Asymmetric Reduction of Ethyl 4-Chloro-3-Oxobutanoate to Ethyl 4-Chloro3-Hydroxybutanoate Directly Catalyzed by Yeast Fermentation Broth

The asymmetric reduction of ethyl 4-chloro-3-oxobutanoate(COBE) to optically active ethyl 4-chloro-3-hydroxybutanoate(CHBE) directly catalyzed by yeast fermentation broth and the influence of chiral additives and reaction conditions on this reaction were studied.The concentrations of COBE and(S)-CHBE,and the optical purity of the product were determined by gas chromatography and high-performance liquid chromatography with a Chiralcel OB column,respectively.In the yeast fermentation broth without any chiral additive,the substrate was decomposed and the pH value of the reaction mixture decreased sharply.When β-cyclodextrin was used as the chiral additive,the yield and enantiomeric excess of(S)-CHBE reached as high as 76% and 92%,respectively.Under specified conditions,high β-cyclodextrin concentration favored(S)-CHBE formation.The optimum reaction conditions are 29～31 ℃,pH 7.2,and yeast cultivation time of 16～18 h.