LY A S D /3 FORMS O F THE SUGARS1
THE ISOILIERISM OF THE
BY ERNEST ANDERSON
Most chemists now assume t h a t the various crystalline modifications of the pentose and hexose sugars do not possess a free carbonyl group in the molecule but have a j-atomic lactone of the general type -~ 0 CH2OH - CHOH - C H - (CHOH)2 - C(0H)H. From this standpoint CY and 13 d-glucose have the same lactone and differ only in the space relations about the end asyrnmetric carbon atom which in one form has the structure -O\c/I1 -C/ \OH' in the other, the structure
-0 'Cc:", -C/ This same relation is supposed to hold for the CY and d forms of all pentoses and hexoses as well as for the corresponding glucosides. A careful comparison of the configurations of the sugars with their optical rotations led the author some years ago to conclude that the above-described assumptions may be incorrect and that CY d-glucose may have a qatomic lactone while 3 d-glucose may have a 3-atomic lactone,? and, furtherContribution from the Llassachusetts Agricultural College. Hedenburg: Jour. Akn.Chem. Soc., 37, 346 (191j). This requires that there be a t least four forms t o every sugar, two forms corresponding t o the CY lactone and two forms to the B lactone. Very probably these different forms will be discovered. Hudson (Jour. Am. Chem. SOC.,37, 1591 i 1 9 1 j ) ) shows that three penta-acetates of &galactose are known. Fischer (Ber. deutsch. chem. Ges., 47, 1980 (1914) has discovered three monomethylglucosides of dglucose. Nef (Liebig's Ann., 403, 2 7 3 , 306 (1914));Jour. Am. Chem. SOC.,37, 345 (1915)) with his assistants and students has isolated two lactones of d gluconic and d-mannonic acids. All of this indicates that much work remains t o be done in connection with the structure of the sugars and their derivatives. 2
27 0
Ernest &4nderson
more, that the same relation may also hold for the a and 9 forms of all pentoses and hexoses as well as the corresponding glucosides. I The principal evidence, aside from t h a t given by the work of Nef and his collaborators, in favor of the views presented here lies in the relation between the configuration and rotation of sugars. This is given below together with some other facts t h a t tend to support it It has long been known that the monobasic sugar acids form 5-atomic lactones. Hudson? has shown t h a t for all monobasic sugars acids forming lactones the position of the hydroxyl group on the y-carbon atom gil-es the direction of optical rotation of the lactone. For example d-gluconic acid is H H O H H CH20H - C - C - C - C - COOH. OH OH H OH The hydroxyl on the y-carbon atom is below the structure hence the lactone will be H H O H H CH2OH - C - C - C - C - C OH H OH
=
0.
L--O-__J
This lactone rotates dextro and the lactone of every other acid having the hydroxyl on the y-carbon atom below the structure will rotate dextro. If the hydroxyl on the y-carbon atom is above the structure, the lactone will rotate levo. The same relation holds for the lactones of all monobasic and some dibasic acids in the sugar and saccharinic acid groups3 The author pointed out (Jour. Am. Chem. SOC.,33, I j I o ( 1 9 1 r j j the close connection between the optical rotation of sugars and the configuration of the cy and B carbon atoms. The present esplanation was suggested b u t not given a t t h a t time (LOC.cit., 1j11).I n view of the large amount of theoretical and experimental work being published (Hedenburg, Fischer, Hudson, Nef) showing t h e insufficiency of the generally accepted views on the pentoses and hexoses, it seems t h a t the relations described in this article, together with the possible explanation, should be considered by chemists. Jour. Am. Chem. Soc., 32, 338 (1910). 3 Anderson: Ibid., 34, j r (1912).
