Chemical Diversification of Sialic Acid Glycosides by Stereospecific, Chemoselective Deamination

摘要

The sialic acids are nine-carbon sugars based on the 2-keto-3-deoxy-D-glycero-D-galactononulosonic acids, whose a-glyco-sides adorn the nonreducing termini of many A-glycoproteins and gangliosides and are the monomeric units of the α-(2→ 8)- and α-(2→9)-oligosialic acids. The recognition of these sialyl glycoconjugates by various lectins and the trimming of sialyl residues by sialidase enzymes play important roles in many human disease states, and have stimulated interest in the synthesis of libraries of modified sialyl glycoconjugates and their deployment in the search for improved diagnostics and therapeutics. The difficulties inherent in sialic acid chemistry and particularly in the stereocontroUed synthesis of α-sialosides have, however, restricted the preparation of such libraries to enzymatic approaches, which are limited by the range of substrates accepted.' We describe here a method for the chemical synthesis of sialyl glycoside libraries that combines recent progress in stereocontrolled α-sialoside synthesis with a mild oxidative deamination process to enable late-stage modification of preassembled glycosides, thereby extending the range of accessible diversity.