title: Cytochrome P450 catalyzed oxidative hydroxylation of achiral organic compounds with simultaneous creation of two chirality centers in a single C-H activation step.
abstract: Regio- and stereoselective oxidative hydroxylation of achiral or chiral organic compounds mediated by synthetic reagents, catalysts, or enzymes generally leads to the formation of one new chiral center that appears in the respective enantiomeric or diastereomeric alcohols. By contrast, when subjecting appropriate achiral compounds to this type of C-H activation, the simultaneous creation of two chiral centers with a defined relative and absolute configuration may result, provided that control of the regio-, diastereo-, and enantioselectivity is ensured. The present study demonstrates that such control is possible by using wild type or mutant forms of the monooxygenase cytochrome P450 BM3 as catalysts in the oxidative hydroxylation of methylcyclohexane and seven other monosubstituted cyclohexane derivatives.
authors.affiliation: Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, 45470 Mülheim an der Ruhr (Germany); Department of Chemistry, Philipps-Universität Marburg, Hans-Meerwein-Strasse, 35032 Marburg (Germany).
authors.forename: Gheorghe-Doru
authors.initials: GD
authors.lastname: Roiban
authors.forename: Rubén
authors.initials: R
authors.lastname: Agudo
authors.forename: Manfred T
authors.initials: MT
authors.lastname: Reetz
mesh_terms: D001410:Bacillus megaterium / Q000201:enzymology; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D055162:Biocatalysis; D002244:Carbon / Q000737:chemistry; D020134:Catalytic Domain; D003510:Cyclohexanes / Q000737:chemistry*; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000378:metabolism*; D006859:Hydrogen / Q000737:chemistry; D006900:Hydroxylation; D009251:NADPH-Ferrihemoprotein Reductase / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D013237:Stereoisomerism
chemical_list: D001426:Bacterial Proteins; D003510:Cyclohexanes; D002244:Carbon; D006859:Hydrogen; D003577:Cytochrome P-450 Enzyme System; D009251:NADPH-Ferrihemoprotein Reductase; C052423:flavocytochrome P450 BM3 monoxygenases; C521475:methylcyclohexane
keywords: CH activation; biocatalysis; cytochrome P450; hydroxylation; stereoselectivity