydrolysed 
by acids to rhamnose and quercetin (quercitin) - 1:3:3': 4'-tetra- 
hydroxyflavonol : — 

Ho/\-0 .C-C,H,(OH). 

II 3'. 4' 

k>^— CO . C . OH 

OH 

Quercetin is very widely distributed in plants from many of which 
the glucoside has not been isolated It frequently occurs, together 
with other pigments of the group. It follows indigo and alizarin in 
industrial importance as a natural dye-stuff. 

Incarnatrin, the glucoside of crimson clover {Trtfolium incarnaiufn\ 
contains glucose and quercetin and is hydrolysed by emulsin. 

Monomethyl ethers of quercetin also occur as glucosides. 

X author hamntn^ the glucoside of various species of rhamnose, is 
composed of galactose, rhamnose (two molecules) and rhamnetin 
(monomethyl quercetin). According to Tanret the methoxyl group 
occupies positions i or 3. Wheldale considers it replaces the OH 
group in the 7-pyrone ring. Frangulin, from Rkantnus frangula^ is 
not identical with xanthorhamnin, being a glucoside of emodin. 

An iso-rhamnetin has been isolated by Perkin from an Indian dye, 
asbarg, from Delphinium zalil and from the wallflower : it is i : 3 : 4'- 
hydroxy 3'-methoxy flavonol : — 

Ho/\— O . C— C,H,(OH) (OMe) 

f II 4' 3' 

I J-_CO.C.OH 

A dimethyl ether of quercetin is rhamnazin, present in the fruits 
of Rhamnus species. 



THE NATURAL GLUCOSIDES i6i 

When quercitrin is methylated with diazomethane (Herzig) the 
free hydroxyl groups are readily methylated and ultimately a penta- 
methyl quercitrin obtained, one methyl entering into the rhamnose 
molecule. On hydrolysis a tetramethyl quercetin is formed in which 
the hydroxyl in the pyrone ring is left unmethylated. The attach- 
ment of rhamnose and quercetin must accordingly take place through 
this hydroxyl. 

Quercimeritrin obtained from the flowers of Gossypium herbaceum 
is composed of glucose and quercetin. Acids hydrolyse it with diffi- 
culty. The sugar residue is supposed to be attached either to the 
hydroxyl group I or 3. 

Iso-quercitrin accompanies quercimeritrin in cotton flowers. It 
differs from it in being easily hydrolysed by acids to glucose and 
quercetin. 

Rutifty which is widely distributed in plants, is hydrolysed with 
difficulty by acids to quercetin, glucose, and rhamnose. 

ThujiUy in Thuja occidentalis (arborvitae), consists of quercitrin 
accompanied by traces of another glucoside. 

Serotin^ present in Prunus SerotinUy is easily hydrolysed by acids 
to glucose and quercetin. 

The glucoside of yellow wood {Morus tinctorid) contains morin 
(i 13:2': 4'-tetrahydroxyflavonol) : — 

Ho/\o .C— C6H,(OH)3 

II 2', 4' 

K)qo . c . oh 

OH 

Myricetin (i : 3 : 3' : 4' : S'-P^ntahydroxyflavonol) : — 

HO/No . C— CgH, (OH), 

' 1 II 3'. 4'. 5' 

'cO . C . OH 



\)' 



OH 

is found in the leaves of Rhus species and in the bark of Myrica magi, 
GossypitrtHy one of the glucosides present in Egyptian cotton 
flowers, yields on hydrolysis glucose and gossypetin, — CijHiqOs, it has 
the following formula though the position of the hydroxyl groups in 
the tetrahydroxybenzene nucleus has not yet been determined with 
certainty. The sugar is attached to the tetrahydroxybenzene 
nucleus :-^ 



?(0H) 



/\o .C-CeH,(OH), 



\^C0. 



II- 3.4 
C^OH 



II 




i62 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

Quercetagetin^ from the flowers of the African marigold {Tagetes 

patuld)y IS very closely allied to gossypetin, both containing tetra- 

hydroxybenzene and catechol nuclei. It perhaps has the structure 

of a 1:2:4:3': 4'-pentahydroxyflavonol, though the i : 2 : 3 : 3' : 4' 

alternative is also possible. 

Grossypetin forms an interesting quinone, gossypetone, on hy- 
drolysis, which resembles the quercetone obtained from quercetin by 
the action of chromic acid Gossypitrin yields a similar quinone on 
oxidation by means of benzoquinone. Perkin suggests this has the 

structure : — 

O 

CfiHioOg . o/\o . C— O . CeH3(0H)j 

^ 'cO . C . OH 
O 

Perkin has compared the glucosides of a variety of cotton flowers. 

The red flowers of G.-arboreum contained isoquercitrin ; the yellow 
flowers of the Indian G,-neglectum contained gossypetrin and iso- 
quercitrin ; whereas the yellow flowered Egyptian variety contained 
quercimeritrin as well. White flowered varieties G.-Rossum gave only 
very small quantities of a glucoside resembling apigenin, and the 
pink flowers of G.-sanguinetttn contained only traces of flavones. 

The leaves and flowers of Upland cotton G.-hirsutum contain 
quercimeritrin and isoquercitrin, the latter being present in the petals 
only. 

The xanthone colouring matters also come within this group. 

Euxanthone is formed when cattle are fed with mango leaves. 
The urine contains euxanthic acid (Indian yellow) which is a combina- 
tion of glucuronic acid with euxanthone. The pigment is made in 
Bengal and largely used in India. Euxanthone is 2 : 3'-dihydroxyxan- 

thone : — 

o 




'OH 
OH CO 

Gentisin, the yellow pigment present in Gentiana lutea^ no doubt 
originally in the form of a glucoside, is 4-methoxy'2 : 3-dihydroxy- 
xanthone. 

The hydroxyflavone glucosides are so widely distributed in plants 
in the form of colouring matters in the cell sap that the occurrence of 
the parent substance, flavone, is of quite especial interest. It is present 
as the farina of many species of primula in almost pure condition, as 



THE NATURAL GLUCOSIDES 163 

was shown by Hugo Miiller. No opinion is expressed by him as to 
the physiological function which flavone exercises in the economy of 
the plant life, though the fact that it is excreted so freely would seem 
to imply that it is of no further use in the life process although its 
repellant action towards water is probably of importance. This ob- 
servation has been confirmed by Shibata and Nagai, who find that 
the waxlike or powdery coverings of many plant organs contain flavone 
compounds secreted by the epidermis. 

The same observers have examined the leaves, flowers, bark, wood, 
etc., of over 240 species of tropical plants and find that flavones were 
invariably present. They suggest that the flavone glucosides exert a 
protective action against the solar rays, especially those of short-wave 
length which are injurious to the living protoplasm, and evidence the 
fact that plants grown in the shade contain less flavone glucoside than 
those grown in the open. Similarly, plants provided with a heavy 
cuticle are usually poor in flavones. They further find that flavones 
and anthocyanins often interchange, showing they have the same pro- 
tective function. Thus young shoots contain red anthocyanin which 
changes into the colourless flavone glucoside in the green organ and 
back into the anthocyanin before the fall of the leaves. 

To detect the flavone the tissue is extracted with hot alcohol and 
a few cubic centimetres of the extract are heated with a drop of 
mercury, a little magnesium powder, and a few drops of concentrated 
hydrochloric acid in a test tube. In the presence of a flavone, reduc- 
tion takes place with a vigorous generation of hydrogen gas and the 
production of a red colour. 

Anthocyan Glucosides. 

The soluble red, violet, and blue pigments of the cell sap are all 
glucosides. They are being investigated by Willstatter who has 
shown they are derivatives of the complex benzo-pyrilium nucleus : — 

CH 

which differs from the benzopyrone nucleus of the hydroxyflavones in 
having a CH group n place of the CO group. The oxygen atom in 
the ring is strongly basic and forms quadrivalent stable salts with 
acids. The phenolic hydroxyl groups can form salts with alkali, 

Willstatter explains the existence of the red, violet, and blue 




II* 



i64 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

colours as follows : the red is the acid salt, the blue is the potassium 
or metallic salt, and the violet is the anhydride of the pigment : — 

o o 

o.ci II o.ci 

Ho/'\-/\ /'\j/\ KO^\^\ 

\/\/ \/\/ \/\/ 

Red. Violet. Blue. 

The colour is due to the quinonoid structure of the molecule. 

To prepare the anthocyans the material is extracted with cold 
glacial acetic acid and the extract precipitated with ether. A syrup 
is precipitated which is dissolved in warm aqueous picric acid solution : 
on cooling the crystalline picrate separates. It is converted into the 
chloride which can be crystallised from dilute alcohol containing 
hydrochloric-acid. 

The anthocyans so far investigated are : — 

(i) From cornflower and rose, 

cyanin, C„H^OiJC\ = 2 mols. glucose + cyanidin. 

(2) From cranberry, 

idain, CgiH^O^oCl = galactose + cyanidin. 

(3) From blue grapes, 

cenin, CajH^GisCl = glucose + oenidin. 

(4) From whortleberry, 

myrtillin, C^li^fiifi^ = glucose + myrtillidin. 

(5) From larkspur, 

delphinin, C41H0O32CI a 2 mols. glucose + 2 mols. /-oxy-benzoic acid + del- 
phinidin. 

(6) From geranium, 

pelargonin, C^^^OifiX = 2 mols. glucose + pelargonidin. 

(7) From mallow, 

malvin, C29H,,Oi7Cl = 2 mols. glucose + malvidin. 

(8) From paeony, 

paeonin, CggHssG^eCl = 2 mols. glucose + paeonidin (=: cyanidin methyl ether). 

The close relationship which exists between the anthocyanidins 
and the anthoxanthins is shown by the fact that — 

Cyanidin is isomeric with luteolin, campherol, and fisetin ; 

Delphinidin is isomeric with quercetin and morin ; 

Pelargonidin is isomeric with apigenin and galangin. 

All three compounds give phloroglucinol when heated with alkali. 
Willstatter gives them the following constitutional formulae : — 



THE NATURAL GLUCOSIDES 165 




Hor Y ^ < >0H HOf Y ^ ( \oH 




O OH 

OH OH 

Delphinidin. Oenidin. 

The interconversion of the anthoxanthins and the anthocyanidins 
is a matter of the greatest interest as it undoubtedly takes place in 
the plant probably under the influence of oxidative and reducing 
enzymes. Chemically the change is not easily effected though quer- 
citin has been reduced to cyanidin by Everest. Pelargonidin has been 
synthesised by Willstatter. 

The r61e of oxydases in the formation of the anthocyan pigments 
of plants has been studied by Keeble and Armstrong. 

Digitalis Glucosides. 

The leaves of the foxglove {Digitalis purpurea) contain apparently 
more than five glucosides which form the active constituents of digi- 
talis, but their nature has been but scantily investigated. 

DigitoxiUy the most active principle, is insoluble in water; on 
hydrolysis it forms digitoxigenin and a sugar, C^yfi^^ digitoxose. 

There are apparently two digitoxins, one of which forms a hydrate. 
The commercial product made by Merck changed from one form to 
the other in 1895. Digitoxose is very unstable and much of it is 
resinified when the glucoside is hydrolysed even with 0*5 per cent, 
hydrochloric acid. 

Digitalin possesses in a high degree the physiological action of 
digitalis, decreasing the frequency and increasing the force of the beat 
of the heart ; it yields digitaligenin, glucose, and digitalose, C7H14O5, 
on hydrolysis. 

Digitoniity which comprises one-half of the mixed glucosides of 
the seeds, belongs to the saponins : it dissolves sparingly in water, 
forming opalescent solutions which froth on agitation. It is hydro- 
lysed to glucose (two molecules), galactose (two molecules) and 



i66 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

digitogenin. Characteristic is the formation of a crystalline precipitate 
with cholesterol. 

Merck's preparation of digitonin is a mixture of glucosides ; a 
constituent gitonin, C4j>H8q028, has been isolated by Windaus, as an 
amorphous substance giving an additive compound with cholesterol. 
It is hydrolysed to galactose (three molecules), a pentose (one mole- 
cule) and the crystalline gitogenin, CjjgH^gO*- 

Kraft has studied afresh the glucosides present in digitalis leaves 
and describes a member of the saponin class, digitosaponin, which is 
apparently identical with digitonin, but yields a pentose and digito- 
sapogenin upon hydrolysis. 

Gitalin, CggH^gOi^, an amorphous, neutral and very sparingly 
soluble glucoside possessing physiological activity, was also isolated 
by Kraft. By evaporation of the alcoholic solution he obtained the 
crystalline anhydrogitalin, CagH^^O^. Both gitalin and its anhydro- 
derivative give the same products of hydrolysis, namely, digitoxose 
and anhydrogitaligenin, CjjHj^Og. 

Kiliani states, on the other hand, that gitalin itself is a mixture of 
glucosides, separable by fractional solution in water and a mixture of 
organic solvents into fractions differing in physiological action, solu- 
bility, and hydrolytic behaviour. 

Some of the glucosides of digitalis seeds form crystalline addition 
products with amyl alcohol, thus allowing the separation of digitonin 
and gitonin in the precipitate from digitalin in the solution. 

The work of Windaus and Hermanns has shown that cymarin, the 
active principle of Canadian hemp {Apocynum cannabinuvi)^ belongs to 
the digitalis group of glucosides. When hydrolysed it yields cymari- 
genin and a new sugar cymarose which behaves as the methyl ether of 
digitoxose. Cymarigenin is identical with apocyanamarin obtained 
by Moore from Apocyanum androscemifolium and with strophanthidin 
from strophanthin-Kombe. An interesting relation between the three 
glucosides is thus established : — 



Digitoxin 


Digitoxigenin 


Digitoxose 


C»H440, = 


CssHjiqGq + 


CjHmO. 


Cymarin 


Cymarigenin 


Cymarose 




= Strophanthidin 


s Digitoxose methyl 
ether 


Ca8^640l6 = 


CaaHaoO, + 


Ci,H,40io 


9trophanthin 


Strophanthidin 


Strophantobiose 
methyl ether. 



Strophantobiose is said to be composed of mannose and rhamnose. 



THE NATURAL GLUCOSIDES 167 

Hirohashi states that the youngest leaves of digitalis are the most 
active physiologically : they should be collected before inflorescence. 

There is no difference in activity between red and white flowers. 
Cultivated digitalis is as active as the wild variety and the first year s 
growth is as active as that of the second (Hatcher). 

Oleander leaves contain two crystalline active glucosides similar 
to those in digitalis leaves. The whole of the active substances in 
oleander leaves are readily extracted by cold water : this solubility 
seems due to the large amount of a phenolic glucoside present in the 
leaves which is not a true tannin. 

A careful study of the development of the glucosides in germinating 
and growing digitalis plants has been made by Straub. The amount 
of the glucosides was estimated by a pharmacological method, viz. by 
determining the number of lethal doses for a frog. The glucosides 
studied were digitalinum verum and digitalein, which are soluble in 
water, in the seeds and further digitoxin, which is insoluble in water 
but soluble in chloroform, and gitalin, soluble in both water and chloro- 
form, in the leaves. The glucosides of the seeds are not reserve 
materials but disappear during germination and are stored in the 
leaves, in which organs they do not increase further in quantity. 

The leaf glucosides are found in the earliest foliage leaves and 
continue to increase in quantity until they form one per cent, of the 
dried matter : it is supposed that they are only waste products of the 
metabolism of growth. 

Indican. 

Plants which yield indigo do not contain the colouring matter 
as such but in the form of a glucoside indican, which is readily ex- 
tracted from the leaf by means of acetone. Indican yields glucose 
and indoxyl on hydrolysis ; the indoxyl (colourless) undergoes further 
oxidation to indigotin (the blue colouring matter) : — 

CwH^OeN + H3O = CbHmOb + CgH^ON 2C8H7ON + O^ = 2HjO + Ci^U^fi^T^^ 

Indican. Glucose. Indoxyl. Indoxyl. Indigotin. 

Indigotin is readily obtained on hydrolysing indican with dilute 
acids containing a little ferric chloride as an oxygen carrier, but the 
yield under these conditions is not quantitative. In the plant an 
oxydase plays an important part in the formation of indigotin. 

Indican is also hydrolysed by a specific enzyme, indimulsin, which 
is present in the leaves of the indigo plant. Emulsin also slowly 
hydrolyses indican, but its action is far less intense than that of the 
Indigofera enzyme preparations. The yield of indigotin in this case is 



i68 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

also below the theoretical, especially when hydrolysis is slow : this is 
due to the great instability of indoxyl and in part also to the occlusion 
of indoxyl by the enzyme. It may be improved by adding a small 
quantity of sulphuric acid to the mixture at the commencement of the 
reaction. Technically it is of the greatest importance that the yield 
of natural indigo obtained on the manufacturing scale be a maximum. 

Mustard Oil Glucosides. 

A number of plants belonging to the cruciferae yield glucosides 
containing sulphur. These give rise to mustard oils when hydrolysed 
by the enzyme myrosin which accompanies them in the plant. The 
best-known representatives of this class are sinigrin and sinalbin, 
found in the seeds of the black and white mustard. When the seed 
of black mustard is bruised and moistened, the odour of allylisothio- 
cyanate is easily recognised. The myrosin and the glucoside are con- 
tained in separate cells in the seed, and do not interact until brought 
together by the solvent. 

The recognition of an ethereal oil as the active principle of black 
mustard dates from 1730 (Boerhave). Bussy was the first to isolate 
the glucoside, which he termed potassium myronate, and the accom- 
panying enzyme myrosin. Will and Korner gave the name sinigrin 
to the glucoside, and showed that it is hydrolysed to allylisothio- 
cyanate, glucose, and potassium hydrogen sulphate : — 

CjoHieOjjNSjK + HjO = C3H, . NCS + CeHiaOe + KHSO4 

Sinigrin was subsequently investigated in detail by Gadamer, who 
proposed the formula — 

C3H5 . N : C(S . C,HiiO J . ©(SOjK) 

Schneider's isolation of the silver derivative of thioglucose from 
sinigrin tends to support this view. 

When potassium methoxide is added to sinigrin, potassium sulphate 
separates at once, and on adding ammoniacal silver nitrate the silver 
salt of thioglucose is obtained, proving that the glucose molecule is 
attached to the sulphur atom in the glucoside : — 

CjHj . N : C . (OSGjK) . S . C^U^fis 
^CjHj . N : C(OMe) . S . C.HnOj 



->HS . CeHjiO, 



At the same time another decomposition product, merosinigrin, is 
formed which is characterised by great stability : it forms a triacetate 
and may be a ring compound : — 



THE NATURAL GLUCOSIDES 169 



o 



CH,(OH) . CH(OH) . CH . CH(OH) . CH . CH 

S 

C : N . CjH, 

It is not hydrolysed by emulsin or by yeast extract or any known 
enzyme other than myrosin. As hydrolysis proceeds, the increasing 
quantity of acid potassium sulphate formed renders the ferment less 
active and ultimately stops its action. 

Guignard has very carefully investigated the localisation of myrosin 
in the plant. It occurs in special cells with finely granular contents 
which are free from starch, chlorophyll, fatty matter, and aleurone 
grains. 

Sinalbin is likewise hydrolysed by myrosin, which accompanies it 
in the seeds, to glucose, sinalbin mustard oil (/-hydroxybenzylisothio- 
cyanate) and acid sinapin sulphate : — 

CwH^OisNjSa + HjO = C,HijOe + C^H^O . NCS + CieHa^O^N . HSO4 

Barium hydroxide converts acid sinapin sulphate into choline and 
sinapinic acid : — 

CeH2(0H)(0Me)a . CH : CH . COjH 

It is of interest that the alcohol corresponding with this acid is 
syringenin, a constituent of the glucoside syringin. 

Glucocheirolin^ C^^H^fi^^S^y HgO, occurring in wallflower seeds, 
has been studied by Schneider and found to be a derivative of an 
aliphatic sulphone. Its probable constitution is — 

CH, . SOj . CHj . CHj . CHj . N(0 . SO,K) . S . CgHuOg 

It is hydrolysed to glucose and cheirolin by myrosin. 

Pentosides. 

Barbaloifty CgoH^gOg, is hydrolysed to ^/-arabinose and aloemodin, 
CigHj^Og. This pentose was at first described under the name aloinose 
(Leger) : it affords one of the rare instances of the natural occurrence 
of both ^/and / modifications of a carbohydrate (q. v. arabinose). l-Ara- 
binose is a constituent of the saponins as well as of gums and pentosans. 

Vemin, Q^^^j^^^fiYi^, is guanine-rf-ribose. Originally dis- 
covered by Schulze in the seeds of Lupinus luteuSy it was recognised 
as a pentoside by Schulze and Castoro. It is identical with the guanosin 
obtained by Levene and Jacobs from nucleic acid and with the pentoside 
obtained by Andrlik from molasses. The pentose was recognised as 
^/-ribose by Levene and Jacobs and used by them for the synthesis of 
^allose and ^Itrose. 



I70 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

Dibenzoylglucoxylosey CgjHjgOjg.HjO, the first naturally occurring 
simple glucoside of benzoic acid which has been discovered, was ob- 
tained by Power and Sal way from Daviesia latifolia. It is hydrolysed 
to benzoic acid and glucoxylose, a non-reducing disaccharide. Acid 
hydrolysis of the latter leads to the production of glucose and xylose. 

Amygdalin. 

Amygdalin is perhaps the best known and at the same time the 
most interesting of the glucosides ; it has formed the subject of re- 
peated and fruitful investigation ever since its discovery eighty-nine 
years ago, and even to-day the exact structure is not satisfactorily 
established. It is an example of a glucoside which contains nitrogen ; 
on hydrolysis it yields benzaldehyde, hydrogen cyanide and two mole- 
cules of glucose. It is found in large quantities in bitter almonds and 
in the kernels of apricots, peaches, plums, and most fruits belonging to 
the Rosacea. It is the antecedent of the so-called essence of bitter 
almonds, and is widely used as a flavouring material. Like most 
glucosides it is a colourless, crystalline, bitter substance soluble in 
water. 

The presence of hydrogen cyanide in the aqueous distillate of 
bitter almonds was observed at the very beginning of the nineteenth 
century by Bohm ; the crystalline glucoside was first obtained by 
Robiquet and Boutron Charlard in 1830, who showed its connection 
with the essence of bitter almonds. 

In 1837 Liebig and Wohler found that amygdalin was hydrolysed 
by a certain nitrogenous substance, also existing in the almond, to 
which they gave the name emulsin, in accordance with the equation — 

C20H27O11N + 2HaO = C7H.O + HCN + aCeHjaOj 
Amygdalin. Benzalde- Hydrogen Glucose. 

hyde. cyanide. 

They proved it to be a glucoside of benzaldehyde cyanhydrin. 

Ludwig in 1856 pointed out that hot mineral acids hydrolyse 
amygdalin, giving rise to the same products as emulsin does. Schiflf 
was the first to suggest that the two glucose molecules were united as 
a biose — 

CeHj . CH(CN) . O - CeHjoO^ . O . CeHiiG^, 

and this view became generally accepted when it was shown by 
Fischer that amygdalin may be resolved by an enzyme, contained in 
yeast extract, into a molecule of glucose and one of a new glucoside 
which he termed mandelonitrile glucoside — 

CgH, . CH{CN) . O-CeHjiG, 



THE NATURAL GLUCOSIDES 171 

Fischer came to the guarded conclusion that amygdalin was a deriva- 
tive either of maltose or of a closely related diglucose. The view that 
amygdalin is a maltoside has passed into the literature (cf. Dunstan 
and Henry, British Association Report, York, 1906). 

Recent work, however, does not support this supposition. Neither 
in its behaviour towards enzymes nor in its chemical properties does 
amygdalin behave as a maltoside. 

When hydrolysed by means of strong hydrochloric acid, amygdalin 
gives /-mandelic acid, and Fischer's amygdonitrile glucoside is corre- 
spondingly ^/-mandelonitrile glucoside.^ 

Amygdalin at first sight seems to present an exception to the rule 
that enzymes which attack )8-glucosides are strictly without action on 
a-glucosides, and vice versa. Emulsin hydrolyses amygdalin at both 
glucose junctions ; an enzyme in yeast extract (maltase ?) also attacks 
one of these. This junction must either be attackable by two distinct 
enzymes, or the enzymes in question must be mixtures and contain a 
common constituent. The latter hypothesis has proved to be correct. 

Caldwell and Courtauld, in the course of a quantitative study of 
the hydrolysis of amygdalin by acids, showed that change takes 
place more readily at position Y in the molecule than at position X, 
as indicated in the formula — 

CeH, . CH(CN)0 . CeH^oO . O . C^U^fi, 

X Y 

The first product of acid hydrolysis is therefore the mandelonitrile 
glucoside obtained by Fischer; and this can be prepared in such 
manner. It was further shown that the action of yeast extract on 
amygdalin was due not to maltase but to the presence of a hitherto 
unknown enzyme appropriately termed amygdalase. This is more 
stable towards heat than maltase, and can be obtained almost free 
from maltase by preparing the extract at an elevated temperature. 

The fact that an enzyme distinct from maltase effects the hydro- 
lysis of amygdalin is clear proof that the glucoside does not contain 
maltose. Additional confirmation of this is afforded by the fact that 
the rate of hydrolysis of amygdalin either by amygdalase or by emulsin 
(ter Meulen) is not affected by the presence of maltose. This last 
sugar should have slowed the reaction had it been a constituent of the 

glucoside. 

« 

When amygdalin is hydrolysed by emulsin it is not possible at 
any stage of the reaction to detect the presence of a diglucose. In 
reality, under the influence of emulsin prepared from an aqueous 

^ According to the existing nomenclature /-mandelic acid forms <2-mandelonitrile. 



172 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

extract of almonds, two actions are going on at the same time, viz. 
hydrolysis at the centre Y, forming mandelonitrile glucoside and 
glucose, and, more slowly, hydrolysis of the mandelonitrile glucoside 
at X, forming benzaldehyde cyanohydrin and glucose. By interrupt- 
ing the hydrolysis at the proper point it is possible to isolate the 
mandelonitrile glucoside. Such experiments prove that almond ex- 
tract contains amygdalase in addition to the emulsin proper, which 
hydrolyses )8-^lucosides. Amygdalase is entirely without action on 
)3-glucosides. 

The second enzyme in emulsin has been found in the leaves of 
many plants where it occurs without amygdalase. Since it was first 
found in the leaves of the common cherry laurel it has been named 
prunase and the mandelonitrile glucoside on which it acts is termed 
prunasin. 

" Emulsin '* thus contains two enzymes, amygdalase and prunase, 
which act in turn on amygdalin. It is a remarkable fact that prunase 
is unable to act until the molecule has first been simplified by the 
action of amygdalase : this is taken as proof that the second molecule 
of glucose in some way shields the prunasin part of the molecule from 
attack by prunase. This explains. the many unsuccessful attempts to 
obtain the disaccharide from amygdalin by means of plant enzymes. 

This protective influence does not appear to apply, however, in the 
case of the enzymes present in the intestinal juice of the snail which, 
according to Giaja, are able to hydrolyse amygdalin in the first place 
to benzaldehyde cyanohydrin and a disaccharide, the latter subse- 
quently undergoing further hydrolysis. The new carbohydrate is 
stated not to reduce Fehling's solution, that is, it is a disaccharide of 
the trehalose type. It has not been further investigated. 

The amygdalin molecule is exceptional in containing several centres, 
marked X, Y, Z in the formula — 

NC . CHPh . O . Cffi^fit . O . CeHuOj. 
Z X Y 

totally different in their chemical nature, which are attackable by 
hydrolytic agents; its behaviour is, therefore, of the very greatest 
interest. 

Amygdalin yields the same products (glucose, benzaldehyde and 
hydrocyanic acid) when treated with emulsin as when heated with 
dilute hydrochloric acid. In each instance the primary formation of 
^mandelonitrile glucoside indicates that the biose junction Y is the 
first point to be attacked. The course of hydrolysis by concentrated 
acids is altogether different (Walker and Krieble)., Concentrated 



THE NATURAL GLUCOSIDES 



173 



hydrochloric acid hydrolyses it to atnygdalinic acid and ammonia in 
the first place at centre Z ; subsequently, the amygdalinic acid breaks 
down at junction Y to /-mandelic acid glucoside and glucose so that 
junction X is the last point to be attacked. Concentrated sulphuric 
acid has very little tendency to attack the nitrile group at Z, the 
primary action being to eliminate ^mandelonitrile. The biose junction 
Y is the point most susceptible of attack by sulphuric acid at all con- 
centrations. Sulphuric acid decomposes benzaldehyde cyanohydrin 
(junction Z) only with extreme difficulty. 

In addition to rf-mandelonitrile glucoside two other glucosides hav- 
ing the same composition are known. These are : prulaurasin, first 
described in the amorphous state under the name laurocerasin, and 
since obtained crystalline from the cherry laurel by Herissey ; and 
sambunigrin, separated by Bourquelot and H6rissey from the leaves 
of the common elder {Sambucus niger). These substances are both 
mandelonitrile glucosides ; their properties are set out in the following 
table : — 

TABLE XIV. 





M.p 


Wd. 


Prunasin = dextro mandelonitrile glucoside ^ . . . 
Prulaurasin = racemic mandelonitrile glucoside . 
Sambunigrin = laevo mandelonitrile glucoside . 


I47°-I50° 
120°- 122° 
I5i°-i52" 


- 26-9° 

- 527° 

- 76-3° 



Dunstan and Henry suggested that the differencjss between these lay 
in the nature of the sugar residue. This can feardly be the case, as 
they are all three attacked by emulsin, and therefore derivatives of 
)S-glucose. 

Prulaurasin is, in fact, a racemic mixture of the two stereoisomeric 
cU and /-mandelonitrile )S-glucosides, and is analogous to isoamygdalin, 
the racemic form of amygdalin, which was first prepared by the action 
of alkali on amygdalin by Walker and subsequently studied by Dakin ; 
it yields inactive mandelic acid when hydrolysed by acids ; indeed, 
prulaurasin is obtained by acting on isoamygdalin with yeast extract — 
amygdalase (H6rissey). Sambunigrin is the /8-glucoside of /-mandelo- 
nitrile glucoside, and derived from a still unknown isomeride of amyg- 
dalin. Prulaurasin is obtained from either of the other two isomerides, 
when their aqueous solutions are rendered slightly alkaline. 

The true relationship of these glucosides was first established by 

' According to the existing nomenclature /-mandelic acid forms <2-mandelonitrile. 



