1-N-Iminosugars: Potent and selective inhibitors of β-glycosidases

Yoshitaka Ichikawa, Yasuhiro Igarashi, Mie Ichikawa, Yoshitomo Suhara

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210 Citations (Scopus)

Abstract

A series of 1-N-iminosugars were synthesized to supply the need for glycosidase inhibitors that are both highly potent and selective for β- glycosidases. Designed on the basis of the transition-state model of the β- glucosidase reaction, these iminosugar inhibitors differ from the currently available inhibitors in possessing a nitrogen atom at the anomeric position of the pyranose ring, thereby generating a positive charge on the anomeric position rather than on the ring oxygen of the sugar. Their syntheses, starting with a readily available carbohydrate derivative, involve (i) introduction of an amino functionality as an azido group, (ii) formation of a 1-N-iminopyranose ring with reductive amination, and (iii) stereoselective introduction of a hydroxymethyl or methyl group and were accomplished in a highly stereoselective and efficient manner. The inhibitory potencies of the 1-N-iminosugars were evaluated against several α- and β-glycosidases, and they were found to be extremely potent and highly specific against the corresponding β-glycosidases, with K(i) values in the nanomolar range.

Original languageEnglish
Pages (from-to)3007-3018
Number of pages12
JournalJournal of the American Chemical Society
Volume120
Issue number13
DOIs
Publication statusPublished - 1998 Apr 8

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ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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