手性药物拆分试剂的研究进展  

Research Progress in Chiral Drug Resolution Reagents

作　　者：房政钰 邢逞[1] 胡堃[1] 龚宁波[1] 吕扬[1] Fang Zhengyu;Xing Cheng;Hu Kun;Gong Ningbo;Lv Yang(Beijing Key Laboratory of Polymorphic Drugs,Institute of Materia Medica,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100050,China)

机构地区：[1]北京协和医学院中国医学科学院药物研究所晶型药物研究北京市重点实验室,北京100050

出　　处：《中国药师》2021年第2期339-343,共5页China Pharmacist

基　　金：国家重点研发计划项目(编号:2016YFC1000900);中国医学科学院医学与健康科技创新工程项目(编号:2017-I2M-1-010);国家科技重大专项-重大新药创制项目(编号:2017ZX09101001003、2018ZX09711001-001、2018ZX09711001-001-013、2018ZX09711001-010)。

摘　　要：手性药物是指分子结构中存在手性中心(不对称中心)的药物,彼此之间互为实物与镜像的对映异构体。手性不同,药物对映体之间的理化性质和生物活性可能存在显著差异,进一步影响药物在体内的吸收、分布、代谢和排泄,因此需要对手性药物进行拆分以保证药效,减少不良反应,提高安全性。手性拆分试剂是指含有手性识别位点且能够拆分手性分子的化合物,它们对于手性药物的拆分具有重要意义,常见的手性拆分试剂有环糊精、淀粉衍生物、纤维素衍生物、蛋白类、脂肪酶、金属有机骨架、大环抗生素、冠醚类等。本文将结合近5年手性拆分试剂的研究与应用,探讨手性拆分机制,分析拆分能力影响因素,为手性拆分试剂的选择和开发提供参考。Chiral drugs are those with a chiral center(asymmetric center) in molecular structures,and they are enantiomers with real and mirror images of each other. With different chiralities,there may be significant differences in physical and chemical properties and biological activities between enantiomers,which further affect the absorption,distribution,metabolism and excretion of drugs in body. Therefore,it is necessary to resolve chiral drugs to ensure efficacy,reduce toxic and side effects,and improve safety. Chiral resolution reagents refer to the compounds containing chiral recognition sites and can resolve chiral molecules. They are of great significance for the resolution of chiral drugs. Common chiral resolution reagents include cyclodextrin,starch derivatives,cellulose derivatives,proteins,lipases,metal organic frameworks,macrocyclic antibiotics and crown ethers,etc. This article combined with the research and application of chiral resolution reagents in the past five years,discussed the mechanism of chiral resolution,analyzed the factors affecting the resolution ability,and provided reference for the selection and development of chiral resolution reagents.

关 键 词：手性药物 药物对映体 手性拆分试剂 手性中心 

分 类 号：R917[医药卫生—药物分析学]