174 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 



Caldwell and Courtauld, and their conclusions have been entirely con- 
firmed by Bourquelot and H^rissey. More recently amygdonitrile 
glycoside has been discovered as a natural product, so that all three 
isomerides must play some part in plant economy. H6rissey found 
it in the young branches of Cerasus Padus ; Power and Moore have 
obtained it from wild cherry bark (Prunus serotind). It has been 
named prunasin. 

The kernels of the cherry laurel contain as much as 4 per cent of 
amygdalin : this plant, like most others, stores a more elaborate pro- 
duct in its seeds than is present in the leaves. 

The inter-relationship of these compounds is indicated in the ac- 
companying scheme. Possibly the unknown isomeride of amygdalin 
will also be found in the plant : — 



Amygdalin 



Unknown 



Amyg 



^li 



Isoamygdalin 



dalase 



Pranasin 
<i-mandelonitrile glucoside 
(ex. /-mandelic acid). 



Amyg 




dalase 



Sambunigiin 

=3 /<mandelonitrile glucoside 

{ex, <f-mandelic acid) 




Prulaurasin 
<i/-mandelonitrile 
glucoside 



The synthesis of the mandelonitrile glucosides has been success- 
fully carried out by Fischer and Bergmann, who obtained the acetylated 
glucoside of ethyl mandelate in racemic form by treatment of the 
synthetic ester with acetobromoglucose and silver oxide in the con- 
ventional manner. A methyl alcoholic solution of ammonia transformed 
the ester into the corresponding glucosidic amide, and this was resolved 
into its pure optically-active forms by fractional crystallisation. The 
individual forms were converted by the action of phosphorus oxy- 
chloride into the tetra-acetyl derivatives oid- and /-mandelonitrile gluco- 
sides, which were, of course, identical with the tetra-acetates of prunasin 
and sambunigrin respectively. 

On removal of the acetyl groups by hydrolysis racemisation sets 
in, and the product was found to be r-mandelonitrile glucoside, 
or prulaurasin. The synthetic racemic glucoside was resolved by 



THE NATURAL GLUCOSIDES 175 

fractional crystallisation into rf-mandelonitrile glucoside^ (prunasin) 
and /-mandelonitrile glucoside (sambunigrin). 

Cyanophoric Glucosides. 

Hydrocyanic acid has frequently been isolated from plants, but it 
is only quite recently that its formation has been ascribed invariably to 
the decomposition of a glucoside. Besides amygdalin and the isomeric 
mandelonitrile glucosides a number of other glucosides have been 
isolated, which yield hydrogen cyanide when hydrolysed ; they are 
conveniently grouped together under the term cyanophoric glucosides. 
Although rare compared with the occurrence of saponin in plants the 
distribution of hydrogen cyanide is proving much wider than was at 
one time imagined ; its production has been observed in many plants of 
economic importance. A useful list of plants which yield prussic acid 
has been compiled by GreshoflF. Some of the cyanophoric glucosides 
may be briefly mentioned : — 

Dhurrifiy first isolated by Dunstan and Henry from the leaves and 
stems of the great millet, is a /^r^-hydroxymandelonitrile glucoside, 
and therefore closely related to the three mandelonitrile glucosides 
just described. Like them it is hydrolysed by emulsin. 

Gynocardin^ isolated by Power from the oleaginous seeds of Gyno- 
cardia odoratUy yields prussic acid, glucose and an unknown substance, 
QHgO^, on hydrolysis. It is accompanied in the seeds by an enzyme, 
gynocardase, which also decomposes amygdalin. 

Linamarin or Phaseolunatin^ CgHi^Og . O . CMeg . CN, was first 
isolated by Jorissen and Hairs from young flax plants and subse- 
quently by Dunstan and Henry from Phaseolus lunatus. The latter 
authors consider it to be acetonecyanohydrin-a-glucoside, but it has 
since been shown to be a derivative of )8-glucose. Hydrogen cyanide 
and acetone have been obtained from a number of plants on hydrolysis 
and possibly linamarin is widely distributed. It is the glucoside in 
the seeds of the rubber tree, Hevea brasiliensis. The glucoside is 
accompanied in plants by a specific enzyme linase which has been 
fully investigated by Armstrong and Eyre. Phaseolus lunatus con- 
tains two enzymes — an emulsin which, however, according to Dunstan, 
is without action on phaseolunatin and an enzyme of the maltase type 
which hydrolyses both phaseolunatin and amygdalin, forming man- 
delonitrile glucoside in the latter case. It is perhaps identical with 
the amygdalase described by Caldwell and Courtauld. 

^Fischer uses the inverse notation, deriving the glucosides from d' and ^mandelic 
acids and not from their nitriles. 



176 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

Linamarin has been synthesised by Fischer and Anger from y8- 
acetobromo-glucose thus confirming its structure as a glucoside. The 
acetobromo-glucose condenses with ethylhydroxyisobutyrate to ethyl- 
tetracetyl-glucoside-o-hydroxybutyrate — 

(0Ac)4 • CeH^O, . O . CMe, . CO,Et, 

which is extremely slowly hydrolysed by emulsin. Ammonia con- 
verts it into o-hydroxybutyramideglucoside — 

CeHjiOj . O . CMCa . CO . NH„ 

whilst on treatment with phosphorylchloride it yields tetracetyl lina- 
marin. 

LotusiUy discovered by Dunstan and Henry in Lotus arabicus^ is of 
interest for two reasons. Like amygdalin it gives rise to two mole- 
cules of glucose on hydrolysis and therefore probably contains a 
disaccharide. The other products of hydrolysis are prussic acid and 
lotoflavin — an isomeride of fisetin. In the alkaline hydrolysis one of 
the glucose residues is obtained as heptagluconic acid, indicating that 
the cyanogen radicle is associated with the sugar residue. Lotusin is 
not hydrolysed by almond emulsin but it is resolved by an enzyme 
(lotase) which accompanies it, but as this also decomposes amygdalin 
and salicin it probably contains emulsin. 

Vicianin has been found only in the seeds of a wild vetch, Vicia 
angustifolia. It is decomposed by an enzyme (vicianase) present in 
certain vetches into hydrogen cyanide, benzaldehyde and a disaccharide, 
CuHg^Oj^, vicianose, which is hydrolysed further by the emulsin of 
almonds into glucose and /-arabinose (Bertrand). Accordingly, vici- 
anin represents amygdalin in which one molecule of glucose is re- 
placed by arabinose. 

A common grass Tridens flavens contains a considerable amount 
of hydrogen cyanide, the maximum quantity being present in the 
inflorescence tops. The quantity diminishes from August onwards, 
being nil in October. 

Saponins. 

The saponins are a numerous, widely distributed class of glucosides 
found in a great variety of plants ; they are known to be pMresent 
in more than four hundred plants belonging to about fifty different 
orders, and of these about fifty species have been studied and the 
saponins isolated. 

Their most characteristic properties are the production of a soapy 
foam on mixing with water, and their toxicity, especially to cold-* 



THE NATURAL GLUCOSIDES l^ 

blooded animals such as frogs and fishes ; these were recognised as 
characteristics of the plants containing them in very early times, for 
example, by the Greeks. 

All the saponins have many characteristics in common. Physically 
they are white or cream-coloured powders, in most cases colloidal 
and only dialysable with great difficulty, although recently several 
crystalline members of the group have been discovered. To the latter 
class belong several of the digitonin glucosides, parillin, sarsasaponin 
and cyclamin. 

They are soluble in water, giving clear solutions which froth 
strongly on agitation, form emulsions with oils or resins, prevent the 
deposition of finely divided precipitates, and occlude electrolytes and 
also many soluble dye-stuffs. The saponin of soapwort {Saponaria 
officinalis)^ for example, in its colloidal form gives a blue adsorption 
compound with iodine, although the crystalline constituent does not 
(Barger and Field). In general the saponins are insoluble in ether, 
benzene, chloroform, and cold ethyl alcohol, but freely soluble in hot 
alcohol. 

They possess a very bitter, acrid taste, and the dust of the powdered 
saponins is very irritating and sternutatory. As already mentioned, 
they are strong poisons to fish, the action here being of a chemical 
nature ; on the other hand, they possess haemolytic action of a more 
physical type, occluding the red corpuscles of the blood. The more 
poisonous saponins are referred to as sapotoxins. 

The saponins may be broadly divided, from a chemical standpoint, 
into neutral and acid saponins. Formerly they were classified accord- 
ing to their formulae, the earliest members which were studied forming 
an homologous series of the general formula, C^Hgn-gOio (sometimes 
termed, after its discoverer, Robert's series). Subsequently other 
saponins were found to belong to a similar series, CnHj^.ioOig, whilst 
more recently other glucosides, the properties of which entitle them 
to be classified as saponins, have been isolated and do not fall in 
either homologous series. 

On hydrolysis the saponins yield a variety of sugars (frequently 
several molecules of carbohydrate), and physiologically active sub- 
stances termed sapogenins ; the latter have not as a rule been 
thoroughly examined, but are often compounds of a polyhydroxy- 
lactone nature. The sugars found to exist in combination with the 
sapogenins vary, glucose, galactose, and arabinose being the more 
common, whilst more rarely other pentoses and fructose are obtained. 

All saponins form poisonous additive compounds with cholesterol, 

12 



178 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

Many sapogenins, such as those from guaiacum, saponaria, and 
digitonin give terpene oils when distilled in hydrogen with zinc dust 
(van der Haar). 

The saponins are isolated from the root, leaves, seed, etc., of the 
plants by extraction with water and precipitation with neutral or basic 
lead acetate respectively, according as the saponin is acid or neutral. 
The precipitate is decomposed, and the solution evaporated, the residue 
being extracted with chloroform and precipitated by ether. 

Some of the more interesting saponins will now be briefly dis- 
cussed. 

Saporubrin^ (CigHagOiQ)^, is a sapotoxin found in the root of the 
soapwort, Saponaria officinalis ; on hydrolysis it gives a series of pro- 
ducts, shedding one molecule of sugar at a time, until finally the 
sapogenin, C14H22O2, is obtained, 

Levant sapotoxin^ (CiyHg^Oio, H20)2, is very similar to saporubrin 
and occurs in the roots of Gypsophila arrostii or G. paniculata ; it 
hydrolyses to four molecules of sugar (glucose and galactose) and a 
sapogenin, CjoHi^Og. When gypsophila saponin is heated with dilute 
sulphuric acid a compound prosapogenin is obtained, which when 
heated with 2 per cent, sulphuric acid under pressure gives a mono- 
basic ketonic acid, C24H34O5, also a sapogenin (Rosenthaler and 
Strom). 

Sarsaparilla glucosides, — Sarsaparilla, the dried root of smilax 
species, contains a mixture of saponins, amongst which are : — 

Parillin, Cg^H^^Oio, which hydrolyses to two sugars and parigenin, 
C28H4«04, a phytosterolin, CagHgjO^, which gives glucose and a sitos- 
terol on hydrolysis ; sarsasaponin, C44H78O20, 7H2O, crystals hydrolys- 
ing to three molecules of glucose and sarsasapogenin, C2«H4i02(OH), 
and smilacin or smilasaponin (von Schulz), which is not a homogeneous 
substance, according to Power and Salway, who have most recently 
studied the sarsaparilla group. 

Quillaic acid^ QgHgQOio, ^^^ Quillaia sapotoxin^ Q-^^^^^^^ are 
respectively non-poisonous and poisonous constituents of the glucosides 
present in the bark of Quellaja saponaria. They are amorphous. 

Agrostemma sapotoxin^ ^vi^^i^^x^^^ is a yellowish-white, highly 
poisonous amorphous glucoside found in the corncockle {Lychnis or 
Agrostemma githago) ; it is hydrolysed to four molecules of sugar and 
a sapogenin, C^f^x^O^, 

Digitonin and Digitosaponin^ the saponin glucosides of the foxglove 
{Digitalis purpurea) have already been mentioned with the other 
digitalis glucosides. 



THE NATURAL GLUCOSIDES 179 

The hederins or saponins of the ivy {Hedera helix) have been investi- 
gated by van der Haar and classified provisionally as a- and )8- 
hederins, crystalline saponins insoluble in water, 7-hederin, amorphous 
glucosides insoluble in water, and J-hederin, the saponins soluble in 
water. At present only the a-hederin has been identified as an in- 
dividual; it is a crystalline substance, QaH^j^On, hydrolysing to 
arabinose, rhamnose, and a-hederogenin, CgiHgoO^, a dihydroxylic 
lactone. 

The polysciasaponins occurring in Polyscias nodosa have been studied 
by the same worker, who has separated them by fractional precipita- 
tion into at least two individual members, a-polysciasaponin, C22H3^0io, 
and J-polysciasaponin, C25H42O1Q, Both are white amorphous pow- 
ders, which hydrolyse to one molecule each of arabinose, glucose, and 
a sapogenin, Cg^H^^O^, a saturated lactone containing neither hydroxyl, 
methoxyl, nor ethoxyl groups. 

Other members of the group which may be cited are : — 

Caulosaponifiy C54H8gOi7, and Caulophyllosaponin^ ^^^viS^x^y two 
crystalline saponins found by Power and Salway in Caulophyllum 
thalictroides ; Jegosaponin^ C75H80O26, from Styrax japonicay in which it 
occurs as a crystalline calcium salt : it gives on hydrolysis glucose, 
glucuronic and tiglic acids and a mixture of two sapogenins, C33H520g 
and C38H52O7 ; and two saponins, Q*z^f,fi^^ and C87H58O20, from Yucca 
angustifolia and F. radiosa respectively. 



12 * 



CHAPTER VIIL 

THE SYNTHETIC GLUCOSIDES. 

Several of the natural glucosides have been prepared synthetically, 
and by similar methods the corresponding glucosides of a variety of 
substances can be obtained. The starting-point for the synthesis of 
the natural glucosides was the crude acetochloro glucose prepared by 
Colley (1870) by the action of acetyl chloride on glucose. Michael 
(1879) coupled this with the potassium salt of phenols, preparing in 
this manner phenyl glucoside, helicin, salicin, and methylarbutin ; 
Drouin by the same method obtained the glucosides of thymol and 
a-naphthol. Fischer in 1893 obtained the alkyl glucosides from 
acetochloro glucose, but they are more easily prepared as described in 
Chapter I. 

Following the discovery of the crystalline a- and /S-acetochloro 
glucoses attempts were made to extend and improve Michael's syn- 
thetical method, but were only successful in the case of the /8-com- 
pound As already mentioned, the a-acetochloro glucose in presence 
of alkali undergoes isomeric rearrangement to the /8-acetochloro glucose, 
and accordingly ^-glucosides result instead of a-glucosides. 

Most of the glucosides synthesised have been prepared from the 
non-saccharide constituent and acetobromoglucose in presence of silver 
oxide. Fischer's most recent directions for the production of /8- 
acetobromoglucose have been given previously on p. 27. Other syn- 
thetic glucosides have been derived from triacetylbromoglucosamine 
by Irvine and his co-workers, whilst a third and important group 
of syntheses is that effected, notably by Bourquelot, by means of 
enzymes. 

The experimental methods available make it possible to synthesise 
almost any desired glucoside, especially since Fischer has shown how 
it is possible to obtain synthetic glucosides of the a series. In conse- 
quence, a variety of materials become available for the more exact 
study of the selective action of enzymes and the physiological activity 

of substances in combination with sugar. 

180 



THE' SYNTHETIC GLUCOSIDES i8i 

The influence exercised by the non-sugar group on the stability of 
the glucoside and on its optical properties can also be studied. 

The idea that glucosides are uniformly more reactive physiologi- 
cally than the parent substances has not been well maintained. 

The synthetic purine glucosides, also prepared by Fischer, may 
prove of medicinal as well as of scientific interest ; they were obtained 
by the action of compounds of the type of ^-acetobromoglucose upon 
the silver derivatives of the purines ; glucosides, galactosides, and 
rhamnosides of adenine, guanine, hypoxanthine, theobromine and 
theophylline having thus been made. By condensation with phos- 
phoric acid these compounds would be expected to produce synthetic 
nucleotides, and this was in fact attained when theophylline glucoside 
was treated with phosphorous oxychloride in pyridine solution, the 
product being a hydrated theophyllineglucosidophosphoric acid : — 

[C7HAN4 - QHA - HPOJ, 2H2O 

Purine Glucose Phosphoric 

residue. residue. acid residue. 

The method of production of the purine glucosides has been 
patented by Bayer and Co. 

Another synthetic nitrogenous glucoside is that of morphine 
(Mannich). 

Interesting ^-glucosides obtained by this method are those of 
menthol and borneol ; they represent the first synthetical terpene 
glucosides, and are closely allied to the terpene glucuronic acid com- 
pounds. Similar glucosides include those of geraniol and cyclohexanol 
(Fischer and Helferich), and of citronellol, camphene, dihydrocarveol, 
fenchyl alcohol, terpineol, «j-terpene, sabinol, and santenol (Hama- 
lainen). 

The ^-glucosides of cetyl alcohol, gly collie acid, glycol (Fischer), 
menthol maltoside (E. and H. Fischer), and benzyl galactoside (Unna) 
have also been synthesised. 

Salway has synthesised the similar ceryl and myricyl glucosides, 
and those of sitosterol and cholesterol ; a contemporaneous investiga- 
tion by Power and Salway showed that a number of natural compounds 
previously assumed to be phytosterols were really glucosides (phyto- 
sterolins). Amongst these were ipuranol, from olive bark (Jpomcea 
purpurea), etc., citrullol, found in colocynth and Euonymus atropurpur- 
euMy bryanol in bryony root, and cluytianol from Taraxacum, 

Mauthner has synthesised glucovanillic acid, gluco-/-hydroxy- 
benzoic acid, and other phenolcarboxylic acid glucosides, employing 
their methyl esters in the condensation with acetobromoglucose. He 



1 82 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

has also prepared some of the gluco-hydroxy aceto- and benzo-phen- 
ones, the /-hydroxyacetophenone derivative being found naturally in 
pine needles, and known as picein (Tanret). 

The glucosides of phloroglucinol, resorcinol, and 2.4. 6-tribromo- 
phenol were obtained by shaking an ethereal solution of acetobromo- 
glucose with the alkaline solution of the phenols ; the first mentioned 
is identical with the glucoside obtained from phloridzin by Gremer 
and Seuffert and is capable of inducing diabetes (Fischer and Strauss). 

Glucosides with long side-chains have been prepared by Bargellini 
by condensation of helicin and similar glucosides with different 
hydroxyketones, for example, with /-hydroxy acetophenone, when the 
compound — 

CgHuOj . O . CgH^ . CH : CH . CO . CgH^ . OH 

is formed. 

These glucosides are stated not to be hydrolysed by acids and also 
not to be resolved by emulsin and therefore to belong to the a series. 
Since helicin is a ^-glucoside this conclusion cannot be accepted and 
it is more probable that the long side-chain profoundly alters the pro- 
perties of the glucoside. 

Acetobromoglucose interacts with the silver salts of organic acids 
(Karrer) to form glucosides which are really acetylated glucose salts 
of the acids. The acetyl radicles could not be eliminated without at 
the same time removing the organic acid group so that the influence 
of the glucose molecule on the physiological activity of the acids em- 
ployed could not be observed. 

Irvine and Hynd have prepared a-aminohelicin and a-aminosalicin 
by condensing salicylic aldehyde and saligenin with triacetylbromo- 
glucosamine in presence of morphine, morphine glucosamine appearing 
as a by-product An aminomethylglucoside, different from that obtained 
by the action of ammonia on bromomethyl glucoside (Fischer and 
Zach), was prepared by the same workers from triacetylbromogluco- 
samine and methyl alcohol. 

A new modification of the glucoside synthesis consists in warming 
acetobromoglucose with phenol in the presence of quinoline. During 
this process a rearrangement takes place and a mixture of a- and 
^-phenol glucosides is formed, which are separated by crystallisation 
from carbon tetrachloride. The a-phenol glucoside behaves normally 
in that it is hydrolysed by maltase but not by emulsin ; acids, however, 
hydrolyse it nearly twice as quickly as the ^-isomeride (see p. 131). 

The method has been extended to menthol, and a- and ^-menthyl- 
glucosides so obtained. The former is very sparingly soluble in water 



THE SYNTHETIC GLUCOSIDES 183 

and easily isolated, as much as 50 per cent, being obtained from 
^-acetobromoglucose. It is thus the easiest synthetic cyclic-a-glucoside 
to prepare and will be of interest for physiological studies. The a- 
and ^-menthylglucosides behave normally towards maltase and emulsin 
and in this case the ^-isomeride is somewhat the more rapidly hydro- 
lysed by acids. 

This synthesis of a-glucosides is of the utmost importance, as 
hitherto it has been impossible to obtain them owing to the fact that 
a-acetochloroglucose gave rise to ^-compounds. The synthetic 
a-glucosides will allow of the further study of the influence of the 
arrangement of the groups on optical properties, resistance to hydro- 
lysis by acids, etc. 

It is of interest, further, that quinoline effects the rearrangement of 
the groups on carbon i, whereas in the case of the transformation of 
gluconic into mannonic acid the groups attached to carbon 2 are 
affected. 

Great interest attaches to the synthesis of the glucosides contain- 
ing hydrogen cyanide. As described in the previous chapter Fischer 
has synthesised the natural glucosides derived from d- and /-mandelic 
acid and also linamarin, and the method will doubtless be extended to 
give synthetic material for the study of the many interesting chemical 
and physiological problems presented by these glucosides. , 

Synthetic Sulphur Glucosides. 

Ethy Ithiomercaptal — 

CH,(OH).(CH.OH),.CH<g^J, 

when treated with one molecule of mercuric chloride loses one mer- 
captan residue only and ethylthio-glucoside is formed : — 



CHjCOH) . CH. (CH . 0H)3 . CH(OH) . CH . SEt 

This crystallises in silky needles, m.p. 153°, [aj^ + i20-8°. It 
tastes bitter, does not reduce Fehling's solution, and is hydrolysed by 
acids but stable towards alkalis. No indication is given whether a 
second isomeride is formed at the same time. When excess of 
mercuric chloride is employed the mercaptal is reconverted into 
glucose. 

By the interaction of /8-acetobromoglucose and the potassium salt 
of thiophenol, ^-thiophenol glucoside, C^fHgS . QHijOg, has been ob- 
tained. This is not hydrolysed by emulsin and is very resistant 
towards hydrolysis by dilute acids. Analogous compounds have been 



i84 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

made by Schneider and co-workers from the silver salts of thioure- 
thanes, the products having the general formula — 

R.N: CCOCjHj) . S . CJti^fis 

The products are amorphous and the acetyl free glucosides very 
easily undergo further hydrolysis into urethanes, R . NH . COgEt, 
and thioglucose which is readily isolated in the form of its silver salt 
Decomposition also takes place in another way to form thiourethancs 
and glucose. This latter decomposition is met with in the case of the 
natural mustard oil glucosides, and phenyl thiourethaneglucoside occupies 
an intermediate position between these and the aliphatic thiourethancs. 

Myrosin is without influence on the synthetic thioglucosides. 

Enzyme Sjrnthesis of Glucosides. 

The subject of the synthesis of glucosides by means of enzymes 
belongs properly to the monograph on enzyme action, and therefore 
only certain limited aspects of the question will be considered here. 

Whereas in dilute aqueous solution the hydrolysis of say ^-methyl- 
glucoside by emulsin Is complete, hydrolysis is retarded by the presence 
of increasing amounts of methyl alcohol, until in presence of a certain 
proportion of alcohol the enzyme is able to synthesise glucoside from 
glucose and the alcohol. Definite proof that in this simple case the 
same glucoside is synthesised as is hydrolysed is afforded by its isola- 
tion in a pure state. Hence the reaction — 

glucoside + water ^ glucose + methylalcohol 
is reversible and Bourquelot, to whom the development of this subject 
is primarily due, has proved that the ordinary physico-chemical laws 
governing such reversible reactions apply here also. For example, 
the rates of hydrolysis and synthesis are the same and the same equi- 
librium is reached from both directions. The temperature limits of 
these reactions and the proportions of the various alcohols which can 
be used without destroying the activity of the enzyme have been de- 
termined. Yeast extract, i.e. maltase, effects the synthesis of o-methyl- 
glucoside or galactoside. Emulsin and also Kephir lactase are able to 
produce )8-methylgalactoside. 

The reaction has also been extended successfully to other alcohols, 
the enzyme being allowed to act on sugars dissolved in alcohols con- 
taining varying amounts of water or acetone. In this way crystalline 
glycol, glycerol, geranyl and cinnamyl-^-glucosides and alkyl and 
benzyl galactosides have been obtained by means of emulsin : some 
of these had not been induced to crystallise when made by other 



\ 



THE SYNTHETIC GLUCOSIDES 185 

methods. These synthetic glucosides are hydrolysed by emulsia 
Latterly many other alcohol glucosides have been prepared in like 
manner, for example, those of the terpene alcohols : these, it will be 
remembered, are transformed into glucuronates in the animal system. 

The work more particularly of Armstrong has shown that enzymes 
are very active hydrolytically even when quite insoluble in the medium 
employed. Thus finely ground leaf material, prepared by protracted 
autolysis and frequent washing with water, and therefore divested of 
all soluble matter, was very active towards salicin and other glucosides. 

Similarly emulsin is capable of synthesising and hydrolysing 
^-glucosides in a neutral liquid such as acetone in which it is com- 
pletely insoluble. 

The view that synthesis and hydrolysis are effected by different 
enzymes, though not overlooked by earlier workers, has been brought 
into prominence by the experimental work of Rosenthaler. Emulsin 
in presence of hydrogen cyanide and benzaldehyde brings about the 
formation of optically active benzaldehyde cyanohydrin, a substance 
which it also hydrolyses. Saturation of the enzyme solution with 
magnesium sulphate or half-saturation with ammonium sulphate 
produces a precipitate which is soluble in water. The filtrate has no 
synthetic activity, but is able to effect hydrolysis as before ; the pre- 
cipitate possesses synthetic activity and some hydrolytic activity. It 
is considered by Rosenthaler that emulsin consists of two distinct 
enzymes, one promoting synthesis, the other causing hydrolysis of 
benzaldehyde cyanohydrin. 

It must not be overlooked that enzymes as we know them are 
mixtures of several, often closely related, enzymes. Subtle differ- 
ences exist between different preparations, as is shown by Krieble's 
observation that an emulsin which produced /-mandelonitrile from 
amygdalin, two years later produced the d variety. It is suggested 
that two synthetic enzymes are present in emulsin and acting on 
benzaldehyde and hydrocyanic acid to produce the d- and /-nitrile 
respectively, the latter enzyme being less stable. 

Krieble also states that the emulsin from sweet almonds produces 
the /-nitrile and that from bitter almonds the rf-nitrile. An enzyme 
converting benzaldehyde and hydrogen cyanide into rf-mandelonitrile 
is present in the leaves and bark of Prunus serotina^ which it will be 
remembered contains prunasin, the glucoside of this nitrile. From 
the leaves of the elder, which contains sambunigrin, no optically 
active compound was obtained. Emulsin, as just indicated, forms the 
racemic nitrile and also an excess of one of the optically active forms. 



i86 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

An interesting synthesis of salicin and other glucosides is that 
studied by Ciamician and Ravenna. When plants — well-grown maize 
plants were chosen — are inoculated with glucosides or their aromatic 
products of hydrolysis a reversible change takes place resulting in a 
chemical equilibrium. Salicin is in part hydrolysed, saligenin in part 
transformed into salicin, the final ratio in the full-grown plant of com- 
bined to free saligenin being i : 2. On taking a large number of 
plants it was possible to isolate the salicin synthesised in this manner. 
Confirmation of this work appears desirable. 

It is suggested by Ciamician and Ravenna that the absorption by 
both adult and germinating plants of certain aromatic compounds 
leads to the formation of the corresponding glucosides in the plants. 
Thus maize and beans when treated with weak saligenin solutions 
form salicin. 



CHAPTER IX. 

THE FUNCTION OF CARBOHYDRATES AND GLUCOSIDES IN PLANTS. 

Carbohydrates are of fundamental importance in plants : quite 
apart from the process of assimilation in which starch is formed, the 
carbohydrates and more particularly their glucosidic derivatives are 
now recognised as playing an all-essential part in other physiological 
processes. Sufficient space is not available in the present monograph 
for more than a brief indication of some of the more developed branches 
of this field of inquiry in which work is now being done in many 
directions. 

The last few years have witnessed great progress in the novel in- 
terpretation of the function of glucosides as a means of keeping dor- 
mant substances of great importance in the metabolism of the plant 
until the precise moment at which they are required. The so-called 
respiratory and anthocyanin pigments are derived from glucosides, 
likewise many perfumes. Similarly a large class of substances, which 
are capable of acting as hormones and giving a very delicate but 
directed stimulus to plant metabolism, are constituents of glucosides. 

Since any particular glucoside is only hydrolysed by its specific 
enzyme, the supply of these materials for whatever purpose they are 
required is regulated by a very sensitive control. The glucoside- 
enzyme systems are to be regarded as constituting a controlling 
mechanism for plant metabolism. 

Significance of Glucosides. 

Opinions are divided as to the real significance of glucosides in 
plant economy. Probably they are of use to the plant in a variety of 
ways, and no one explanation will cover the functions of all the mem- 
bers of the group. 

In most, if not in all cases, the glucosides are accompanied by 

appropriate enzymes which are able to hydrolyse the glucoside. 

Enzyme and glucoside do not exist in the same cells as normally there 

is no decomposition. They are brought together should the cellular 

structure be damaged and in some instances during germination. 

187 



1 88 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

In the cherry-laurel, according to Guignard, " emulsin " exists in 
the endodermis ; in the almond, it is found in the axis of the embyro 
in the pericycle which lies immediately under the endodermis, and in 
the cotyledons in both the endodermis and the pericycle. Bourque- 
lot, who prepared both glucoside (gaultherin) and enzyme from the 
stems of Monotropa^ showed they are not present in the same cells. 

The earliest investigations of this nature are due to Marshall Ward. 
The fruits of the Persian berry {Rhamnus infectorius) contain a gluco- 
side known as xanthorhamnin, which, when hydrolysed, yields 
rhamnetin and the two sugars rhamnose and galactose. Marshall 
Ward and Dunlop showed that the seeds contain an enzyme, termed 
rhamnase, capable of hydrolysing the glucoside ; this is confined to 
the raphe of the seed, which is composed of parenchymatous cells 
containing a brilliant oily-looking colourless substance. When the 
pulp or an extract of the pericarp of the fruit is digested with an ex- 
tract of the seeds a copious yellow precipitate of rhamnetin is formed. 

