Configuration of the ketosidic bond of sialic acid.

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.+Knorr synthesis, 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.