Stereoselective Synthesis of α-C-Sialyl Compounds

Sialic acids (or neuraminic acids) are often found at the outmost ends of the oligosaccharide components of cell-surface glycoproteins and glycolipids. They are involved in a number of important biological events including cell recognition and interaction, neuronal transmission, ion transport, reproduction, differentiation, epitope masking, and protection. They are also involved in pathological processes including infection, in-ammation, cancer, neurological, cardiovascular, endocrine, and autoimmune diseases.1-4 Cell surfaces containing sialic acids interact with receptors, hormones, enzymes, toxins, and viruses and other pathogens that use them to localize on the surface of cells they infect.5 The linkage of sialic acid to oligosaccharide is among the most labile glycosidic linkages and is cleaved in vitro under mildly acidic conditions.6 In vivo, sialic acid-containing glycoconjugates are catabolized through the removal of the terminal sialic acid residue by the action of hydrolase-type enzymes called neuraminidases.7 A nonhydrolyzable glycosidic linkage to sialic acid is an attractive approach to design reagents for glycobiology and immunology. The replacement of the interglycosidic oxygen atom with a hydroxymethylene group using SmI2 chemistry affords hydrolytically and metabolically inert α-C-sialyl analogues of natural glycoconjugates. This stable linkage is being studied to improve our understanding of biological recognition and to enhance or suppress biological events at the molecular level.