In very many cases glucosides function as reserve materials, and 
when required they are hydrolysed by the accompanying enzyme and 
pass into circulation. 

It would appear that the glucoside stored in the seed is often of a 
more complex character than that present in the leaves of the same 
plant, containing more than one sugar or two molecules of the same 
sugar in its molecule, whereas the leaf glucoside is a simple one. A 
special enzyme is required to hydrolyse it which is present only in the 
seed and absent from the leaf. 

Thus the seeds of Prunus species contain amygdalin together with 
the enzymes, amygdalase and prunase, required for its complete hydro- 
lysis ; the leaves contain mandelonitrile glucosides and prunase but no 
amygdalase. Complex glucosides are present in the seeds of other 
plants, as indicated in the previous chapter. 

Anaesthetics such as chloroform or ether are well known to have 
a remarkable action on plants in stimulating growth. Of the deepest 
significance in this connection is Guignard *s observation that exposure 
of living plants to the action of anaesthetics brings about interaction 
between the glucoside and the corresponding ferment. Mustard oil is 
formed from the leaves of certain cruciferae, hydrogen cyanide from 
laurel leaves and other cyanophoric plants, when submitted to the 
action of chloroform. The same phenomenon is brought about by 
exposure to extreme cold. 

The investigations of H. E. and E. F. Armstrong have shown 
that a variety of substances, having the property in common that they 



CARBOHYDRATES AND GLUCOSIDES IN PLANTS 189 

have but little affinity for water, are able to penetrate the walls of 
certain plant cells. As a consequence alterations in equilibrium are 
set up within the cell, and changes are induced which involve altera- 
tion of the concentration and the liberation of hydrolytic enzymes. 

The general name hormone has been applied to substances which 
are active in this manner : it has been shown that the group includes 
not only carbon dioxide but materials such as hydrogen cyanide, hydro- 
carbons, alcohols, phenols, ethers, esters, aldehydes, mustard oils, etc., 
all of which are normal products of hydrolysis of the plant glucosides. 
The hormones include most of the substances which Overton, Lob, 
Czapek and others have classed as solvents of lipoids. 

The result of the liberation of enzymes within the cell will be 
hydrolysis of complex carbohydrates, glucosides, proteins, etc., and the 
materials so formed will be active in still further stimulating change. 
If unchecked, change will proceed until autolysis is complete : in 
practice the intervention of oxydases is made manifest by the appear- 
ance of brown and other pigments. 

It will be seen that the plant cell carries its own hormones or 
activators in an inactive form bound up as glucosides. If for any 
reason during the twenty-four hour period a little of the glucoside be- 
comes hydrolysed, the hormone will be liberated and a very delicate 
stimulus given to the cell to begin down-grade changes such as normally 
take place at night. 



Glucosides and Animal Nutrition. 

The recognition of the potent effect of the constituents of glucosides 
in acting as stimuli and starters of active metabolism may be of im- 
portance in studying the nutrition of animals. It is well known that 
the herbage of one pasture may have the power of fattening an animal 
whereas similar grass on an adjoining field, though equally readily con- 
sumed by the animal, fails to bring it into condition for the market. 

This is especially the case in Romney Marsh, where one field will 
fatten six or eight or more sheep to the acre whereas an adjoining 
field will do little more than keep the sheep in a growing condition. 
Hall and Russell, who investigated this difference in 191 2, found that 
the floral type in the two fields was constant but that a leafy habit of 
growth obtained in the fattening field and a stemmy habit in the poorer 
fields. The ordinary methods of chemical analysis failed to reveal any 
difference either in the herbage or the soils. Since this date much 
evidence has accumulated in favour of the importance of quality as 



190 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

well as of quantity in animal feeding and the subject is one of the 
greatest importance to agriculturalists. 

Subtle differences between the grasses of these two fields have 
hitherto defied detection, but it is not impossible that the presence or 
absence of certain glucosides or similar constituents may have some 
bearing on the difference. 

H. E. and E. F. Armstrong have made observations on the be- 
haviour of Lotus corniculatus collected during several years both over 
Great Britain and a greater part of Europe. Whereas L, corniculatus 
usually contains a cyanogenetic glucoside and the corresponding 
enzyme, it is established that a botanically indistinguishable form 
exists from which the glucoside is absent. 

Lotus uliginosus^ which some botanists regard as a distinct species, 
is free both from the glucoside and the correlated enzyme : it grows, 
as a rule, in damp situations and is distinguished by its rank growth 
and coarse tubular stem. The normal form of L, corniculatus con- 
tains both glucoside and enzyme ; a widely distributed second form 
is rich in enzyme but lacks the glucoside, and a third rare form lacks 
both glucoside and enzyme. 

Lotus ranks rather as a weed than as a fodder plant and is a 
■ minor constituent of most pastures but it is of great interest that 
white clover, Trifolium repens^ shows similar differences. Two varieties 
are recognised by seedsmen — the cultivated and wild — of which the 
latter is often said to be the more valuable. The wild variety con- 
tains a cyanogenetic glucoside and the correlated enzyme, whereas the 
cultivated lacks glucoside and has very little enzyme. 

A further example is afforded by linseed cake, which is considered 
superior to all other cakes as a food in bringing cattle into condition. 
Owing to the presence of the cyanogenetic glucoside linamarin in the 
unripe seed a small quantity of hydrogen cyanide is usually to be 
found in linseed cake. 

Glucosides are likely to play a very important part as "test 
materials " in the solution of this and many problems of plant chemistry. 
Their non-sugar constituents can frequently be detected with great 
accuracy and delicacy and even localised in situ in the tissue and 
they also can be estimated quantitatively. In this respect the glu- 
cosides which yield hydrogen cyanide on hydrolysis are of particular 
value, more especially as many hundreds of qualitative tests can be 
made in relatively short time. 

In testing for cyanide it is most convenient to make use of stout 
glass tubes, about 3^ inches long and \ inch wide, provided with good 



CARBOHYDRATES AND GLUCOSIDES IN PLANTS 191 

corks. The leaf material having been pushed into the tube, two or 
three drops of chloroform or toluene are added and a slip of moist 
picrate paper is inserted ; the tube is then corked up. It is conveni- 
ently incubated in a waistcoat breast-pocket or in the trousers pocket. 
When cyanide is present the paper reddens perceptibly within half an 
hour, as a rule ; to make certain, the test should be prolonged over 
24 hours. To prepare the picrate paper, slips of filter paper about 
f inch wide are dipped into a solution of 5 grm. picric acid and 50 
grms. sodium carbonate in X litre of water ; after draining the paper, 
it is hung from a pin to dry until it is only just perceptibly moist ; it 
is then cut up into f-inch lengths and stored in a closed tube. It is 
well to keep a piece of the paper in each of the stock of tubes carried, 
so as to make sure that hydrogen cyanide has not been stored up in 
the cork. 

Glucosides may also serve as a method of putting harmful waste 
products out of action : thus phenolic residues are rendered soluble 
by combination with glucose and are transferred osmotically to other 
portions of the plant. 

Bunge has pointed out that very many of the non-sugar constituents 
of glucosides are antiseptic and therefore bactericidal in character. In 
the seeds of plants the reserve stores of food-stuffs form an excellent 
medium for the development of micro-organisms which would rapidly 
spread but for the protective action of the glucoside. In the almond, 
directly the seed is penetrated, the amygdalin is hydrolysed and all 
bacterial action prevented. The universal presence of glucosides in the 
bark of plants may be similarly explained : they ensure an antiseptic 
treatment of all wounds in the integument. 

Easily decomposable substances, such as many acids or aldehydes, 
are protected against oxidation by being transformed into glucosides, 
just as, in the animal organism, similar substances are converted into 
paired glucuronic acid derivatives. 

Glucosides possessing a bitter taste or having poisonous properties 
serve to protect such important organisms as the seeds or fruits of 
plants against animals. In some instances the plant is only poisonous 
at certain stages of its growth. Thus an Egyptian plant, Lotus A rabicuSy 
is poisonous in the early stages, but becomes a useful forage when 
allowed to mature: it contains the glucoside lotusin, which yields 
hydrogen cyanide when hydrolysed. 

Glucosides containing acetonecyanohydrin are regarded by Treub 
as primary material for protein synthesis. Guignard, working with 



192 THE SIMPLE CARBOHYDRATES AND GLUCOSlDES 

phaseolunatin, has obtained no evidence that hydrocyanic acid is liber- 
ated during germination of Phaseolus beans. 

The amount of glucoside present varies considerably in different 
species of the same plant, and varies also according to the time of year. 
It also differs in the male and female plant of the same species. Un- 
fortunately, the material at present available for the discussion of this 
question is very scanty. Jowett and Potter, who investigated the bark 
from thirty-three samples of willow and poplar, found considerable 
variation in the occurrence of salicin. In April the bark from the female 
tree contained about three times as much salicin as that from the male ; 
three months later the conditions were reversed. It is suggested that 
salicin acts as a reserve material ; it is stored away in the winter for 
use in the coming spring, when it is hydrolysed by the accompanying 
ferment, both saligenin and glucose being used by the plant. The plant 
is enabled to store in the form of a glucoside a material which it 
can neither tolerate in quantity nor produce at short notice when 
required. Owing to their special functions the reserve is drawn upon 
to an unequal extent by the male and female trees. Taxicatin, the 
glucoside of the leaves and young shoots of the yew {Taxus baccatd)^ 
occurs in greatest quantity in the plant during the autumn and winter ; 
apparently it is utilised in the spring when the young shoots b^in 
to assimilate. The cyanophoric glucoside in the leaves of Sanibucus 
nigrUy according to Guignard, seems to fulfil a different function, as its 
amount diminishes only slightly with age, and at the end of the 
vegetative period the glucoside does not migrate to the stems but 
remains in the leaves till they drop off. 

The variations in the composition of the root of the gentian 
during a year's growth have been studied by Bridel. The gentian 
root contains a glucoside, gentiopicrin, and the carbohydrates glucose, 
fructose, sucrose, and gentianose (p. 112), the last of which is hydrolysed 
by invertase. The amount of carbohydrate hydrolysed by invertase 
increases from a minimum (i*2 per cent.) early in June to a maximum 
(7*8 per cent.) in August and then remains constant. The amount of 
glucoside (2 per cent) does not vary much ; it increases a little in June 
and July. In May and June gentianose is largely replaced by gentio- 
biose. The sucrose increases from i per cent, in July to 4 per cent, 
or more in November : it is absent when growth commences in the 
spring. 

According to Cavazza the amount of tannin in the leaves of forest 
trees reaches a maximum in September, whereas the amount in the 



CARBOHYDRATES AND GLUCOSIDES IN PLANTS 193 

twigs shows maxima in July and December and varies inversely as that 
in the leaves. 

A comparison of the amount of glucoside and enzyme in linseeds 
grown under conditions of drought and high temperature with those 
grown under damp and low temperature conditions has been made by 
Collins and Blair. Under the latter conditions the total amount of 
hydrogen cyanide produced falls 20 per cent, but the activity of the 
enzyme increases by a like amount. This is the general effect of 
growing linseed in this country, whereas seeds of oriental origin are 
rich in total hydrogen cyanide. 

Respiration in Plants. 

Carbohydrates and glucosides are concerned likewise in the pheno- 
mena of respiration in plants, during which oxygen is absorbed, carbon 
dioxide given off and the energy necessary for carrying out the life- 
work of the plant liberated. The process of oxidative decomposition 
of food substances is separable into two stages : in the first, alcohol 
and carbon dioxide are produced, as may be demonstrated by allow- 
ing pea seeds to germinate without the access of air. The anaerobic 
process of carbohydrate decomposition, if not identical with, is very 
similar to the alcoholic fermentation of glucose by yeast. 

The second stage in respiration comprises the aerobic oxidation of 
the alcohol produced in the first stage : this is effected, according to 
the present view, by the agency of the respiratory pigments which are 
themselves present originally as glucosides and liberated by hydrolysis. 
No doubt, salts of iron, manganese, etc., play some part in the oxida- 
tive changes, but their precise function is not yet understood. 

Important light has been thrown on the function of the aromatic 
substances in plants and on the existence of enzymes, which act only 
on them, by the researches of Palladin. Following the line of thought 
originated by Reinke, who discovered substances in the plant which, 
under the influence of enzyme (oxydase) and air, gave coloured oxida- 
tion products, Palladin made a systematic search for these respiratory 
chromogens. He supposes them to be cyclic compounds bound to 
carbohydrates in the form of insoluble glucosides. Glucoside-splitting 
enzymes separate the cyclic compounds, which by the aid of the oxy- 
dases are then enabled to take up oxygen from the air to give it up 
again later under the influence of reducing substances. During life the 
chromogens normally remain colourless so long as there is a balance 
in the activities of the three types of enzyme concerned, but, on treat- 
ment with chloroform or other hormones, or after death due to cold 

13 



194 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

or injury, the inter-relationship of the enzymes is disturbed and the 
coloured oxidised chromogen becomes evident 

Prochromogen (i.e. glucoside) + water -» chromogen + sugar. 
Chromogen + oxygen -^ respiration pigments. 

The soluble pigments of flowering plants — red, purple, and blue — 
which are termed collectively anthocyanin by botanists, are regarded 
similarly as oxidation products of chromogens of an aromatic nature, 
probably in many cases members of the flavone and xanthone groups 
(Wheldale) : there is little doubt that these colourless chromogens are 
present in the living tissues as glucosides. 

In the flavone glucosides one or more hydroxyl groups are replaced 
by sugar : hence, since the auxochrome group is replaced, the crude 
plant extracts are only pale yellow. On hydrolysis the sugar is split 
off and the colour deepens and a deposit of flavone is formed as the 
glucoside is more soluble than the pigment. Wheldale suggests that 
the reactions involved are in general terms as follows : — 

glucoside + water ^ chromogen (flavone) + sugar, 
chromogen + oxygen -^ anthocyanin. 

The evidence in favour of this hypothesis is summarised by Whel- 
dale in her monograph on the anthocyan pigments. 

Everest, however, obtains anthocyanin by cautious reduction in 
the cold of the pigments in a number of pale yellow or white flowers. 
Under these conditions no anthocyanidin is produced and no oxidation 
after reduction is necessary for the production of the anthocyanin pig- 
ment. 

Combes has found that red leaves of which the coloration is 
attributed to anthocyanin contain proportionately greater amounts of 
glucosides and sugars than green leaves of the same plant ; Kraus has 
proved the same to hold for the aromatic constituents. The evidence 
as to the formation of anthocyanin has been summarised by Whel- 
dale ; it is regarded as due to the accumulation of glucosides. Sugar 
feeding increases both the amount of glucoside and of free aromatic 
chromogen. 

The autumnal coloration of leaves is attributed (Overton, Tswett) 
to the same series of changes brought about by the slowing up of the 
metabolic processes of the plant by frost and other influences resulting 
jn the disturbance of the enzyme balance. Tannins, for example, 
when set free from their glucoside form by the hydrolytic enzymes, 
yield pigments on oxidation (cf. p. 68). 

The production of pigment may involve something more than the 
interaction of the aromatic chroniogen with the oxydase, Chodat has 



CARBOHYDRATES AND GLUCOSIDES IN PLANTS 195 

accumulated evidence showing that protein decomposition products, i.e. 
the amino acids or polypeptides, also take part in the reaction, and the 
precise shade of colour produced depends on the nature and quantity 
of these as well as on that of the aromatic compound derived from the 
glucoside. 

The formation of the anthocyan pigments is of great interest from 
the point of view of genetics. The three groups of factors concerned 
are : — 

(i) Actual formation of the pigment. 

(2) Amount of pigment formed. 

(3) Modification of the colour of the pigment 

For the formation of the pigment two factors, the chromogen and 
the oxidising agent or enzyme, are required. The work of Keeble 
and Armstrong has correlated the distribution of the oxydases with 
that of anthocyan. The amount of pigment formed may be controlled 
by an enzyme liberating more or less from the corresponding glucoside. 
The variation in the colour from red to blue or purple is regarded by 
Willstatter and others as determined by the nature of the accompany- 
ing substances in the cell sap, but this explanation is not in harmony 
with the biological facts. It is more likely that other substances are 
present, as for example, in centaurea, in which the purple, red, and 
blue types contain cyanin and the pink variety pelargonin. 

Carbohydrates and the Enzyme Balance. 

In dealing with carbohydrate metabolism in plants there is abund- 
ant evidence that a very delicate balance exists between the various 
enzymatic processes which take place simultaneously, leading, it may 
be, to the building up of starch or to the transference of a glucoside 

into anthocyanin. 

It is obvious that the introduction from without of agencies which 

will affect this balance will have a more or less profound influence in 

altering the changes which take place. 

One of the most delicate means of regulating the balance is that 
afforded by change of temperature. A rise or fall in the temperature 
does not influence all enzyme reactions alike — for example, some are 
retarded by cold much more than others. 

A typical case is that afforded by the potato tuber during storage 
(Miiller-Thurgan). Three changes take place simultaneously : starch 
is being transformed into sugar, sugar into starch, and also by the 
process of respiration into carbon dioxide. A decrease in the tem- 
perature hinders all three reactions but it has least effect on the 

13 * 



196 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

formation of sugar from starch. Accordingly, when the potato is 
stored at o° sugar is formed till the amount increases to 3 per cent. 
At - 1° all enzyme action ceases. At + 3° there is still formation of 
sugar but the enzymes acting to destroy it tend to keep the amount 
down to 0'5 per cent. At + 6° the rate of formation of sugar from 
starch and that of the reverse change are equal ; above this tempera- 
ture the formation of starch predominates. In consequence no sugar 
is stored and any sugar previously present is destroyed. 

The effect of a further rise in temperature on the enzyme balance 
has not been worked out in such detail but there is no doubt that the 
influence is equally profound. This conception of the regulation of 
metabolism affords an explanation of the sudden development of plant 
growth due to a warm day in spring when the rise in temperature 
favours synthetic changes ; or of the injury caused to hot-house plants 
by exposing them to a temperature colder than that to which they 
are accustomed, whereby an abnormal preponderance of hydrolytic 
activity is favoured which, if unduly prolonged, may lead to the dis- 
integration of the protoplasmic structure and death of the plant. 

In the case of plants which are killed by frost it is supposed that 
as a result of the removal of the water as ice the concentration of the 
cell fluid becomes such that the soluble proteins are precipitated from 
solution. This salting out of the proteins is prevented by the presence 
of non-electrolytes such as sugar : Lidforss, to whom this explanation 
is due, has shown that the leaves of winter plants are free from starch 
but contain much sugar. The warm days of early spring bring about 
the regeneration of starch and partial disappearance of sugar ; in con- 
sequence the cell is but ill protected against the effects of a subsequent 
frost 

The Ripening of Fleshy Fruits. 

In the first stages after fertilisation the changes in the young fruit 
resemble those in the leaf: a variety of acids, tannins, and sometimes 
starch then accumulate, and ultimately, as the fruit becomes ripe, 
carbohydrates and fruit ethers or aromatic substances are formed and 
the bitter, acid, or astringent taste disappears together with the starch. 

The interrelationship of the materials concerned and the enzymes 
which effect their transformation possesses numerous points of interest 
— the scope of the present work limits discussion here mainly to the 
carbohydrates. A distinction has been drawn between three types of 
fruit (Gerber) which in the preliminary stages are rich either in acids. 



CARBOHYDRATES AND GLUCOSIDES IN PLANTS 197 

tannins, or starch : the subsequent changes differ somewhat in each 
type. 

As a typical starchy fruit the banana may be considered. During 
ripening there is an evolution of carbon dioxide and a considerable 
conversion of starch into sugar. Thus Prinsen-Geerligs found during 
six days the amount of starch decreased from 31 to 9 per cent, the 
cane sugar rose from 0*8 to 13*6 per cent., and the invert sugar from 
0*25 to 8*3 per cent. The presence of oxygen is necessary for ripen- 
ing ; in an atmosphere of nitrogen the starch remains intact. 

A careful study of the enzymes present in extracts of bananas 
gathered at different stages of ripening has been made by Tallarico. 
The catalytic enzyme which decomposes hydrogen peroxide is very 
active in the green fruit but weakens as it ripens. Diastase is only 
active in the green fruit or at the beginning of ripening, it then dis- 
appears. Invertase is absent during the green stage, the amount very 
rapidly increases during ripening and then gradually disappears. A 
proteoclastic enzyme is evident during ripening and then likewise 
vanishes. Maltase is not present at any period. 

During ripening the skin of the banana changes from green to 
yellow, deep brown, and finally black ; the fruit is then fully ripe. This 
change is due to an oxydase acting on some aromatic substance 
liberated from a glucoside. The black colour is quickly produced 
when a yellow banana skin is disintegrated by mincing or when the 
entire skin is exposed to the vapour of some hormone. Under natural 
conditions the stimulus which leads to blackening is given from within 
the fruit by the liberation of the characteristic ester of the banana, 
which acts as a powerful hormone. In the case of most fruits, it 
would seem that the final appearance which is associated with ripeness 
is conditioned by stimulus from within rather than by any environ- 
mental influence. 

Vinson has found that invertase is present in the date throughout 
the green stages but remains in an insoluble endo form : during ripen- 
ing it becomes readily soluble, changing to the ecto form. The change 
coincides very closely in point of time with the conversion of the 
soluble tannins into an insoluble form. The unripe date contains 
much cane sugar ; in the ripe fruit this is converted into invert sugar. 
Influences, such as have been considered under the name of hormones, 
which destroy the structure of the protoplasm, liberate the endo- 
enzyme, provided always that the dates have reached a certain stage 
of development. 

The acids in fruits are chiefly malic, tartaric, and citric. Gerber 



198 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

considers that during ripening they are in part converted into sugar 
and in part oxidised to carbon dioxide. Temperature has an im- 
portant influence on the rate of oxidation. Experiments with fungi 
{Sterigmatocytis) have shown that whereas at 1 2° glucose is attacked 
preferentially to tartaric acid, at 20** the rate of attack is equal, at 37° 
the tartaric acid is least resistant. Malic acid is oxidised more easily 
than glucose at all temperatures : fruits containing it, such as apples, 
can ripen, therefore, in colder climates than those containing tartaric 
acid, like grapes. Citric acid is still more resistant to attack, and 
fruits such as oranges and lemons require warmer climates in order to 
ripen. 

In apples, according to Kelhofer, the percentage of sugar is highest 
in the flesh, the acidity increases towards the centre, the tannin from 
the centre outwards. The distribution is the same in ripe as in unripe 
apples, but during ripening the amount of acid greatly diminishes. 

In oranges (Scurti and Plato) citric and malic acids are present ; 
during ripening the quantity- at first increases but then becomes much 
smaller. Sucrose diminishes in amount, glucose and fructose increase. 

During the ripening of sloes (Otto and Kooper) the amount of 
fructose increases whilst that of glucose decreases together with the 
acids and tannin : the loss is in part due to respiration. The same 
authors have studied the changes in medlars and quinces during 
ripening. 

In the ripening of cereals the object is to store starch instead of 
converting it into sugar. The enzymes act synthetically and there is 
a gradual accumulation of carbohydrate within the endosperm tissue. 
The slowly matured, plump grains contain a higher proportion of 
starch than the small and rapidly ripened grains. 

In the sweet potato, Ipomoea batatas^ the conversion of starch into 
sugar is apparently connected with the cessation of the activity of the 
leaves, as until the stem is cut off" or the tubers harvested very little 
sugar is formed. The transformation results first in the production of 
reducing sugars from starch which are then converted into sucrose. 
It is of interest that the change, although slower at low temperatures, 
ultimately goes much further, so that much more sugar is formed. 



CARBOHYDRATES AND GLUCOSIDES IN PLANTS 199 

Products Derived from Carbohydrates in Plants. 

Carbohydrates are the first products of synthesis in the plant, and 
the other products of plant activity must be expected in large measure 
to arise from them. For example, unripe seeds, nuts or fruits contain 
carbohydrates, which as ripening proceeds are transformed into fats 
and oils. This change is of the greatest interest, particularly in regard 
to the variety of fats found in nature and their great commercial im- 
portance. Two changes are involved : the alcoholic hydroxyl groups 
must be reduced and the short carbon chains of the carbohydrates 
must be condensed to form the long chains characteristic of the higher 
fatty acids. It will be remembered that these consist always of an 
even number of carbon atoms and are unbranched, suggesting that a 
decomposition .product of glucose containing two carbon atoms is 
formed and takes part in the condensation, the reaction being repeated 
so that each successive acid has two more carbon atoms. Nefs work 
has shown that the glucose molecule may be disjointed at either the 
a- or yS- or 7-carbon atoms : in the latter case lactic acid is formed, as 
happens when glucose is acted on by bacteria or by weak alkalis. 
The first product of fission is perhaps glycerose — 

CH3(0H) . CH(OH) . CHO 

which by rearrangement becomes lactic acid — 

CHj . CH(OH) . COaH 

Both glucose and lactic acid can undergo butyric fermentation in 
which butyric acid, CH3 . CHg . CHg . CO2H, is formed. 

Nencki suggested that lactic acid breaks down into acetaldehyde, 
hydrogen and carbon dioxide and •that the aldehyde undergoes re- 
peated aldol condensation followed by the same rearrangement as in 
the case of the formation of lactic acid from glycerose : — 

CHj . CHO + CH3 . CHO -> CH3 . CH(OH) . CHj . CHO -> CHj . CHj . CHj . COjH 

The reaction involved in the reduction of the yS-alcoholic hydroxyl 
accompanying the oxidation of the aldehyde group is apparently a 
general one in carbohydrate metabolism. The further study of this 
fascinating subject belongs to the domain of fat chemistry, for which 
the monograph of Dr. Leathes should be consulted. 

The aldehydes present in green leaves have been investigated by 
Curtius and Franzen who worked up 600 kilograms of the leaves of 
the hornbeam for this purpose. They identified formaldehyde, acet- 
aldehyde, 17-butylaldehyde, valeraldehyde, a)8-hexylene aldehyde and 
higher homologues. The hexylene aldehyde — 

CH, . CHo . CH, . CH : CH . CHO 



200 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

formed the greater part, and considerable quantities of acetaldehyde 
and butyric aldehyde were present, the other aldehydes being present 
only in small amounts. 

It is suggested that this aldehyde is produced from glucose by the 
repetition of the following series of changes : — 

CHa . (CH . OH)^ . CHO glucose, 

I 
OH 

CH2:C(OH).(CH.OH)3.CHO water eliminated, 

CH3 . CO. (CH . 0H)3 . CHO water added and 

eliminated, 

CH3 . CH(OH) . (CH . 0H)3 . CHO reduced, 

involving, in the first place, the formation of a methylpentose, and sub- 
sequently, on repetition of the reduction, of an ethyl tetrose which 
would have the same composition as digitoxose. Kiliani assigns a 
different structure to this sugar, but it requires reinvestigation from 
this point of view. 

The constitution of the enzymes which act on the carbohydrates 
has long been a subject of speculation. According to H. E. and 
E. F. Armstrong the enzyme has the double function of retaining the 
hydrolyte in circuit while hydrolysis is being effected by an electrolyte 
formed from an active radicle present in the enzyme. The acceptor 
portion of the enzyme must be compatible with a grouping common 
to all the members of the series of glucosides which it hydrolyses, and 
it has been postulated as an amino glucose composing part of a large 
colloid molecule. Carbohydrates have been shown to be a component 
even of highly purified enzymes though it is not yet possible to carry 
the purification very far without destroying the activity of the enzyme. 

Willstatter finds that the purest and most active peroxydase he 
could prepare from a very large quantity of horse radish consisted 
chiefly of a nitrogenous glucoside containing about 30 per cent, of a 
pentose and the equivalent proportion of a hexose with about 3 atoms 
of nitrogen. Peroxydase is not, of course, generally regarded as an 
enzyme in the same sense as the sugar-splitting compounds, and the 
method of purification would have inevitably destroyed the sucrolastic 
enzymes. It is none the less of considerable interest that a very active 
catalytic agent should be composed so largely of sugar molecules. 



BIBLIOGRAPHY. 

Reference to the literature subsequent to zgoo is much facilitated by the Annual Volumes of the Inter- 
national Catalogue of Scientific Literature. Papers referring to Carbohydrates are indexed in Volume D 
{Chemistry) under 1800 et seq. in the original language^ namely^ z8oo General^ z8io Monosaccharides^ z8ao 
DisacchartdeSt 1830 Trisaccharides^ 1840 Polysaccharides^ 1830 Glucosides, Papers referring to the Car- 
bohydrate Enzymes are indexed under 8ooo>8oz4, Fermentation under 8c»o, arul Vegetable Metabolism under 
8030. The same system of numbering is used in the forthcoming publication of the Royal Society's Catalo^e 
of Scientific Papers up to 1900. A further means of reference is provided by the Annual Reports of the Chemical 
Society, 

TEXTBOOKS. 

£. F. Armstrong. Dictionary of applied chemistry. 1912. {Carbohydrates^ Glucosides.'] 

F. CzAPBK. Biochemie der Pfianzen. Jena, 1905. 

F. CzAPBK. Chemical phenomena in lije. London, 191 1. 

H. EuLER. Pflanzenchemie. Braunschweig, 1908. 

H. EuLER UND LuNOBERG. Glucoside, Biochemisches Handlexikon, 1911. 

E. FtscHBR. Untersuchungen uber Kohlenhydrate und Fermente. 1884-1908. Berlin, 
1909. [A reprint of all the original papers.] 

J. Reynolds Green. The soluble ferments and fermentation, 

V. Henri. Lois gSnerales des diastases, Paris, 1903. 

O. Jacob^bn. Die Glycoside, 

H. Landolt. Das optische Drehungsvermogen organischer Substanzen und ' dessen 
praktische Anwendungen, Braunschweig, 1898. ^ 

E. VON LiPPMANN. Die Chemie der Zuckerarten. 3rd edition, 1904. 

L. Maqubnne. Les Sucres et leurs principaux derives, Paris, 1900. 

R. H. Adbrs Plimmbr. The chemical changes and products resulting from fermentations, 
London, 1903. 

Van Rijn. Die Glucoside, Berlin, 1900. 

RoscoB-ScHORLBMMBR*s Chemie^ Band 8. Pflanzenglycoside, Braunschweig, 1901. 

B. ToLLENS. Kurzes Handbuch der Kohhnhydrate. 2nd edition, 1898. 
M. Wheldalb. The anthocyan pigments of plants. Cambridge, 1916. 

