THE CONFIGURATION OF THE MONOSACCHARIDES* R. HARMAN ASHLEY, THEST. LAWRENCE UNIVERSITY, CANTON, NEWYORK The Aldopentoses The determination of the configuration of the monosaccharides when discussed before a class in organic chemistry presents some difficulties to the instructor if only the labor of writing the structural formulas on the blackboard and the considerable space required for this he considered. The following method of presentation has been successfully used a t The St. Lawrence University with good results. The figures and, if need be, the reactions may be thrown upon a screen with a projection lantern. Taking up first the aldoses, aldotriose, CH20HCEIOHCH0, would be the simplest member and would exist in two optical isomers. Each of the aldoses likewise would have its optical opposite, so for the sake of simplicity only the dextro family will be considered, since the same line of argument applies to the levo family. In Figure 1 (page 2132) the right-handedness of the d-aldotriose is shown by the symbol for the -CHOH group extending to the right With this substance as a parent, all the other members of the dextro aldoses may be regarded as having been derived. In conformity with this i t will be noted that in Figure 1 all the bottom -CHOH groups in each and every derivative are represented as in the dextro form. The method of lengthening the carbon chain to produce the next higher aldoses consists of the addition of hydrocyanic acid, the hydrolysis of the resulting cyanhydrin to the acid which changes over to the lactone, and the reduction of the latter to the aldehyde. Thus from d-aldotriose would he produced the aldotetroses 1' and 2' in Pignre 1. The reactions are: CN
COOH
H
H
I
I
I
H-?--OH
I
I
H
I H-COH
H
I
\
I
H 1'
CN
I HD--C-H I n-c-on 1 H-C-OH I H
COOH
CHO
I
HO--C-H HIO
--+ n-A-on
I I
I
H-C-OH H
I
H
I El I --+ H-c-OH I H-C-OH I H
HO--C-H
2'
* The basic idea of the method of presentation of the configuration of the monosaccharides given herein was obtained from Reid's "College Organic Chemistry," D. Van Nostrand Co., Inc., New York City, 1929. 2131
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In a similar manner the aldopentoses, 1, 2, 3, and 4 of Figure 1are derived. These are known as arabinose, ribose, lyxose, and xylose. The problem is to determine the configuration of these aldopentoses. Arabinose and ribose on treatment with phenyl hydrazine produce the same osazone, hence, knowing that this reagent reacts with the -CHO group and the adjacent -CHOH group in forming the osazone, it follows that the configuration of arabinose and ribose must be identical for the end groups C H Z O H C H O H C H O H . . The reactions for the formation of the osazones may be represented in the case of the aldopentoses 1 and 2: CHO
I I H-C-OH I H-C-OH I H-C-OH I
H-C-OH
".i;+ H
C=N-NHCsHa
I
C=N-NHCSHI
H
H-Lo=
1 CHO
I I
G
y
HSC-H
+
H-C-OH
I
H-C-OH
I ~ H-C-OH YI H-C-OH I
H Osazonc
H A o H
I
H 2
Hence arabinose and ribose must be either pairs 1 and 2 or pairs 3 and 4. But which? This is represented in Figure 1. Each of the aldopentoses may be converted into dibasic acids as exemplified in the case of the aldopentose 1: CHO
COOH
I
I
H-C--OH
I
H-C--OH
I I H-C-OH I
H-C-OH
H-C-OH 0
-+
I
H-C-OH
I I
H-C-OH COOH
H 1
I t will be noted that the above dibasic acid has only two asymmetric carbon atoms, those next to the -COOH groups. From the configurations
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given it will be seen that optically active acids will be produced from the aldopentoses 2 and 4 (Figure 1) while the aldopentoses 1 and 3 would produce optically inactive acids due to internal compensation. In experimental fact, arabinose and lyxose produce dibasic acids which are optically active. Ribose and xylose on oxidation produce optically inactive dibasic acids which cannot he separated into optically active opposites, hence the inactivity of these acids must be due to internal compensation. The dibasic acids produced from ribose and xylose are not identical. The dibasic acids derived from 1 and 3 would be optically inactive yet differentacids. Hence, ribose and xylose are 1and 3, but which is which? This leaves arabinose and lyxose for 2 and 4, but again which is which? If the carbon chain of the aldopentoses 2 and 4 are lengthened by the addition of hydrocyanic acid, the cyanhydrins hydrolyzed to the acid and the acids oxidized to the dibasic acids, these acids would contain six carbon atoms. The reactions in the case of the aldopentose 2 (Figure 1)would be: CN
CHO
I
1 H-C-OH I HO--C-H I H-C-OH I
H-C-OH
H-C-OH
H
H-c-OH
CN
I
2
COOH
I H-C-OH I H,O HO--C-H + H-C-OH I I H-C-OH I H-C-OH I
H-C-OH
I
H-C-OH I
I I 0 HSC-H --+ H-C-OH I I H-C-OH I H-C-OH
COOH
H
COOH
I
HSC-H I HZO HO-C-H
HSLH I H-C-OH I
COOH
+
I H-C-OH I H-C-OH I
H-C-OH I
COOH
o
I
HGC-H I HO-C-H
I I H--C-OH I H-C-OH
COOH
