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Biocatalytic One-Carbon Ring Expansion of Aziridines to Azetidines via a Highly Enantioselective [1,2]-Stevens Rearrangement

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. 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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1021/jacs.2c00251DOIArticle
https://doi.org/10.26434/chemrxiv-2021-8fq9b-v3DOIDiscussion Paper - version 3
ORCID:
AuthorORCID
Miller, David C.0000-0002-4560-8824
Lal, Ravi G.0000-0001-6943-4147
Marchetti, Luca A.0000-0002-6100-4465
Arnold, Frances H.0000-0002-4027-364X
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.
Funders:
Funding AgencyGrant Number
Army Research Office (ARO)W911NF-19-D-0001
Army Research Office (ARO)W911NF-19-2-0026
NIH Postdoctoral FellowshipF32GM128247
Subject Keywords:Carbene compounds, Hydrocarbons, Aziridines, Peptides and proteins, Rearrangement
Issue or Number:11
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:05 Apr 2022 20:14

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