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

Resource type
Date created
2015-11-06
Abstract
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.
Document
Identifier
DOI: 10.1002/anie.201507985
Published as
Bergeron-Brlek, M., Goodwin-Tindall, J., Cekic, N., Roth, C., Zandberg, W. F., Shan, X., Varghese, V., Chan, S., Davies, G. J., Vocadlo, D. J., & Britton, R. (2015). A Convenient Approach to Stereoisomeric Iminocyclitols: Generation of Potent Brain-Permeable OGA Inhibitors. Angewandte Chemie International Edition, 54(51), 15429–15433. https://doi.org/10.1002/anie.201507985
Publication title
Angewandte Chemie International Edition
Document title
A Convenient Approach to Stereoisomeric Iminocyclitols: Generation of Potent Brain‐Permeable OGA Inhibitors
Date
2015
Volume
54
Issue
51
First page
15429
Last page
15433
Copyright statement
Copyright is held by the author(s).
Scholarly level
Peer reviewed?
Yes
Language
English

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