Isonzerisw o j the
CY
axd /3 Forms o j thc Sxgars
271
The positions of the hydroxyl groups on the CY and /3 carbon atoms in acid lactones never affect the direction of rotation of the lactone. A comparison of d-mannonic with d-talonic lactone and of d-gluconic with d-galactonic lactone will make this clear. These four lactones have, in pairs, the same configuration about the CY, 9 and 6 carbon atoms but different configurations about the y-carbon atom. 0 0 0I 0
HOCH 1
' 0
HOCH
I
HOCH
HCOH
0
HOCH
HOCH
I
HC-I
HCOH
-~
CH
1
0
1
HCOH
0 HOCH
1
I HC-
I
I -__CH
I
HbOH
I
HCloH
HCOH
I
CHiOH
I
CHZOH
d-Talonic d-Xannonic lactone lactone [a],, = ~ j 6[elD= -[strongly)
CH2OH d-Gluconic lactone [.ID = 4-68
CH20H d-Galactonic lactone [.ID = -78
It is evident t h a t the y carbon atom determines the direction of rotation of the acid lactone; that the ct and 6 carbon atoms do not affect the direction of rotation of the acid lactone, and that acid lactones having the ring on the same side of the structure rotate in the same direction whereas acid lactones having the ring on opposite sides of the structure rotate in opposite directions. If sugars have j-atomic lactones they also should show the same relation between configuration and rotation that the acid lactones shorn. Such is not the case For sugars there is no connection between position of the hydroxyl on the y carbon atom and direction of rotation. On the other hand the positions of the hydroxyl groups on the CY and 9 carbon atoms give at once the direction of rotation of the two forms of the sugars.' Thus d-glucose and d-galactose have the same configurations about the oi and 8 carbon atoms I
Anderson Jour. Am Chem S O C ,33,
TjIo
(1911).
Ernest '4nderson
272
but different configurations about the Y carbon atom. All forms of these sugars rotate dextro. If CY d-glucose and a dgalactose are both 4-atomic lactones they have the ring on the same side of the structure and should rotate in the same direction. Also if P d-glucose and 13 d-galactose are both 3-atomic lactones they have the ring on the same side of the structure and should rotate in the same direction.' CY
&Galactose
LY
= +Ilo
[.ID
H
OH-L-oH
I
C-H
__ C
I
HO-C-H
I
H-C-OH I
CHzOH
p &Glucose
9 &Galactose = t j 3
[..ID
[.ID
H
I r-C-OH I I OH-C-OH
r C - O H
L__
= +I09
H
I
I
&Glucose
[LYID
H
I HC-OH I HC-OH I
CH20H
H
I
HO-C-
HO-C-7
H-C--
I
HO
C-H
HO
C-H
= +20
O
H-C--
I
1 0
HO-C-H
1
I I HC-OH I
H-C-OH
I
H-C-OH I
CH20H
CHzOH
If, however, these sugars have j-atomic, or Y lactones, d-galactose has the ring on one side of the structure and dglucose has it on the other side. Such lactones should rotate in opposite directions. The facts here indicate that the sugar lactones are not the same as the acid lactones. Furthermore, a I-rhamnose rotates levo while /3 I-rhamnose rotates dextro. If both a and 8 I-rhamnose have the y lactone they should rotate in the same direction. If, however, LY 1-rhamnose has a 4-atomic ring and 13 1-rhamnose has a
1
The +atomic
lactone, or p lactone, - C - C - C - H,
I
1
rotates
OH dextro and its image rotates levo. On the other hand, the 3 atomic lactone, H OH I 1 or CY lactone, - C - C - H, rotates dextro and its image levo LOA
Isomerism o j the
CY
and P Forms of the Sugars
273
3-atomic ring the two forms should rotate in opposite directions. The same is true for CY and p d-mannose. p I-Rhamnose
I-Rhamnose -7
CY
[a],
[a],
H
+31
H I
HO - C y ,
I
HO - C I
y O
HLOHO
C H-
H C-
HC-OH
I
HOCH HOCH
1
CH3
I
I I
HOCH HO-C-H
I
CH3
If the sugars form y lactones the ring in any acid lactone will be on the same side of the structure as the ring in the CY and fl forms of the corresponding sugars. Since d-gluconic acid lactone as well as CY and 8 d-glucose all rotate dextro it is natural to expect, if they all have the 5-atomic ring, that d-galactonic acid lactone, will rotate in the same direction as CY and P d-galactose. Such is not the case. The acid lactone here rotates levo while the CY and P forms of the sugar rotate dextro. Aside from the relations between rotation and configuration there are other facts indicating that sugars do not have the same rings as the acid lactones. According t o Baeyer’s Tension Theory, 3-atomic and 4-atomic rings should be unstable and should open readill-, whereas 5-atomic rings should be stable. It is well known that sugar rings are not stable but open with remarkable ease. The 5-atomic lactones of the sugar acids, on the other hand, are much more stable. The new 4-atomic lactones of d-mannonic and d-gluconic acids, described by Hedenburg and by Nef,’ are perfectly similar to the sugar lactones in the ease with which they open. 1
LOC.cit.
