A Convenient Approach to Stereoisomeric Iminocyclitols: Generation of Potent Brain-Permeable OGA Inhibitors

Milan Bergeron-Brlek, Jake Goodwin-Tindall, Nevena Cekic, Christian Roth, Wesley F. Zandberg, Xiaoyang Shan, Vimal Varghese, Sherry Chan, Gideon J. Davies, David J. Vocadlo*, Robert Britton

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Pyrrolidine-based iminocyclitols are a promising class of glycosidase inhibitors. Reported herein is a convenient epimerization strategy that provides direct access to a range of stereoisomeric iminocyclitol inhibitors of O-GlcNAcase (OGA), the enzyme responsible for catalyzing removal of O-GlcNAc from nucleocytoplasmic proteins. Structural details regarding the binding of these inhibitors to a bacterial homologue of OGA reveal the basis for potency. These compounds are orally available and permeate into rodent brain to increase O-GlcNAc, and should prove useful tools for studying the role of OGA in health and disease.

Original languageEnglish
Number of pages6
JournalAngewandte Chemie International Edition
Early online date6 Dec 2015
Publication statusPublished - 14 Dec 2015

Bibliographical note

© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


  • Enzymes
  • Glycosides
  • Heterocycles
  • Hydrolases
  • Inhibitors

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