Miller, David C. and Lal, Ravi G. and Marchetti, Luca A. and Arnold, Frances H. (2022) Biocatalytic One-Carbon Ring Expansion of Aziridines to Azetidines via a Highly Enantioselective [1,2]-Stevens Rearrangement. Journal of the American Chemical Society, 144 (11). pp. 4739-4745. ISSN 0002-7863. PMCID PMC9022672. doi:10.1021/jacs.2c00251. https://resolver.caltech.edu/CaltechAUTHORS:20210821-140525422
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Abstract
We report enantioselective one-carbon ring expansion of aziridines to make azetidines as a new-to-nature activity of engineered “carbene transferase” enzymes. A laboratory-evolved variant of cytochrome P450_(BM3), P411-AzetS, not only exerts unparalleled stereocontrol (99:1 er) over a [1,2]-Stevens rearrangement but also overrides the inherent reactivity of aziridinium ylides, cheletropic extrusion of olefins, to perform a [1,2]-Stevens rearrangement. By controlling the fate of the highly reactive aziridinium ylide intermediates, these evolvable biocatalysts promote a transformation which cannot currently be performed using other catalyst classes.
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Additional Information: | © 2022 American Chemical Society. Received: January 8, 2022; Published: March 8, 2022. This research was sponsored by the U.S. Army Research Office and accomplished under contracts W911NF-19-D-0001 and W911NF-19-2-0026 for the Institute for Collaborative Biotechnologies. D.C.M. was supported by a Ruth Kirschstein NIH Postdoctoral Fellowship (F32GM128247). The authors wish to thank Dr. Sabine Brinkmann-Chen, Dr. Nathaniel Goldberg, and Dr. Nicholas Porter for assistance preparing the manuscript. The authors declare no competing financial interest. | ||||||||||
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Subject Keywords: | Carbene compounds, Hydrocarbons, Aziridines, Peptides and proteins, Rearrangement | ||||||||||
Issue or Number: | 11 | ||||||||||
PubMed Central ID: | PMC9022672 | ||||||||||
DOI: | 10.1021/jacs.2c00251 | ||||||||||
Record Number: | CaltechAUTHORS:20210821-140525422 | ||||||||||
Persistent URL: | https://resolver.caltech.edu/CaltechAUTHORS:20210821-140525422 | ||||||||||
Official Citation: | Biocatalytic One-Carbon Ring Expansion of Aziridines to Azetidines via a Highly Enantioselective [1,2]-Stevens Rearrangement. David C. Miller, Ravi G. Lal, Luca A. Marchetti, and Frances H. Arnold. Journal of the American Chemical Society 2022 144 (11), 4739-4745; DOI: 10.1021/jacs.2c00251 | ||||||||||
Usage Policy: | No commercial reproduction, distribution, display or performance rights in this work are provided. | ||||||||||
ID Code: | 110345 | ||||||||||
Collection: | CaltechAUTHORS | ||||||||||
Deposited By: | Tony Diaz | ||||||||||
Deposited On: | 21 Aug 2021 16:57 | ||||||||||
Last Modified: | 13 Jun 2022 23:29 |
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