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Whole‐Cell‐Catalyzed Multiple Regio‐ and Stereoselective Functionalizations in Cascade Reactions Enabled by Directed Evolution
Author(s) -
Li Aitao,
Ilie Adriana,
Sun Zhoutong,
Lonsdale Richard,
Xu JianHe,
Reetz Manfred T.
Publication year - 2016
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201605990
Subject(s) - stereoselectivity , cyclohexane , cyclohexanol , cyclohexanone , cascade , chemistry , catalysis , combinatorial chemistry , cascade reaction , stereochemistry , organic chemistry , chromatography
Biocatalytic cascade reactions using isolated stereoselective enzymes or whole cells in one‐pot processes lead to value‐added chiral products in a single workup. The concept has been restricted mainly to starting materials and intermediate products that are accepted by the respective wild‐type enzymes. In the present study, we exploited directed evolution as a means to create E. coli whole cells for regio‐ and stereoselective cascade sequences that are not possible using man‐made catalysts. The approach is illustrated using P450‐BM3 in combination with appropriate alcohol dehydrogenases as catalysts in either two‐, three‐, or four‐step cascade reactions starting from cyclohexane, cyclohexanol, or cyclohexanone, respectively, leading to either ( R , R )‐, ( S , S )‐, or meso ‐cyclohexane‐1,2‐diol. The one‐pot conversion of cyclohexane into ( R )‐ or ( S )‐2‐hydroxycyclohexanone in the absence of ADH is also described.