REFERENCES TO CHAPTER I, 

E. BucHNBR, J. Meisenheimer UNO H. ScHADB. Vcrgdhrung des Zuckers ohne Enzyme, 
Ber., 1906, 39, 4217-4231. 

E. Fischer. Ueber die Configuration des Traubenzuckers und seiner Isomeren, I., II. 
Ber., 1891, 24, 1836- 1845, 2683-2687. 

E. Fischer und R. S. Morrbll. Ueber die Configuration der Rhamnose und GalcLctose, 

Ber., 1894, 27, 382-394. 
E. Fischer. Konfiguration der Weinsdure, Ber., 1896, 29, 1377-1383. 

C. S. Hudson. Certain numerical relations in the sugar group, J. Amer. Chem. Soc, 

1909, 31, 66-86. 

A. Hyno. Configuration in the sugar group, British Association Report, 19 15. 

P. A. Levene and W. a. Jacobs. Hexoses from d-ribose. Ber., 1910, 43, 3141-3147. 

W. LoBB. Zur Kenntnis der Zuckerspaltungen, I. Die Einwirkung von Zinkcarbonat auf 
Formaldehydlosungen, Biochem. Zeit., 1908, 12, 78-96. 

W. LoBB. Zur Kenntnis der Zuckerspaltungen. II. Die Einwirkung von Zinkstaub und 
Bisen auf FormaldehydWsungen ; die Einwirkung von Zinkstaub auf Trauben- 
zucker, Biochem. Zeit., 1908, I2, 466-472. 

J. Mbisbnhbimbr. Das Verhalten der Glucose^ Fructose und Galactose gegen verdunnte 
Natronlange, Ber., 1908, 41, 1009-1019. 

20I 



202 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

J. U. Nbf. Das VerhalUn der Zuckerarien gegtn die Fehlingscke Losung sowie gegen 
andere OxydaHonsmittel, Annalen, 1907, 357, 214-312; 1910, 376, 1-119; 19141 
403, 204-283. 

O. PiLOTY. Ueher eins neue Totalsynihese des Glycerins und des Dioxyacetons, Ber., 1897, 
30, 3161-3169. 

H. ScHADB. Vergahrung des Zuckers ohne Enzyme, ZeiL physikaL Chem., 1906, 57, 1-46. 

H. ScHADB. Uher die Vorg&nge der Garung vom Standpunkt der Kaialyse, Biochem. 
Zeitsch., 1908, 7, 299-326. 

A. WoHL. Ueber die Acetate des Acroleins und des Glycerinaldehyds, Bcr., 1898, 31, 
1796- 1801. 

A. WoHL. Synthese des i-Glycerinaldehydes. Ber., 1898, 31, 2394-2395. 

A. WoHL UND F. MoMBBR. Die sterische Beziekung Zwischen Glycerinaldehyd und Wein- 
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A. WoHL UND C. Nbubbrg. Zur Kenntnis des Glycerinaldehyds. Ber., 1900, 33, 
3095-3110. 

REFERENCES TO STRUCTURE AND MUTAROTATION OF GLUCOSE. 

E. Frankland Armstrong. Studies on enzyme action. I. The correlaiion of the 
stereoisomeric a- and fi-glucosides with the corresponding glucoses. J. Chem. Soc., 
1903, 83, 1305-1313. 

E. Frankland Armstrong and S. L. Courtauld. Formation of isodynamic glucosides 
with reference to the theory of isomeric change and the selective action of enzymes- 
PreparaHon of fi-methyl glucoside. J. Physiol., 1905, 33, Proc. iv. 

R. Bbhrbnd. Zur Kenntniss der ^-Glucose. Annalen, 1910, 377, 220-223. 

R. Bbhrbnd und P. Roth. Ueber die BirotaHon der Glucose. Annalen, 1904, 331, 359- 
382. 

E. Bourqublot. Rotatory powers of the a- and fi-alkyl-d-glucosides and alkyl-d-galacto- 
sides. Compt. rend., 1916, z(^ 374-377* 

H. T. Brown and G. H. Morris. The action, in the cold, of diastctse on starch-paste. 
J. Chem. Soc., 1895, 67, 309-313. 

H. T. Brown and S. Pickbrino. Thermal phenomena aitending the change in rotcUory 
power of freshly prepared solutions of certain carbohydrcUes, with some remarks on 
the cause of muliirotation, J. Chem. Soc., 1897, 71, 756-783. 

Dubrunfaut. Note sur quelques phenomenes rotatoires et sur quelques proprietes des 
sucres. Compt. rend., 1846, 23, 38-44. Ann. Chim. phys., 1846, 189 99-107; 18(7, 
21, 178-180. 

E. FiscHBR. Einige Sauren der Zuckergruppe. Ber., 1890, 23, 2625-2628. 

R. GiLMOUR. Mutarotation of glucose and its nitrogen derivatives. Proc. Chem. Soc., 
1909, 25, 225-226. 

H. Grossmann und F. L. Block. Studien Uber Rotaiionsdispersion und Mutarotaiion 
der Zuckerarten in Wasser, Pyridin und Ameisensdure. Zeitsch. der. deut. Zuckerind, 
1912, 19-74. 

G. Hbitbl. BirotaHon der Galactose. Annalen, 1905, 338, 71-107. 

C. S. Hudson. Ueber die Multirotation des Milchzuckers. Zeit. physik. Chem., 1903, 

44» 487-494. 
C. S. Hudson. The hydration of milk-sugar in solution. J. Amer. Chem. Soc., 1904, 
26, 1065- 1082. 

C. S. Hudson. Catalysis by acids and bases of the mutarotation of glucose. J. Amer. 
Chem. Soc, 1907, 29, 1571-1576. 

C. S. Hudson. The significance of certain numerical relcUions in the sugar group. J. 
Amer. Chem. Soc., 1909, 31, 66-86. 

C. S. Hudson. A review of discoveries on the mutarotation of the sugars. J. Amer. 
Chem. Soc., 1910, 32, 889-894. 

C. S. Hudson. Some numerical relations among the rotatory powers of the compound 
sugars. J. Amer. Chem. Soc., 1916, 38, 1566-1575. 

C. S. Hudson. Relation between the chemical constitution and the optical rotatory power 
of the phenylhydrazides of certain acids of the sugar group. J. Amer. Chem. Soc, 
1917* 39» 462-470. 

C. S. Hudson. Rotatory powers of the amides ofcLctive a-hydroxy adds. J. Amer. Chem. 
Soc, 1918, 40, 813-817. 



BIBLIOGRAPHY 203 

C. S. Hudson and J. K. Dalr. A comparison of the optical rotatory powers of the a- and ^- 
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C. S. Hudson and J. K. Dale. Forms of d-glucose and their mutarotation. J. Amer. 
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C. S. Hudson and J. M. Johnson. Rotatory powers of some new derivatives of gentioHose, 
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C. S. Hudson and R. Sayre. Optical rotatory powers of some acetylated derivatives of 
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C. S. Hudson and E. Yanovsky. Indirect measurements of the rotatory powers of some a 
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J. C. Irvine, A. W. Fyfe and T. P. Hogg. Derivatives of a new form of glucose, J. 
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J. C. Irvine and A. M. Moodie. Addition of alkylhalides to alkylated sugars and 
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J. C. Irvine and £. S. Steele. Mechanism of mutarotation in aqueuos solution, J. Chem. 
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C. L. Jungius. The mutual transformation of the two stereoisomeric methyl-d-glucosides. 
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C. L. Jungius. The mutual transformation of the two stereoisomeric pentacetates of 
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C. L. Jungius. Ueber die Umlagerung zwischen einigen isomeren Glukose-derivaten und 
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J. Landini. Influenza delta formalina sul potere rotatorio del glucosio in rapporto alia 
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E. VON LippMANN. Bemerkung zur Frage uber die Ursache der Birotation, Ber., 1896, 
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T. M. Lowry, Equilibrium in solutions of glucose and galactose, J. Chem. Soc, 1904, 

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J. A. MiLRoY. Einfluss inaktiver Substanzen auf die optische Drehung der Glucose, 

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E. Parous und B. Tollens. Die Mehr-oder Weniger -Drehung (Multirotation oder sog, 
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W. H. Pbrkin, Sen, The magnetic rotcUion of some polyhydric alcohols, J. Chem. Soc, 

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E. Roux. Sur la polyrotation des sucres, Ann. Chim. phys., 1903, 30, 422-432. 
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C. O'Sullivan and F. W. Tompson. Invertase : a contribution to the history of an 

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B. Tollens. Das Verhalten der Dextrose zu ammoniakalischer SilberWsung, Ber., 1883, 

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B. Tollens. Die Ursache der Birotation des Traubenzuckers. Ber., 1893, 26, 1799- 
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204 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

H. Trby. Expmmentalbeiirag »ur Birotation dif Glykose, Zeit physikal. Chem., 

1895, 18, i93-ai8 ; 1897. 23, 4a4-463. 
F. Urbch. ' Zur strobometrischen Bestimmung der Invertirungsgesckwindigkeit von 

RohrMucker und das Uehergang dsr BirotaHan von Milchzucker zu seiner constanten 

Drehung, Ber., 1882, X5i 2 130-2133. 

P. Urbch. Ursdchlicher Zusammsnhang zwischen Ldslichkeits und optischer Drehungs 
erscheinung hei Milchzucker und Formulirung der Uehergangsgeschwindigkeit seiner 
Birotation in die normale. Ber., 1883, x6y 2270-2271. 

F. Urech. Ueber den BirotationsrOckgang der Dextrose, Ber., 1884, 17, 1547-1550. 

F. Urbch. Ueber die Reihenfolge einiger Biosen und Glycosen betreffend Reactions- und 
BirotationsruckgangS'Gescnwindigkeit mit Riicksicht auf die Constitutionsformeln 
und den Begriff der AffinitdtsgrHsse, Ber., 1885, x8» 3047-3060. 

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F. VON Arlt. Zur Kenntnis der Glucose. Monatsh., 1901, 22, 144-150. 

E. Frankland Armstrong and P. S. Arup. Stereoisomeric glucoses and the hydrolysis 
ofglucosidic acetates, J. Chem. Soc, 1904, 85, 1043-1049. 

LoBRY DB Bruyn AND A. VAN Ekbnstbin. Formal derivatives of sugars, Proc. K. 
Akaid. Wetensch., Amsterdam, 1902, 5, 175-177; Rec. trav. Chim., 1903, 22, 
159-165. 

J. K. Dalb. Preparation of bromoacetyl glucose and certain other bromoacetyl sugars, J. 
Amer. Chem. Soc., 1916, 38, 2187. 

A. VAN Ekbnstbin. Le second mithylglucoside, Rec. trav. Chim., 1894, Z3> 183-186. 

E. Erwio und W. Konios. Pentacetyldextrose, Ber., 1889, 22, 1464-1467. 

E. Erwio und W. Konios. Funffach acetylirte Galaktose und Dextrose. Ber., 1889, 22, 
2207-2213. 

E. Fischer. Ueber die Glucoside der Alkohole. Ber., 1893, 26, 2400-2412 ; 1895, 28, 
1145-1x67. 

E. Fischer. Ueber die Verbindungen der Zuckerarten mit den Mercaptanen. Ber., 1894, 

27, 673-679. 

E. Fischer. Notiz uber die Acetohalogen-glucosen und die p-Bromphenylosazone von 
Maltose und Melibiose. Ber., 191 1, 44, 1898-1904. 

E. Fischer. Glucal and hydroglucal. Ber., 1914, 47, 196-210. 

E. Fischer und E. F. Armstrong. Ueber die isomeren Aceiohalogen-Derivate der Zucker 
und die Synthese der Glucoside^ I., II., III. Ber., 1901, 34, 2885-2900; 1902, ^ 
833-843; 3153-3155. 

E. Fischer und L. Bbensch. Ueber einige synthetische Glucoside. Ber., 1894, 27, 2478- 
2486. 

E. Fischer und H. Noth. Partial acylation of polyhydric alcohols and sugars. Ber., 
i9i8,5X, 321-352. 

E. Fischer und K. Raske. Verbindung von Acetobromglucose und Pyridin. Ber., 1910, 

43» 1750-1753. 
E. Fischer und K. Zach. Neue Anhydride der Glucose und Glucoside. Ber., 1912, 45, 

456-465. 

E. Fischer and K. Zach. Reduction of cLcetobromoglucose. Sitzungsber. K. Akad. wiss., 
Berlin, 1913, 311-317. Ber., 1912, 45, 2068-2074. 

A. P. N. Franchimont. Les deux pentacitates de la glucose. Rec. trav. Chim., 1893, 12, 

310-314. 
V. Fritz. Ueber einige Derivate des Benzoylcarbinols und des Diphenacyls. Ber., 1895, 

28, 3028-3034. 

C. S. Hudson. Existence of a third crystalline pentacetate of galcu:tose, J. Amer. Chem. 

Soc, 1915, 37, 1591-1593. ^ 
C. S. Hudson. Acetyl derivatives of the sugars, J. Ind. Eng. Chem., 1916, 8, 379. 

C. S. Hudson and D. H. Brauns. Crystalline d-fructose pentacetcUe. J. Amer. Chem. 

Soc., 1915, 37, 1283-1285 ; a second crystalline d-fructose pentacetate. Ibid., 2736- 

2745. 
C. S. Hudson and J. K. Dale. Isomeric pentcLcetates ofmannose. J. Amer. Chem. Soc., 

1915, 37, 1280-1282. 

C. S. Hudson and J. K. Dale. Isomeric tetracetaies of l-arabinose. J. Amer. Chem. 
Soc., 19 18, 40, 992-997. 



BIBLIOGRAPHY 205 

C. S. Hudson and J. M. Johnson. Isomtric UtraceiaUs of xylose, J. Amer. Chem. See., 

1915, 37» 3748-2753. 
C. S. Hudson and J. M. Johnson. A fourth crystalline penictcetats of galactose. J. Amer. 

Chem. Soc., 1916, A 1223-1228. 

C. S. Hudson and H. O. Parker. Conversum of galactose pentacetate to an isomeric form, 
J. Amer. Chem. Soc, 1915, 37, 1589-1591. 

C. S. Hudson and E. Yanovsky. Isomeric a- and fi-hexctcetates of a-glucoheptose* J. 
Amer. Chem. Soc, 1916, 381 1576-1578. 

J. C. Irvinb and R. Gilmour. The constitution of glucose derivatives. Glucose 
anilide, oxime and hydrazone, J. Chem. Soc, 1908, 93, 1429-1442. 

J. C. Irvine and R. Qilmour. Constitution of glucose derivatives, H. Condensation 
derivatives of glucose with aromatic amino compounds, J. Chem. Soc, 1909, 95, 
1545-1555. 

J. C. Irvine and A. Hynd. o-Carhoxyanilides of the -sugars, J. Chem. Soc, 1911, 
99, 161-168. 

J. C. Irvine and D. McNicoll. The constitution and mutarotaHon of sugar anilides. 
Trans. Chem. Soc, 1910, 97, 1449-1456. 

W. KoNiGS UND £. Knorr. Ueher einige Derivate des Traubenzuckers, Sitzungsber. 
K. Akad., Miinchen, 1900, 30, 103-105. 

W. KoNiGS UND E. Knorr. Ueber einige Derivate des Traubenzuckers und der Galactose, 

Ber., 1901, 34, 957-981. 
R. Kremann. Ueber die Verseifungsgeschteindigkeit von Monose und Biose Acetaten, 

Monatsh., 1902, 23, 479-488. 

L. Maqubnne. La preparation du fi-methylglucoside. Bull. Soc. Chim., 1905, [iii], 33, 
469-471. 

J. Moll van Charante. Sur les d^v^ acityliques des deux methylglucosides et sur 
Vacitobromglucose. Rec trav. Chim., 1902, 2X, 42-44. 

R. S. Morrell and J. M. Crofts. Action of hydrogen peroxide on carbohydrates in the 
presence of ferrous sulphcUe, J. Chem. Soc, 1902, 8X9 666-675 » i903« 83^ 1284- 
1292. 

R. S. Morrell and J. M. Crofts. Modes of formation of osones, Proc. Camb. Phil. 
Soc, 1903, 12, 115-121. 

W. Schneider. Action of hydrogen sulphide on glucose, Ber., 1916, 49, 1638-1643. 

W. Schneider and J. Sepp. Bthylthioglucoside. Ber., 1916, 49, 2054-2057. 

N. ScHOORL. Urea derivatives of monohexoses, Rec. trav. Chim., 1903, 22, 31-37. 

Z. H. Skraup und R. Kremann. Ueber AcetochlorglucosCj -Galactose und Milchzucker, 
Monatsh., 1901, 22, 375-384, 1037-1048. 

C. Tanret. Les Hhers acHiques de quelques sucres. Bull. Soc. Chim., 1895, [iii], 13, 

261-273. 

E. VotoSek. Beitrag zur Nomenklatur der Zuckerarten. Ber., 1911, 44, 360-361. 

E. VoTO^EK and V. Veselv. Resolution of racemic sugars by means of optically active 
amyl mercaptans, Zeitsch. Zuckerind. Bohm., 1916, 40» 207-211. 

W. Will und F. Lenzb. Nitrirung von Kohlehydraten. Ber., 1898, 31, 68-90. 

REFERENCES TO ALKYLATED SUGARS. 

W. N. Haworth. a new method of preparing alkylated sugars, J. Chem. Soc, I9i5f 
107, 8-16. 

J. C. Irvine and A. Cameron. The alkylation of galactose. J. Chem. Soc, 1904, 85, 
1071-1081. 

J. C. Irvine and A. Cameron. Study of alkylated glucosides, J. Chem. Soc, 1905, 87» 
900-909. , 

J. C. Irvine and A. Hynd. Monomethyl lavulose and its derivatives: constitution of 
lavulose dicu^etone. J. Chem. Soc, 1909, 95, 1220-1228. 

J. C. Irvine and J. L. A. Macdonald. Formation and preparation of glucosemonoacetone, 
J. Chem. Soc, 1915, 107, 1701-1710. 

J. C. Irvine and A. M. Moodie. Alkylation of mannose, J. Chem. Soc, 1905, 87* 
1462-1468. 

J. C. Irvine and A. M. Moodie. Derivatives of tetramethylglucose, J. Chem, Soc, 
1908, 93, 95-107' 



2o6 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

J. C. Irvine and J. P. Scott. Partially methylated glucoses^ I., II., III. J. Chem. Soc., 

1913. I03» 564-575. 575-586 ; 1914, 105, 1386-1396. 
T. PuRDiB AND R. C. Bridobtt. Tfimetkyl a-methylglucoside and irimethylglucose, 

J. Chem. Soc, 1903, 83, X037-1041. 

T. PuRDiB and J. C. Irvinb. Alky lotion 0/ sugars, J. Chem. Soc., 1903, 83, 1021-1037. 

T. PuRDiB AND J. C. Irvinb. The stereoisomeric tetramethyl methyl glucosides and tetra- 
methyl glucose, J. Chem. Soc., 1904, 8s X049-1070. 

T. PuRDiB AND J. C. Irvinb. Synthesis from glucose of an octamethylated disacchande, 
Methylation of sucrose and maltose, J, Chem. Soc., 1905, 87, 1022-1030. 

T. Purdie and D. M. Paul. Alky lotion of d-fructose, J. Chem. Soc., 1907, 91, 289-299. 

T. Purdib and R. E. Rose. Alky lotion of l-orabinose, J. Chem. Soc., 1906, 89, 1204- 
1210. 

T. Purdib and C. R. Young. Alky lotion of monnose, J. Chem. Soc, 1906, 89, Z194- 
1204. 

REFERENCES TO CHAPTER II. 

I. Bang. Ueber die Darstellung der Mentholglucuronsdure. Biochem. Zdt, 191 1, 32, 445. 

D. Berthelot and H. Gaudbchon. Photolysis of ketoses by solar and ultraviolet light. 
Compt. rend., 19 12, 15^ 401-403 ; ioz6. 

D. Berthelot and H. Gaudbchon. Photo-chemical decomposition of glucose and galac- 

tose. Compt rend., 19 12, Z5S ^3 1-833. 

K. H. BoDDENER UND B. ToLLBNs. Arobonsdure, Ber., 1910, 43, 1645-1650. 

H. H. BuNZEL. Raie of oxidation of the sugars in on acid medium, J. Biol. Chem., 1908, 
4, vii. 

H. H. BuNZBL. Mechanism of the oxidation of glucose by bromine in neutral and acid 
solutions, J. Amer. Chem. Soc, 1909, 31, 464-479. 

L. E. Cavazza. Ricerche sperimentali : contributo alio studio dei tannini, Zeitsch. wiss. 
Mikroskopie, 1908, 25, 13-20 ; 1909, 26, 59-64. 

F. Ehrlich, Galocturonic acid from pectin. Chem. Zeit., 1917, 4Z» 197-200. 

A. VAN Ekbnstbin et J. J. Blanksma. Transformation du \-gulose et du l-idose en 
l-sorbose, Rec. trav. Chim., 1908, 27, 1-4. 

W. A. VAN Ekbnstbin and J. J. Blanksma. Bildung von Lavulinsaure aus Hexosen, 
Chem. Weekblad, 1910, 7, 387-390. 

W. A. VAN Ekbnstbin and J. J. Blanksma. »-Oxymethylfurfurol als Ursache einige 
Farbreaktionen der Hexosen, Ber., 1910, 43, 2355-2361. 

H. J. H. Fbnton. Oxidation in presence of iron, Proc Camb. Phil. Soc, 1902, zz, 

358-374. 
A. Fbrnbach and M. Schobn. Products of the decomposition of glucose in alkaline 
medium, Compt. rend., 1914, Z^ 976- 978. 

E. FiscHBR. Reduktion von Sduren der Zuckergruppe, Ber., 1889, 22, 2204-2205 ; 1890, 

23, 930-938 ; 2625-2628. 

E. Fischer. Ueber Kohlenstoffreichere Zuckerarten aus Glucose, Annalen, 1892, 270^ 
64-107. 

E. Fischer. Ueber Kohlenstoffreichere Zucker aus Galactose, Annalen, 1895, 268» 139- 

157. 
E. Fischbr UND M. Bergmann. Ueber das Tannin und die Synthese ahnlicher Stoffe, 
Ber., 19x8, 5Z, 1760- 1804. 

E. Fischbr und M. Bergmann. Structure of fi-glucosidogallic acid, Ber., 1918, 5Z, 
1804- 1808. 

E. Fischer und K. Freudenberg. Ueber das Tannin und die Synthese Uhnlicher Stoffe, 

Ber., 1912, 45, 915-935. 
E. Fischer und K. Hbss. Verbindungen einiger Zucker-Detivaie mit Methyl-magne- 

siumjodid, Ber., 1912, 45, 912-915. 

E. Fischer und W. Passmorb. Ueber Kohlenstoffreichere Zuckerarten aus d-Mannose, 
Ber., 1890, 23, 2226-2239. 

E. Fischer und O. Piloty. Ueber Kohlenstoffreichere Zuckerarten aus Rhamnose, Ber., 
1890, 23, 3102-3110. 

£. Fischbr and K. Zach. New anhydrides of glucose and glucosides, Ber., 1912, 45, 456- 
465, 2068-2074. 



BIBLIOGRAPHY 207 

A. V. Grotb, E. Kehrbr und B. Tollbns. Untersuchungen uehir die Ldvulinsaure oder 
$-acetopropionsaure, I. Dcarstellung und Eigenschafien der Lavulinsdure. Annalen, 
1881, ao6} 207. II. Bildung der Ldvulinsaure aus verschiedenen Kohlenkydraten. 
Annalen, 1881, 206, 226. 

M. GuEBERT. Transformation des oxyacides-a en aldehydes par ebulition de la solution 
aqueuse de leurs sels mercurique^ application d la preparation de Varabinose gauche 
au moyen du gluconate mercurique, Compt. rend, 1908, 146^ 132-134. 

M. M. Harrison. Action of acids on fructose and glucose, J. Amer. Chem. Soc, 1914, 

36, 586-603. 
M. Hauriot. Chloraloses (Resumi). Ann. Chim. Phys., 1909, i8» 466-502. 

O. F. Hbdenburg. Esters cmd monomolecular ^- and y-lactones of d-mannonic and d- 

gluconic adds, J. Amer Chem. Soc, I9i5» 37> 345-372. 
H. HiLDBBRANDP. Zur froge der glycosidischen Struktur gepaarter Glykuronsduren. 

Beitr. Chem. path., 1905, 7, 438-454. 

C. S. Hudson. A relation between the chemical constitution and the optical rotatory 
power of the sugar lactones, J. Amer. Chem. Soc., 1910, 32, 338-346. 

K. Inouye. Die Einwirkung von Zinkoxyd-Ammoniak auf d-Galaktose und UAraJdnose. 
Ber., 1907, 40, 1890-1892. 

H. Kiliani. Das Cyanhydrin der Ldvulose, Ber., 1885, x8y 3066-3072. 

H. Kiliani. Dos Cyanhydrin der Ldvulose, Ber., 1886, 19, 221-227. 

H. Kiliani. Derstellung von Glycolsdure aus .Zucker. Annalen, 1880, aoS 191- 193* 

H. Kiliani. Die Einwirkung von Blausdure auf Dextrose. Ber., 1886, 19, 767-772. 

H. Kiliani. Die Constitution der Dextrosecarbonsdute, Ber., 1886, 19, 1128-Z130. 

H. Kiliani. Die C^-Zucker aus Meta- und Para-Saccharin, Ber., 1908, 41, 120-124. 

H. Kiliani. Saccharinsduren, Ber., 1908, 41, 469-470. 

H. Kiliani. Ueber die Einwirkung von Calciumhydroxyd auf Milchxucker. Ber., 1909, 

42, 3903-3904. 
W. T. Lawrence. Ueber Verbindungen der Zucker mit dem Athylen^ Trimethylen und 

Benzylmercaptan, Ber., 1896, 29, 547-552. 

C. A. LoBRY DE Bruyn. Action des Alcalis diluessurles hydrates decarbonne. Rec. trav. 
Chim., 1895, 14, 156-165. 

C. A. LoBRY DE Bruyn et A. van Ekenstein. Action des alcalis sur les suctes, II. 
Transformation riciproque des uns dans les auttes des sucres glucose ^ fructose et 
mannose. Rec. trav. Chim. 1895, 14, 204-216. 

A. Magnus-Levy. Ueber Paarung der Glukuronsdure mit optischen Aniipoden, Biochem. 

Zeit., 1907, 2, 319-331. 
P. Mayer. Vber cLsymmetrische Glucuronsdurepcuarung, Biochem. Zeit., 1908, 9, 

439-441. 

R. S. MoRRELL AND A. £. Bellars. Some compounds of guanidine with sugars, J. 
Chem. Soc, 1907, 91, iozo-1033. 

J. U. Nef. Dissociation processes in the sugar groups I., II. and III. Annalen, 1907, 357, 

214-312; 1910, 376, 1-119 ; 19141 403» 204-283. 
C. NsuBBRG. Zur Kenntniss der Glukuronsdure, Ber., 1900, 33, 3317-3323. 

C. Neuberg und £. Kretschmer. Ueber p-Kresolglucuronsdure, Biochem. Zeit., 191 1, 

36, 15-21. 
C. Neuberg und S. Lachmann. Ueber einneues V erf ahren zur Gewinnung von Glucuron- 

sdure und Menthol-Glucuronsdure, Biochem. Zeit., 1910, 24, 416-422. 

Th. R. Offer. Eine neue Gruppe von stichstoffhaltigen Kohlenhydrate, Beitr. Chem. 
Physiol. Path., 1906, 8, 399-405. 

L. H. Philippe. Les acides glucodeconiques, Compt. rend., 1910, 151, 986-988, 1366- 

1367. 
L. H. Philippe. Recherches sur les matieres sucries superieures derivees du glucose, Ann. 

Chim. Phys., 1912, [viii], 26, 289-418. [A r6sum6.] 

O. Ruff. Die Verwandlung der d-Gluconsdure in d-Arabinose, Ber., 1898, 31, 1573-1577. 

O. Ruff, d- und t-Arabindse, Ber., 1899, 32, 550-560. 

O. Ruff. d-Erythrose, Ber., 1899, 32, 3672-3681. 

E. Salkowski und C. Neuberg. Zur Kenntniss der Phenolglukuronsdure, Biochem. 
Zeit, 1907, 2, 307-311. 

M. h. Saurb^, 4n isomeride of glucuronic acid, Chem. Zeit, 1917, 41, 87. 



2o8 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

K. Smolbnski. Ueber eins gepaarte glukuronsdure aus der Zuckerrube. Zeitsch. physioL 
Chem., ZQix, 7Z> 266-269. 

B. ToLLBNS UNO K. H. BoDOBNBR. Untersuchungeti uberdie Arabonsdure. Z. Ver. Deut. 
Zuckerind., 1910, 6o» 727. 

k» WiNDAUS USD F. Koop. Ueberfuhfung voH Troubenzucker in^MethylimidazoL Ber., 
1905* 381 1166-1170. 

A. WiNDAUS. Zersetzung von Traubenzucker durch Zinkhydroxyd-Ammoniak bei Gegen- 
wart von Acetaldehyd, Ber., 1906, 59, 3886-3891. 

A. WiNDAUs. Binwirkung von Zinkhydroxyd-Ammoniak auf einige Zuckerarien. Ber., 

1907, 40^ 799-802. 

A. WoHL. Abbau des Traubenzuckers, Ber., 1893, 26» 730-744. 
A. WoHL. Abbau dsr Galactose, Ber., 1897, 30, 3101-3108. 
A. WoHL. Abbau der UArabinose, Ber., 1899, 32, 3666-3672. 

REFERENCES TO PHENYLHYDRAZONES, OSAZONES, ETC, 

R. Bbhrbnd und F. Lohr. Ph&nylhydrazone der Glucose. Annalen, 1907, 553, 106-122 ; 

1908, 362, 78-114 ; 1910, 377, 189.220. 

R. Bbhrbnd und W. Rbinsbbro. Ober die Phenylhydrazone der Glucose, Annalen* 
1910, 377, 189-220. 

J. V. Braun. Behaviour of sugars towards diphenylmethane dimethylhydrazine. Ber., 

1917. So» 42-43. 

A. VAN Ekbnstbin bt J. J. Blanksma. Hydrazones derivSes des nitrophenylhydrazines, 

Rcc. trav. Chim., 1903, 22, 434-439 ; i905» 24, 33-39- 
A. VAN Ekbnstbin und Lobby de Bruyn. Isomerie bei den fi-Naphthylhydrazonen der 

Zucker, Ber., 1902, 3082-3085. 

