title: Olefin cyclopropanation via carbene transfer catalyzed by engineered cytochrome P450 enzymes.
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.
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Pedro S
authors.initials: PS
authors.lastname: Coelho
authors.forename: Eric M
authors.initials: EM
authors.lastname: Brustad
authors.forename: Arvind
authors.initials: A
authors.lastname: Kannan
authors.forename: Frances H
authors.initials: FH
authors.lastname: Arnold
mesh_terms: D000475:Alkenes / Q000737:chemistry*; D001410:Bacillus megaterium / Q000201:enzymology; D002384:Catalysis; D003521:Cyclopropanes / Q000737:chemistry*; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry* / Q000235:genetics; D008697:Methane / Q000031:analogs & derivatives* / Q000737:chemistry; D008956:Models, Chemical; D015202:Protein Engineering; D013237:Stereoisomerism
chemical_list: D000475:Alkenes; D003521:Cyclopropanes; C030011:carbene; D003577:Cytochrome P-450 Enzyme System; C030797:cyclopropane; D008697:Methane