多糖衍生物手性固定相对甲磺酸艾日布林中间体E3手性分离的考察  

Enantiomeric Separation of the Intermediate E3 for Eribulin Mesylate on Polysaccharide-based Chiral Stationary Phases

作　　者：孙运栋 付杰超 陈国辉 贺志龙 SUN Yundong;FU Jiechao;CHEN Guohui;HE Zhilong(Jiangsu Hansoh Pharmaceutical Group Co.,Ltd.,Lianyungang 222069;Jiangsu Hengrui Medicine Co.,Ltd.,Lianyungang 222002)

机构地区：[1]江苏豪森药业集团有限公司,江苏连云港222069 [2]江苏恒瑞医药股份有限公司,江苏连云港222002

出　　处：《中国医药工业杂志》2021年第9期1224-1229,共6页Chinese Journal of Pharmaceuticals

摘　　要：建立了多糖-苯基氨基甲酸酯类衍生物手性固定相对甲磺酸艾日布林(1)的中间体E3(2)23位和27位手性异构体的拆分方法,并探讨了其可能的分离机制。通过分析2个手性中心(C23、C27)的取代基结构,推测包合作用和疏水作用是潜在主要拆分作用力。针对作用力考察了多种多糖衍生物类手性固定相,发现不同类型多糖(纤维素、直链淀粉)带来的包合作用是C23(R)C27(R)异构体(3)、C23(R)C27(S)异构体(5)的主要拆分作用力,不同取代基位置的苯基氨基甲酸酯带来的疏水作用是分离C23(S)C27(S)异构体(4)的主要作用力,利用这一分离机制可以选择固定相。此外,进一步研究了影响其分离性能的主要色谱条件(柱温、流速),优化后的试验条件可以较好地实现目标体系的分离分析。A method for separation of the isomers from C23 and C27 on the intermediate E3(2)of eribulin mesylate(1)on chiral stationary phase based on polysaccharide-phenyl carbamate derivatives was established,and its possible separation mechanism was discussed.It was speculated that the inclusion and hydrophobic effects were the potential main resolution forces by analyzing the structure of the two chiral centers of 2(C23,C27).A variety of chiral stationary phases based on polysaccharide derivatives were investigated,and it was found that the inclusion effect of different types of polysaccharides(cellulose,amylose)was the main resolution force of C23(R)C27(R)isomer(3)and C23(R)C27(S)isomer(5).The hydrophobic effect of phenyl carbamates with different substituents was the main resolution of C23(S)C27(S)isomer(4).The stationary phase could be selected from this separation mechanism.In addition,the main chromatographic conditions,such as the column temperature and flow rate,affecting separation performance were further studied.The optimized test conditions can realize the separation and analysis of the target compounds.

关 键 词：高效液相色谱 甲磺酸艾日布林 中间体 手性异构体 多糖衍生物类手性固定相 

分 类 号：R917[医药卫生—药物分析学] O657.7[医药卫生—药学]