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 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-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 microM) against the enzyme, whereas, compounds 1a-c as the methyl alpha-glycosides were found to be practically inactive (IC50 > 100 microM).
Murakami
M
M
School of Pharmaceutical Sciences, University of Shizuoka, Japan.
Ikeda
K
K
Achiwa
K
K
D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009980:Influenza A virus / Q000187:drug effects / Q000201:enzymology*; D009682:Magnetic Resonance Spectroscopy; D008358:Mannose / Q000031:analogs & derivatives / Q000378:metabolism; D015394:Molecular Structure; D019158:N-Acetylneuraminic Acid / Q000031:analogs & derivatives*; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D007652:Oxo-Acid-Lyases / Q000378:metabolism; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D012794:Sialic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D004791:Enzyme Inhibitors; D011773:Pyruvates; D012794:Sialic Acids; C036137:2-deoxy-2,3-dehydro-N-acetylneuraminic acid; D019289:Pyruvic Acid; D009439:Neuraminidase; D007652:Oxo-Acid-Lyases; C018728:N-acetylneuraminate lyase; D019158:N-Acetylneuraminic Acid; D008358:Mannose