Chemo-enzymatic fluorination of unactivated organic compounds.
Fluorination has gained an increasingly important role in drug discovery and development. Here we describe a versatile strategy that combines cytochrome P450-catalyzed oxygenation with deoxofluorination to achieve mono- and polyfluorination of nonreactive sites in a variety of organic scaffolds. This procedure was applied for the rapid identification of fluorinated drug derivatives with enhanced membrane permeability.
Rentmeister
Andrea
A
Department of Chemistry and Chemical Engineering, California Institute of Technology 210-41, 1200 East California Boulevard, Pasadena, California 91125, USA.
Arnold
Frances H
FH
Fasan
Rudi
R
D001410:Bacillus megaterium / Q000201:enzymology; D001426:Bacterial Proteins / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D054879:Halogenation; D015394:Molecular Structure; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism*; D009930:Organic Chemicals / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity
D001426:Bacterial Proteins; D009930:Organic Chemicals; D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System; D009251:NADPH-Ferrihemoprotein Reductase; C052423:flavocytochrome P450 BM3 monoxygenases