Controlled oxidation of remote sp3 C-H bonds in artemisinin via P450 catalysts with fine-tuned regio- and stereoselectivity.

ABSTRACT: The selective oxyfunctionalization of isolated sp(3) C-H bonds in complex molecules represents a formidable challenge in organic chemistry. Here, we describe a rational, systematic strategy to expedite the development of P450 oxidation catalysts with refined regio- and stereoselectivity for the hydroxylation of remote, unactivated C-H sites in a complex scaffold. Using artemisinin as model substrate, we demonstrate how a three-tier strategy involving first-sphere active site mutagenesis, high-throughput P450 fingerprinting, and fingerprint-driven P450 reactivity predictions enabled the rapid evolution of three efficient biocatalysts for the selective hydroxylation of a primary and a secondary C-H site (with both S and R stereoselectivity) in a relevant yet previously inaccessible region of

SUBMITTER: Zhang K 

PROVIDER: S-EPMC3498520 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature