Chiral oxazolidinones via biocatalytic aziridination of unactivated alkenes.

Authors

Zi-Qi Li, Deirdre Hanley, Yu Zhang, Pei-Pei Xie, Sophia J Wu, Zi-Yang Qin, Chi Zhang, Edwin Alfonzo, Francesca-Zhoufan Li, Sabine Brinkman-Chen, Peng Liu, Frances H Arnold

Published in

Nature. Sep 23, 2026. Epub Sep 23, 2026.

Abstract

Chiral oxazolidinones are privileged heterocycles broadly used in asymmetric synthesis (1) and drug discovery (2-3). Conventional synthetic routes rely on a "chiral pool" strategy, where enantiopure amino alcohols are required as key intermediates. Of particular importance are a class of 5-(S)-aminomethyl oxazolidinones that are key scaffolds in next-generation antibiotics targeting multidrug- and extensively drug-resistant Mycobacterium tuberculosis (4-6). While many strategies exist to construct chirality at the 4-position (α-to-nitrogen), methods to install the desired 5-stereocentre (α-to-oxygen) remain underdeveloped. Here we report a haemprotein-catalysed aziridination/ring-expansion cascade that enables direct, enantioselective synthesis of clinically relevant and discovery-stage oxazolidinones from simple alkenes. This work advances haemprotein-catalysed nitrene transfer by enabling functionalisation of unactivated alkenes, a reactivity previously limited to conjugated systems such as styrenes. Computational analysis further reveals that key mutations introduced through directed evolution are responsible for the enantioselective formation of these products.

PMID:
42778177
Bibliographic data and abstract were imported from PubMed on 24 Sep 2026.

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