Chemoenzymatic synthesis of an N-acetylneuraminic acid analogue having a carbamoylmethyl group at C-4 as an inhibitor of sialidase from influenza virus.
5,9-Diacetamido-2,6-anhydro-O-4-carbamoylmethyl-3,5,9-trideo xy-D-glycero- D-galacto-non-2-enonic acid (1) was synthesized via a key intemediate 2 through the Neu5Ac aldolase [E.C.4.1.3.3]-catalyzed aldol reaction of 2-acetamido-2,6-dideoxy-6-azido-D-glucose with sodium pyruvate operating under alkaline conditions (pH 10.5) in order to accelerate epimerization C-2 of N-acetyl-D-glucosamine (D-GlcNAc) derivatives. Compound 1 showed inhibitory activity against sialidase.
Ikeda
K
K
School of Pharmaceutical Sciences, University of Shizuoka, Japan.
Kimura
F
F
Sano
K
K
Suzuki
Y
Y
Achiwa
K
K
D004791:Enzyme Inhibitors / Q000138:chemical synthesis*; D008956:Models, Chemical; D019158:N-Acetylneuraminic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D009975:Orthomyxoviridae / Q000201:enzymology*; D007652:Oxo-Acid-Lyases / Q000378:metabolism
D004791:Enzyme Inhibitors; D009439:Neuraminidase; D007652:Oxo-Acid-Lyases; C018728:N-acetylneuraminate lyase; D019158:N-Acetylneuraminic Acid