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

Yoshitaka Ichikawa, Yasuhiro Igarashi, Mie Ichikawa, Yoshitomo Suhara

Research output: Research - peer-reviewArticle

  • 195 Citations

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.

LanguageEnglish
Pages3007-3018
Number of pages12
JournalJournal of the American Chemical Society
Volume120
Issue number13
DOIs
StatePublished - 1998 Apr 8
Externally publishedYes

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Glycoside Hydrolases
Amination
beta-Glucosidase
Sugars
Nitrogen
Carbohydrates
Oxygen
Derivatives
Atoms
Glucosidases

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

1-N-Iminosugars : Potent and selective inhibitors of β-glycosidases. / Ichikawa, Yoshitaka; Igarashi, Yasuhiro; Ichikawa, Mie; Suhara, Yoshitomo.

In: Journal of the American Chemical Society, Vol. 120, No. 13, 08.04.1998, p. 3007-3018.

Research output: Research - peer-reviewArticle

Ichikawa Y, Igarashi Y, Ichikawa M, Suhara Y. 1-N-Iminosugars: Potent and selective inhibitors of β-glycosidases. Journal of the American Chemical Society. 1998 Apr 8;120(13):3007-3018. Available from, DOI: 10.1021/ja973443k
Ichikawa, Yoshitaka ; Igarashi, Yasuhiro ; Ichikawa, Mie ; Suhara, Yoshitomo. / 1-N-Iminosugars : Potent and selective inhibitors of β-glycosidases. In: Journal of the American Chemical Society. 1998 ; Vol. 120, No. 13. pp. 3007-3018
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