E. Fischbr. Verbindungen des Phenylhydrazins mit den Zuckerarten, I.-V. Ber., 1884, 
17, 579-584; 1887, 20, 821-834 ; 1888, 21, 988-991, 2631-2634; 1889, 22, 87-97. 

E. Fischbr. Schmelzpunkt des Phenylhydrazins undeiniger osazone, Ber., 1908, 41, 73-77. 

E. Fischbr und E. F. Armstrong. Darstellung der Osone aus den Osazonen der 
Zucker, Ber., 1902, 35, 3141-3144. 

A. HiLOBR UND S. ROTHBNFUSSER. Ueber die Bedeutung der fi-Naphthylhydrazone der 
Zuckerarten fur deren Erkennung und Trennung, Ber., 1902, 35, 1841-1845, 4444- 

4447. 
H. Jacobi. Birotation und Hydrazonbildung bei einigen Zuckerarten. Annalen, 1892, 
272, 170-182. 

E. C. Kendall and H. C. Sherman. Detection of reducing sugars by condensation with 
p-bromobenzylhydrazine. J. Amer. Chem. Soc., 1908, 30^ 1451-1455. 

C. A. Lobry OB Bruyn bt A. van Ekbnstbin. Quelques nouvelles hydrazones des sucres : 
les naphthylhydrazones et les phSnylhydrazones alcylies (methyl-, ethyl-, amyl-, 
allyl-f et benzyl), Rec. trav. Chim., 1896, 15, 97-99, 225-229. 

L. Maquennb. L^emploi de la phenylhydrazine d la determination des sucres. Compt. 
rend., 1891, 112, 799-802. 

A. MuTHBR und B. Tollens. Einige Hydrazone und ihre Schmelzpunkte, Fucose, 
Rhodeose, Ber., 1904, 37, 298-305, 311-315. 

C. Neubbbg. Ueber die Reinigung der Osazone und zur Bestimmung ihrer optischen 
Drehungsrichtung, Ber., 1899, 32, 3384-3388. 

C. Nbubero. Ueber die Isolirung der Ketosen, Ber., 1902, 35, 959-966, 2626-2633. 

C. Nbubbrg. Die Methylphenylhydrazinreaction der Fructose, Ber., 1904, 37, 46 16-4618. 

C. Nbubbrg und M. Fedbrbr. Ueber d-Amylphenylhydrazin Ber., 1905, 38, 866-868. 

C. Nbubbrg und H. Strauss. Ueber Vorkommen und Nachweis von Fruchtzucker in den 
menschlichen Korpersaften, Z, physiol. Chem., 1902, 36, 227-238. 

R. Ofner. Einwirkung von Benzylphenylhydrazin auf Zucker, Ber., 1904, 37, 2623- 
2625. 

R« Ofner. Einwirkung von Methylphenylhydrazin auf Zucker. Ber., 1904, 37, 3362- 

3363. 
R. Ofner. Abscheidung von Aldosen durch secunddre Hydrazine, Ber.,' 1904, 37, 4399- 

4402. 

A. Rbclairb. Beitrage zur Kenntnis der Hydrazone der Zuckerarten ; 0, m-, undp-Nitro- 
phenyl hydrtszone, Ber., 1908, 41, 3665-3671. 



BIBLIOGRAPHY 209 

O. Ruff und G. Ollendorff. Verfahren »ur Reindatstellung und Trennung von Zuckem. 

Ber., 1899, 32, 3234-3237. 
L. J. Simon bt H. Benard. Sur Us phenyl hydrazonss du d-glucose ei Uur multirotation, 

Compt. rend., 190 1, 132, 564-566. 

R. St ABEL. Derivaie des Diphenylhydrazins und Methylphenylhydrazins. Annalen, 
1890, 258, 242-251. 

B. ToLLBNS UND A. D. Maurbnbrbchbr. Ueber die Diphenylhydrazone der l-Arabinose 
und der Xylose, Ber., 1905, 53» 500-501. 

F. Tutin. The melting-point of d-phenylglucosazone, Proc, Chem. Soc, 1907, 23, 250- 
252. 

E. VoTo^EK UND R. VoNDRA^EK.^ Ttennung und Isolirung reducirender Zuckerarten 
mittels aromatischer Hydrazine, Bar., 1903, 36, 4372 ; 1904, 37, 3854-3858. 



REFERENCES TO AMINOGLUCOSES. 

R. Breuer. Dasfreie Chitosamin, Ber., 1898, 31, 2193-2200. 

£. Fischer und E. Andrbae. Ueber Chitonsdure und Chitarsdure, Ber., 1903, 36, 2587- 
2592. 

E. Fischer und H. Leuchs. Synthese des Serins, der l-Glucosaminsdure und anderer 
Oxyaminosduren, Ber., 1902, 35, 3787-3805. 

£. Fischer und H. Leuchs. Synthese des d-Glucosamins, Ber., 1903, 36* 24-29. 

E. Fischer und F. Tiemann. Ueber das Glucosamin, Ber., 1894, 27, 138-147. 

E. Fischer und K. Zach. Neue Synthese von Basen der Zuckergruppe. Ber., 1911, 44, 

132-135. 
S. FrXnkel und a. Kelly. Constitution des Chitins, Monatsh., 1902, 23, 123-132. 

C. S. Hudson and J. K. Dale. The isomeric pentacetates of glucosamine and of chondro- 
samine. J. Amer. Chem. Soc, 1916, 38, 1431-1436. 

J. C. Irvine. A polarimetric method of identifying chitin, J. Chem. Soc., 1909, 95, 
564-570. 

J. C. Irvine and A. Hynd. Conversion of d-glucosamine into d-glucose. Trans. Chem. 
Soc., 1912, xox, 1128-1146. 

J. C. Irvine and A. Hynd. The conversion of d-glucosamine into d-mannose, J. Chem. 
Soc., 1914, X05, 698-710. 

J. C. Irvine, D. McNicoll and A. Hynd. New derivatives of d-glucosamine. Trans. 
Chem. Soc, 191 1, 99, 250-261. 

G. Ledderhosb. Ueber Chitin und seine Spaltungsprodukte, Zeit. physiol. Chem., 1878, 
2, 213-227. 

P. A. Levenb. Chondrosamine, J. Biol. Chem., 1916, 26, 143-154. 

P. A. Levenb. Synthesis of hexosamines, J. Biol. Chem., 1916, 26» 155-162. 

P. A. Levenb. Chondrosamine and its synthesis, J. Biol. Chem., 1917, 31, 609-621. 

P. A. Levenb and F. B. la Forge. d-Lyxohexosamic acid and om'-anhydromucic acid, 

J. Biol. Chem., 1915, 22, 331-335. 
P. A. Levenb and F. B. la Forge. Xylohexosamic acid : its derivatives and their bearing 

on the configuration of isosaccharic and epi-isoscucharic acids. J. Biol. Chem., 1915, 

3I» 351-359. 
P. A. Levenb and F. B. la Forge. Chondroitin sulphuric acid, J. Biol. Chem., 1915, 20, 

433-444. 
C. A. LoBRY DE Bruyn. Uu derive ammoniacal du fructose, Rec. trav. Chim., 1899, 18, 

72-76; La chitosamine libre, I.e., 77-85. 

C. A. Lobry de Bruyn et F. H. van Lebnt. Dirives ammoniacaux de quelques sucres. 
Rec. trav. Chim., 1895, 14) 134-148. 

C. A. Lobby de Bruyn et A. P. N. Franchimont. Derives ammoniacaux cristallisis 
dehydrates de carbonne, Rec. trav. Chim., 1894, 12, 286-289 ; 1896, 15, 81-83. 

C. A. Lobby de Bruyn und A. P. N. Franchimont. Die Ammoniakderivate der Kohlen- 
hydrate. Ber., 1895, 26, 3082-3084 ; Dcufreie Chitosamin, Ber., 1898, 31, 2476- 
2477. 

L. Maquenne et E. Roux. Sur une nouvelle base derivie du glucose, Compt. rend., 1901, 

132, 980-983 ; 1903* X37» 658. 

C. Neubbrg. Ueber d-Glucosamin und Chitose, Ber., 1902, 351 4009-4023. 

14 



210 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

C. Nbubbro und H. Wolff. Uiber a- und ^i-Amino-A-Glucoheptonsdure, Ber., 1903, 

36» 618-620. 
Th. R. Offbr. Vhar Chitin. Biochem. Zeitsch., 1907, 7, 117-127. 

H. Prinoshbim. M$thylation of glucosamic acid, A way from sugar to hetaine. Ber., 
1915. 48, 1158-1161. 

W. Ross. Origin of the glucosamine obtained in the hydrolysis of " Boletus edulis '*. Bio- 
chem. J., 1915. 9, 313-319. 

E. Roux. Sur des nouvelles bases derivees des pentoses et du mannose. Compt. rend., 1903, 

1316^ 1079-1081 ; 1904, I38> 503-505' Ann. chim. phys., 1904, i, 72-144, 160-185. 
H. Stbudbl. Eine neue Methode gum Nachweis von Glukosamin und ihre Anwendung 
auf die Spaltungsprodukte der Mucine, Zeit. physiol. Chem., 1902, 54, 353-384. 

K. Stoltb. Ueber das Verhalten des Glucosamins und seines ndchsten Umwandlungs- 
produktes im Thierkorper. Beitr. Chem. Physiol. Path., 1907, zz, 19-34. 

K. Stoltb. Ueber den Abbau des Fructosagins (Ditetra-oxybutyipyrasins) im Thier- 
korper, Biochem. Zeitsch., 1908, Z2, 499-509. 

£. E. SuNDwiK. Zur Constitution des Chitins, Zeit. physioi. Chem., 1881, 5, 384-394. 

C. Tanrbt. Les Glucosines. Bull. Soc. Chim., 1897, [iii], Z7, 801-802. Le chlorhydrate 
de Glucosamin, Bull. Soc. Chim., 1897, Lc, 802-805. 

F. TiBMANN. EinigesUber den Abbau von salzsauren Glucosamin, Ber., 1884, Z7, 241- 

251. 

F. TiBMANN. Glucosamin, Ber., z886, 19, 49-53. 

F. TiBMANN. Isoguckersdure, Ber., 1886, 19, 1257-1281. 

F. TiBMANN UND E. FiscHBR. Das Glucosamin, Ber., 1894, 27, 138-147. 

£. WiNTBRSTBiN. Zur Keuntniss der in den Membran der Pilze enthaltenen Bestandtheile I. 
Zeit. physioi. Chem., 1894, 19, 521-562. 

REFERENCES TO GLUCOSE PHOSPHATES. 

P. CARRi. Les Others polyphosphoriques de la mannite, de la quercite^ du glucose, et de 
Vinosite, Bull. Soc. Chim., 191 1, [iv], 9, 195-199. 

A. CoNTARDL Eteri fosforici di alcuni idrati di Carbonia. Rend. Ace. Lin. Sci., 19 10, 
825-827. f 

A. Hardbn and W. J. Young. Composition of the hexose phosphoric acid formed by yeast 
Juice, L, H. Biochem. Zeitsch., 19 11, 52, 173-188. 

K. Langheld. Ueber Dioxyaceton- und Fructose-phosphorsaure, Ber., 1912, 45, 1125- 
1127. 

A. VON Lebbdbpf. Ueber Hexosephosphorsdure Ester, L, IL Biochem. Zeitsch., 1910, 
28,213-229; 1911,36,248-260. 

C. Neuberq und E. Kretschmbr. Weiteres uber kunstliche Darstellung von Kohlen- 
hydratphosphorsaureestem und Glycerinphosphorsaure, Biochem. Zeitsch., 191 1, 

36, 5-14. 

C. Nbubbro and H. Pollak. Ueber Phosphorsaure- und Schwefelsdure Ester von 

Kohlenhydraten, Biochem. Zeitsch., 1910, 26, 514-528. 

W. J. Young. Hexose phosphate formed by yeast juice from hexose and a phosphate, 
Proc. Roy. Soc., 1909, Z3, 81, 528-545. 

REFERENCES TO CHAPTER III.— HEXOSES. 

G. Bbrtrand. Sur la preparation biochimique de Sorbose, Compt. rend., 1896, 122, 

900. Bull. Soc. Chim., 1896, Z5, 627. 

G. Bbrtrand. Action de la bactirie du Sorbose sur les alcools plurivalents, Compt. 
rend., 1898, Z26, 762. 

D. H. Brauns. Lcevulose pentacetate, Proc. K. Akad. Wetensch., Amsterdam, 1908, 10, 

563. 
A. VAN Ekbnstbin and J.J. Blanksma. Lavorotation of mannose, Chem. Weekblad., 

1907. 4. 5"*5i4. 
A. VAN Ekbnstbin and J. J. Blanksma. Sugars [lyxose, gulose, talose, etc,"], Chem. 

Weekblad, 1907, 4, 743-748 ; 19081 Si 777-78i- 
A. VAN Ekbnstbin et J. J. Blanksma. Transformation du \-gulose et du l-idose en 

{-sorbose, Rec. trav. Chim., 1908, 27* z-4* 
H. J. H. Fenton and M. Gostling. Btomomethylfurfuraldehyde, The action of hydrogen 

bromide on carbohydrates. J. Chem. Soc., 1899, 75, 423 ; 1901, 79, 361. 



BIBLIOGRAPHY an 

£. FiscHBR UND L. Bbbnsch. Ueber die beiden optisch isomeren Methylmannoside, Ber., 
i8g6, 29, 2927-2931. 

£. Fischer und J. Hirschbergbr. Ueber Mannose, I.-IV. Ber., 1888, 2Z, 1805-1809; 

1889, 22, 365-376 ; 1155-1156; 3218-3224. 
F. B. La Forge. A-Mannoketoheptose, a new sugar from the Avocado. J. Biol. Chem., 

1917. 28, 511-522. 

F. B. La Forqb and C. S. Hudson. Sedoheptose^ a new sugar from **Sedum spectabile^\ 
J. Biol. Chem., 1917, 30, 61-77. 

K. Freudenberg. Configuration of the glyceric and lactic adds. Ber., 1914, 47, 2027- 

2037. 
A. Hilger. Zur Kenntniss der Pflanzenschleime, Ber., 1903, 36, 3197-3203. 
C. S. Hudson. American sources of supply for the various sugars, J. Ind. Eng. Chem., 

1918, 10, 176. 

C S. Hudson and D. H. Brauns. Crystalline fi-methyl fructoside and its tetracetate. 
J. Amer. Chem. Soc, 1916, 38, 1216-1223. 

C. S. Hudson and H. L. Sawyer. Preparation of pure crystalline mannose and a study 
of its mutarotation, J. Amer. Chem. Soc., 1917, 39, 470-478. 

J. C. Irvine and C. S. Garrett. Acetone derivatives of ^-fructose, J. Chem. Soc, 
1910, 97, 1277-1284. 

J. C. Irvine and G. Robertson. Existence of a new variety of fructose, A reactive 
form of methyl fructoside, J. Chem. Soc, 1916, 109, 1305-1314. 

A. JoLLES. Zur Kenntniss des Zerfalls der Zuckerarten, Biochem. Zeitsch., 1910, 29, 
152-201. 

A. JoLLES. Einwirkung von Ammoniak und von Natriumcarbonat auf verschiedene 

Zuckerarten in verdunnter wasseriger Losung. Biochem. Zeitsch., 191 1, 32, 97-100. 

H. Kiliani. Inulin. Annalen, 1880, 205, 145-190. 

H. Kiliani. Saccharinsdure. Ber., 191 1, 44, 109-113. 

H. Kiliani und C. Schbibler. Die Constitution der Sorbinose. Ber., z888, 21, 3276- 

3281. 

P. A. Levenb and W. a. Jacobs. Ueber die Hexosen aus der d-Ribose. Ber., 1910, 43, 
3141-3147. 

£. O. VON LipPMANN. Ein Vorkommen von d-Galaktose. Ber., 1910, 43, 3611-3612. 

W. Lob. Zur Geschichte der chemischen Garungshypothesen. Biochem. Zeitsch., 1910, 

29. 311-315. 
W. Lob und G. Pulvbrmacher. Elektrolyse des Glycerins und des Glykols. Biochem. 

Zeits., 1909, 17, 343-355. 

W. Lob und G. Pulvbrmacher. Zur Kenntnis der Zuckerspaltungen. Ueber die 
Zuckersynthese aus Formaldehyd, Biochem. Zeitsch., 1910, 26, 231-237. 

W. Lob und G. Pulvbrmacher. Zuckerspaltungen^ VII, Die Umkehrung der Zucker- 
synthese, Biochem. Zeitsch., 1909, 23, 10-26. 

P. Maybr. Ueber Zerstorung von Traubenzucker durch Licht. Biochem. Zeitsch., 1911, 
32, 1-9. 

J. U. Nbf. Dissoziationsvorgdnge in der Zuchergruppe, I., II., III., Verhalten der Zuck- 
erarten gegen Aetzalkalien. Amialen, 1907,357, 214-312; 1910,376, z-119; 1914* 
403, 204-283. 

C. Neuberg und J. Wohlgemuth. Ueber die Darstellung der dUundl-galactose, Zeit. 
physiol. Chem., 1902, 36, 219-226. 

G. Pbircb. Heptoses. J. Biol. Chem., 1913, 17, 35-36. 

E. Rbiss. Die in den Samen als Reservestoff abgelagerte Cellulose und eine daraus 
erhaltene neue Zuckerart, die " Seminose . Ber., 1889, 22, 609-613. 

E. S. Steele. Structure of crystalline fi-methyl fructoside. J. Chem. Soc, 1918, 113, 

257-263. 

B. ToLLBNS UND R. Gans. Quitten- und Salepschleim. Annalen, 1888, 249, 245-257. 

F. W. Upson. Action of normal barium hydroxide on glucose and galcictose, Amer. 

Chem. J., 191 1, 45, 458-479. 

REFERENCES TO PENTOSES. 

W. Alberda van Ekbnstbin and J. J. Blanksma. Transformation of l-arabinose into 
Uribose. Chem. Weekbiad, 1913, 10, 213. d-Ribose. Ibid., 664; 1914, li, 182. 
\-lyxose. Ibid., 1914, IX, 189. 

14 • 



/ 



212 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

G. Bbrtrand. Recherches sur quelques derives du xylose. Bull. Soc. Chim., 1891, 5, 

546-554. 
T. BoKORNY. Assimilation von Pentosen und PentiUn dutch Pflanzen, Chem. Zeit., 

I9IO, 34, 220-22I. 

G. Chavannb. Quelques derives de VaraHnose [acetohromo et tuetochloro-arabinose']. 
Compt. rend., 1902, 154, 661-663. 

J. K. Dale. Bromoacetylxylose and fi-triacetyl methyl xyloside, J. Amer. Chem. Soc., 1915, 

37. 2745- 
R. Feulgbn. Carbohydrate group of the true nucleic acids. Zeitsch. physiol. Chem., 
1917, 100, 241-258. 

£. Fischer und H. Herborn. (fber Isorhamnose, Ber., 1896, 29, 1961. 

£. Fischer und C. Libbbrmann. Ueher Chinovose und Chinovit. Ber., 1893, 26, 2415, 
2420. 

£. Fischer und J. Tapbl. Oxydation der mehrwerthigen Alkahole, Ber., 1887, 20, 
1088- 1094. 

E. Fischer und J. Tafbl. Oxydation des Glycerines^ I.-II. Ber., 1888, 21, 2634-2637 ; 

1889, 22, 1 06- no. 
E. Fischer und J. Tafbl. Ueher Isodulcit. Ber., 1888, 21, 1657-1660 ; 2173-2176. 

E. Fischer and K. Zach. Conversion of d-Glucose into a methylpentose, Ber., 1912,45, 
3761-3773. 

A. Gunther und B, Tollens. Ueberdie Fukose^einender Rhamnoseisomeren Zucker aus 
dem Seetang, Ber., 1890, 23, 1751-1752, 2585-2586. 

C. S. Hudson. Stereochemical configuration of fucose and rhodeose. J. Amer. Chem. 
Soc., 1911, 33, 405s4io. 

C. S. Hudson and L. H. Chernoff. Methyltetronic acid and its amide, J. Amer. 
Chem. Soc., 1918, 40, 1005. 

C. S. Hudson and J. K. Dale. Triacetyl-d-xylose and a-triacetylmethyl-d-xyloside, J. 
Amer. Chem. Soc., 1918, 40, 997-1001. 

H. KiLiANi. Die Zusammensetzung und Constitution der Arabinosecarbonsaure bezw. 
d^ Arabinose, Ber., 1887, 20, 282, 339-346. 

H. Kylin. Biochemistry of sea-weeds. Zeitsch. physiol. Chem., 1915, 94, 337-425. 
£. Legbr. Sur Valoinose ou sucre d'alotne. Compt. rend., 1910, 150, 983-986. 
E. Leobr. Sur Valoinose cristallise; son identite avec Varabinose-d. Compt. rend., 1910, 
ISO, 1695-1697. 

A. Mux HER UND B. ToLLENS. Die Fucose und die Fuconsdure und die Vergleichung 

derselben mit der Rhodeose und Rhodeonsaure. Ber., 1904, 37, 306-311. 

C. Neuberg. Die Harnpentose, ein optisch inactive^ natUrlich vorkommendes Kohlenhydrat. 
Ber., 1900, 33, 2243-2254. 

C. Neuberg und J. Wohlgemuth. Ueber d-Arabinose, d-Arabonsdure und die quantitative 
Bestimmung von Arabinose. Zeit. physiol. Chem., 1902, 35, 31-40. 

E. PiNOFF. Studien ueber die Tollensche Phloroglucin-Salzsaure-Reaktion auf Pentosen. 
Ber., 1905, #, 766. 

C. Ravenna e O. Cbrbser. SulV origine e sulla funzione fisiologica dei pentosani nelle 
piante. Atti. R. Accad. Lincei, 1909, [v], z8, ii, 177 183. 

B. Rayman. Isodulcite. Bull. Soc. Chim., 1887, [ii], 47, 668-677. 

O. Ruff, d- und d\-Arabinose. Ber., 1899, 32, 550-560. 

E. Salkowski und C. Neuberg. Die Verwandlung von d-Glucuronsdure in l-Xylose, 
Zeit. physiol. Chem., 1902, 36, 261-267. 

C. ScHULZB UND B. ToLLENs. Ueber die Xylose und ihre Drehungserscheinungen. 

Annalen, 1892, 27X1 40-46. 

C. O' Sullivan. Gum tragacanth (l-Xylose). J. Chem. Soc, 1901, 79, 1164-1185. 

B. Tollens. Ueber den Nachweis der Pentosen mittelst der Phloroglucin-Salzsaure- 
Methode. Ber., 1896, 29, 1202-1209. 

E. VbNGERiCHTBN. Vber Apiin und Apiose. Annalen, 1901, 318, 121-136. 

E. VoNGBRiCHTBN. Ueber Apiose^ eine fi-Oxymethylerythrose. Annalen, 1902, 321, 71-83. 

E. VoNGBRicHTBN UND Fr. Mullbr. Apiose. Ber., 1906, 39, 235-240. 

H. J. Wheeler und B. Tollens. Ueber die Xylose oder den Holzzucker^ eine zweite 

Pentose, Annalen, 1889, 254, 304- 
E. VoTO^BK. Rhodeose. Chem. Centralblatt, 1900, i, 803, 816 ; 1901, i, 1042 ; 1902, ii, 

1361. 



BIBLIOGRAPHY 213 

E. VotoCek. Ueher die Glykosidsauren des Convolvulins und die Zusammensetsung der 
rohen Isorhodeose, Ber., 1910, 43, 476-482. 

£. VoTocEK. IsO'Rhodeose, Ber., igii, 44t 819-824. 

E. VotoCek. Configuration der Rhodeose. Ber., 1910, 43, 469-475. 

E. VoTOCEK. Derivatives ofRhodeose. Ber., 191 7, 50, 35-41. 

E. VoTocEK AND C. Krauz. Epi-Rhodcose, Ber., 1911,44, 362-365. 

E. VoTOCEK UND H. N^MECEK. Kinetiscke Studien in der Zuckerreihe, Zeit. Zucherind. 
Bohm., 1910, 34, 237-248. 

E. VoTocEK AND R. PoTMESiL. FucitoL Ber., 1913, 46) 3653-3655. 

E. VotoCek und R. Vondracek. Zuckercomponenten des jfalapins und anderen Pfianzen- 
glucoside. Chem. Centralblatt, 1903, i, 884, 1035. 

REFERENCES TO CARBOHYDRATE ALCOHOLS. 

J. BouGAULT ET G. Allard. Sur la presence de la volemite dans quelques Primulacies» 

Compt. rend., 1902, 135, 796-797. 
E. Fischer. Ueber Adonit^ einen neuen Pentit, Ber., 1893, 26, 633-639. 
E. Fischer. Ueher den Volemite einen neuen Heptit, Ber., 1895, 28, 1973-1974. 
E. Fischer. Galactitol. Ber., 1914, 47, 456. 
J. C. Irvine and B. M. Patbrson. Constitution of mannitoltriacetone, J. Chem. Soc, 

1914, 105, 898.915. 
J. C. Irvine and B. M. Paterson. Formation of ethers from mannitol, J. Chem. Soc, 

1914. los 915-923. 
J. C. Irvine and E. S. Steele. Effect of boric acid on the conductivity and specific 

rotation of methylated derivatives of mannitol, J. Chem. Soc, 1915, I07> 1221- 

1229. 
H. Kylin. Biochemistry of sea-weeds. Zeitsch. physiol. Chem., 1913, 83, 171-197. 
L. Maquenne. Perseite. Compt. rend., 1888, io6| 1235-1238. 
L. Maquenne. Le poids moleculaire et sur la valence de la perseite, Compt. rend., 1888, 

I07» 583-586. 
L. Maquenne. Synthese partielle deVerythrite gauche, Compt. rend., 1900, 130, 1402- 

1404. 
L. Maquenne et G. Bertrand. Sur les erythrites actives et racemique, Compt rend., 

1901, 132, 1419 1421, 1565-1567. Bull. Soc. Chim., 1901, 25, 740-745. 

E. Merck. Adonite. Arch. Pharm., 1893, 231, 129- 131. 

A. MuNTZ ET V. Marcono. La Perseite^ matiere sucree, analogue d la mannite, Compt. 
rend., 1884, 99, 38-40. 

G. Peirce. Heptitols, J. Biol. Chem., 1913, 17, 35-36 ; 23, 327-337- 

O. Treboux. Stdrkebildung aus Sorbit bei Rosaceen. Ber. Deut. Bot. Ges., 1909, 27, 

507-511. 
C. Vincent et J. Meunier. Un nouveau sucre accompagnant la sorbite, Compt. rend., 
1898, 127, 760-762. 

REFERENCES TO THE CYCLOSES. 

R. J. Anderson. Phytin and phosphoric esters of inositol, J. Biol Chem., 1912, 11, 471- 

488; 1912, 12, 97-113; 19141 I7» 171. 
M. Berthelot. Pinitol. Compt. rend., 1856, 41, 392. 
A. CoNTARDi. Inositol hexaphosphate, Gazetta, 1912, 42, [i], 408-418. 
L. Maquenne. Pinitol, Compt. rend., 1859, 109, 812. 

H. MiJLLBR. Occurrence of quercitol (quercite) in the leaves of Chamerops humilis. 
Trans. Chem. Soc, 1907, 91, 1766. Cocositol (cocosite), a constituent of the leaves of 
Cocos nuHfera and Cocos plumosa. J. Chem. Soc, 1907, 91, 1767- 1780. Inositol 
and some of its isomerides (scyllitol), J. Chem. Soc, 1912, lOi, 2383-241 1. 
Inositol {inosite), J. Chem. Soc, 1907, 91, 1780-1793. 

C. Neuberg. Relation of the cyclic inositol to the aliphatic sugars, Biochem. Zeitsch., 
1908, 9, 551-556. 

F. B. Power and F. Tutin. A Icevorotatory modification of quercitol, J. Chem, 

Soc, 1904, 85, 624-629. 



214 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

ScHBRRR. Colour teacUons of the inositols, Annalen, 1850, 73, 322. 
Stabdblbr and Friedrichs. On scyllitol, J. pr. Chem., 1858, 73, [ij, 48. 
C. Tanrbt. The Icevo- and racemic forms of inositol, Compt rend., 1889, Z09, 908 ; 

19071 145. 1196. 
C. Tanret and Villiers. Inactive forms of inositol. Compt. rend., 1877, 84, 393 ; 
1878, 86, 486. 

W. VoRBRODT. Phytin and its derivatives. Bull. Acad. Sci., Cracow., 1910, A, 414-5 11. 
E. WiNTERSTEiN. Constitution of phytin, Zeitsch. physiol. Chem., 1908, 58, ii8-i2i. 

REFERENCES TO DISACCHARIDES. 

A. Albkhinb. Meletitose, Ann. Chim. Phys., 1889, [vi], 18, 532-551 ; J. Russ. Chem. 
Soc., 1889, 21, 407-421. 

A. Bau. Beitrdge zur Kenntniss der Melibiose, Chem. Zeit., 1897, 2Z, 186; und 1902, 
26, 69-70. 

G. Bbrtrand. Constitution de Vicianose: hydrolyse diastasique. Compt. rend., 1910, 

iSh 325-327. 
G. Bbrtrand bt A. Compton. Sur Vindividualite de la cellase et de Vemulsine, Compt. 

rend., 1910, 151, 402-404. 

G. Bbrtrand bt A. Compton. Influence de la tempirature sur Vactivite de la cellase. 
Compt. rend., 1910, 151, 1076- 1079. 

G. Bbrtrand et A. Compton. Influence de la reaction du milieu sur VacHvite de la 
cellase. Nouveau caractere distinctif d^avec Vemulsine, Compt. rend., 1911, 153, 
360-363. 

G. Bbrtrand and M. Holderer. La cellase et le dedouhlement diastasique du cellose, 
Compt. rend., 1909, 149, 1385-1387 ; 1910, 150, 230-232. 

