Synthesis of Nor-C-linked Neuraminic Acid Disaccharide: A Versatile Precursor of C-Analogs of Oligosialic Acids and Gangliosides

摘要

The Neu5Acα(2,8)Neu5Ac disaccharide is an important constituent of tumor related antigen, however, the O-linkage is catabolically unstable. Vaccination with a catabolically stable sialic acid C-glycoside analog might enhance immu-nogenicity. The synthesis of NeuSAc nor-C-disaccharide 20R/S, corresponding to versatile precursors of C-analogs of oligosialic acid and gangliosides, is reported. The synthesis of the protected acceptor was not straightforward, as ester, silyl ether, and isopropylidene protection failed to afford desired C-linked disaccharide. Allyl ether protection of hydroxyl groups and acetyl protection of the acetamido facilitated the successful synthesis of the 8-aldehyde neurami-nyl acceptor. Samarium mediated C-glycosylation afforded the desired nor-C-disaccharide as a mixture of two separable diastereomers.