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Olefin Cyclopropanation via Carbene Transfer Catalyzed by Engineered Cytochrome P450 Enzymes

Coelho, Pedro S. and Brustad, Eric M. and Kannan, Arvind and Arnold, Frances H. (2013) Olefin Cyclopropanation via Carbene Transfer Catalyzed by Engineered Cytochrome P450 Enzymes. Science, 339 (6117). pp. 307-310. ISSN 0036-8075. doi:10.1126/science.1231434. https://resolver.caltech.edu/CaltechAUTHORS:20130208-132114060

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Abstract

Transition metal–catalyzed transfers of carbenes, nitrenes, and oxenes are powerful methods for functionalizing C=C and C–H bonds. Nature has evolved a diverse toolbox for oxene transfers, as exemplified by the myriad monooxygenation reactions catalyzed by cytochrome P450 enzymes. The isoelectronic carbene transfer to olefins, a widely used C–C bond–forming reaction in organic synthesis, has no biological counterpart. Here we report engineered variants of cytochrome P450_BM3 that catalyze highly diastereo- and enantioselective cyclopropanation of styrenes from diazoester reagents via putative carbene transfer. This work highlights the capacity to adapt existing enzymes for the catalysis of synthetically important reactions not previously observed in nature.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1126/science.1231434 DOIArticle
http://www.sciencemag.org/content/339/6117/307PublisherArticle
ORCID:
AuthorORCID
Brustad, Eric M.0000-0002-7031-5433
Arnold, Frances H.0000-0002-4027-364X
Additional Information:© 2013 American Association for the Advancement of Science. Received 12 October 2012; accepted 30 November 2012; published online 20 December 2012. This work was funded by the Division of Chemical Sciences, Geosciences, and Biosciences, Office of Basic Energy Sciences of the U.S. Department of Energy through grant DE-FG02-06ER15762. E.M.B. was supported by a Ruth M. Kirschstein National Institutes of Health (NIH) postdoctoral fellowship, award number F32GM087102, from the National Institute of General Medical Sciences and a generous startup fund from the University of North Carolina Chapel Hill. P.S.C., E.M.B., and F.H.A. have filed through the California Institute of Technology a provisional patent application that is based on the results presented here. The authors thank Z. J. Wang for helpful discussions during the preparation of the manuscript.
Funders:
Funding AgencyGrant Number
Department of Energy (DOE)DE-FG02-06ER15762
NIH Predocotral FellowshipF32GM087102
National Institute of General Medical SciencesUNSPECIFIED
University of North Carolina Chapel HillUNSPECIFIED
Issue or Number:6117
DOI:10.1126/science.1231434
Record Number:CaltechAUTHORS:20130208-132114060
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20130208-132114060
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:36827
Collection:CaltechAUTHORS
Deposited By:INVALID USER
Deposited On:08 Feb 2013 23:01
Last Modified:09 Nov 2021 23:24

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