Synthesis of Glycopyranosyl-(1→2)-N-Acetylneuraminic Acid Nonreducing Disaccharides and Their Evaluation as Neuraminidase Substrates

Abstract

A series of unique nonreducing disaccharides, galactopyranosyl-(1→2)-N-acetylneuraminic acids and glucopyranosyl-(1→2)-N-acetylneuraminic acids, which had N-acetylneuraminic acid linked to the anomeric position of another sugar, were synthesized. In these syntheses, the anomeric thiophenyl group of phenyl 2,3,4,6-tetra-O-benzyl-1-thio-β-D-galactopyranoside and phenyl 2,3,4,6-tetra-O-benzyl-1-thio-β-D-glucopyranoside was deprotected selectively to afford the corresponding hemiacetals that were used as glycosyl acceptors. These glycosyl acceptors were then coupled with phenyl (methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-2-thio-D-glycero-D-galacto-2-nonulopyranosid)onate using N-iodosuccinimide and trifluoromethanesulfonic acid as promoters in acetonitrile at −30°C, followed by sequential deprotection of the acetyl, methyl ester, and benzyl groups, to afford the title compounds. The ability of neuraminidase to hydrolyze these compounds was evaluated, and a correlation between the hydrolysis rates and structures was observed.