Ernest ,4nderson
2 74
There is a difference in the stability of the a and 0 forms of the sugars. If the two forms have different rings this would be expected, but if they differ merely in the position of H and OH on the end asymmetric carbon atom they should have the same stability. The same is true for the CY and /3 glucosides. The difference between the specific rotations of the CY and p forms of a sugar is too great to be caused merely by a difference of H and OH on the end carbon atom. This difference between the specific rotations of the a and forms of a sugar where these are accurately known is usually above 65" and generally 80" to 100'. The difference in the specific rotations of any two acid lactones which differ merely in the positions of H and OH on one carbon atom is never above 56" and usually is about I j O to 2 0 ' . Further, acid lactones that differ spatially only in the position of H and OH on one carbon atom never differ in the direction of rotation: Q and 0 I-rhamnose differ in the direction of rotation. The theoretical explanation of the relation between lactone configuration and optical rotation in the sugars is essentially that given by Hudson1 for the acid lactones. The rotations of the alcohols, free acids and free aldehydes or ketones are so small in comparison with those of the sugars that the rotations of the latter may be assumed as a first approximation to be due entirely to the lactone.2 There are two possible stereo structures for the 4-atomic or 13 lactone in sugars, I and 2 below, and two for the 3-atomic or a lactone, 3 and 4. The a and 3 forms of every sugar -
l7"7 c -c - c - x x , 3 1
H (I)
1
OH
Dextro
H
OH
I I I - c- c - c - 3 I 1 L O -
I z ) Levo
Jour. Am Chem. Soc., 32, 338 (1910). This is not entirely correct. I n some cases the rotations of the alcohols and free acids are strong and may counterbalance the rotation due to lactone formation (Anderson. Jour. Am. Chem. SOC..34, j2, note 6). 3 x may be H or CHlOH. 1
2
Isomerism o j the
aiid 3 F o r m - 01 the Sugars
CY
H
r--0-1
I
-cI
c-xx,.
H
I
OH
( 3 ) Lero
I
275
OH
:
-c-c-x.
