for substances which do not have large differences in the glycosidic group.

TABLE 54.-Sum of the molecular rotations (2B) for some alpha and beta derivatives of d-glucose

The value of 2B obtained for the alpha and beta phenyl glucosides (+28,140) differs considerably from the value (+24,220) obtained for the alpha and beta methyl glucosides and related substances. The introduction of an unsaturated chromophoric group appears to induce a change in the optical rotation of the rest of the molecule. The chromophoric group is particularly influential when adjacent to the asymmetric center. Its influence is small when it is at some distance from the asymmetric center, as for example, in the benzylglucosides. As may be observed from the data given in table 55, the sums for the molecular rotations of the alpha and beta sugars do not differ widely from the sums for the molecular rotations of the corresponding methyl glycosides.

TABLE 55.—Sums of the rotations of the alpha and beta sugars in comparison with those of the a- and ß-methyl glycosides (second rule of isorotation)

The value for the rotation of ẞ-d-xylose was taken from Hudson's indirect measurements by means of solubility experiments.

The accumulation of a large amount of experimental data has brought out other approximations which are useful for correlating optical rotation and structure. One of the most obvious is the striking similarity in the optical rotations of substances which have like configurations for the carbon atoms comprising the pyranose ring. This generalization can be expressed in a rule which states that changes in the side chains attached to the pyranose ring affect in only a minor degree the rotation of the remainder of the molecule. The optical rotations of a few sugar derivatives, which differ merely in the groups attached to the pyranose ring, are given in table 56.

As might be anticipated from the close similarity in structure, the molecular rotations of the configurationally related hexoses and heptoses resemble one another more closely than they resemble the rotations of the configurationally related pentoses and methyl pen

toses. A number of unexplained variations may be noted in table 56; these call for further investigation to ascertain whether they arise from errors or from unknown differences in structure.

TABLE 56.-Molecular rotation of substances of like configuration of the pyranose ring

Several relationships connecting the optical rotations and configurations of the sugar acids and their derivatives have been noted. The first of these is the Hudson lactone rule [44, 45], which states that lactones, in which the oxygen ring lies to the right when the projectional formulas are written in the conventional manner, are more dextrorotatory than the parent acids, and if the oxygen ring lies on the left, the lactone is the more levorotatory. The rule was originally derived from the optical rotations of gamma lactones, but it appears to apply equally well to the delta lactones. With the exception of allonic, manno-nononic, and digitoxonic lactones, the sign of rotation in water solution corresponds with the configuration of the ringforming carbon. That is, lactones in which the oxygen ring lies to the right are usually dextrorotatory, while lactones in which the oxygen ring lies to the left are usually levorotatory. Levene [46, 47] and also Hudson [48] have pointed out that the phenylhydrazides and amides of the aldonic acids are dextrorotatory when the hydroxyl on the alpha carbon lies to the right. These relationships are very useful for determining the structures of new acids formed by extending the carbon chain, because frequently the phenylhydrazides and amides

are used for separating the products. Levene [46, 47] has shown that the alkali salts of the aldonic acids are more dextrorotatory than the free acids when the hydroxyl on the alpha carbon lies to the right, and Isbell [49] has shown that the lead salts are more levorotatory than the alkaline earth salts when the hydroxyl on the alpha carbon lies to the right. These empirical rules make the classification of newly prepared sugar acids a very simple matter.

TABLE 57.-Molecular rotation of the aldonic acids and related products

I Value derived from the enantiomorph by reversing the sign of the rotation.

The marked parallelism between the optical rotations and configurations which has been considered briefly is but one of many correlations which exist between the properties and the configurations of the sugars and their derivatives. In the next section, some of the chemical properties will be considered in relation to structure and configuration.

6. CORRELATIONS BETWEEN THE CONFIGURATIONS AND THE CHEMICAL PROPERTIES OF THE SUGARS

The alpha and beta sugars have diverse configurations for their reducing carbons and marked differences have been found in their properties. An extensive investigation of the alpha and beta sugars was initiated by Isbell, who sought to determine the effect of configuration on the relative reactivity of the alpha and beta sugars. Some of the data obtained in this investigation are given in table 58, from which it may be observed that the beta sugars are oxidized by bromine water more rapidly than the corresponding alpha sugars.

