Welcome to the new version of CaltechAUTHORS. Login is currently restricted to library staff. If you notice any issues, please email coda@library.caltech.edu
Published March 23, 2022 | Supplemental Material + Accepted Version + Submitted
Journal Article Open

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

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.

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.

Attached Files

Accepted Version - nihms-1787244.pdf

Submitted - biocatalytic-one-carbon-ring-expansion-of-aziridines-to-azetidines-via-a-highly-enantioselective-1-2-stevens-rearrangement.pdf

Supplemental Material - ja2c00251_si_001.pdf

Supplemental Material - ja2c00251_si_002.xlsx

Files

biocatalytic-one-carbon-ring-expansion-of-aziridines-to-azetidines-via-a-highly-enantioselective-1-2-stevens-rearrangement.pdf
Files (4.9 MB)
Name Size Download all
md5:760f3e282405bf326f2c5d60488ceec5
964.8 kB Preview Download
md5:70b367ff3cfb266122f745583b4ebe7d
771.9 kB Preview Download
md5:f16f3b532ad2a544427c28acc505a3d1
3.1 MB Preview Download
md5:118623951b98b57a8d575b0e7d1e2f71
15.3 kB Download

Additional details

Created:
August 20, 2023
Modified:
December 22, 2023