~L O _ 1
(4) Dextro
differ in t h a t the CY form has ring I or 2 while the 9 form has ring 3 or 4.l If the rotation is due entirely to the lactone, rings I and 2 make oppositely rotating sugars as do also rings 3 and 4. It is evident that the positions of the hydroxyl groups on the oc and 3 carbon atoms will determine which two of the four possible rings are present. If the hydroxyl on the CY carbon atom is above the structure, the 3 form of the sugar has ring 3 and will rotate levo, if the hydroxyl on the ,B carbon atom is above the structure, the CY form of the sugar has ring I and will rotate dextro. It is evident t h a t d-glucose, H H O H H CH20H - C - C - C - C - CHO, OH OH H OH can have only rings I and 4. Since both CY and 9 d-glucose rotate dextro it is evident t h a t rings I and 4 make dextro rotating sugars while rings 2 and 3 make levo rotating sugars. TVhen either the o! or 3 form of a sugar is dissolved in water it changes rapidly into an equilibrium mixture of these two forms called the Y form.? Where the cy and /3 forms of a sugar rotate in the same direction, the a form is defined as the one rotating the stronger The attempt is made later in this article to show that the a form in such cases has a 4-atomic ring and the
p form has a 3-atomic ring. If future investigations prove the correctness of this point which now rests upon very few data, it would seem more correct to reverse the present method of naming the cy and forms of sugars Hedenburg. Jour. Am. Chem. SOC.,37, 346 (191j). Armstrong, in “The Simple Carbohydrates and Glucosides,” discusses the mechanism of this change. This interchange probably comes about by the lactone opening with water to give the hydrated, lower rotating form which afterwards by loss of water gives the other lactone. ST’hen equilibrium is finally reached in the solution, some of the hydrated form with no lactone in it, will be present. This form will rotate but little in comparison with the lactone, which fact explains why the rotation finally reached in solution is usually be-
Erxest rlwdersox
276
For most sugars the specific rotation is known only for this equilibrium mixture of Q and p forms. However, it is easy to decide from the rotation of this equilibrium mixture in which direction the cy and forms of the sugar will rotate. If the equilibrium mixture rotates strongly dextro or levo, the LY form rotates in the same direction as the p form. If, on the other hand, the equilibrium mixture rotates but slightly dextro or levo, then the 01 form rotates in the opposite direction from the /3 form. In brief, where a sugar has any one of the four following configurations about the Q and B carbon atoms, the CY, j3 and y forms of the sugar rotate as indicated. Configuration
OH (I)
(2)
a rotates
- L c - c
iI
H
OH 0
H
OH
-c-c-c OH
p rotates
y rotates
H
H
x1 dextro, strongly
x
i
dextro,
strongly
dextro, strongly2
levo,
levo,
levo,
strongly
strongly
strongly
dextro, strongly
levo, strongly
dextro or
0
OH OH (3)
(4)
-C -C -C -x I
H
H
H
H
-C -C
I
I
-
C -x Ii
OH OH 0
levo,
slightly
0 levo,
strongly
dextro, strongly
dextro or
levo, slightly
low the mean of the CY and p forms, though of course these two forms may not be present in equal amounts. The more concentrated the water solution the higher the rotation a t equilibrium. This should be so if there is an equilibrium between lactone and water on one side and hydrated, no lactone sugar, on the other side. The higher the temperature, the lower should be and is, the rotation a t equilibrium, since the lactone opens more readily in hot than in cold water. 1 x may be H or -CHzOH. 2 The dividing line between strongly and slightly rotating is about 2 0 degrees, i. e . , those rotating strongly will usually rotate more than 2 0 degrees
Isonzerisw
01the
CY
aizd
p Forws
of,
the Sugars
277
The CY and @ forms, i. e . , the lactone forms, usually rotate strongly;' the Y form or equilibrium mixture will rotate strongly or slightly depending upon whether the two lactone forms of which i t is composed rotate in the same direction or in opposite directions. It happens t h a t when the hydroxyl groups on the CY and p carbon atoms are on opposite sides of the structure, the CY and 8 forms of the sugar rotate in the same direction and the y form will hence rotate strongly; when these two hydroxyl groups are on the same side of the structure. the CY and 3 forms rotate in opposite directions and the Y form will rotate but slightly. In order to test out the ideas presented in this paper the configurations and rotations of sixteen sugars are given below. These are all the sugars for which configuration and rotation are accurately known. All of the following sugars agree with the rules laid down in this paper. 4nderson3 has already shown that this relation between rotation and configuration of the CY and 8 carbon atoms makes possible the determination of the unknown configurations of some sugars whose rotations are known and furthermore makes possible the prediction of the relative rotations of some sugars whose configurations are known but rotations unknown. This holds true not merely for the y form as gil-en by Anderson3 but for the CY and 3 forms as well. This last point is important because in the greater number of cases the rotation of the CY and 3 forms are unltnown. Howe\-er by a glance a t the configuration of the CY and carbon atoms in any sugar i t is easy to decide in which direction the CY and while those rotating slightly will usually- rotate less than 2 0 degrees. This does not hold for one form of the following sugars: l-Rhamnose, d-mannose and dOne is t h a t lyxose. There are two possible explanations for this discrepancy. these sugars have not been obtained pure and the other is that given in h-ote 2, page 2 7 5 . See preceding footnote for exceptions. * This table is given in part, together with references by Anderson: Jour. Am. Chem. SOC., 33, I ~ I (1911). I LOC.cit.