G. Bbrtrand bt G. Weiswbillbr. Le Vicianose, nouveau sucre rBducteur en Cn. Compt. 
rend., 1910, 150, 180-182. 

G. Bbrtrand bt G. Weiswbillbr. Le Constitution du vicianose et de la vicianine. 
Compt. rend., 1910, 151, 884-886. 

Em. Bourquelot. Les matilres sucrees de quelques especes de champignons, Compt. 

rend., 1889, Z08, 568-570. 
Em. Bourquelot. Les matieres sucrees ches les champignons. Compt. rend., 1890, iiz, 

578-580. 
Em. Bourquelot. La repartition des matieres sucries dans les differentes parties du Cepe 

comestible {Boletus edulis. Bull.). Compt. rend., 1892, 113, 749-751. 

Em. Bourquelot. Sur un ferment soluble nouveau dedoublant le trehalose en glucose. 

Compt. rend., 1893, zz6» 826. 
A. J. Daish. Action of cold concentrated hydrochloric acid on starch and maltose. J. 

Chem. Soc, 1914, Z05, 2053-2065. 
A. J. Daish. Velocity of hydrolysis of starch and maltose by cold concentrated and fuming 

hydrochloric acid. J. Chem. Soc, 1914, 105, 2065-2073. 

W. S. Denham and H. Woodhousb. Trimethylglucose from cellulose. J. Chem. Soc, 

1917. "i» 244-249. 
E. Fischer and K. v. Fodor. Cellobial and hydrocellobial, Ber.,1914, 47, 2057-2063. 

E. Fischer und G. ZBMPLi:N. Verhalten der Cellobiose und ihres Osons gegen einige 

Enzyme, Annalen, 1909, 3651 1-6. 
E. Fischer und G. Zempl^n. Verhalten der Cellobiose gegen einige Enzyme, Annalen, 

1910, 372, 254-256. 
E. Fischer und G. Zempl^n. Derivaie der Cellobiose, Ber., 1910, 43, 2536-2543. 
R. FoERG. Ueber die Glycolisierung von Biosen, Monatsh., 1903, 24, 357-363» 
J. Giaja. Sur Visolement d'un sucre biose derivant de Vamygdaline. Compt. rend., 1910, 

ISO, 793-796. 
P. Harang. Recherche et dosage du trehalose dans les vegitaux d Vaide de la trehalase, 

J. Pharm. Chim., 1906, 23, 16. 
E. R. VON Hardt-Stremayr. Acetylderivate der Cellobiose, Monatsh., 1907, 28» 63-72. 

M. M. Harrison. Action of adds upon fructose and glucose, J. Amer. Chem. Soc, 1914, 

36, 586-603. 
W. N. Haworth and J. Law. Constitution of the disaccharides. J. Chem. Soc, 1916, 

X09, 1314-1325. 



BIBLIOGRAPHY 215 

C. S. Hudson. Inversion of sucrose by invertase, h, II. J. Amer. Chem. Soc., 1908, 30, 
1160-1166; 1564-1583. 

C. S. Hudson and T. S. Harding. Preparation of melibiose, J. Amer. Chem. Soc, 

1915* 37» 2734-2736. 
F. Klein. Acetolytic degradation of cellulose, Z. angew. Chem., 1912, 25, 1409-1415. 
L. Maquenne et W. Goodwin. Cellose. Bull. Soc. Chim., 1904, 31, 854-859. 

W. Schlibmann. Ueber die Cellobiose und die Acetolyse der Cellulose, Annalen, 191 1, 
378, 366-381. 

Z. H. Skraup. t)ber Starke^ Glykogen und Cellulose, Monatsh., 1905, 26» 1415-1472. 

Z. H. Skraup und J. K5nig. Ueber die Cellobiose, Monatsh., 1901, 22, xoii-1036. 
Bcr., 1901, 34, 1115-1118. 

REFERENCES TO LACTOSE. 

H. BiBRRY BT J. GiAjA. Le dedoubUment dicutasique, du lactose, du maltose et de leurs 
derives, Compt. rend., 1908, 147, 268-270. 

A. BoDART. Heptacetylchlormilchzucker, Monatsh., Z902, 23, 1-8. 

R. DiTTMAR. Abkommlinge des Milchsuckers, Ber., 1902, 35, 1951-1953. 

DuBRUNFAUT. MUk-sugar, Compt. rend., 1856, 42, 228-233. 

E. O. Erdmann. Ueber wasserfreien Milchzucker, Ber., 1880, 13, 2180-2184. 

E. Fischer and G. O. Curmb. Lactal and hydrolactal, Ber., 19x4, 47, 2047-2057. 

E. Fischer und H. Fischer. Derivate der Maltose, Ber., 1910, 43, 2521-2536. 

E. Fischer und J. Meyer. Oxydation des Milchsuckers, Ber., 1889, 22. 361-364. 

W. N. Haworth and G. C. Lbitch. Constitution of the disaccharides Lactose and 
Melibiose, J. Chem. Soc., 1918, Z13, 188-199. 

C. S. Hudson. Ueber die Multirotation des Milchsuckers, Zeit. physikal. Chem., 1903, 

44, 487-494- 
C. S. Hudson. The hydration of milk sugar in solution, J. Amer. Chem. Soc, 1904, 26, 

1065- 1082. 

C. S. Hudson. Forms of lactose, J. Amer. Chem. Soc, 1908, 30, 1767-1783. 

C. S. Hudson and F. C. Brown. Heats of solution of the three forms of lactose, J. Amer. 
Chem. Soc, 1908, 30, 960-971. 

C. S. Hudson and J. M. Johnson. The isomeric octacetates of lactose, J. Amer. Chem. 

Soc, 1915, 37, 1270-1275. 

F. H. A. Marshall and J. M. Kirkness. Formation of lactose, Biochem. J., 1906,2, 

1-6. 

D. Noel Eaton and E. P. Cathcart. On the mode of froduction of lactose in the 

mammary gland, J. Physiol., 1911, 42, 179-188. 

R. H. Adbrs Plimmbr. Presence of lactase in the intestines of animals and the coaptation 
of the intestine to lactose, J. Physiol., 1906, 35, 20-31. 

Ch. Porchbr. Sur la lactophenylosasone. Bull. Soc Chim., 1903, 20, 1223-1227. 

Ch. Porcher. Sur Vorigine du lactose, Compt rend., 1904, 1381 833-836; 924-926; 

1457-1459. 
Ch. Porcher. Sur Vorigine du lactose, Compt rend., 1905, 140, 1279. 

Ch. Porcher. Sur Vorigine du lactose, Compt. rend., 1905, 141, 73-75 ; 467-469. 

O. Reinbrecht. Lactose- und Maltosecarbonsdure, Annalen, 1892, 272, 197-200. 

M. Schmobgbr. Notis uber acetylirten Milchsucker und Uber die im polarisirten Licht 
sich verschieden verhaltenden Modifcationen des Milchsuckers, Ber., 1892, 25, 
1452-1455. 

Z. H. Skraup und R. Krb^ann. Ueber Acetochlormilchsucker, Monatsh., 1901, 22, 

375-384. 

B. ToLLENS UND W. H. Kent. Untersuchungen Uber Milchsucker und Galactose, 

Annalen, 1885, 227, 221-232. 

H. Trey. Rotationserscheinungen der Laktose. Zeit. physikal. Chem., 1903, 46, 620-719. 

REFERENCES TO MALTOSE. 

J. L. Baker and F. E. Day. The preparation of pure maltose. Report Brit. Assoc. 
Dublin, 1908, 671-672. 

Dubrunfaut, Le Glucose, Ann, Chim. phys., 1847, [iii], 21, 178-180. 



2i6 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

E. F18CHBR UND H. Fischer. DerivaU des Milchsuekers und der Maltose; und zwH 
neue Glucoside* Ber., 1910, 43, 2521-2536. 

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C. S. Hudson and J. M. Johnson. The isomeric or and fi-octwetates of maltose and eel- 
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W. L. Lewis and S. A. Buckborouoh. Structure of maltose and its oxidation products 
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T. Db Saussurb. La decomposition de Vamidon a la temperature de Vatmosphere^ par 
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Em. Bourqublot. Sur la physiologie du gentianose ; son dedoublement par les ferments 
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E. BouRQyBLOT BT M. Bridel. Un Sucre nouveau^ le Verhascose, retire de la racine de 
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Em. Bourqublot bt H. H^rissby. Sur Vhydrolyse du miUzitose par les ferments 
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Em. Bourqublot bt L. Nardin. Sur la preparation du gentianose. Compt. rend., 
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C. S. Hudson and S. F. Sherwood. Occurrence of melexitose in a manna from the 

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H. KiLiANi. Ueh'er die Formeln der Polysaccharide. Chem. Zeit., 1908, 32, 366. 

J. Khouri. La prhence du stcu^hyose, mannotetrose et d'un glucoside didoublable par 

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E. VON LiPPMANN. Die Quelle der in den Producten der Zuckerfabrikation enthaltenen 
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L. Maquenne. La composition de la miellee du Tilleul. Compt. rend., 1893, 1x7, 
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Pautz und Vogbl. Ueber die Einwirkung der Magen und Darmschleimhaut auf einige 
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A. VON Planta und E. Schulze. Bin neues krystallisbares Kohlenhydrat, Stachyose, 
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H. RiTTHAUSBN. MeUtose aus Baumwollsamen. J. pr. Chem., 1884, 29, 351-357* 
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C. ScHBiBLBR. Die Zusammensetzung und einige Eigenschaften der Raffinose, Ber., 
1885, x8, 1779-1786. 



BIBLIOGRAPHY 217 

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21 8 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

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Em. Bourqublot. Gineralites sur les ferments solubles qui determinent Vhydrolyse des 
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E. Bourqublot et M. Bridbl. Action de Vinvertine sur les polysaccharides derives du 

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A. J. Brown. The chemical cu:tion of pure cultivations of bacterium aceti. J. Chem. 
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R. J. Caldwell and S. L. Courtauld. Enzyme action. IX. The enzymes of yeast 
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W. A. Davis. The distribution of maltase in plants. Biochem. J., 1916, zo^ 31-48. 

A. J. Daish. The presence of maltase in foliage leaves. Biochem. J., 1916, zo^ 49-55. 

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P. Dibnert. Sur la secretion des diastases. Compt. rend., 1899, Z29, 63-64. 

F. Dibnert. Sur la fermentation du Galactose et sur Vaccoutumance des levures d ce 
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O. Emmerlino. Das verhalten von Glycerinaldehyd und Dioxy acetone gegen Hefe. Ber., 

i899» » 542-544- 
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E. Fischer und W. Niebbl. Ueber das Verhalten der Polysaccharide gegen einige 

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E. Fischer und H. Thibrfeldbr. Verhalten der verschiedenen Zucker gegen reine 
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P. F. Frankland and J. J. Fox. Fermentation of mannitol and glycerol. Proc Roy. 

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J. Chem. Soc., 1892, 6z, 254-277. 

P. F. Frankland and J. S. Lumsden. The decomposition of mannitol and dextrose by 
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P. F. Frankland and J. MacGregor. The fermentation of arabinose by Bacillus 
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E. C. Grey. Enzymes concerned in the decomposition of glucose and mannitol by Bacillus 
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A. Harden. The chemical action on glucose of the Uutose fermenting organisms of the 
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A. Harden. The chemical action of Bacillus coli communis and similar organisms on 
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A. Harden and G. S. Walpolb. Chemical action of bacillus lactis arogenes on glucose 
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T. A. Henry and S. J. M. Auld. On the probable existence of emulsin in yeast. Proc. 
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BIBLIOGRAPHY 219 

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E. Frankland Armstronq. Enzyme action, V. Hydrolysis of isomeric glucosides and 
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E. Frankland Armstrong and R. J. Caldwell. Enzyme action. IV. and VI. The 
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H. E. Armstrong and W. H. Glover. Enzyme action. XI. Hydrolysis ofraffinose by 
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S. Arrhenius. Die Reaktionsgeschwindigkeit bei der Inversion von Rohrzucker durch 
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220 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

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H. T. Brown and G. H. Morris. On the germinaiion of some of the graminece, 
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E. Fischer. Synthesen in der Zucketgruppe^ I., II., III. Ber., 1890, 23, 2114-2x41; 
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E. Fischer. Synthesg der Mannose und Lavulose. Ber., 1890, 33, 370-394. 

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E. Fischer und F. Passmore. Bildung von Acrose aus Formaldihyde. Ber., 1889, 22, 

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S. Strakosch. Bin Beiirag nur Kenntnis des Kohlenhydratstoffwechsels von Beta 
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F. L. Usher and J. H. Pribstlby. A study of the mechanism of carbon assimilation in 

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F. L. Usher and J. H. Priestley. The photolytic decomposition of carbon dioxide in 
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O. Emmerling. Synthetische Wirkung der Hefemaltase, Ber., 1901, 34, 600-605, 2206- 
2207, 3810-381 1. 

E. Fischer. Synthese einer neuen Glucobiose. Ber., 1890, 23, 3687-3691 ; 1895, 28, 3024- 
3028. 

£. Fischer und E. F. Armstrong. Synthese einiger neuer Disaccharide. Ber., 1902, 35» 

3144-3153. 



222 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

E. FxscHBR UND K. Dblbruck. Synikese neuer Disaccharide von Typus der Trehalose, 
Bcr., 1909, 42, 2776-2785. 

A. Harden and W. J. Youno. The enzymatic formation of polysaccharides by yeast 
preparations. Biochem. J., 19x3, 7, 630-636. 

T. A. Henry and S. J. M. Auld. The probable existence of emulsin in yeast. Proc. 
Roy. See., Z905, 76 B, 568-580. 

R. O. Herzoq. On the action of emulsin, Proc K. Ak'ad. Wetensch., Amsterdam, 1903, 

6, 332-339- 
A. Croft Hill. Reversible symohydrolysis, J. Chem. Soc., 1898, 75, 634-658. 

A. Croft Hill. Taka-diastase and reversed ferment action, Proc. Chem. Soc., 1901, 
17, 184. 

A. Croft Hill. Synthetic action on dextrose with pancrecUic ferment. Joum. of 
Physiol., 1902, 28, Proc. xxvi. 

A. Croft Hill. The reversibility of enzyme or ferment action. J. Chem. Soc., 1903, 

831 578-598. 
A. Croft Hill. Bemerkung zu O. Emmerling. Synthetische Wirkung der Hefenmaltase, 

Ber., 1901, 34, 1380. 

J. H. Van't Hoff. Synthetische Fermentwirkungy I., \l, Sitz. Ber. Akad. Wiss., Berlin, 

1909, 1065-Z076 ; 19x0, 963-970. 

J. Pbklo. Vorkommen von St&rke in der Zuckerriibenwurzel, Bied. Zentr., 191Z, 40^ 
386-387. 

H. PoTTBViN. Actions diasUuiques reversibles. Formation et dedoublement des ethers-sels 
sous Vinfluence des diastases du pancrias. Ann. Inst. Pasteur, 1906, ao, 901-923. 

R. A. Robertson, J. C. Irvinb and M. E. Dobson. A polarimetric study of the sucroclasHc 
enzymes in Beta vulgaris, Biochem. J., 1909, 4, 258-273. 

L. Rosenthaler. Dutch enzyme bewirkte tuymmetrische Synthesen, I., II. Biochem. 
Zeitsch., 1908, 14, 238-253 ; 1909, 17, 257-269. 

W. ScHNEiOBR AND F. Wredb. Synthesis of disaccharides containing sulphur and 
selenium. Ber., 19 17, 50, 793-804. 

A. W. VissBR. Reaktionsgeschwindigkeit und chemisches Gleichgewicht in homogenen 
Systemen und der en Anwendung auf Enzymwirkungen. Zeit. physikal Chem., 
1905, S2» 257-309. 

A. WoHL. Zur Kenntniss der Kohlenhydrate, Ber., 1890, 35, 2084-21 10. 

G. Zbmplbn. Gentiobiose. Ber., 1915, 48, 233-238. 

REFERENCES TO GLUCOSIDES. 

G. Bertrand and G. Wbissweillbr. Constitution of vicianose and vicianin. Compt. 
rend;, 1910, 151, 884-886. 

L. Bourdibr. La presence de ** Vaucubine " dans les diffirentes espices du genre Plantago. 
J. Pharm. Chim., 1907, [vi], 26, 254-266. 

Em. Bourqublot and M. Bridbl. Action of emulsin on gentiopicrin in alcohol. J. 
Pharm. Chim., 191 1, [vii], 4, 385-390. 

Em. Bourqublot et A. Fichtbnholz. Arbutine et mithylarbutine. Caractlres, distinction 
et recherche dans les vegStaux. .J. Pharm. Chim., 1910, [vii], z, 62-66, Z04-Z09. 

Em. Bourqublot bt A. Fichtbnholz. Leglucoside desfeuilles depoirier. Compt. rend., 

1910, X5Z, 8z-84 ; Z9ZZ, Z53, 468-47Z. 

Em. Bourqublot et A. Fichtbnholz. Le glucoside desfeuilles depoirier; son rdle dans 
la production des teintes automnales de ces organes. J. Pharm. Chim., Z9zz, [vii], 5, 
5-13. 

Em. Bourqublot et A. Fichtbnholz. Sur la presence de I* arbutine dans les feuilles du 
Grevillea robusta. Compt. rend., Z9Z2, 154, zzo6-zzo8. 

Em. Bourqublot bt H. HiRissBV. Action de Vemulsine de VAspergillus niger sur 
quelques glucosides. Bull. Soc. Mycol., Z896, zz, Z99. 

Em. Bourqublot bt H. HI&rissby. Sur Vaucubine, glucoside de VAucuba japonica, 
Ann. Chim. Phys., Z905, [viii], 4, 289-3x8. 

Em. Bourqublot et H. HiRissBV. Uarbutine et quelques-uns de ses derives, considires 
au point de vue de leur pouvoir rotatoire et leur didoublement par Vemulsine. 
Compt. rend., 1908, Z46, 764-766. 

Em. Bourqublot bt J. Vintilbsco. L^oleuroPHne, nouveau prindpe de nature gluco- 
sidique retiri de VOlivier {Olea europcea^ £.). Compt. rend., 1908, Z47, 533-535. 



BIBLIOGRAPHY ^23 

M. Br i DEL. La MHiatine, nouveau glucoside, hydroly sable par Vemulsine, reiiri du 

Trefle dUau. Compt. rend., igii, 152, 1694-1696. 
M. Bridbl. Occurrence of gentiopicrin in Gentiana and Swertia spp. Compt. rend., 1912, 

153, 1029-1031, 1164; 1913, 156, 627-629. J. Pharm. Chim., 1913, [vii], 7, 289-292, 

392-395. 481-484. 486-492 ; 1914. [vii], 10, 62-66. 
M. Bridel. Gentiacaulin. J. Pharm. Chim., 1914, [vii], 10, 329-335- 
C. Charaux. Occurrence of fraxin in Diervilla lutea. J. Pharm. Chim., 191 1, [vii], 4, 

248-250. 
L. Danzel. Aralin, a glucoside of Aralia japonica. J, Pharm. Chim., 1912, [vii], 5, 

530-534. 
E. Fischer. Ueber einige Derivate des Helicins, Ber., 1901, 34, 629-631. 

E. Fischer und W. von Loeben. Ueber die Verbrennungswdrme einiger Glucoside, 

Sitzungsber. K. Akad. Wiss., Berlin, 1901, 323-326. 
J. Gadamer. Les glucosides des moutardes noire et blanche, J. Pharm., 1896, 4, 462. 
H. Herissby. Preparation de VArbutine vraie, Compt. rend., 1910, 151, 444-447. J. 

Pharm. Chim., 1910, [vii], 2, 248-253. 
H. HiRissEY ET C. Lebas. Prhence de Vaucubine dans plusieurs espices du genre 

Garry a, J. Pharm. Chim., 1810, 2, 490-494. 

H. Hlasiwetz und J. Habermann. Das Arbutin, Ann. Chem. pharm., 1875, 177, 

334-343- 
H. A. D. Jowett and C. E. Potter. Variations in the occurrence ofsalicin and salinigrin 
in different willow and poplar barks. Pharm. J., 1902, August 16. 

A. Kawalier. Untersuchung der Blatter von Arctostaphylos uva ursi. Ann. Chem. 
Pharm., 1852, 84, 356-360. 

Y. Kotake and Y. Sera. Lycoperdin^ a new glucosamine compound^ and the composition 
of chitin, Zeitsch. physiol. Chem., 1913, 88, 56-72. 

C. LiBBERMANN UND O. HoRMANN. Die Farbstoffc und den Glycosidzucker der Gelb- 
beeren, Annalen, 1879, 196, 299-338. 

E. O. LiPPMANN. Der Zucker des Populins. Ber., 1879, Z2, 1648-1649. 

C. Mannich. Arbutin and its synthesis. Arch. Pharm., 1912, 250, 547-560. 

G. Masson. Chemical composition of Dulcamara^ and solacein. Bull. Sci. Pharm., 191 2, 
19, 283-289. 

F. Marino-Zugo AND V. Pasquero. Clavicepsin^ a new glucoside from Secale comutum, 

Gazzetta, 191 1, 41, [ii], 368-374. 

H. TER Mbulbn. Sur quelques glucosides contenant des shiivols. Rec. trav. Chim., 
1900, 19, 37-45. 

G. Oddo and M. Cesaris. Solanine extracted from Solanum sodomaum, Gazzetta, 19x1, 

4l» [>]. 490-534 ; 1914. 44f [i]. 680-696; 1914, 44, [ii], 181-208. 

R. PiRiA. Untersuchungen uber das Salicin, Ann. Chem. Pharm., 1845, 56, 35-77. 

R. PiRiA. Das Populin, Ann. Chem. Pharm., 1852, 8z, 245-247; 1855, 96, 375-383. 

F. B. Power and A. H. Salway. Constituents of the leaves and stems of Daviesia lati- 
folia, J. Chem. Soc., 1914, 105, 767-778. Dibenzoylglucoxylose : a natural 
benzoyl derivative of a new disaccharide. Ibid., 1914, Z05, 1062-1069. 

E. H. Rennie. On Phloridzin, J. Chem. Soc., 1887, 51, 634-637. 

C. Reichard. Glucoside recictions ; convallamarin and convallarin, Pharm. Zeit., 191 1, 
52, 183-188. 

H. Schiff. Constitution Arbutins, Ann. Chem. Pharm., 1880, 206, 159-167. 

H. Schiff und G. Pellizzari. Methylarbutin, Bensylarbutin und Benzyldioxybensole, 
Annalen, 1883, 22Z, 365-379. 

W. Schneider and W. Lohmann. The glucoside of cheirolin, Ber., 19x2, 45, 2954-296X. 

W. Schneider and L. A. Schutz. Mustard oil glucosides, II. Glucocheirolin, Ber., 
X9X3, 46, 2634-2640. 

W. Schneider and F. Wrede. Mustard oil glucosides, V. Constitution of sinigrin, 
Ber., X914, 47, 2225-2229. 

W. Schneider. Mustard oil glucosides. III. and IV. Synthetic glucosides from thio- 
urethanes, Ber., 1914, 47, 1258-1269, 22x8-2224. 

E. ScHULZB UND G. Tribr. Identitdt des Vernins und des Guanosins nebst Einigen 
Bemerkungen uber Vicin und Convicin, Zeitsch. physiol. Chem., X9xi,70, X43-151. 

ScHUNCK. On rubin and its products of decomposition, Phil. Trans. Roy. Soc., 185 x, 433. 



224 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

ScHUNCK. Erythrogyms, Phil. Trans., 1853, 74, 

E. Srel and C. Kblbbr. Molecular weight and oxidation products of ahin. Ber., 1916, 
49, 2364-2368 ; 1917, 50, 759-764- 

E. SiBBURO. HelUhorHn. Arch. Phann., 1913, 251, 154-183. 

Spatzibr. Ueher das Auftreten und die physiologische Bedeutung des Myrosins in der 
Pjianse. Pringsheim's Jahib., 1893, 25, 39. 

A. Strbckbr. Das Arbutin und seine Verwundlungen. Ann. Chera. Pharm., 1858, X07, 
228-234. 

F. TiEMANN. Vanillins&ure, Ber., 1875, 8» 509-515. 

F. TiBMANN. Coniferylalkoholt das bei Einwirkung von Emulsin auf Coniferin neben 
Traubenzucker entstehende Spaltungsprodukte sowie Aethyl und Methyl vanillin. 
Ber., 1875, 8, 1127-1136. 

F. TiBMANN. Die der Coniferyl und Vanillin Reihe angehorigen Verbindungen, Ber., 
1876, 9, 409-423, 1278-1284. 

F. TiBMANN. Glucovanillin und GlucovanillylcUkohol. Ber., 1885, z8, 1595- 1600. 

F. TiEMANN AND W. Haarmann. Das Coniferin und seine Umwandlung in das 
aromatische Princip der Vanille, Ber., 1874, 7, 608-623. 

F. TuTiN. Constituents of senna leaves (Kcempferin). J. Chem. Soc., 1913* X03, 
2006-2023. 

F. TuTiN AND H. W. B. Clbwbr. Constituents of Solanum Angustifolium : isolation of a 
new gluco-alkaloid, solangustine. J. Chem. Soc., 1914, 105, 559-576. 

E. VotoCbk. Ueber die Ghkosidsduren des Convolvulins und die Zusammensetzung der 
rohen Isorhodeose, Ber., 1910, 43, 476-482. 

A. Vibhoever, G. a. Geiger and C. O. Johns. Cedrin, a glucoside ftom the seeds of 
Simaba Cedron. J. Biol. Chem., 1916, 24. 

REFERENCES TO BIOCHEMICAL DETECTION OF GLUCOSIDES. 

Em. Bourquelot. Recherche dans les vegetaux du sucre de canne d Vaide de VinverHne et 
des glucosides d Vaide de Vemulsien. J. Pharm. Chim., 1901, 14, 481. 

Em. Bourquelot. Sur Vemploi des enzymes comme reactifs dans les recherches de labor a- 
toire, (Contains a bibliography.) J. Pharm. Chim., 1906, 54, 165; 1907, 35, 16 
et 378. 

Em. Bourquelot and Mlle. A. Fichtenholz. Application of the method to Kalmia 
latifolia and identification of the glucoside. Compt. rend., 1912, 154, 1500-1502 ; 
526-528. J. Pharm. Chim., 1912, (vii), 5, 49-58; 296-300. 

Em. Bourquelot and Mlle. A. Fichtenholz. Application of the biochemical method 
to the detection of sucrose and glucosides in certain Ericacece. J. Pharm. Chim., 
1913, (vii), 8, 158-164. 

Em. Bourquelot and Mlle. A. Fichtenholz. Glucosides hydrolysable by emulsin in 
some pa/nlionaceous and scrofularinaceous plants. J. Pharm. Chim., 19 15, (vii) IX, 
219-226. 

Em. Bourquelot and M. Bridel. Biochemical investigation of the glucosides hydrolysable 
by emulsin^ in indigenous Orchidacece. J. Pharm. Chim., 19 14, (vii) 10, 14-18, 66-72. 

M. Bridel. Application of the biochemical method to Gentiana acaulis ; isolation of a new 
glucoside, gentiacaulin. J. Pharm. Chim., 1913, (vii), 8, 241-250. Application of 
the biochemical method to the examination of the stone-kernels of the cherry laurel. 
Ibid., 1915, (vii), 12, 249-252. 

C. Lepebvre. Anwendung der biochemischen Methode zum Nachweis der Zuckercurten und 
der Glykoside in den Pflanzen und der Familie der Taxinen. Arch. Pharm., 1907, 
245, 493-502. J. Pharm. Chim., 1907, 26, 241-254. 

REFERENCES TO OXYFLAVONE GLUCOSIDES. 

J. Herzig and R. Schonbach. Methylation of glucosides (quercitrin). Monatsch, 1912, 
33, 673-680. 

N. Krasovski. Rhamnoxanthin and frangulin from Rhamnus spp. J. Russ. Phys. Chem. 
Soc, 1913, 45, 188-193. 

Hugo Muller. The occurrence of flavone as the farina of the primula. J. Chem. Soc., 

i9i5» xo7» 872-878. 
A. G. Perkin. Quercetagetin. J. Chem. Soc, 1913) Z03, 209-219. 



BIBLIOGRAPHY 225 

A. G. Pbrkin. Gossypetin. Trans. Chem. Soc., 1913, Z03, 650-662. 

A. G. Pbrkin. Thujin, J. Chem. Soc., 19 14, Z05, 1408. 

A. G. Perkin. The colouring matter of cotton flowers^ III. J. Chem. Soc., 1916, Z09, 

145-154. 
£. Schmidt. Zur Kenntnis der Rhamnoside. I. Rutin. II. Sophorin. III. Cappem^ 

Rutin, IV. Robinin, Arch. Pharm., 1904, 242, 210-224. 

Y. Shibata and Naqai. Flavone derivatives in plants, J. Biol. Chem., 1916, 28, 93-108. 
Physiol. Abstr., 1918, 3, 68-69. 

Ch. bt G. Tanrbt. Sur la rhamninase et la xanthorhamnine. Bull. Soc. Chim., 1899, 
21, 1073. 

M. Whbldale and H. L. Bassbtt. The chemical interpretation of some mendelian factors 
for flower colour. Proc. Roy. Soc, 1914, 87 B, 300-311. 

R. WiLLSTATTBR AND A. E. EvERBST. Ucbcr den Farbstoff der Kornblume. Ann., 1913, 
40Z, 189-232. 

R. WiLLSTATTBR UND E. K. BoLTON. Ucbcr den Parbstoff der Scharlcuihpelargonie. Ann., 

I9I5) 408, 42-61. 
R. WiLLSTATTBR UND H. M ALLISON. Ueber den Farbstoff der Preiselbeere. Ann., 1915, 

408, 15-41. 
R. WiLLSTATTBR UND K. Martin. Vcber den Farbstoff der Althcea rosea, Ann., 1915, 

408, 110-121. 

R. WiLLSTATTBR UND W. MiBO. Ueber ein anthocyan des Bittersporus. Ann., 1915, 408, 
61-82. 

R. WiLLSTATTBR UND W. MiBO. Ueber den Farbstoff der wilden Malve. Ann.^ 19 15, 408, 
122-135. 

R. WiLLSTATTBR UND T. J. NoLAN. Ueber den Farbstoff der Rose, Ann., 1915, 408, 1-14. 

R. WillstXttbr UND E. H. Zollinger. Ueber den Farbstoff der Weintraube und des 
Heidelbeere, Ann., 1915, 408, 83-109. 

REFERENCES TO AMYGDALIN. 

