酶促水解法拆分布洛芬乙酯的工艺研究

Study on the Process of Resolution of Ibuprofen Ethyl Ester by Enzymatic Hydrolysis

以布洛芬乙酯为反应底物,探索了酶促水解法拆分布洛芬的工艺.以曲拉通X-100为表面活性剂,利用南极假丝酵母脂肪酶B(CAL-B)催化拆分外消旋布洛芬乙酯,并对表面活性剂含量、有机溶剂种类和添加量、酶量、缓冲溶液pH、温度及时间等反应条件进行了优化,得到的最佳反应条件为:在pH为9.0的缓冲溶液中,添加80 mg曲拉通X-100、50μL二氯甲烷和15 mg CAL-B,于30℃下反应48 h,在该条件下,S-布洛芬乙酯的剩余率(C)为65%,布洛芬乙酯的对映体过量值(ees)为94%.

The process of resolution of ibuprofen by enzymatic hydrolysis was explored using ibuprofen ethyl ester as the reaction substrate.The racemic ibuprofen ethyl ester was hydrolyzed by CAL-B(lipase B from Candida antarctica)using Triton X-100 as a surfactant.The reaction parameters such as surfactant content,organic solvent type,organic solvent content,enzyme loading,pH of buffer solution,temperature and time were optimized.The optimal reaction conditions were as follows:in a buffer solution of pH 9.0,80 mg of Triton X-100,50μL of dichloromethane,and 15 mg of CAL-B were added and reacted at 30℃for 48 h.Under the above conditions,the residual rate of S-ibuprofen ethyl ester(C)was 65%and the enantiomeric excess value of ibuprofen ethyl ester(ees)was 94%.