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目的依折麦布是目前唯一上市的胆固醇吸收抑制剂,本文对其关键中间体手性苄位羟基侧链的不对称合成方法进行研究。方法以Sharpless不对称环氧化反应为核心,通过两次区域选择性开环策略,以(E)-3-(4-氟苯基)丙基-2-烯-1-醇为起始原料,经5步反应制备得到该关键中间体。结果与结论新工艺路线与现有合成方法相比,操作简便、原料价廉易得、更适用于放大生产。中间体的绝对构型及光学纯度经HPLC及ECD确证和检验,验证了新工艺手性控制的高选择性。
Objective Ezetimibe is the only cholesterol absorption inhibitor currently on the market. In this paper, the asymmetric synthesis of the chiral benzyl side-chain of its key intermediate was studied. Methods Based on the Sharpless asymmetric epoxidation reaction, a series of regioselective ring-opening strategies were employed. Starting from (E) -3- (4-fluorophenyl) propyl-2- The key intermediate was prepared through five steps. Results and Conclusion Compared with the existing synthesis method, the new process route is easy to operate, the raw materials are cheap and easy to be obtained, and is more suitable for enlarging production. The absolute configuration and optical purity of intermediates were confirmed and verified by HPLC and ECD, which verified the high selectivity of new process chirality control.