Study On New Methods Of Stereoselective Bioreduction

Ethyl (S)-hydroxybutyrate which can be used to synthesisβ-lactam and other antibacterial medicines has been obtained by bioreduction of ethyl acetoacetate with bakers'yeast. But the traditional bioreduction with bakers'yeast was time-consuming, difficult to separate and always with low enantiomerie excess.An improved method of bioreduction with bakers'yeast was studied. Ethyl acetoacetate was chosen as the model substrate. The effects of heating temperature and heating time during the pretreatment of baker'yeast cells on the conversion and stereoselectivity of the reduction reaction were investigated. The results showed that the heating pretreatment could remarkably improve the stereoselectivity of the S-(D)-product.A new bioreductive system made up of baker'yeast and rice wine koji was developed. Under appropriate conditions, the reduction of ethyl acetoacetate to ethyl (S)-hydroxybutyrate can be completed in only 2-3 hours and the ee of ethyl (S)-hydroxybutyrate could reach to over 90%. This bioreductive system was also used to reduce some other compounds containing unsaturated double bonds. These compounds were ethyl benzoylacetate, 2-phenyl-acrylonitrile and 2-phenyl-acrylic acid.