Chemoenzymatic synthesis of neuraminic acid analogs structurally varied at C-5 and C-9 as potential inhibitors of the sialidase from influenza virus

The 9-amino or 9-N-acyl-5-trifluoroacetyl methyl α-ketosides (1a–c) and their their 2,3-didehydro analogs (2a–c) have been synthesized through Neu5Ac aldolase-catalyzed aldol reaction of 6-azido-2-benzyloxycarbonylamino-2-deoxy-d-mannose with sodium pyruvate. The six compounds were investigated as inhibitors of sialidase from influenza virus. Compound 2b, a 2,3-didehydro type, showed the most potent inhibitory activity (IC50 > 7.8 μM) against the enzyme, whereas, compounds 1a–c as the methyl α-glycosides were found to be practically inactive (IC50 > 100 μM).