Rhodococcus fascians

In another study, screening was carried out for reduction of substituted benzazepin-2,3-dione 23 to a 3-hydroxy derivative 24 (Scheme 19.14). This was accomplished by a bacterial strain of Rhodococcus fascians ATCC 12975 (Norcardia salmonicolor SC 6310) with a conversion of 97% and an optical purity of >99.9%. This reaction product 24 is a key intermediate in the synthesis of the calcium antagonist SQ 31,765 (25).104 105 The Bristol-Myers Squibb group has also shown the selective reduction of the (3-keto ester, methyl-4-chloro-3-oxobutanoate, by the fungus Geotrichum candidum SC 5469 to the corresponding (,S )-hydroxy ester.106... 

Kyslikova, E., Babiak, P., Maresova, H., Palyzova, A., HajiCek, J., and Kyslik, P. (2010) Diastereoselective reduction of l-(4-fluorophenyl)-3(R)-[3-oxo-3-(4-fluorophenyl) -propyl] -4( S)- (4-hydroxyphenyl)azetidin-2-one to Ezetimibe by the whole cell catalyst Rhodococcus fascians M022.J. Mol. Catal. B Enzym.,... 

Ezetimibe is a dmg with cholesterol absorption inhibitor properties used to treat hypercholesterolemia. Its active form, (3R,4S)-l-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-(4-hydroxyphenyl)azetidin-2-one, was successfully obtained via microbial diastereoselective reduction of (3R,4S)-l-(4-fluorophenyl)-3-[3-oxo-3-(4-fiuorophenyl)-propyl]-4-(4-hydroxyphenyl)azetidin-2-one using whole cells of Rhodococcus fascians M022 (Figure 13.5b) [19]. Conversion of 94% was obtained after 4h in highly diluted system (0.1 g/1 substrate) with 20% cell suspension, along with excellent de value (99.9%). 

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