Synthesis and kinetic analysis of the N-acetylhexosaminidase inhibitor XylNAc-isofagomine.

作者信息

Knapp Spencer, Yang Chunhua, Pabbaraja Srihari, Rempel Brian, Reid Steven, Withers Stephen G

机构信息

Department of Chemistry and Chemical Biology, Rutgers-The State University of New Jersey, 610 Taylor Road, Piscataway, New Jersey 08854, USA.

出版信息

J Org Chem. 2005 Sep 16;70(19):7715-20. doi: 10.1021/jo051117e.

DOI:10.1021/jo051117e

PMID:16149804

Abstract

[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.

摘要