Abstract
Chiral compounds are enantiomers of the non-superimposable mirror-images. Drugs with different enantiomers would produce different results on the treatment of disease. The increasing attention is therefore on the development of optically active compounds, so as to produce drugs with more selective, hence with less dosage and side effects. The object of this project is to establish the asymmetric reduction of ethyl-4-chloroacetoacetate (ECA) to ethyl-(S)-4-chloro-3-hydroxybutanoate ((S)-ECHB). The (S)-ECHB is the intermediate for the synthesis of fluvastatin and other antibiotics. The following studies have been investigated : 1. Screen of an effective microorganism which can reduce the ketone of the ECA. 2. Optimize the cultivation conditions of the microorganism strain. 3. Investigate the effects of physical and chemical factors on the microbial reduction reaction. 4. Examine the effects of operation factors on yield and the optical purity of the ECHB, and then optimize the reaction conditions. 5. Estimated the kinetic constants of the ECA substrate-inhibition system. The results of this project will help us to understand more thoroughly the biochemical characteristics of the microbial ECA reduction system. Moreover, the results will also provide us useful engineering data for the design of bioreactor and for the development of cell-immobilized process in the future.