278
? -
x
.
'
H H
I I
u
x
'3
-0
m
7 L___
0
x0 x
8
' d
A
ci H
k
,
x
'c
C
z
C
Isomerism o j the
cy
and 8 Forms o j the Sugars
*
0 0
r 0
I I1
.-x' E .e
1
0
;r:
0
x
0
I c)
I P
ci
I
x
0 c)
x
x
0
1 0
1 c)
0
I
"
I
s c)
a
3
Ernest Anderson
280
__c_-
-----
--
---
A
x
'3 '3
x
0
x
x0 U
!
x 0
8 H"
G
'3
x3
w c . (
0
'2
'3
sl
u I
H H
H
z 0
x0
'3
t)
LC 0
0, x Y
c4
'3
sl
x
; i I
'3
5 x C
0
H
'3
H
i
H
'3
x0
x
x
I
x3
I
ii
z 3 x z 0
g x
Isonzerisw o j the
CY
and p Forms o j ihe Sugars
281
forms of the sugar will rotate and relatively how much they will rotate. For instance, in the case of I-ribose, OH OH OH CHzOH - C - C - C - CHO, H H H the Q form must rotate dextro strongly, the 13 form levo strongly and the y form, or equilibrium mixture, either dextro or levo, but in either case it will rotate only slight1y.l The ideas presented here enable one to decide upon the probable configuration of the CY and p carbon atoms of any of those sugars described by Browne? where the rotations are known. The>- also afford a check upon the correctness of many experimental observations. For example, the rotation -3 3’ given by Fischer and Passmore3 for d-mannooctose cannot be correct for the pure sugar because this would lead to the formula4 H H OHOHH H CHnOH - C - C - C - C - C - C - CHO OH OH H H OH OH for this sugar. This formula is incorrect because d-mannononosej [ a ] , j o ” , must have the configuration OH H
+
-
about the
CY
and
C - C - CHO H OH
13 carbon atoms and must therefore be H OH OH H OH H C - C - C - C - C - C - C - CHO. OH OH H H OH H OH
H
CH20H-
The formula for d-manno-octose must be 1
Strongly and slightly here mean respectively above and below
20
grees. “Handbook of Sugar Analysis” (1912 Ed., Chap. XIX). Ber. deutsch. chem. Ges., 23, 2 2 2 6 (1890). 4Anderson: Jour. Am. Chem. Soc., 33, 1513 (1911). Fischer and Passmore: LOC.cit.; Browne: “Sugar Analysis,” p. 641. 2
de-
Ernest A n d e r s o n
282
H H OH OH H OH CHzOH - C - C - C - C - C - C - CHO. OH OH H H OH H Such a sugar when pure must rotate strongly levo. As a matter of fact, Fischer and Passmore never obtained the pure crystalline form of manno-octose but made their observations on a non-crystalline syrup. When the hydroxyl groups on the a and 13 carbon atoms are on the same side of the structure, one form of the sugar will rotate dextro and the other levo. Hence a chemist, having the a and /3 forms of such a sugar, can easily decide by reference to the lactones on page 2 7 5 , which form has the +atomic ring and which has the 3-atomic ring. On the other hand, when the hydroxyl groups on the a and p carbon atoms are on opposite sides of the structure, the two forms of the sugar rotate in the same direction and a chemist having the a and /3 forms of such a sugar cannot decide by reference to the lactones on page 2 7 5 , which form has the 4-atomic ring and which has the 3-atomic ring. I t is possible to prove for d-glucose and d-galactose by a comparison of the rotations of the methyl glucosides with the rotations of the sugars that the a form, i. e., the higher rotating form, of the sugar, has the +atomic lactone and the p form or lower rotating form has the 3-atomic lactone. The following table gives the specific rotations of the a and 13 forms of three sugars and their corresponding methyl glucosides. Rotation
Methyl glucoside
Rotation
( a +109"
Q
+Ij7O
( P +zoo
P
-32
a
+199O
P
O0
Sugar
&Glucose
cy
&Galactose '\
1 1-Rhamnose
+140°
P +53O Q
-jo
{
P +31°
Q
-62
O
"
Isowzerisu2 oj tlze
01
and P Forms o j tlze Sugars
283
From the above table it appears that the - O - C H 3 group in place of the OH group on the end carbon atom in one case increases the dextro rotation of the sugar 55' and in the other cases decreases the dextro rotation j j o . The form of 1-rhamnose rotating -j ' must have the configuration OH OH H H OH CH3 - C - C - C H
H
-C
I
-C -H
I O H I -0-d
and the corresponding methyl rhamnoside rotating -62 must have the configuration CH3-
OH OH H C -C -C H
H
I
H OCH3 - C -- C - H.
