A Complex Process of Asymmetric Synthesis of (beta)-Hydroxy Ester by Bakers Yeast Accompanied by Resin Adsorption

Asymmetric reduction of (beta)-oxo ester to chiral (beta)-hydroxy ester by yeast cells is one of the most promising routes for synthesis of chiral pharmaceutical intermediates. But the stereoselectivity and initial substrate concentration of this asymmetric reduction reaction are usually unsatisfactory. When asymmetric reduction of ethyl 4-chloro-3-oxobutanoate to chiral ethyl 4-chloro-3-hydroxybutanoate by bakerʹs yeast was chosen as the model reaction, it was investigated to improve the stereoselectivity and initial substrate concentration of this asymmetric reduction reaction by introducing resin to slowly release the substrate and in situ adsorb the product. The experiments indicated that the stereoselectivity could be promoted from about 78% to 95% with this technique, and the initial substrate concentration could be increased from 70 to 150 mmol/L, but the yield and stereoselectivity were still satisfactory with introducing resin.