Work

Enantioselective Total Synthesis of Nigelladine A via Late-Stage C–H Oxidation Enabled by an Engineered P450 Enzyme

Year: 2017

Type: article

Abstract: An enantioselective total synthesis of the norditerpenoid alkaloid nigelladine A is described. Strategically, the synthesis relies on a late-stage C-H oxidation of an advanced intermediate. While traditional chemical methods failed to deliver the desired outcome, an engineered cytochrome P450 enzyme was employed to effect a chemo- and regioselective allylic C-H oxidation in the presence of four oxidizable positions. The enzyme variant was readily identified from a focused library of three enzymes, allowing for completion of the synthesis without the need for extensive screening.

Source: Journal of the American Chemical Society

DOI: 10.1021/jacs.7b05196

Authors: Steven A. Loskot, David K. Romney, Frances H. Arnold, Brian M. Stoltz

Institution: California Institute of Technology

Language: English

Topic: Enzyme Catalysis and Immobilization

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funders: Novartis, Center for Selective C-H Functionalization, National Science Foundation, California Institute of Technology, National Institute of General Medical Sciences

Awards: G5060317656, Synthesis of Biologically Active Molecular Scaffolds via Enzyme-Catalyzed Asymmetric Carbene Transfer