Datensatz

Zusammenfassung

Directed evolution utilizing an unconven- tional approach to saturation mutagenesis has been applied to cytochrome P450-BM3 as a catalyst in the asymmetric sulfoxidation of 1-thiochroman-4- one and two deriva tives thereof with complete che- moselectivity as well as ( S)- and (R)-selectivity on an optional ba sis. Whereas wild-type P450-BM3 shows in the case of the parent compound poor enantioselectivity in slight favor of the (S)-sulfoxide (er = 75:25), (S)-selectivity was enhanced to er = 93:7, while reversal of enantioselectivity favoring the (R )-sulfoxide was also achieved (er = 7:93). Two derivatives of the parent substrate underwent simi- lar stereoselective sulfoxidation reactions. Sulfox- ides of this type are of poten tial pharmaceutical in- terest. This biocatalytic approach nicely comple- ments synthetic methods.