These syntheses are represented diagrammatically in Figure 1, from which it is seen that 2 would yield two acids, both optically active, while4 would yield one optically active acid and another inactive acid (due to internal compensation). In experimental fact, arabinose yields, by the above given transformations, two dibasic six-carbon atom acids, both optically active, while lyxose
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The problem is to assign to each its configuration. The eight possible daldohexoses are shown in the top line of Figure 2, numbered from l to 8. The configuration of the four d-aldopentoses has already been established. Beginning with arabinose, the argument would be as follows: I. (See Figure 3). By acting on arabinose with hydrocyanic acid, hydrolysis of the product and reduction with sodium amalgam, glucose, and mannose are obtained, hence the structures of these are known up to the symbol 6 which represents a secondary hydroxyl group which may extend to the left or the right. Configurations 3 and 4 satisfy this condition, hence
glucose is either 3 or 4 and mannose is the other. Figure 3 (a). It will be noted in Figure 3 that the secondary hydroxyl groups in gulose are not represented. This is to indicate that up to this stage of the argument, nothing is known about them. Glucose and gulose on oxidation yield the same dicarboxylic acid, hence these two substances must have the same structure except that the aldehyde and primary alcoholic groups are transposed. From Figure 2 it is seen that 5 and 3 show this relationship. In experimental fact, the dicarboxylic acid obtained from d-mannose is not obtained from the oxidation of any other sugar. These facts are shown in Figure 3, (b) and (c). It follows then
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that mannose must be 4, glucose 3, and gulose 5. Parenthetically, it may be added that glucose and mannose produce the same osazone. This fact is not needed in the proof of configuration as outlined. 11. Gulose and idose produce the same osazone, hence they must be alike up to the secondary hydroxyl group next to the aldehyde group, consequently, if 5 is known to be gulose, 6 fulfils this condition and idose must be 6. See Figure 4. 111. The structures unassigned are 1, 2, 7, and 8. See Figure 2. Galactose on oxidation gives an optically inactive dicarboxylicacid. Of the four structures left, only 1 and 7 would do this, hence galactose is either 1 or 7. But which? See Figure 5 (a) and (b) (page 2138). Galactose and talose with phenyl hydrazine yield the 5 6 same osazone. By adding another carbon atom to galactose and oxidizing to the dicarboxylic acid, two optically active acids are produced. 9 %4 ? 4 With this treatment 1 would give an active and an inactive , '' I ! , r ; carboxylic acid while 7 would produce two dicarboxylicacids, 9, both active. See Figure 5 (d) Sf and ( e ) . Accordingly galactose h must be 7 and from the osazone 0 evidence talose is 8. IV. d-Allose and d-altrose may be synthesized from dU b ribose by the action of hydrocyanic acid, hydrolysis of the @ = =wN product, and subsequent re- h g ~ r e 'C, 4 duction of the acid produced. Knowing the configuration of d-ribose, the structure of allose and altrose is known up to the secondary hydroxyl group next to the aldehyde group. Allose on oxidation produces an optically inactive dicarboxylic acid while altrose by the same process yields an optically active acid. See Figure 6 (page 2138). It is seen that 1 would produce an optically inactive acid by this process while 2 would produce an optically active acid, hence allose is 1 and altrose is 2. Allose and altrose give the same osazone.
*
$41 L\
j$
g
2
4
The Ketohexoses Knowing the configuration of the aldohexoses, the configuration of the ketoses follows readily from the fact that the carbonyl group in a ketose is always next to a primary hydroxyl group, hence phenyl hydrazine will form
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Figure
6
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the same osazone from the aldose and the related ketose. Confining the argument to the dextro compounds, if d-glucose and d-fructose and dmannose produce the same osazone, as they do, their configurations are alike except for the two end carbon atoms carrying the carbonyl group. CHO I
H-c-OH I I H-C-OH I
CHzOH
Glucosc
I I CHOH I I
H C=N-NHCsH5
I
C=N-NHCsHs
I I
HGC-H H-C4H
CHO
1 I
HO--C-H HO-C-H H-A-OH
I I
H-C--OH CHSOH Osezone
CHIOH Mennose
YHOH
CHzOH Fructose
Fructose must have the configuration given in Figure 7. d-Sorbose and d-gulose produce the same osazone. This same osazone is also produced from idose:
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CHO
I I
H-C-OH H-C-OH
I 1 H-C--OH I
HO--C-H
CHO
I 1 H-C4H I
HO-C-H
CHZOH
Gulose
CHSOH
H-C-OH
I
HO-C-H H-C-OH
HO--C-H
%
5'
H-C-OH
I
CH.OH
I I
CHOH
Osaeone
Idose
CHOH CHzOH Sorbore
Sorbose must have the configuration shown in Figure 7. In the method of presentation of the configuration of the monosaccharides described above it is necessary to make some assumption, but after fixing one structure, all the others must be as given.
