Download MendeleyEnzyme-controlled nitrogen-atom transfer enables regiodivergent C-h amination.
Hyster, T.K., Farwell, C.C., Buller, A.R., McIntosh, J.A., Arnold, F.H.(2014) J Am Chem Soc 136: 15505-15508
- PubMed: 25325618
- DOI: https://doi.org/10.1021/ja509308v
- Primary Citation of Related Structures:
4WG2 - PubMed Abstract:
We recently demonstrated that variants of cytochrome P450BM3 (CYP102A1) catalyze the insertion of nitrogen species into benzylic C-H bonds to form new C-N bonds. An outstanding challenge in the field of C-H amination is catalyst-controlled regioselectivity. Here, we report two engineered variants of P450BM3 that provide divergent regioselectivity for C-H amination-one favoring amination of benzylic C-H bonds and the other favoring homo-benzylic C-H bonds. The two variants provide nearly identical kinetic isotope effect values (2.8-3.0), suggesting that C-H abstraction is rate-limiting. The 2.66-Å crystal structure of the most active enzyme suggests that the engineered active site can preorganize the substrate for reactivity. We hypothesize that the enzyme controls regioselectivity through localization of a single C-H bond close to the iron nitrenoid.
Organizational Affiliation:
Division of Chemistry and Chemical Engineering 210-41, California Institute of Technology , 1200 East California Boulevard, Pasadena, California 91125, United States.
