Synthesis and kinetic analysis of the N-acetylhexosaminidase inhibitor XylNAc-isofagomine.
[reaction: see text] An efficient 10-step preparation from 4-methoxypyridine of (2R,3R,4R)-2-acetamido-3,4-dihydroxypiperidine ("XylNAc-isofagomine") in optically active form is described. Key steps include an enantioselective reduction with catecholborane/(S)-2-methyl-CBS-oxazaborolidine, and a stereoselective pseudo-glycosylation of lithium azide by a cyclic sulfite ester. The title compound showed a Ki = 21 microM when evaluated against the N-acetyl-beta-hexosaminidase from Streptomyces plicatus.
Knapp
Spencer
S
Department of Chemistry and Chemical Biology, Rutgers-The State University of New Jersey, 610 Taylor Road, Piscataway, New Jersey 08854, USA. knapp@rutchem.rutgers.edu
Yang
Chunhua
C
Pabbaraja
Srihari
S
Rempel
Brian
B
Reid
Steven
S
Withers
Stephen G
SG
D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism; D050112:Imino Pyranoses / Q000138:chemical synthesis; D007700:Kinetics; D010880:Piperidines / Q000138:chemical synthesis*; D001619:beta-N-Acetylhexosaminidases / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D050112:Imino Pyranoses; D010880:Piperidines; C098432:isofagomine; D001619:beta-N-Acetylhexosaminidases