S. J. M. Auld. The hydrolysis of amygdalin by emulsin, I., II. J. Chem. Soc, 1908, 
93, 1251-1281. 

R. J. Caldwell and S. L. Courtauld. The hydrolysis of amygdalin by acids. J. Chem. 
Soc, 1907, 9Z, 666-671. 

R. J. Caldwell and S. L. Courtauld. Mandelonitrile glucosides. Prulaurasin. 
J. Chem. Soc, 1907, 9Z, 671-677. 

H. D. Dakin. The fractional hydrolysis of amygdalinic acid. isoAmygdalin. J. Chem. 
Soc, 1904, 85, 1512-1520. 

K. Fbist. Die Spaliung des Amygdalins unter dem Einfluss von Emulsin. Arch. Pharm., 
1908, 2461 206-209. Optisch aktive Benzaldehydcyanhydrine. Ibid., 1909, 247, 226- 
232. Zersetzung von Amygdalin. Ibid., 1909, 247, 542-545. Spaltung racemischer 
Cyanhydrine durch Emulsin. Ibid., 1910, 2^ 101-104. 

£. Fischer. Einfluss der Configuration auf die Wirkung der Enzyme, Ber., 1894, 27, 
2985-2993. 

£. Fischer. Ueber ein neues, dem Amygdalin dhnliches Glucosid, Ber., 1895, 28, 1508- 
15". 

£. Fischer und M. Berom ann. Synthese von Mandelonitril glucosid und Sambunigrin. 
Ber., 1917, 50, 1047-1069. 

G. GiAjA. Sur Visolement d*un sucre biose dirivant de Vamygdaline, Compt. rend., 1910, 

ISO. 793-796. 
H. Hi^RissBY. Etude comparee de Vemulsine des amandes et Vemulsine d* Aspergillus niger. 

Bull. Soc Biol., 1896, 640. 

Johansen. Sur la localisation de Vimulsine dans les amandes. Ann. Sci. Nat. (Bot.), 
1887, 6, 118. 

J. Liebio und F. Wohlbr. Die Bildung des Bittermandelols. Annalen, 1837, 22, 1-24. 

J. Liebio und F. Wohlbr. Sur la formation de Vhuile d* amandes amires. Ann. Chim. 
phys., 1837, 64, 185-209. 

H. LuDWio. Eigenthumliche Pflanzenstoffe. Jahresbericht, 1856, 679. 

RoBiQUET BT BouTRON. Les Amondes amhres et Vhuile volatile qu*elles fournissent. 
Ann. Chim. phys., 1830, 44, 352-382. 

15 



226 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

L. RosBNTHALER. Amygdalin, Arch. Pharm., 1908, 245^ 684-685. Die Spaltung des 
Amygdalitis unter (Um Einftuss von Emulsin. Ibid., 1908, 24/S9 365-366, 710 ; 1910, 
248, 105-112, 534-535. 

L. RosBNTHALER. Distribution of amygdalin. Arch. Pharm., 1912, 250, 298-301. 

H. ScHiFP. Die Constitution des Amygdalins und der Amygdalins&ure. Annalen, 1870, 

lS4t 337-353. 
Thom^. Ueber das Vorkommen des Amygdalins und des Emulsins in den bittern Mandeln, 
Bot. Zeit., 1865, 240. 

Thomson and Richardson. Ueber die Zersetzung des Amygdalins durch Emulsin. Ann. 
de Pharm., 1839, 29, 180. 

F. TuTiN. isoAmygdalin and the resolution of its hepta-acetyl derivative. J. Chem. Soc, 

I909» 9S 663-668. 
A. ViEHOBVER, C. O. Johns, and C. L. Alsbbrb. Cyanogenesis in Plants. Tridens Jlavens. 
J. Biol. Chem., 19 16, 25^ 141- 150. 

J. W. Walker. The catalytic racemisation of amygdalin. J. Chem. Soc., 1903, 83, 
472-479. 

J. W. Walker and V. K. Kribble. The hydrolysis of amygdalin by acids. J. Chem. 

Soc., 1909, 9S 1369-1377. 
J. W. Walker and V. K. Krieblb. The amygdalins. J. Chem. Soc., 1909, 95^ 1437- 

1449. 

REFERENCES TO CYANOPHORIC GLUCOSIDES. 

G. Bbrtrand. La vicianine, nouveau glucoside cyanhydrique contenu dans les graines de 

Vesce. Compt. rend., 1906, 143, 832-834. 

G. Bbrtrand et L. Riokind. La repartition de la vicianine et de sa diastase dans les 
graines de Ligumineuses. Compt. rend., 1906, 143, 970. ' 

G. Bbrtrand und G. Weiswbiller. La constitution de la Vicianine. Compt rend., 
1908, 147, 252-254. 

Em. Bourquelot bt Em. Danjou. Sur la sambunigrine, glucoside cyanhydrique 
nouveau retire des feuilles du sureau noir, Compt. rend., 1905, 141, 59-61 ; 
598-600. 

W. R. DuNSTAN AND T. A. Henry. Chemical aspects of cyanogenesis in plants. Brit. 
Assoc. Report, York, 1906, 145-157. 

W. R. DuNSTAN and T. a. Henry. The nature and origin of the poison of Lotus 
Arabicus. Proc. Roy. Soc., 1900, 67, 224; 1901, 68» 374-378. Phil. Trans. Roy. 
Soc., 1901, 194 B, 515-533. 

W. R. DuNSTAN AND T. A. Henry. Cyanogenesis in plants. II. The great millet^ 
Sorghum vulgare. Phil. Trans. Roy. Soc., 1902, 199 A» 399-4ia 

W. R. DuNSTAN AND T. A. Henry. III. Phaseolunatin, the cyanogenetic glucoside of 
Phaseolus lunatus. Proc. Roy. Soc., 1903, 72, 285-294. 

W. R. DuNSTAN, T. A. Henry and S. J. M. Auld. Cyanogenesis. IV. Occurrence of 
Phaseolunatin in common flax. V. Occurrence of phaseolunatin in cassava. Proc. 
Roy. Soc, 1906, 78 By 145-158. 

W. R. DuNSTAN, T. A. Henry and S. J. M. Auld. Cyanogenesis. VI. PhasMunaHn 
and the associated enzymes in flax^ cassava and the lima bean. Proc. Roy. Soc., 
1807, 79 B, 315-322. 

T. H. Easterpield and B. C. Aston. Corynocarpin^ a glucoside occurring in the kernels 
of the Karaka fruit. Proc. Chem. Soc, 1903, 19, 191. 

M. Greshopf. The distribution of prussic cuid in the vegetable kingdom. Report Brit. 
Assoc, 1906, 138-144. 

L. GuiQNARD. Sur la localisation dans les plantes des principes qui fournissent Vacide 
cyanhydrique. Compt. rend., 1890, no, 477. 

L. GuiONARD. Sur la localisation dans les amandes et le lauriercerise des principes qui 
fournissent Vacide cyanhydrique. Journal de Botanique, 1890, 4, 3. 

L. GuiONARD. Sur Vexistence dans le sureau noir d*un compose fournissent de Vacide 
cyanhydrique. Compt. rend., 1905, 141, 16-20, 448-452. 

L. GuiGNARD. Sur la metamorphose des glucosides cyanhydriques pendant la germinaiion. 
Compt. rend., 1908, 147, 1023-1038. 

L. GuiONARD ET J. HoNDAS. Sur la nature du glucoside cyanhydrique du sureau noir, 
Compt. rend., 1905, 141, 236-238. 



BIBLIOGRAPHY 227 

L. GuiGNARD. La formation et Us variations quantitative du Principe cyanhydrique du 
sureau noir, Compt. rend., 1905, 141, 1193-1201. 

L. GuiONARD. Nouveaux exemples de Rosacies a acide cyanhydrique, Compt. rend., 
1906, 143, 451-458. 

L. GuiGNARD. La metamorphose des glucosides cyanhydriques pendant la germination, 
Compt. rend., 1908, 147, 1023-1038. 

H. Hbrissby. La Prulaurasine^ glucoside cyanhydrique cristallise^ retire des feuilles de 
Laurier-cerise, Compt. rend., 1905, 141, 959-961. 

H. Hbrissey. Dos Prulaurasin, das Blausaure liejernde Glycosid der Blatter von Prunus 
laurocerasus. Arch. Pharn^., 1907, 245, 463-468, 473-474. 

H. Hbrissey. L*Existence de la *' Prulaurasin " dans le Cotoneaster microphylla Wall, 
J. Pharm. Chim., igo6, [vi], 24, 537-539- 

H. HBRISSBY UND Em. Bourquelot. Die Isomerie hei den Blausaure liefemden 
Glykosiden Sambunigrin und Prulaurasin, Arch. Pharm., 1907, 245, 474-480. 

H. HBRISSEY. Das Vorkommen von Amygdonitrilglykosid in Cerasus Padus Delarb, 
Arch. Pharm., 1907, 245, 64Z-644. 

A. W. K. DE JoNQ. La decomposition de la gynocardine par V enzyme des feuilles de 
pangium edule, Rec. trav. Chim., 191 1, 50, 220-221. 

A. JoRissBN. Recherches sur la formation de Vacide cyanhydrique. Bull. Acad. Roy. 
Belg., 1910, 224-233. 

JoRissBN ET Hairs. La linamarine, nouveau glucoside foumissent de Vacide cyan- 
hydrique par dedouhlement. Bull. Acad. Roy. Belg., 1891, 21, 529. 

C. W. MooRB AND F. TuTiN. Notc on gynocardin and gynocardase, J. Chem. Soc., 
1910, 97, 1285-1289. 

F. B. Power and F. H. Lees. Gynocardin^ a new cyanogenetic glucoside. J. Chem. 
Soc., 1905, 87, 349-357. 

F. B. Power and C. W. Moore. The constituents of the bark of Prunus serotina, Isola^ 
tion of Umandelonitrile glucoside. J. Chem. Soc, 1909, 95, 243-261. 

C. Ravenna b M. Tonegutti. Alcune osservazioni sulla presenza delV acido cianidrico 
libero nellepiante, Atti. R. Accad. Lincei, 1909, [v], 19, ii., 19-25. 

C. Ravenna e M. Zamorani. Sulla formazione delV acido cianidrico nella germinazione 
dei sensi. Ibid., 356-361. 

Treub. Sur la localisation, le transport et le role de Vacide cyanhydrique dans le Pangium 
edule. Ann. du Jardin. bot. de Buitenzorg, 1895, 13, i. 

REFERENCES TO INDICAN. 

C. Berqthbil. The fermentation of the indigo-plant, J. Chem. Soc, 1904, 85, 870-892. 

W. Beyerinck. On the fermentation of indigo from the wood (Isatis tinctoria.) Proc. K. 
Akad. Wetensch., Amsterdam, 1900, 2, 120-129. 

W. Beyerinck. Further researches on the formation of indigo from the wood (Isatis 
tinctoria). Proc. K. Akad. Wetensch., Amsterdam., 1900, 3, 101-116. 

J. J. Hazewinkbl. Indican — its hydrolysis and the enzyme causing the same. Proc. K. 
Akad. Wetensch., Amsterdam, 1900, 2, 512-520. 

S. Hoooewerfp bt H. tbr Meulbn. Indican. Proc. K. Akad. Wetensch., Amster- 
dam, 1900, 2, 520. 

S. HooGBWERFF ET H. TER Meulbn. Contribution it la connaissance de Vindican. Rec. 
trav. Chim., igoo, 19, 166-172. 

H. TBR Meulbn. Recherches experimentales sur la nature de quelques glucosides 
[Indican"], Rec. trav. Chim., 1905, 24, 444. 

A. G. Perkin and W. P. Bloxam. Indican, Part I. J. Chem. Soc, 1907, 91, 
1715-1728. 

A. G. Perkin and F. Thomas. Indican, II. J. Chem. Soc, 1909, 95, 793-807. 

P. VAN RoMBURG. On the formation of indigo from indigoferas and from Marsdenia 
tinctoria. Proc K. Akad. Wetensch., Amsterdam, 1900, 2, 344-348. 

F. Thomas, W. P. Bloxam and A. G. Perkin. Indican, III. J. Chem. Soc, 1909, 95, 
824-847. 

15* 



r 

I 



228 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

REFERENCES TO DIGITALIS GLUCOSIDES. 

H. KiLiANi. Digiioxose, Ber., 1905, 38, 4040-4043. 

H. KiLiANi. DigHoxin and gitalin. Arch. Pharm., 1913, 251, 562-587. ^^Gitaliuy^ a 
mixture. Ibid., 19149 252, 13-26. Digitinalum verum. Ibid., 1914, 252, 26-32. 

H. KiLiANi. Digitalis substances. Ber., 1918, 51, 1613-1639. 

F. Kraft. Glucosides of digitalis purpurea leaves. Arch. Pharm., 1912, 250, 118-141 
Glucosides from the leaves of digitalis purpurea, Schweiz. Wochensch. Chem. 
Pharm., 191 1, nos. Z2, i^ Vj. 

L. RosENTHALBR. The gitalin question, Schweiz. Apoth.-Zeit., 1914, 52, 349-350. 

W. Straub. Development of the typical glucosides of the leaf in germinating and growing 
digitalis plants. Biochem. Zeitsch., 1917) 82, 48-59. 

A. WiNDAUS AND L. HERMANNS. Cymorin^ the active constituent of Apocynum cannabinum, 

Ber., 1915, 48, 979-994- 
A. WiNDAUS AND A. ScHNBCKBNBUROBR. Gitonint a new digitalis glucoside. Ber., 1913, 

46, 2628-2633. 

REFERENCES TO SAPONINS. 

Y. AsAHiNA AND M. MoMOYA. The saponin from Styrax japonica. Arch. Pharm., 1914, 
252, 56-69. 

Y. AsAHiNA AND T. Shimidzu. Saponin from the epicarp of Sapindus mukurosi, J. Pharm. 
Chim., 1916, (vii), 14, 188-190. 

H. Blau. Beitrdge xur Kenntnis der Saponins. (Thesis.) 

C. O.Johns, G. A. Gbiger and A. Viehoevbr. Saponin from Yucca radiosa, J. Biol. 
Chem., 19 16, 24. 

F. Kraft. Glucosides of digitalis purpurea leaves. Arch. Pharm., 1912, 250, 118-14Z. 

F. B. Power and A. H. Salway. Constituents of the rhizome and roots of Caulophyllum 

thalictroides. Trans. Chem. Soc, 1913, 103, 191-209. Identification of ipuranol 
and some allied compounds as phytosterol glucosides. Ibid., 1913, 103, 399-406. 
Chemical examination of sarsaparilla root. Ibid., 1914, 105, 201-219. 

L. RosENTHALER AND K. T. Strom. Saponin of the white soapwort. Arch. Pharm., I9i2» 
250, 290-297. 

A. W. VAN DER Haar. Untersuchungen in der Familie der Araliacecey speziell uber die 
Glykoside und Oxydasen aus den Bldttern von Polyscias nodosa Forst, und Hedera 
Helix Linn. (Thesis.) 

A. W. VAN DER Haar. Saponin-like glucosides from the leaves of Polyscias nodosa and 
Hedera helix. Arch. Pharm., 1912, 250, 424-425. Structure of the natural saponins 
and production of terpenes therefrom. Ibid., 1913, 251, 217-222. 

A. W. van der Haar. The Araliacece family with special reference to glucosides and 
oxidasei of the leaves of Polyscias nodosa and Hedera helix, Pharm. Weekblad., 
1913, 50» 1350-1359, I38i-i393» 1413-1427. 

A. W. van der Haar. The chemistry and pharmacology of the saponins. Biochem. 
Zeitsch., 1916, 76, 335-358. 

A. Viehoevbr, L. H. Chbrnofp, and C. O. Johns. Saponin from Yucca angustifolia, 
J. Biol. Chem., 1916, 24. 

E. Winterstein and H. Blau. Beitrdge zur Kenntnis der Saponins. Zeitsch. physiol. 
Chem., 191I) 75, 410-442. 

REFERENCES TO GLUCOSIDE SYNTHESIS. 

G. CiAMiciAN ET C. Ravenna. Sintesi delta salicina per mezzo delle piante, Atti. R. 

Accad. Lincei, 1909, [v], z8, i., 419-422. 

G. CiAMiciAN ET C. Ravbnna. Sulla formazione dei glucosidi per mezzo delle piante, 
Atti. R. Accad. Lincei, 1909, [v], z8, ii., 594-596. 

G. L. CiAMiciAN ET C. Ravenna. Sul contegno delV alcool benzilico delle piante, Atti. 
R. Accad. Lincei, 191 1, [v], 20, i., 392-394. 

A. CoLLEY. Action des Haloides libres et de quelques Chlorures sur la Glucose, Ann. Chim. 
phys., 1870, [iv], 21, 363-377- 

R. Drouin. Reactions et la composition de thymolglucoside et de Va-naphtholglucoside. 
Bull. Soc. Chim., 1895, [iii], 13, 5. 



BIBLIOGRAPHY 229 

E. Fischer. Synthetic glucosides of the purines, Ber., 1914, 47, 210-235, 1058-1061, 

i377-i393» 3193-3205. Bayer & Co., D.R.P. 281008. 
E. Fischer und E. F. Armstronq. Synthese der Glucoside, I., II., III. Ber., 1901, 54* 

2885-2900; 1902, 35, 833-843 ; 3153-3155. 
E. Fischer and M. Bbrgmann. Synthesis of mandelonitrile glucoside, samhunigrin, and 

similar substances. Ber., 1917, 50, 1047- 1069. 

E. Fischer and M. Bbrgmann. Further synthesis of glucosides by means of acetobromo- 
glucose and quinoline. Ber., 1917, 50, 711-722. 

E. Fischer und K. Delbruck. Thiophenolglucoside. Ber., 1909, 42, 1476- 1482. 

E. Fischer und H. Fischer. Zwei neue Glucoside. Ber., 1910, 43, 2521-2536. 

E. Fischer und B. Helferich. Neue synthetische Glucoside. Annalen, 1911, 3831 68-91. 

E. Fischer and L. von Mechbl. Synthesis of phenol glucosides. Ber., 1916, 49, 
2813-2820. 

E. Fischer und K. Raske. Synthese einiger Glucoside. Bar., 1909, 42, 1465- 1476. 

E. Fischer, H. Strauss and J. Severin. Synthesis of phenolic glucosides. Ber., 1912, 

4& 2467-2474. 
J. HXm ALAiNEN. Synthetic ^glucosides of terpene alcohols. Biochem. Zeitsch., 1913, 49, 
398-412; 50, 209-219; 53, 423-428; 1914, 61, 1-5- 

H. HiLDEBRANDT. Bomcolglucosid. Biochem. Zeitsch., 1909, 21, i. 

J. C. Irvine and A. Hynd. Synthetic aminoglucosides derived from d-glucosamine. J. 
Chem. Soc, 1913, Z03, 41-56. 

J. C. Irvine and R. E. Rose. Constitution of salicin. Synthesis of pentamethyl salicin, 
J. Chem. Soc, 1906, 89, 814-822. 

C. Mannich. Morphine glucoside. Annalen, 1912, 394, 223-228. 

F. Mauthner. Die Synthese der Glucosyringasaure. J. prakt. Chem., 1910, 82, 271-274. 

F. Mauthner. Synthese der Glucovanillinsdure und der Gluco-p-oxybenzassaure. J. 
prakt. Chem., 1910, [ii], 82, 271 ; 1911, 83, 556-560. 

F. Mauthner. Synthesis of glucovanillic acid^ etc. J. pr. Chem., 191 1, [ii], 831 556-560. 
F, Mauthner. Synthesis of picein^ the glucoside of the pine {Pinus picea). J. pr. Chem., 

1913, [ii], 88, 764-770. 
A. Michael. Synthesis ofhelicin and phenolglucoside. Amer. Chem. J., 1879, z, 305-312. 

A. Michael. Synthetical researches in the glucoside groups II. Amer. Chem. J., 1883, 5, 
171-182. 

A. Michael. Synthetical researches in the glucoside group, III. Amer. Chem. J., 1884, 

6y 336-340. 

A. Michael. Die Synthese des Methylarbutins. Ber., 1881, 14, 2097-2102. 

H. Ryan. Synthetical preparation of glucosides. J. Chem. Soc, 1899, 75, 1054-1057. 

H. Ryan and W. S. Mills. Preparation of synthetical glucosides. J. Chem. Soc, 1901, 

79, 704-707. 
H, Ryan and G. Ebrill. Synthesis of glucosides. Some derivatives of arabinose. Proc 

Roy. Irish Acad., 1903, 24, 379-386. 

H. Ryan and G. Ebrill. Synthesis of glucosides. Some derivations of xylose. Sci. Proc* 
Roy. Dubl. Soc, 1908, 11, 247-252. 

H. Ryan and W. S. Mills. Preparation of synthetical glucosides. J. Chem. Soc, 1901, 

79, 704-707. 
A. H. Salway. Synthetic preparation of glucosides of sitosterol, cholesterol, and some fatty 

alcohols. J. Chem. Soc, 1913, 103, 1022-1029. 
W. Schneider. Mustard oil glucosides, III. and IV. Synthetic glucosides from thioure- 
thane. Ber., 1914, 47, 1258- 1269, 2218-2224. 

P. Schutzenberger. Synthese von Glucosiden mittelst der Acetylderivate der Zuckerarten. 
Annalen der Pharmacie, 1871, i60y 95-100. 

REFERENCES TO GLUCOSIDE ENZYME SYNTHESIS. 

A. Aubry. Most appropriate experimental conditions for the biochemical pteparation of 
a-methyl and a-ethyl glucosides. J. Pharm. Chim., 1914, [vii], 10, 202-207. 

A. Aubry. Specific nature of a-glucosidase. J, Pharm. Chim., 1914, [vii], zo, 23-^6. 

A. Aubry. Influence of alcohol concentration and temperature on the biochemical synthesis 
of a-methylgalactoside. J. Pharm. Chim., 1916, [vii], 14, 289-294. 



230 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

G. Bertrand and a. Compton. Supposed reversibility of the hydrolysis of salicin by 
enzymes, Compt. rend., 1912, 154, 1646-1648. 

E. BouRQUBLOT. Synthesis ofglueosides by means of ferments. Bull. Soc. chim., Z913, 

E. BouRQUBLOT. Specific action of enzymes considered from the point of view of thdr syn- 
thetic power, J. Pharm. Chim., 1914, [vii], 9, 603-606. 

E. BouRQUBLOT. Biochemical synthesis of A-glucosides of monohydric alcohols, II. 
a-Alkyl-d-glucosides, Ann. Chim., 1915, [ix], 3, 287-337. 

E. BouRQUBLOT. Biochemical synthesis of alkyl glucosides. III. Monoglucosides of poly- 
hydric alcohols, Ann. Chim., 1915, [ix], 4, 310-379. 

E. BouRQUBLOT. Rototory powers of the a- and fi-alkyl-d- glucosides and alkyl-d-galac- 
tosides, Compt. rend., 1916, 163, 374-377. 

E. BouRQUBLOT. The biochemical synthesis of alkyl glucosides, IV. Alkyl galactosides. 
Ann. Chim., 1917, [ix], 7, 153-226. 

E. BouRQUBLOT AND A. AuBRY. Influence of strength of alcohol on biochemical synthesis 
of glucosides. Compt. rend., T914, 158, 70-72. J. Pharm. Chim., 1914, [vii], 9, 
19-23, 62-66. 

E. BouRQUBLOT AND A. AuBRY. Influence of acetic acid on synthesising and hydrolysing 
properties of a-glucosidase, Compt. rend., 1915, z6o» 742-745. J. Pharm. Chim., 
1915, [vii], 12, 15-22. 

E. BouRQUBLOT AND A. AuBRY. Influence of sodium hydroxide on synthesising and hydro- 
lysing properties of a-glucosidase. Compt. rend., 191 5, 16I9 184-186. 

E. BouRQUBLOT AND A. AuBRY. Biochcmical synthesis^ by means of a-glucosidase ^ of the 
a-monoglucoside of ordinary propylene glycol, Compt. rend., 1915, l6lt 364-367. 
J. Pharm. Chim., 1915, [vii], 12, 283-289. 

E. BouRQUBLOT AND A. AuBRY. The activity f during biochemical synthesis by fi-glucosidcue^ 
of the other ferments accompanying it tn emulsin. Compt. rend., 1915,161)463-466. 
J. Pharm. Chim., 1915, [vii], 12, 305-314. 

E. BouRQUBLOT AND A. AuBRY. Biochemical synthesis of $-salicylgalacfeside, Compt. 
rend., 1916, z62, 610-612. J. Pharm. Chim., 1916, [vii], 13, 273-279. 

E. BouRQUBLOT AND A. AuBRY. Biochcmicol synthesis of a-propyl-d-galactoside by means 
of a ferment contained in the air-dried bottom yeast of beer, Compt rend., 1916, 16$, 
312-315. J. Pharm. Chim., 1916, [vii], 14, 193-199. 

E. BouRQUBLOT AND A. AuBRY. Influence of acetic acid on the synthesising and hydrolys- 
ing properties of $-glucosidase, J. Pharm. Chim., 1916, [vii], 14, 359-363. 

E. BouRQUBLOT AND M. Bridel. Synthetic actions of emulsin in alcoholic solutions. 
Compt. rend., 1912, 154, 944-946, 1375-1378, 1646-1648, 1737-1739. J. Pharm. 
Chim., 1912, [vii], 6, 13-18. Compt. rend., 1912, 155, 319-322. 

E. BouRQUBLOT AND M. Bridbl. Synthesis of alkylglucosides by means of emulsin, 

Compt. rend., 1912, 155, 86-88, 437-439, 523-524, 854-857. J. Pharm. Chim., 1912, 

[vii], 6, 298-301, 442-445. 
E. BouRQUBLOT AND M. Bridbl. Synthesis of alkyl glucosides by means of emulsin. 

Compt. rend., 1913, 156, 827-829. J. Pharm. Chim., 1913, [vii], 7, 335-340. Ann. 

Chim. Phys., 1913, [viii], 28, 145-218. Compt. rend., 1913, 157, 72-74. J. Pharm. 

Chim., 1913, [vii], 8, 109-112. Compt. rend., 1913, 157, 405-408. 

E. BouRQUBLOT and M. Bridbl. Synthesis of alkyl galactosides by means of emulsin, 
Compt. rend., 1913, 156, 1 104- 1 106. J. Pharm. Chim., 1913, [vii], 7, 444-448. 
J. Pharm. chim., 1913, [vii], 8, 108-109. 

E. BouRQUBLOT and M. Bridbl. Reversibility of ferment cu:tions, Ann. Chim. Phys., 
1913, [viii], 28, 145-218. 

E. BouRQUBLOT and M. Bridbl. Identity of hydrolytic and synthetic activities of 

emulsin, J. Pharm. Chim., 1913, [vii], 8, 15-19. 
E. BouRQUBLOT AND M. Bridbl. Biochemical Synthesis of o-glucosides, Compt. rend., 

1913* IS7> 1024-1027 ; 158, 1219-1222. J. Pharm. Chim., 1914, [vii], 9, 514-519. 
E. BOURQUBLOT AND M. Bridbl. Biochcmical synthesis of $-glucosides, Compt rend., 

I9i4» 158, 898-900. J. Pharm. Chim., 1914, [vii], 9, 383-388. 
E. BouRQUBLOT AND M. Bridel Fermentation equilibria. Division and displacement in 

an alcoholic medium containing glucose and two glucosidases, Compt. rend, 1914, 

I58» 370-373. J. Pharm. Chim., 19141 [vii], 9> 155-158. 
E. BOURQUBLOT, M. Bridbl and a. Aubry. Biochemical synthesis, by means of emulsin, 

of the $-monoglucoside of ordinary propylene glycol, Compt rend., 1915, 160, 

214-216. 



BIBLIOGRAPHY 231 

£. BouRQUBLOT, M. Bridbl and a. Aubry. Biochemical synthesis of the fi-mono- 
galactoside of ethylene glycol, Compt. rend., 1915, x6o» 571-573. J. Pharm. Chim., 
igi5, [vii], zz, 201-204. 

E. BouRQUELOT, M. Bridel and a. Aubry. Biochemical synthesis of the a-mono- 
galactoside of ethylene glycol. Compt. rend., 1915, z6o, 674-676. J. Pharm. Chim., 
1915, [vii], zz, 290-294. 

£. BouRQUBLOT, M. Bridbl and a. Aubry. Glucosidificaiion of glycerol by fi-glucosidase 

(emulsin). Compt. rend., 1915, z6o» 823-825. J. Pharm. Chim., 1915, [vii], 12 
33-34. 

£. BouRQUBLOT, M. Bridbl and a. Aubry. Glucosidificaiion of glycerol by a-glucosidase, 
Compt. rend., 1915, z6z, 41-43. 

£. BouRQUELOT, M. Bridel and a. Aubry. Crystallisation and properties of a fi-mono- 
glucoside of glycerol previously obtained by biochemical synthesis. Compt. rend., 1917, 
164, 831-833. 

£. BouRQUBLOT AND J. CoiRRE. Reversibility of ferment action of emulsin. Compt. 
rend., 1913, ZS6, 643-646. J. Pharm. Chim., 1913, [vii], 7, 236-240. 

£. BouRQUELOT AND H. Hbrissey. Synthesis of alkylgalactosides by means of emulsin, 
Compt rend., 1912, Z55, 731-733. J. Pharm. Chim., 1912, [vii], 6, 385-390. 

£. BouRQUELOT AND H. H&RissEY. Synthesising action between galactose and ethyl 
alcohol under the influence of kephir. Compt. rend., 1912, 155, 1552-1554. BiO' 
chemical synthesis, by means of emulsin^ ofaglucoside isomeric with salicin. Ibid., 

1913, 156, 1790-1792. 

£. BouRQUELOT, H. HBRISSEY AND M. Bridel. Synthesis of alkyl galactosides by means 
of emulsin. Compt. rend., 19 13, Z56, 330-332. 

E. BouRQUBLOT, H. Herissby and M. Bridel. Synthesis of alkyl a-glucosides by 
means of a-glucosidase. Compt. rend., 1913, Z56> 168-170, 491-493, 1493-1495. J. 
Pharm. Chim., 1913, [vii], 7, 233-236, 525-529. 

E. BouRQUELOT AND A. LuDwio. Biochemical synthesis of fi-glucosides {of aromatic 
alcohols), Compt. rend., 1914, z^ 1037-1040, i377-i379 ; I9i4» IS9» 213-215. J. 
Pharm. Chim., 1914, [vii], 9, 441-446, 542-547; 1914, [vii], 10, 111-116. 

