hide
Free keywords:
asymmetric sulfoxidation; directed evolution; P450 monooxygenase; saturation mutagenesis; sulfoxidation; thiochroman-4-one sulfoxides
Abstract:
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.