TABLE 58.-Rates of oxidation of alpha and beta sugars [35, 36, 37]

[In aqueous solutions at 0° C containing 0.05 mole of sugar, and approximately 0.08 mole of free bromine per liter and buffered with barium carbonate and carbon dioxide]

In many reactions the arrangement of the hydroxyls in relation to the plane of the ring is an especially important factor in influencing the rate and course of the reaction. Condensations in which two hydroxyls combine with another group take place when the hydroxyls lie on the same side of the ring. Thus the behavior of the sugars and their derivatives in their reactions with acetone, benzaldehyde, boric acid, and many other substances is largely conditioned by the cis or trans arrangement of the hydroxyl groups [50, 51, 28]. The facility with which boric acid combines with cis-hydroxyls on adjacent atoms was mentioned with respect to the structure of alpha and beta glucose (p. 422). The property of increasing the electrical conductivity of boric acid appears to be characteristic of all sugars which have two hydroxyl groups on adjacent carbon atoms on the same side of the ring. Normally, condensation with acetone involves cis-hydroxyl groups on adjacent carbon atoms, making a cyclic link of five atoms [52], while condensation with benzaldehyde usually involves alternate cis-hydroxyls, making a cyclic link of six atoms [53].

In the presence of acid catalysts the free sugars react in the furanose or the pyranose form, depending upon which form is the more favorable for the condensation reaction. Thus glucose forms a 1,2-3,5-diacetone derivative, even though the free sugar exists in the pyranose modification. Correlations have been made also between the cis-trans configurations and the tendency to form anhydrosugars and sugar anhydrides. Thus a-d-glucose yields a glucosan by condensation between the hydroxyls of carbons 1 and 2; B-d-glucose, however, yields a glucosan by condensation between the hydroxyls of carbons 1 and 6 [54]. Apparently the configuration of carbon 1 determines the nature of the product formed. The importance of cis-trans configura

tional relationships in the formation of anhydrosugars and ortho acetates was reviewed recently by Isbell [55], who suggested that many carbohydrate reactions can be explained by Werner's concept [56] for the Walden inversion. Intramolecular condensation reactions involving Walden inversion appear to take place only on the side of the carbon opposite the departing group.

The influence of the cis-trans configuration of the sugars and their derivatives in relation to their biological behavior has been recognized for a long time. The sorbose bacterium, for example, oxidizes sugar alcoH H

hols to ketoses when they contain the grouping, -C-
C-C
-C-

-CH2OH, он он with the CH(OH) groups having a cis configuration in the projectional formula [57]. The relationship between cis-trans configuration and rates of enzyme action has also been studied [58].

Even though many generalizations can be reached by considering only certain aspects of the molecule, each group influences to some extent the properties of the others, and therefore it is essential to consider also the configuration of the molecule as a whole. In the pyranoses, the carbon and ring oxygen atoms are tied up in a ring and cannot exhibit free rotation; consequently the pyranose ring forms a fundamental structure about which the hydroxyls and hydrogens are distributed according to the configurations of the constituent carbon atoms. The arrangement of the groups on either side of the ring makes up the thickness and general conformation of the molecule. The different configurations for the 5 asymmetric carbon atoms of the ring give rise to 32 isomeric pyranoses, which consist of 16 pairs of enantiomorphs. These fundamental configurational types are represented by the alpha and beta modifications of glucose, mannose, galactose, talose, gulose, idose, allose, and altrose and are illustrated by the formulas on p. 426. By substitution, all pyranose sugars are derived from these fundamental types, or from their enantiomorphs. The aldopentoses, methylpentoses, and heptoses differ from the aldohexoses in that the CH2OH group of the latter is replaced by hydrogen, the methyl group, or by the CHOH.CH2OH group, respectively. The ketoses differ from the aldoses in that the H on the first carbon of the aldose is replaced by a CH2OH group. If the sugars are considered in this manner, sorbose, xylose, B-galaheptose, maltose, lactose, and cellobiose are merely substituted glucoses, or levulose, perseulose, arabinose, a-mannoheptose, and ß-guloheptose are merely substituted galactoses.

The tendency of a sugar or a sugar derivative to form five- or sixmembered lactol rings is dependent on the character of the substituent groups, and on the configuration of the carbon atoms involved in forming the furanose and pyranose rings. This subject will be considered more fully in the next chapter.

7. REFERENCES

[1] E. O. von Lippmann, Geschichte des Zuckers, 2d ed., p. 683 (Julius Springer, Berlin, 1929).

[2] Lowitz, Chem. Ann. von Crell 1, 218, 345 (1792).

[3] Chevreul, Ann. der Chym. 95, 319 (1815).

[4] Braconnot, Ann. Phys. Chim. 12, 172 (1819).

[5] F. J. Bates, Facts About Sugar 21, 250 (1926).