依折麦布3种杂质的合成  

Synthesis of three impurities in ezetimibe

作　　者：程进波[1] 赵世明[2] 罗振福[2] 吴学丹[2] 

机构地区：[1]天津理工大学化工学院,天津300384 [2]天津药物研究院化学制药部,天津300193

出　　处：《中国新药杂志》2013年第14期1697-1699,1716,共4页Chinese Journal of New Drugs

摘　　要：目的:合成依折麦布原料药中的3种主要杂质。方法:以依折麦布中间体(S)-3-{(R)-2-(S)-4-苄氧苯基-[4-氟苯基胺-甲基]-4-[2-(4-氟苯基)-[1,3]二氧环戊烷-2-基]-丁酰}-4-苯基-噁唑烷-2-酮为原料,经过关环、脱保护反应得到杂质4,脱苄反应得到杂质5。依折麦布原料药水解得到杂质6。结果:3种目标杂质的结构经1H-NMR和ESI-MS确证,纯度经HPLC检测可达98%以上。结论:合成的3种杂质可作为依折麦布原料药质量控制的杂质对照。Objective： To synthesize three impurities（4,5 and 6） in ezetimibe.Methods：（S）-3-{（R） 2-（S）-4-benzyloxyphenyl-[4-fluorophenylamine-methyl]-4-[2-（4-fluorphenyl）-[1,3]dioxolane-2-yl]-butyryl}-4phenyl-oxazolidine-2-ketone was used as starting material to prepare impurty 4,by which impurty 5 was synthesized through debenzylation reaction and impurty 6 was gained from ezetimibe by alkaline degradation.Results： The structures of all impurities were verified by 1H-NMR and ESI-MS,and their purities were over 99.5% by HPLC.Conclusion： The three impurities can be used as the reference substance of the impurities in the quality control of ezetimibe.

关 键 词：依折麦布 胆固醇抑制剂 杂质 合成 

分 类 号：R914.5[医药卫生—药物化学]