CHEMOENZYMATIC SYNTHESIS OF NEURAMINIC ACID ANALOGS STRUCTURALLY VARIED AT C-5 AND C-9 AS POTENTIAL INHIBITORS OF THE SIALIDASE FROM INFLUENZA VIRUS

摘要

The 9-amino or 9-N-acyl-5-trifluoroacetyl methyl alpha-ketosides (1a-c) and their 2,3-didehydro analogs (2a-c) have been synthesized through Neu5Ac aldolase-catalyzed aldol reaction of 6-azido-2-benzyloxycarbonylamino-2-deoxy 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 mu M) against the enzyme, whereas, compounds 1a-c as the methyl alpha-glycosides were found to be practically inactive (IC50 > 100 mu M). [References: 15]