A SIMPLE PROOF OF THE STEREOCHEMICAL CONFIGURATIONS OF &GLUCOSE AND OF &GALACTOSE* J. A. ABLBLER, U. S. DEPARTMENT OF A G R I C U I . ~WASHINGTON, , D. C.
The recent work of Haworth and co-workers1 on the position of the oxygen bridge in the formulas of the normal reducing sugars has made possible the derivation of their stereochemical configuration by a method which is much more simple and direct than the classic ones which it has been necessary to use up to the present time,%and which students often find troublesome to follow and master. After the configuration of the pentoses, as developed, for example, by Armstrongz has been demonstrated, that of the epimeric hexoses derived from d-arabinose may be deduced by the following method: (1) d-Glucose (I or 11) and d-mannose (I or 11) are formed by the cyanhydrin synthesis from d-arabinose. Therefore it follows that both these hexoses contain an arabinose configuration of substituents on carbon atoms 3,4, and 5, and it remains only to determine the configuration of the groups about carbon atom 2 in the respective epimers. (2) Haworth has demonstrated that oxidation of 2,3,4,6-tetramethyld-glucose yields xylo-2,3,4-trimethoxyglutaricacid, which is also formed by oxidation of 2,3,4-trimethyl-d-xylose. Therefore 2,3,4,6-tetramethyld-glucose mnst contain the same asymmetric system as 2,3,4-trimethyl-dxylose, and the original d-glucose mnst contain a d-xylose residue. This xylose residue must be derived from a sequence of carbon atoms other than the 3,4,5 atoms, which represent the arabinose system. The only other possible sequence of three asymmetric carbon atoms in glucose is the 2,3,4 series. Therefore, it follows that the hydrogen and hydroxyl groups attached to carbon atoms 2,3, and 4 must be arranged in the same asymmetric manner as in d-xylose. Thus, in d-glucose, carbon atoms 3, 4, and 5 constitute the d-arabinose residue and carbon atoms 2, 3, and 4 the d-xylose portion. Whence the complete formula (I) for d-glucose is at once evident. The structure of mannose is derived from the fact that it is the epimer of glucose and hence differs from it only in the orientation of the groups around carbon atom 2, and therefore mannose must have formula 11. The independent derivation of the formula of mannose by reasoning
* Contribution No. 95 from the Carbohydrate Division, Bureau of Chemistry and Soils, U. S. Departmeut of Agriculture, Washington, D. C. ' Haworth, "The Constitution of the Sugars," Longmans, Green & Co., London, 1929, pp. 1 4 6 . a E. Fischer, "Synthesen in der Zuckergnrppe, 11." Ber., 27, 3189 (1894). E. F. Armstrong, "The Simple Carbohydrates snd the Glucosides," Longmans, Green & Co., London, 1924, pp. 3 3 4 . M. Cramer, "Les Suaes et leurs D&iv&," Dim, Paris. 1927, pp. 139-51. J. B. Cohen, "Organic Chemistry for Advanced Students," Part 111, Longmans, Green & Co., New York, 1928, pp. 24-31. 1599
JOURNAL OF CHEMICAL EDUCATION
1600
JULY,
1930
analogous to that just given is impossible owing to the fact that on oxidation the tetramethyl mannose yields 2,3,4-trimethoxy-d-glutaricacid, a derivative common to both d-arabinose and d-lyxose. This throws no light on the asymmetry of carbon atom 2, because Haworth's oxidation method does not in itself exclude the possibility of the identity of this d-arabinose system with that already known to be present by reason of the possible synthesis of mannose from d-arabinose. The reasoning applicable to the derivation of the configuration of dglucose is valid also for the epimeric pair, d-galactose and d-talose. These may be synthesized from d-lyxose, and this fixes the orientation of the groups about carbon.atoms 3, 4, and 5 . d-Galactose yields by methylation and oxidation, according to Haworth, 2,3,4-trimethoxy-1-glutaric acid, which is a derivative of 1-arabinose. Thus, d-galactose contains both a d-lyxose and an 1-arabinose system, and the complete formula is evident. H-'C=O
H-C=O
HO-sC-H
HO-C-H
I
I
+ H-'C-OH
H-C-'OH
I H-C-OH I
I
CHaO-C-H
I
+
1CII*OH I
H-C-OCHa
1
COOH
H-C=O
I
+-
H-LocH2
I
I
-- -- -
CHIO-C-H
Ho-LH
cHIo-CI-H
I1
I I
HO-C-H
I H-c-cHa I
+ H-c-on
A_--
CH3OH Xylo-trimethoxy2.3.4-Trimethylglvtarie acid d-xylonc H-C=O COOK H-C=O
- HD--C-H -
&&OH
H-bOH
CH.0-C-H1
--L C-OOH
H-4-OH
H-C=O
I
H-C-OCH.
CH,O-bH
H--C[-oH
+
CH~OCHI 2.3.4.6-Tetramethyl-I
H-C-OCHs
H-C=O
+
+CH8o-L-H I H-c-ocH.
H-?-OH I
&H*OCH:, 2.3.4.6-Tetramethyl-I1
C&O--&-H
C-OOH I Trimethoxy-dglutprie acid
/
CH2OH d-Xylose H-C=O
I
I
CHaO-C-H
H-OocHI
H-C=O
L
H-C-OCHr
- -I- -- -- -- I - -- - - -H-W-OH H-C-OH I 1
CHIOH d-Arabinose
-
I
I
- - - - -H-'C-OH -- - - - I 1
-. H-C=O -
1
CHIO-C-H
I
cH~o-c-H
t
I I
H-C-OCHI
AO-C-H
+
CHnOH 2.3.4-Trimethyld-IYXOEC
I
Ho-c-H
-
H-C-OH
I
CHIOH d-Lyxore
VOG. 7, NO.7 PROOF OF STEREOCHEMICAL CONFIGURATIONS
1601
Since Haworth has not yet reported on the oxidation products of dtalose, its configuration is obtained by the same procedure as that used for mannose. For the other rare aldohexoses, Fischer's method must be used, since these sugars have not yet been studied by the methylation and oxidation method. The aldehydic formulas on page 1600 illustrate more clearly than is possible in words the chain of reasoning.
