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Chemo‐ and Stereoselective Cytochrome P450‐BM3‐Catalyzed Sulfoxidation of 1‐Thiochroman‐4‐ones Enabled by Directed Evolution
Author(s) -
Wang Jianbo,
Ilie Adriana,
Reetz Manfred T.
Publication year - 2017
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201700414
Subject(s) - chemistry , stereoselectivity , sulfoxide , chemoselectivity , selectivity , saturated mutagenesis , directed evolution , catalysis , divergent synthesis , stereochemistry , substrate (aquarium) , combinatorial chemistry , organic chemistry , biochemistry , gene , oceanography , mutant , geology
Directed evolution utilizing an unconventional 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 derivatives thereof with complete chemoselectivity as well as ( S )‐ and ( R )‐selectivity on an optional basis. 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 similar stereoselective sulfoxidation reactions. Sulfoxides of this type are of potential pharmaceutical interest. This biocatalytic approach nicely complements synthetic methods.