Synthesis of 2-thioglycosides and isothiocyanates of N-acetylneuraminic acid as potential inhibitors of trans-sialidase

With the purpose of synthesizing free 2-thioglycosides of N-acetylneuramini c acid as potential inhibitors of trans-sialidases, a reinvestigation of gl ycosylation methods was performed. Treatment of methyl (5-acetamido-2,4,7,8 ,9-penta-O-acetyl-3,5-dideoxy-alpha,beta-D-glycero-D-galacto-2-nonulopyrano sid)oate (1) with thiols in the presence of SnCl4 afforded the beta-2-thiog lycosides as major products. The methyl (5-acetamido-4,7,8,9-tetra-O-acetyl -2-bromo-3,5-dideoxy-beta-D-glycero-D-galacto-2-nonulopyranosid)oate (5) wa s prepared from I with trimethylsilyl bromide. This activated compound led to the 2-thio-alpha-glycosides when reacted with thiophenols, and to the be ta anomer by reaction with phenylmethanetiol. These products were character ized as the free ammonium sails. On the other hand, treatment of bromide 5 or the analogue chloride 2, with potassium thiocyanate in acetone led regio selectively to methyl (5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-2-iso thiocyano-D-glycero-D-galacto-2-nonulopyranosid)oates, being the beta-anome r 13 the major product.