Cargando…

Enzyme-Controlled Nitrogen-Atom Transfer Enables Regiodivergent C–H Amination

[Image: see text] We recently demonstrated that variants of cytochrome P450(BM3) (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 en...

Descripción completa

Detalles Bibliográficos
Autores principales: Hyster, Todd K., Farwell, Christopher C., Buller, Andrew R., McIntosh, John A., Arnold, Frances H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2014
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4227740/
https://www.ncbi.nlm.nih.gov/pubmed/25325618
http://dx.doi.org/10.1021/ja509308v
Descripción
Sumario:[Image: see text] We recently demonstrated that variants of cytochrome P450(BM3) (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 P450(BM3) 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.