Issue 62, 2021

Design and enantioselective synthesis of 3-(α-acrylic acid) benzoxaboroles to combat carbapenemase resistance

Abstract

Chiral 3-substituted benzoxaboroles were designed as carbapenemase inhibitors and efficiently synthesised via asymmetric Morita–Baylis–Hillman reaction. Some of the benzoxaboroles were potent inhibitors of clinically relevant carbapenemases and restored the activity of meropenem in bacteria harbouring these enzymes. Crystallographic analyses validate the proposed mechanism of binding to carbapenemases, i.e. in a manner relating to their antibiotic substrates. The results illustrate how combining a structure-based design approach with asymmetric catalysis can efficiently lead to potent β-lactamase inhibitors and provide a starting point to develop drugs combatting carbapenemases.

Graphical abstract: Design and enantioselective synthesis of 3-(α-acrylic acid) benzoxaboroles to combat carbapenemase resistance

Supplementary files

Article information

Article type
Communication
Submitted
08 Jun 2021
Accepted
17 Jun 2021
First published
14 Jul 2021
This article is Open Access
Creative Commons BY license

Chem. Commun., 2021,57, 7709-7712

Design and enantioselective synthesis of 3-(α-acrylic acid) benzoxaboroles to combat carbapenemase resistance

Y. Xiao, X. Chen, J. Deng, Y. Yan, K. Zhu, G. Li, J. Yu, J. Brem, F. Chen, C. J. Schofield and G. Li, Chem. Commun., 2021, 57, 7709 DOI: 10.1039/D1CC03026D

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