Faculty of Engineering, Department of Chemical Engineering, Ankara University, Ankara, Turkey.
Prep Biochem Biotechnol. 2010;40(4):389-404. doi: 10.1080/10826068.2010.525433.
Optically active 1-phenyl 1-propanol is used as a chiral building block and synthetic intermediate in the pharmaceutical industries. In this study, the enantioselective production of 1-phenyl 1-propanol was investigated systematically using response surface methodology (RSM). Before RSM was applied, the effects of the enzyme source, the type of acyl donor, and the type of solvent on the kinetic resolution of 1-phenyl 1-propanol were studied. The best results were obtained with Candida antartica lipase (commercially available as Novozym 435), vinyl laurate as the acyl donor, and isooctane as the solvent. In the RSM, substrate concentration, molar ratio of acyl donor to the substrate, amount of enzyme, temperature, and stirring rate were chosen as independent variables. The predicted optimum conditions for a higher enantiomeric excess (ee) were as follows: substrate concentration, 233 mM; molar ratio of acyl donor to substrate, 1.5; enzyme amount, 116 mg; temperature, 47 °C; and stirring rate, 161 rpm. A verification experiment conducted at these optimized conditions for maximum ee yielded 91% for 3 hr, which is higher than the predicted value of 83%. The effect of microwave on the ee was also investigated and ee reached 87% at only 5 min.
光学活性 1-苯基-1-丙醇可用作手性构建块和制药工业中的合成中间体。在本研究中，使用响应面法（RSM）系统地研究了 1-苯基-1-丙醇的对映选择性生产。在应用 RSM 之前，研究了酶源、酰基供体的类型和溶剂对 1-苯基-1-丙醇动力学拆分的影响。使用南极假丝酵母脂肪酶（商业上称为 Novozym 435）、月桂酰基乙烯酯作为酰基供体和异辛烷作为溶剂可获得最佳结果。在 RSM 中，选择底物浓度、酰基供体与底物的摩尔比、酶用量、温度和搅拌速度作为自变量。预测得到更高对映体过量（ee）的最佳条件如下：底物浓度 233mM；酰基供体与底物的摩尔比为 1.5；酶用量为 116mg；温度为 47°C；搅拌速度为 161rpm。在这些最佳条件下进行的最大 ee 的验证实验在 3 小时内产生了 91%，高于预测值 83%。还研究了微波对 ee 的影响，仅在 5 分钟内 ee 就达到了 87%。
