水相体系中固定化Acetobacter sp.CCTCC M209061细胞催化(S)-3-氯苯丙醇不对称合成

Asymmetric Synthesis of(S)-3-Chloro-1-phenylpropanol with Immobilized Acetobacter sp. CCTCC M209061 Cells in a Monophasic System

光学纯的3-氯苯丙醇是合成抗抑郁类药物的重要中间体。本论文报道了水相体系中固定化Acetobacter sp.CCTCC M209061细胞高效、高选择性地催化3-氯苯丙酮不对称还原为(S)-3-氯苯丙醇,采用聚乙烯醇与海藻酸钠的混合载体对醋酸杆菌细胞进行固定化,所得的固定化细胞的稳定性(热稳定性、p H稳定性及操作稳定性)均明显优于游离细胞。同时,固定化后的微生物细胞具有较好的重复利用性,连续反应3个批次后固定化细胞仍保留了80.0%以上的活性,而游离细胞的相对活性则小于20%。在所研究的体系中,葡萄糖为该反应的最佳辅底物,其最适浓度为50.0 mmol/L;该反应体系中的最适缓冲液p H值、反应温度、底物浓度分别为5.5、30℃和3.0 mmol/L。在此条件下,反应的初速度、产率以及产物的e.e.值依次为1.77 m M/h,88.9%和99.0%以上。

Optically pure 3-chloro-1-phenyl-1-propanol is an important intermediate for the synthesis of drugs for treating depression. In the present study, biocatalytic asymmetric reduction of 3-chloropropiophenone to(S)-3-chloro-1-phenyl-1-propanol with immobilized Acetobacter sp. CCTCC M209061 cells was successfully conducted in a monophasic aqueous system with high efficiency and selectivity. The immobilized Acetobacter sp. CCTCC M209061 cells exhibited higher stabilities(thermal, p H, and operational stability) than the free cells. In addition, the immobilized microbial cells exhibited a relatively good recyclability; the relative activity of immobilized cells remained over 80%, while that of the free cells under the same condition was less than 20%. In the studied system, glucose was the best co-substrate at an optimum concentration of 50 mmol/L. The optimum buffer p H, reaction temperature, and substrate concentration in this reaction system were 5.5, 30 ℃, and 3.0 mmol/L, respectively. Under the optimized reaction conditions, the initial reaction rate, yield, and product e.e. were 1.77 m M/h, 88.9%, and above 99.0%, respectively.