Synthesis of α-N-ketosides of N-acetylneuraminic acid by using phase-transfer catalysis

α-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. Zemplen 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.