Rentmeister Andrea, Arnold Frances H, Fasan Rudi
Department of Chemistry and Chemical Engineering, California Institute of Technology 210-41, 1200 East California Boulevard, Pasadena, California 91125, USA.
Nat Chem Biol. 2009 Jan;5(1):26-8. doi: 10.1038/nchembio.128. Epub 2008 Nov 16.
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.
氟化在药物研发中发挥着越来越重要的作用。在此,我们描述了一种通用策略,该策略将细胞色素P450催化的氧化反应与脱氧氟化反应相结合,以实现各种有机骨架中非反应性位点的单氟化和多氟化。该方法用于快速鉴定具有增强膜通透性的氟化药物衍生物。