I
I
Y. Z. F r o h w e i n Hebrew University Jerusalem, Israel
A Sim~lifiedProof of the Constitution and the configuration of D - G ~ J C O S ~ The carbon atoms are numbered from 1 to 6 starting with the aldehyde group. It will be seen that four carbon atoms namely, 2, 3 , 4 , and 6 are asymmetric and this means that there are z4 or 16 possible isomers of glucose all having the same formula I. All the isomers are known. To determine which configuration (i.e., relative arrangemcnt of H aud OH with respect to the carbon atoms) applies to glucose, or for that matter any other aldosc, the following scheme may be used: Thc simplest sugar showing asymmetry is glyceraldehyde. The two optical isomers of this triose (3-carbon sugar) are D and L-glyceraldebyde.
The classical proof of the structure of D-glucose by Emil Fischerl is impeccable on chemical and logical grounds. I t is, however, rather complicated for students being introduced into carbohydrate chemistry. Special difficulty is encountered in explaining, on the one hand, the identity of D-glucaric acid and Lgularic acid and, on the other hand, that mannaric acid can he derived from mannose only. The following proof of the structure of glucose does not require these and other facts and is, therefore, simpler. Glucose has an empirical formula of CHzOand molecular weight determination shows it to be (CH20)aor CeHI2OB. One of the oxygen atoms pertains to a carhonyl group because hydrocyanic acid adds on to the sugar. CsH,,Os
+ HCN
-
GI10
HoJH AH,oa n-glyceraldehyde
CrHlsO&N
The cyanhydrin thus formed can be reduced with hydriodic acid and phosphorus to give, on hydrolysis, heptanoic acid.
+ H I + P + HzO
CaHlrOsCN
-
CHO
I1
CaHlsCOOH
This may be shown to be the normal acid, CHlCHz CH2CH2CH2COOHthus proving that glucose has a straight chain of carbon atoms and that the HCN adds on at the end of the chain. Thus, glucose is an aldehyde-sugar, or aldose, and may be written CIHI1OICHO. Glucose forms a pentacetate, so we may assume that the fivc oxygen atoms other than the one belonging to the aldehyde are in alcoholic groupings. As the substance is rather stable we may further assume that there is only one OH group attached to each carbon atom. The formula of glucose would then be (1) (2) (3) (4) ( 5 ) (6)
C-C4-C-C-C H H H H H H , 0 0 0 0 0 0 H H H H H
AH,oH bglyeerddehyde 111
The structures I1 and I11 were a t first arbitrarily assigned to the D and L isomers respectively hut X-ray analysis of their derivatives have proved that these are correct. Glyceraldehyde may he converted to a Ccarbon compound by addition of HCN. This addition results in a second asymmetric center being formed and thus each of the two glyceraldehydes gives rise to 2 cyanhydrins which, by hydrolysis, lactonization and reduction may be converted to 2 sugars. n-Glyceraldehyde gives Derythrose and D-threose and L-glyceraldehyde 'gives L-threose and L-erythrose and the reaction is shown in Figure 1. To prove thc respective structures of D-erythrose and D-thrcose, one either reduces the aldehyde to a sugar alcohol or oxidizes it to a dicarboxylic acid. FrscEIEn, E., Beriehte, 24,1836, 2683 (1891).
cN
CO---
COOH H+
-+
- HZO
I O H I HCOH
I -~
0
a
Hz0
CHO
/
~
I I HCOH
mCOH
g
D-erythroae IV
AIT%oH
HO~H D-glyceraldehyde Figure 1.
I
HcoH
Ht
+ H1O
AHzoH
HO~H HAoH AH1oH
--
H+
-I110
CO-7 Ho(H
1 --
HCoH 0
' I
cH,
Ns/m
Ha0
CHO
Hob
n-threose
A o H
I
CHsOI1
The reaction of n-glyceroldehydo. Volume 46, Number 7 , January 7969
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