A preparative small-molecule mimic of liver CYP450 enzymes in the aliphatic C-H oxidation of carbocyclic N-heterocycles.

ABSTRACT: An emerging trend in small-molecule pharmaceuticals, generally composed of nitrogen heterocycles (N-heterocycles), is the incorporation of aliphatic fragments. Derivatization of the aliphatic fragments to improve drug properties or identify metabolites often requires lengthy de novo syntheses. Cytochrome P450 (CYP450) enzymes are capable of direct site- and chemo-selective oxidation of a broad range of substrates but are not preparative. A chemoinformatic analysis underscored limited structural diversity of N-heterocyclic substrates oxidized using chemical methods relative to pharmaceutical chemical space. Here, we describe a preparative chemical method for direct aliphatic oxidation that tolerates a wide range of nitrogen functionality (chemoselective) and matches the site o

SUBMITTER: Chambers RK 

PROVIDER: S-EPMC10629554 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature