卤醇脱卤酶催化合成(R)-1-氯-3-苯氧基-2-丙醇的工艺优化

以卤醇脱卤酶重组湿菌体E. coli BL21（pET28a-HHDH）为催化剂，催化外消旋的1-氯-3-苯氧基-2-丙醇的动力学拆分可以获得光学纯的(R)-1-氯-3-苯氧基-2-丙醇。本文系统地研究了卤醇脱卤酶催化合成光学纯(R)-1-氯-3-苯氧基-2-丙醇的影响因素，对反应pH、反应温度、菌体浓度、亲核试剂 {\mathrm{N}}_{\mathrm{3}}^{-} 浓度和底物浓度进行了探究。结果表明，卤醇脱卤酶催化合成(R)-1-氯-3-苯氧基-2-丙醇的最佳工艺条件为：pH为7.0，反应温度为28℃，菌体浓度为22.5g/L，亲核试剂NaN₃的浓度为50mmol/L，底物外消旋1-氯-3-苯氧基-2-丙醇的浓度为10mmol/L。在此工艺条件下，(R)-1-氯-3-苯氧基-2-丙醇的ee值和收率分别为100%和16.97%。

Process optimization for synthesis of (R)-1-chloro-3-phenoxy-2-propanol by halohydrin dehalogenase

Halohydrin dehalogenase (HHDH) was produced by recombinant strain E. coli BL21 (pET28a-HHDH). This recombinant E. coli was used as whole-cell catalysis to synthesize enantiopure (R)-1-chloro-3-phenoxy-2-propanol. The influencing factors of HHDH catalyzed synthesis of (R)-1-chloro-3-phenoxy-2-propanol were studied in the experiment. The reaction pH, reaction temperature, catalyst concentration, nucleophilic concentration (NaN₃) and substrate concentration were investigated. The results showed that the optimal conditions were as follows: pH was 7.0, reaction temperature was 28℃, the concentration of catalyst was 22.5g/L, the concentration of sodium azide was 50mmol/L, the concentration of racemic 1-chloro-3-phenoxy-2-propanol was 10mmol/L. Under these conditions, the ee and yield of (R)-1-chloro-3-phenoxy-2-propanol was 100% and 16.97%, respectively.