E. BouRQUELOT AND G. MouGNE. Biochemical synthesis of fi-ethyl galactoside. J. 
Pharm. Chim., 1914, [vii], zo, 157-163. 

E. BouRQUBLOT AND E. Verdon. Reversibility of ferment actions, Compt. rend., 1913, 
1561 957-959. J. Pharm. Chim., 1913, [vii], 8, 19-21. Biochemical synthesis ofglucoside 
in neutral liquid, not participating in the reaction. Compt. rend., 19 13, Z56, 1264- 
1266. J. Pharm. Chim., 1913, [vii], 7, 482-486. 

E. BouRQUBLOT AND E. Verdon. Usc of increasing proportions of glucose in the bio- 
chemical synthesis of ^-methyl glucoside ; influence of the glucoside formed on the 
arrest of the reaction, Ann. Chim. Phys., 1913, [viii], 28, 145-218. 

J. CoiRRB. Optimum experimental conditions for biochemical synthesis of $-ethyl glucoside. 
J. Pharm. Chim., 1913, [vii], 8, 553-559. 

J. Hamalainen. Synthesis of glucosides of terpene alcohols by means of emulsin. Biochem. 
Zeitsch., 1913, 52, 409-411. 

J. Hamalainen. Biochemical oxidation of certain glucosides. Chem. Zentr., 1913, [ii], 
1319; from Skand. Arch. Physiol., 1913, 30, 187-190. 

H. HiRissEY AND A. AuBRY. Biochemical synthesis of a-galactosides, Compt rend., 

1914, XS8, 204-205. J. Pharm. Chim., 1914, [vii], 9, 225-230, 327-331. 

G. MouoNE. fi'Galactosidase in the vegetable kingdom, J. Pharm. Chim., 1917, [vii], Z5, 

339-345. 
G. MouGNE. Preparaiion of fi-ethylgalactoside by means of kernels of apricots, peaches, 

etc. J. Pharm. Chim., 1917, [vii], Z5, 345-348. 

REFERENCES TO THE FUNCTION OF CARBOHYDRATES AND 

GLUCOSIDES IN PLANTS. 

H. E. AND E. F. Armstrong. Function of hormones in stimulating enzymic change in 
relation to narcosis and the phenomena of degenerative and regenerative change in 
living structures Proc. Roy. Soc, 1910, 82 B, 588-602. 

H. E. AND E. F. Armstrong. The function of hormones in regulating metabolism. Studies 
on enzyme action, xiv, Ann. Bot., 1911, 98, 507-519. 

H. E. AND E. F. Armstrong. The differential septa in plants with reference to the 
translocation of nutritive materials. Proc. Roy. Soc, 191 1, 84 B, 226-229. 



232 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 

H. £. Armstrong, E. F. Armstrong and E. Horton. Herbage studies, I. Lotus 
Corniculatus, a cyanophoric plant, Proc. Roy. Soc., 1912, 84 B, 471-484. 

M. Bridbl. Variations dans la composition de la rapine de Gentiane au cours de la 
vegetation d*une annie, J. pharm. Chim., igii, [vii], 3, 294-305. 

R. Chodat. Nouvelles recherches sur les ferments oxydant, IV. et V. Arch. Sci. Phys. 

nat., 1912, 33, 70-95, 225-248. 
G. CiAMiciAN ET C. Ravbnna. Sul contegno di alcune sootanze organiche net vegetali, 

Gazetta, 1908, 38, i, 682-697. Atti. R. Accad. Lincei, 1909, z8. i, 419-422. 
C. L. CiAMiciAN and C. Ravenna. Formation of glucosides by means of plants. Atti. R. 

Accad. Lincei., 1916, [v], 25, [i], 3-7. 
S. H. Collins and H. Blair. Rate of liberation of hydrogen cyanide from commercial 

varieties of linseed, Chem. News, 1915, ill, 19-20. 

R. CooMBES. Du rdle de Voxyg&ne dans la formation et la destruction des pigments 
rouges anthocyaniques chez les vegetaux, Compt. rend , 1910, 150, 1186-1189. 

T. Curtius und H. Franzen. Ueber die ckemischen Bestandtheile gruner PJlanzen, 

Ueber den Bldtteraldehyde, Annalen, 1912, 390, 89-129. 
W. R. DuNSTAN AND T. A. Henry. The nature and origin of the poison of Lotus arabicus, 

Proc. Roy. Soc., 1900, 67, 224 ; 1901, 68, 374-378. Phil. Trans. Roy. Soc, 190 1. 

X94 B, 515-533. 
A. GoRis. Role of glucosides in plants, Chem. Zentr., 1916 [i], 851. 
L. GuiGNARD. Sur la localisation des principes actifs des cruciferes, Compt. rend., 1890, 

III, 249, 920. 
L. GuiGNARD. Sur quelques proprietes chimiques de la myrosine. Bull. Soc. Bot., 1894, 

Z, 418. 
L. GuiGNARD. Influence de Vanathesie et du gel sur le dedoublement de certains glucosides 

chez les piantes, Compt. rend., 1909, 149, 91-93. 

H. Hasselbring and L. A. Hawkins. Transformation of carbohydrates in sweet potatoes. 

J. Agric. Research, 1915, 6, 543-560. 
Jadin. Localisation de la myrosine et de la gomme chez les moringa, Compt. rend., 1900, 

130, 733. 
H. A. D. JowETT AND C. E. PoTTER. Variations in the occurrence ofsalicin and salinigrin 

in different willow and poplar barks, Pharm. J., 1902, August 16. 

F. Kbbblb AND E. F. Armstrong. The distribution of oxydases in plants and their role 
in the formation of pigments, Proc. Roy. Soc., 1912, 85 B, 214-218. 

C. Lefebvre. Anwendung der biochemischen Methode zum Nachweis der Zuckerarten 
und der Glykoside in den Pflanzen der Familie der Taxinen, Arch. Pharm., 1907, 
245* 493-502. J. pharm. Chim., T907, 26, 241-254. 

H. ter Meulen. Sur quelques glucosides contenant des senevols. Rec. trav. Chim., 
1900, 19, 37-45. 

M. Mirande. Influence exerchpar certaines vapeurs sur la cyanogenese vegetale, Procede 
rapide pour la recherche des piantes d acide cyanhydrique, Compt. rend., 1909, 149, 
140-142. 

E. Overton. Auftrefen von rothem Zellsaft bet PJlanzen, Prings. Jahr. f. wiss., Bot., 
1899, vol. 33. 

W. Palladin. Bildung der verschiedenen Atmungsenzyme in Abhdngigkeit von dem 
Entwicklungs-stadium der Pflanzen, Ber. Bot. Ges., 1906, 24, 97-107. Die Arbeit der 
Atmungsenzyme der Pflanzen unter Verschiedenen Verhdltnissen, Zeitsch. physiol. 
Chem., 1906, 47, 406-451. 

W. Palladin. Die Verbreitung der Atmungschromogene bei den PJlanzen, Ber. Bot. Ges., 
1908, 26a, 378-389- 

W. Palladin. Ueber die Wirkung von Giften auf die Atmung lebender und abgetdteter 
Pflanzen sowie auf Atmungsenzyme, Jahrbiicher Wiss. Botanik, 1910, 47, 431-461. 

W. SiGMUND. Ueber salicinspaltende und arbutinspaltende Enzyme. Monatsh., 1909, 

30, 77-87. 

W. SiGMUND. Ueber ein askulinspaltendes Enzym und ueber ein fettspaltendes Enzym in 
Aesculus Hippocastanumf L, Monatsch., 1910, 31, 657-670. 

A. E. Vinson. The endo- and ecto-invertase of the date, . J. Amer. Chem. Soc., 1908, 
30, 1005-1020; 1910, 32, 208. 

J. ViNTiLESco. Rdle of glucosides in plants, Chem. Zentr., 1916, [i], 851. 

O. Walther. Zur Frage der Indigo Bildung, Ber. Deut. bot. Ges., 1909, 27, 106-110. 



BIBLIOGRAPHY 233 

Marshal Ward and Dunlop. On some points on the histology and physiology of the 
fruits and seeds in Rhamnus, Ann. of Botany, 1887, x, i. 

Th. Weevbrs. Die physiologische Bedeutung einiger Glykoside, Proc. K. Akad. 
Wetensch., Amsterdam, 1909, X2, 193-201. 

M. Whbldalb. Plant oxydases and the chemical inter-relationships of colour-varieties. 
Prog. Rei. Bot., 1910, 3, 457-474. 

M. Wheldale. On the formation of anthocyanin. J. of Genetics, 1911, x, 133-158. 

M. Wheldale. The chemical differentiation of species, Biochem. J., 191 1, 5, 445-456. 

REFERENCES TO RIPENING OF FRUITS. 

E. M. Bailey. Studies on the banana, J. Biol. Chem., 1906, i, 355-361. 

C. Gerber. Recherches sur la maturation des fruits charnus, Ann. Sc. Nat. Bot., 1896, 
[viii], 4, 1-279. 

H. C. Prinsen Geerligs. Rapid changes in some tropical fruits during their ripening, 
Proc. K. Akad. Wetensch., Amsterdam, 1908, xx, 74-84. 

W. Kblhofbr. Distribution of sugar , acid and tannin in apples, Chem. Soc. Abstr., 
1909, ii., 1047. 

F. E. Lloyd. Ueber den Zusammenhang zwischen Gerbstoff und einem anderen Kolloid 

in reifenden Fruchten, insbesondere von Phbnix^ Achras und Diospyros. Zeitsch. 
Chem. Ind. Colloide, 191 1, 9, 65-73. 

R. Otto und W. t). Kooper. Beitrdge zur Kenntnis des ** Nachreifens " von Fruchten. 
Zeitsch. Nahr. Genussm., 1910, XQ, 10. 

F. ScuRTi AND G. De Plato. The chemical processes of ripening. The ripening of 

oranges, Chem. Soc. Abstr., 1909, ii, 174, from Staz. sperim. agrar. ital, 1908, 4X, 
435-455- 

G. Tallarico. The hydrolytic and catalytic ferments acting during the process of ripen- 

ing of fruit, Chem. Soc. Abstr., iqo8, ii, 724. 

K. YosHiMURA. Beitrdge zur Kenntnis der Banane. Zeitsch. Nahr. Genussm., 191 1, 2X, 
406-411. 



INDEX. 

The references in heavy type denote the more detailed descriptions of the compounds or 

subjects indexed. 



ACBTOBROMOGLUCOSE, 27-29, 33. 

Acetochloroglucoses, 22, 26, 33. 
Acetonitroglucoses, 26, 33. 

Acrose, X34-Z3S ^i?* 

Adonitol, 87, 88, 127. 

Aesculin, 151, 152, 157. 

Agrostemma sapotoxin, 153, 178. 

Aldehydes from carbohydrates, 199. 

AUiin, 73, 150. 

AUose, 35, 36, 38, 70. 

Aloinose, 78. 

Altrose, 35, 36, 38, 70. 

Aminoglucosides, synthetic, 64, z82. 

Aminohelicin, 1&2. 

Aminohexoses, 61-67. 

Aminosalicin, i82. 

Amygdalase, 151, 154, 171. 

Amygdalin, 150-152, 170. 

Anhydroglucose, A, 

Anhydromentholglucoside, 29. 

Anhydromethylglucoside, 28. 

Anhydrosedoheptose, 85. 

Anhydrosorbitol, 29. 

Anthocyan glucosides, 163-165, 193-195. 

Anthoxanthin glucosides, 158-163. 

Antiarin, 150. 

Apiin, 152, 159. 

Apiose, 86, 159* 

Arabinoketose, 137. 

Arabinose, 23, 24, 36-38, 70, 72, 78-82, 

150. 

— tetracetate, 41. 

Arabitol, 87, 88, 126. 
Arbutin, 151, 152, 155. 
Aucubin, 151, 154. 

Baptisin, 150, 152. 
Barbaloin, 78, 150, 154, 169. 
Benzylphenylhydrazones, 50. 

— rotatory power, 43. 
Bornesitol, 94. 
Bromomethylfurfuraldehyde, 75. 

Calmatambin, 154. 
Campferitrin, 150, 152, z6o. 
Cane sugar, see Sucrose. 
Carbohydrates, classification of, 1-3. 

— formation in mangold, 139. 

potato, 140. 

snowdrop, 139. 

Tropaeolum, 139. 

— symbols for stereoisomerides, 37, 38. 
Carnose, 79. 



127, 



Caulophyllosaponin, 153, 179. 
Caulosaponin, 153, 179. 
Cellose, 23, 24, 97, Z04-105. 

— octacetate, 41. 
Cerebrose, 73. 
Cerebrosides, 73. 
Chinovin, 83. 
Chinovose, 83. 
Chitin, 61. 
Chitosamine, 61-63. 
Chitose, 62. 

Cholesterol glucosides, synthetic, i8z. 
Chondroitin, 66. 

— sulphuric acid, 65. 
Chondrosamine, 65-67. 

— pentacetate, 41, 67, 
Chrysin glucoside, 159. 
Cocositol, 94. 
Coniferin, 151, 152, X57, 
Convallamarin, 150. 
Convolvulin, 83, 150, 152. 
Convolvulinic acid, 83. 
Coumarin glucosides, 157. 
Cyanin, 153, 164. 
Cyanohy^in syntheses, 58, 81, 83. 
Cyanophoric glucosides, Z75-Z76. 
Cycloses, 90-95. 

Cymarin, 153, z66. 
Cjrmarose, 86, 166. 



Dambonitol, 94. 

Dambose, 93. 

Daphnin, 152, Z57. 

Datiscin, 150, 154. 

Degradation of sugars, 59, 60. 

Delphinin, 153, Z65. 

Dextrose, see Glucose. 

Dhurrin, 152, Z75, 

Diastase, loi, 102, 108. 

Dibenzoylglucoxylose, 154, Z70. 

Dibromotriacetylglucose, 28. 

Digitalin, 153, Z65. 

Digitalis glucosides, 165-167. 

Digitalose, 86. 

Digitonin, 150, 153, z6S 178. 

Digitosaponin, 153, 178. 

Digitoxin, 153, 165. 

Digitoxose, 86, 166. 

Dimethyl glucoses, 3Z-53. 

Dioxyacetone, 3, 70, 118, 126, 137. 

Diphenylhydrazones, 50. 

Diphenylmethane dimethylhydrazones, 50. 

Disaccharides, 96-IZO. 

335 



236 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 



Disaccharides, behaviour to enzymes, 98. 

— hydrolysis of, 129. 
Dulcitol, 53, 72, 87, 88, 126, 127. 

Emulsin, II, 31, 65, 98, 101-106, 108, no, 
III, 113, 120-124, 141. i47» 150. 151. 
154, 167, 171, 172, 184-186. 

Enzymes, attachment of, to carbohydrates, 
122-124. 

— balance, and carbohydrates, 195-196. 

— detection of glucosides, 151. 

— hydrolytic action of, 134. 

— nomenclature, 120. 

— oxidising, 126. 

— synthesis of glucosides, 184-186. 
Epimerism, 10. 

Epirhodeose, 70, 83. 
Erythritol, 86-88, 126. 
Erythrose, 38, 70, 80. 
Erythrozjrm, 158. 
Erythrulose, 70, 87. 
Ethylthioglucosides, 183. 
Euxanthic acid, 56, 152, z62. 
Euxanthone, 56, z62. 

Fatty acids, from carbohydrates, 199. 
Fermentation, z 15-1 19. 

— intermediate products of, 118. 
Flavones, 83, z62, i93-i95- 
Formaldehyde, i, 3, 137, 138, 141. 
Frangulin, 150, 152, z6o. 
Fraxin, 152, Z57. 

Fructose, 6, 23, 24, 70, 73-77, 106, 108, in, 
115, 119, 126, 128, 134, 137, 150. 

— behaviour to alkalies, 45-49. 

— butylene oxide forms, 74. 

— ethylene oxide forms, 13, 74. 

— methylphenylosazone, 76. 

— mono- and diacetones, 76. 

— rotatory power, 39. 
Fructoseazine, 64. 
Fructosides, 13. 
Fucose, 23, 70, 83. 
Furfiiraldehyde, 82. 
Fustin, 150, 152, z6o. 

Galactoarabinose, 107. 

Galactobioses, synthesised by emulsin, 143, 

147. 
Galactoheptitol, 85. 
Galactoheptose, 71, 84. 
Galactonic acid, 55. 

— phenylhydrazide, 42. 
Galacto-octose, 71. 

Galactose, 23, 24, 35, 38, 70, 72-73, 78, 81, 
no, 117, 126, 127, 150. 

— conversion into glucose, 124. 

— ethylene oxide forms, 73, 144, 145. 

— pentacetates, 25, 41. 
Galactosides, 97, 106-109. 
Galactosidoglucose, 143. 
Galacturonic acid, 57, 58, 126. 
Galangin glucoside, Z59. 
Gaultherase, 154, 157. 
Gaultherin, 152, Z57. 
Gentianose, 97, 106, ZZ2, 128, 192. 
Gentiin, 150, 154. 

Gentiobiose, 97, 105, Z06, 112, 147, 192. 



Gentiobiose, biochemical synthesis, 106. 

— octacetate, 41. 
Gentiopicrin, 154, 192. 
Gentisin, z62. 
Gitalin, 153, 166. 
Gitin, 153. 

Gitonin, 153, z66. 
Glucal, 39, 79. 
Glucocheirolin, 153, 169. 
Glucodecose, 71. 
Glucoheptose, 23, 24, 71. 

— hexacetate, 41. 
Gluconic acid, 54, 55, 117, 126. 

— phenylhydrazide, 42. 
Glucononose, 71. 
Gluco-octose, 71. 
Glucoproteins, 65. 
Glucosamine, 6Z-63. 

— pentacetate, 41, 67. 
€- Glucosamine, 64. 
Glucose, anilides, 33. 

— behaviour to alkalies, 45-49. , 

— butylene oxide forms, 9, Z5-Z8. 

— conductivity, 19. 

— configuration, 36-38. 

— constitution, 6. 

— conversion to ^-isorhamnose, 84. 

— diacetone, 31. 

— enolisation, 45, 115. 

— ethylene oxide forms, Z3. • 

— fermentation, ZZ5-ZZ9. 

— formula, 7-9. ^ 

— hydrazones, 33. 

— mercaptals, 32. 

— monoacetone, 32. 

— osone, 52, 117, 127. 

— oxidation, 54, 126. 

— oximes, 33. 

— pentabenzoates, 28. 

— pentacetates, 22, 24-26, 33» 4it 67. 

— phenylhydrazones, 49-50. 

— phenylosazone, 5Z-52. 

— reduction, 53. 

— solubilities, initial and final, 24. 

— sjmthesis, 58. 

— tetracetates, 28. 
Glucoseimine, 63. 
Glucosides, 97-106, 109, Z49-Z86. 

— and animal nutrition, 189-191. 

— biochemical detection of, 151. 

— hydrolysis of, 120. 

— natural, 149-179. 

— significance of, 187-189. 

— synthetic, 180-186. 

— table, 152-154. 
Glucosidogalactose, 143. 
Glucosidogallic acid, 69. 
Glucotropaeolin, 153. 
Glucovanillin, 157. 
Glucoxylose, 170. 
Glucuronic acid, 54, 56, 57» ^79* 
Glyceric acid, configuration, 81. 
Glycerose, 3, 38, 70, 80. 

— synthesis of active forms, 80, 8z. 
Glycol glucosides, rotatory powers, 41. 
Glycollic acid glucoside, 103. 

— aldehyde, 3, 70, 137. 
Glycyphyllin, 150, 152. 



INDEX 



237 



Gossypitrin, 152, x6z. 
Gulose, 35, 37, 38, 70, 78, 83. 
Gynocardin, 154, 175. 
Gypsophila sapotoxin, 153, 178. 

Hederin, 153, 179. 

Helicin, 152, 156. 

Hesperidin, 150, 152. 

Hexonic acid lactones, rotatory power, 42. 

— phenylhydrazides, rotatory power, 42. 
Hexosamic acids, rotatory power, 66. 
Hexose phosphates, 67, 116, 1X8, 119. 
Hydroflavone glucosides, 158-163. 
Hydroglucol, 29. 

Hudson's rule (rotatory power), 59-431 66, 81. 

IDAIN, 153, Z64. 

Iditol, 87. 

Idose, 35, 38, 70, 78. 

Incarnatrin, 152, z6o. 

Indican, 151, 154, 167. 

Inosinic acid, 67, 68, 79. 

Inositol phosphoric acid, 94. 

Inositols, 90-95. 

Interconversion of glucose, mannose, fructose, 

45. 
Inulin, 73. 

Invertase, 75, 99, loi, 102, 104, 108, 109, iii, 

113, 128, 141, 147, 151. 

Iridin, 152. 

Isoglucosamine, 63. 

Isolactose, 97, 108. 

Isomaltose, 97, 104, 106, 142, 145, 146. 

Isoquercitrin, 152, i6l. 

Isorhamnetin, 160. 

Isorhamnose, 70, 83* 84. 

Isorhodeose, 83. 

Isotrehalose, 97, 102, 134, Z43, Z44. 

Jalapin, 152. 
Jegosaponin, 153, 179. 
Jesterin, 150. 

Kerasin, 73. 

#• 
Lactase, 102, 108, 120, 121, 125. 

— Kephir, 72, 105, io8, 109, 125. 
Lactones, rolatory power, 54, 55. 
Lactose, 23, 24, 97, 105, zo6-zo8| 125, 128- 

130, 133. 

— constitution, Z07. 

— octacetate, 41. 
Laevulinic acid, 75, 79. 
Laevulose, see Fructose. 
Laurocerasin, Z73. 
Laminareose, loi. 
Laminarin, loi. 

Levant sapotoxin, 153, Z78. 

Limettin, Z57. 

Linamarin, 152, Z75. 

Linase, 154. 

Lotusin, 152, X76. 

Lupeose, 113. 

Luteolin glucoside, Z59. 

Lyxose, 23, 24, 36-38, 7o» 80, 81, 83. 



Madder, 158. 

Maltase, 11, 12, 75, 98, 101-105, 108, 109, 

120-122, 141, 145. 
Maltose, 23, 24, 97, Z02-Z04, 130, 142, 146. 

— octacetate, 41. 

— rotatory power, 39. 
Malvin, 153, Z64. 

Mandelonitrile glucoside, Z72y Z74. 
Mannitol, 53, 71, 75, 87, 88, 90, 126, 127. 

— triacetone, 77, 89. 
Mannoheptitol, 84, 85. 
Mannoheptose, 71, 72, 84. 
Mannoketoheptose, 71, 84. 
Mannonic acid, 54, 55. 
Mannononose, 71, 118. 
Manno-octose, 71. 

Mannose, 23, 24, 35, 36, 38, 70, 7Z-72, 83, 
115, 127, 150. 

— behaviour to alkalies, 45-49. 

— pentacetate, 41. 
Mannotriose, 97, ZZO, 113. 
Melibiase, 108, iii. 
Melibiitol, 109. 

Melibiose, 23, 24, 73, 97. 108, Z09, iir, 133. 
Melicitose, 97, 109, ZZ2. 
Menthyl glucosides, synthetic, 182. 
Methylarbutin, 152, Z55. 
Methylfructosides, 75. 
Methylgalactosides, 121, 130-132. 

— ethylene oxide forms, 73. 
Methylglucoses, 14, 19, 22, 29-32. 

Methyl glucosides, Z0-Z4, 16, 22, 33, 117, 

120, 122, 130-132. 
Methylglycerose, 3, 70. 
Methylmaltoside, 103. 
Methylmannosides, 120. 
Methylpentoses, 82-84. 
Methylphenylhydrazones, 50. 
Methylrhamnosides, 121. 
Methylxylosides, 121. 
Monomethylglucoses, 3Z-33, 118. 

— rotatory powers, 41. 
Morin glucoside, 161, 
Mucic acid, 56, 72. 
Mucins, 65. 

Mustard oil glucosides, z68, Z69. 
Mutarotation, Z5-24, 39, 40. 

— of disaccharides, 98. 

— velocity-coefficients for various sugars, 

23- 
Myricetin, 161, 

Myrosin, 150, 154, 168, 184. 

Myrtillin, ,153, zd4. 



Narinqin, 152. 
Nomenclature of hexoses, 9. 
Nucite, 93. 

Nucleic acids, 36, 67, 78. 
Nucleoproteins, 78. 



Obnin, 153, Z64. 

Optical rotatory power of sugars, relation to 

configuration, 38-43, 54. 
Osones, 52. 
Ouabain, 150. 
O^onium compounds, 18-23. 



238 THE SIMPLE CARBOHYDRATES AND GLUCOSIDES 



Pabonin, 164. 

Parillin, 153, 178. 

Pectins, 58, 72. 

Pelargonin, 153, 164. 

Pentadigalloylglucose, 68. 

Pentamethylglucoses, 30^ 33. 

Pentamethylmannitol, 89. 

Pentosans, 79, 80. 

Pentoses, 4, 7M4. 

Peroxidase, sugars in, 200. 

Perseitol, 72, 84, 85, 88, 126. 

Perseulitol, 84. 

Perseulose, 71, 84* 

Phaseolunatin, 175. 

Phenol carboxylic acid glucosides, z8x. 

— glucosides, synthetic, 132, z82. 
Phenylhydrazones, 50, 52. 
Phenylosazones, 50-52. 
Phloridzin, 152, 155. 
Phrenosin, 73. 

Phytin, 94. 

Phytosterolin, 153, z8z. 

Picein, z82. 

Pinitol, 93. 

Polyamyloses, 113. 

Polygonin, 152. 

Polysciasaponin, 153, Z79. 

Populin, 152, 156. 

Prulaurasin, 152, 173. 

Prunase, 172. 

Prunasin, 152, Z72, Z73. 

Purgic acid, 83. 

Purine glucosides, synthetic, x8z. 

Purpurin, Z58. 

Pyridine, action on hexonic acids, 55. 

Pyruvic acid, 119, 127. 

QUBBRACHITOL, 93. 

Quercetagetin, z62. 

Quercimeritrin, 152, z6z. 

Quercitol, 91, 94, 95. 

Quercitrin, 83, 150, 153, z6o. 

Quillaic acid, 153, 178. 

Quinic acid, 91, 95. 

Quinoline, action on acetobromoglucose, Z83. 

— action on hexonic acids, 55. 
Quinovin, 150, 154. 

Raffinosb, 24, 73, 97, 109, zxz, 128, 151. 

Respiration in plants, 193-195. 

Revertose, 104, 145. 

Rhamnase, 154. 

Rhamnasin, 160. 

Rhamnetin, 11 1. 

Rhamninase, 11 1. 

Rhamninose, 97, 107, IZZ, 151. 

Rhamnose, 3, 23, 24, 70, 83^ iii, 127, 150. 

Rhodeose, 70, 83. 

Ribose, 35-38, 70, 78, 80, 150. 

— phosphoric acid, 68. 
Ripening of fleshy fruits, 196-198. 
Robinin, 150, 160. 
Ruber3rthric acid, 152, Z58. 
Rubiadin, 152, Z58. 

Rutin, 150, 153, 161, 

Saccharic acid, 36, 55, 56. 
Saccharinic acids, 48, 54. 



Saccharinic lactones, rotatory power, 42. 

Sambunigrin, 152, X73. 

Salicase, Z56. 

Salicin, 151, 152, ZS6, 186, 192. 

Salinigrin, 152, 157. 

Sapindus saponin, 150. 

Saponarin, 154. 

Saponins, 150, 176-Z79. 

Saporubrin, 153, X78. 

Sapotoxin, 150. 

Sarsasaponin, 153, 178. 

Scopolin, 152, Z57. 

Scyllitol, 94. 

Sedoheptitols, 85. 

Sedoheptose, 71, 85. 

Selenoisotrehalose, 144. 

Serotin, 153, x6x. 

Shikimic acid, 95. 

Sinalbin, 153, Z69. 

Sinigrin, 151, 153, 168. 

Skimmin, 152, X57. 

Smilacin, 153. 

Solanin, 150. 

Solubilities, initial and final, of sug^s, 24. 

Sophorin, 153. 

Sorbitol, 53, 75, 77, 87, 88, 126, 127. 

Sorbose, 70, 77, 78, 126, 137. 

Sphingosin, 73. 

Stachyose, 97, ZZ31 128. 

Stereoisomerides, 3, 4, 34-38. 

— of inositols, 92. 
Strophantin, 150, 153, z66. 
Strophantobiose, XZO, 166. 
Styracitol, 29. 

Sucrose, 24, 73, 97, 99-zoz, 102, 128, 129, 
133, 142, 151. 

— constitution, 99-zox. 

— phosphate, 67. 
Sunlight, action on sugars, 44. 
Synthesis, chemical, of sugars, 58, 59, X34- 

Z37, z4a.Z4S. 

— of sugars by enzymes, Z45-Z48. 

in the plant, X37-Z42. 

Syringin, 152, Z57, 169. 

Taoatosb, 70, 72, 117. 

Talonic acid, 55. 

Talose, 35, 38, 70, 72, 117. 

Tannins, 6l^-6g. 

Tartaric acids, 80. 

Taxicatin, 151. 

Terpene glucosides, synthetic, x8l . 

Terpenes, from saponins, 178. 

Tetramethylglucoses, 14, 19, 22, 30, 3X, 33. 

Tetramethyl methylglucosides, 14, 22. 

Tetroses, 4. 

Theophylline glucoside phosphoric acid, z8i. 

Thioglucose, 32. 

Thioisotrehalose, X44. 

Thiophenolglucoside, 183. 

Threose, 38, 70, 80, 87. 

Thujin, 153, 161. 

Thymus nucleic acid, 68, 79. 

Trehalase, loi. 

Trehalose, 24, 97, IOZ-Z02, 134, X43, Z44. 

Triacetylmethylglucoside bromohydrin, 28. 

Trifolin, 150. 

Trimethylglucoses, 32, 33, 105. 



INDEX 



Trioses, 4. 

Turanose, 97, X09, iii, 133. 

Turpethin, 150. 



Ultra-violbt light, action on sugars, 44. 



Vbrnin, 150, 154, Z69. 
Vicianase, 176. 
Vicianin, 150, 152, 176. 



Vicianose, zzo, 176. 
Volemitol, 8S 88. 



239 



Xanthopurpurin, 158. 

Xanthorhamnin, 83, iii, 150, 151, 153, I60. 

Xylonic acid, 82, 126. 

Xylose, 23, 36-38, 70, 78, 80-82, 150. 

— rotatory power, 39. 

— tetracetate, 41. 

Yeast nucleic acid, 68. 



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