Synthesis of α‐N‐Ketosides of N‐Acetylneuraminic Acid by Using Phase‐Transfer Catalysis

Abstract

Abstractα‐N‐Ketosides of N‐acetylneuraminic acid (Neu5Ac) can be synthesized by using azide and thiocyanate salt as aglycone under conditions of phase‐transfer catalysis (PTC). The catalytic hydrogenation of the 2‐α‐azido ketoside 3 leads to the 2‐α‐amino ketoside 4 in good yield. This 2‐α‐amino ketoside 4 can be transformed into the 2‐α‐acetamido ketoside 5 and the 2‐α‐benzoylamido ketoside 6. Zemplén deacetylation and saponification give the corresponding 2‐N‐acyl ketosides 7 and 8, which cannot be hydrolyzed by neuraminidase (Clostridium perfringens). Treatment of the 2‐α‐amino ketoside 4 with p‐nitrobenzaldehyde results in the formation of p‐nitrobenzylideneamine 9. Based on the strict stereoselectivity of the PTC glycosidation reaction with sialic acid derivatives and the exclusive formation of the N‐ketoside 10 in the reaction with potassium thiocyanate, a model of the mechanism of the PTC glycosidation procedure with sialic acid derivatives has been evaluated.