Configuration of the Ketosidic Bond of Sialic Acid

Abstract

The stereochemistry of the ketosidic bond of sialic acid has been elucidated by a study of the two anomeric methyl ketosides.Isomer I was prepared by Koenig.+Knorrsynthesis, and isomer II by direct methylation with methanol and an acid catalyst.These two anomeric configurations were established by conversion with periodate-borohydride to III and IV, respectively, followed by lactonization of one isomer.Dreiding models demonstrate that only one anomer is potentially able to lactonize, and this was accordingly assigned Structure IV.This anomer and its precursor (II) were resistant to neuraminidase, whereas Compounds I and III were hydrolyzed by the enzyme.The configuration of the ketosidic bond of sialic acid in naturally occurring substances, such as gangliosides, glycoproteins, and the like, is therefore the less stable anomer I, with the ketosidic bond equatorial and the carboxyl group axial to the pyranoid ring.It is assigned the OA-D configuration in accordance with the rules of nomenclature.The sialic acids are a group of widely distributed amino sugars that occur in several glycoproteins, oligosaccharides, and glycolipids (1,2).These acids are the naturally occurring derivatives of neuraminic acid in which the parent substance is acylated at the amino group with an acetyl or glycolyl moiety.The work of Comb and Roseman (3) showed that sialic acid can be enzymatically cleaved to N-acylmannosamine and pyruvate and this served to establish the configurations of C-5 through C-8.Subsequently, Kuhn and Baschang (4) elucidated the stereochemistry at C-4 by unequivocal means.The only aspect of stereochemistry remaining to be determined is the configuration of the ketosidic bond joining sialic acid to the adjacent sugar.The two possible forms are shown in Fig. 1.