摘要
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。
Ezetimibe,which is the only commercialized cholesterol absorption inhibitor,is applied to clinical for lowering cholesterol levels.This article intends to describe a newstereoselective synthesis of ezetimibe chiral side chain key intermediate.Distinguished from the present method,the construction of the chiral benzyl hydroxyl side chain was achieved by Sharpless asymmetric epoxidation reaction utilizing（E）-3-（4-fluorophenyl） prop-2-en-1-ol as the starting material and two regioselective ring opening steps were also involved in this strategy.The newmethodology is efficient and cost-effective than the existing synthesis method.The absolute configuration and the optical purity of desired intermediate were confirmed by HPLC and ECD.
出处
《中国药物化学杂志》
CAS
CSCD
2016年第4期313-317,329,共6页
Chinese Journal of Medicinal Chemistry