:
OH
o---
1
n'here the - 0 - CH3 in the glucoside is above the structure the glucoside rotates roughlj- j j o le\-o from the corresponding sugar rotation. n'here the - 0 - CH3 is below the structure the glucoside rotates roughlv j j dextro from the corresponding sugar. Those forms of the sugar then whose glucosides rotate dextro from the sugar rotation ha\-e the free OH group on the end carbon atom below the structure while those forms of the sugar whose methyl glucosides rotate levo from the sugar have the free OH group above the carbon structure. The following table gives the configurations of the cy and 3 d-glucose and d-galactose deduced by the above reasoning : -0-H H i 1 3 ,
I
1090 C H ~ O H - C - C - ~ - C - C - H
OH OH H &Glucose
OH OH
'
H
H OH
H
OH I
Ernest Andersou
284
O--
OH H &Galactose
H
OH OH
I
H
OH OH H
' p, +j30 CH~OH-C-C-C-C-C-H OHH
H
~
OH
i
LOA
A comparison of d-glucose and d-galactose shows that the Q form rotating the more strongly has the 4-atomic lactone. If then the two lactones rotate in the same direction, the 4-atomic lactone, having three asymmetric carbon atoms in the ring rotates more strongly than the 3-atomic lactone which has only two asymmetric carbon atoms in the ring. The Q form of the sugar has then the /3 lactone, while the p form of the sugar has the Q lactone. This last relation has been tested for only the three sugars described because the necessary data are not available for other sugars. Hudson and his collaborators have published a number of articles dealing with the optical rotatory powers of the sugars and derivatil-es.l In all probability other series of compounds in the sugar group will be found to exhibit similar relations between optical rotation and configuration when they have been investigated systematically and thoroughly. In conclusion, the author wishes to state that he is familiar with the work of Purdie and Irvine,? and E. F. Xrmstrong,3 which has been regarded as establishing the y lactone structure for sugars. In spite of this work and much other of a similar nature the relations4 pointed out in this article seem 1
Jour. Am. Chem. Sot., 31, 66 (1909);
32, 388
(1910); 37, 1264, 1591
(191.5). 3 4
Jour. Chem. Soc., 83, 1026 (1903); 85, 1049 (1904); 87, 1022 (1905). Ibid., 83, 1305 (1903). The relations pointed out in this paper are all between specific rotations.
Isonierisnz oj the
CY
uiid 3 Forms o j the Sugars
285
sufficiently important to warrant their publication, especially since both Fischer' and Hudson' have suggested the possibility of other lactones in the glucosides in addition to the y lactone and since S e f 3 has definitely taken his stand against the ordinary accepted view as t o the structiire of the sugars. Anzirtvst, ,lfuss. Dec. 2-2,191j 1
Ber. deutsch. chem Ges , 47, 1980 (1914). Jour Am Chem. Sac., 37, I j 9 3 (191j) I b i d , 37, 34j ( 1 9 1 5 ) .
