氟代巴拉苏酰胺的色谱拆分及拆分机理研究  

Chromatographic Resolution and Chiral Recognition Mechanism of 3F-balasurbramide

作　　者：苏金龙 罗旭娜 方成乔 饶雨 何冠涛 林汉森 SU Jin-long;LUO Xu-na;FANG Cheng-qiao;RAO Yu;HE Guan-tao;LIN Han-sen(College of Pharmacy,Guangdong Pharmaceutical University,Guangzhou 510006,China)

机构地区：[1]广东药科大学药学院,广东广州510006

出　　处：《化学试剂》2020年第6期641-645,共5页Chemical Reagents

基　　金：广东省科技厅资助项目(2015A020211031、2016A020217022)。

摘　　要：建立了HPLC法对氟代巴拉苏酰胺进行手性分离,并研究其分离机理。通过考察2种不同的多糖手性固定相(CSP)(Chiralpak AD-H和Chiralcel OJ-H手性柱)、不同比例的流动相(正己烷和异丙醇),得到最佳手性分离条件,设置不同柱温得出相应的色谱参数,建立分子模型应用软件Autodock对氟代巴拉苏酰胺和手性固定相结构进行对接。结果表明,以V(正己烷)∶V(异丙醇(IPA))=70∶30为流动相,在手性柱Chiralpak AD-H上获得最佳分离,其选择因子α为1.54,分离度R_s为6.50,且方法学验证均在合理范围内。另外,通过热力学研究和分子模拟对分离机理进行简要探讨,得出氢键和π-π相互作用是氟代巴拉苏酰胺与多糖手性固定相手性识别的重要相互作用。A high performance liquid chromatography(HPLC)method was established for chiral separation of 3 F-balasurbramide.During chiral separation process,different chromatographic conditions were investigated to obtain the best separation method.Optimization of chiral separation method was conducted in two different chiral stationary phases(CSPs)and different ratio of mobile phases(n-hexane and iso-propanol).Under different conditions,better chiral separation and resolution were obtained in the organic mode with n-hexane and iso-propanol(IPA)with V(n-hexane)∶V(iso-propanol(IPA))=70∶30 on Chiralpak AD-H column.Enantioselectivity and resolution(αand R_s,respectively)levels with values 1.54 and 6.50,respectively.In addition,thermodynamic study and molecular simulations were also carried out to perform a brief probe into the separation mechanism,which showed that the hydrogen bonds andπ-πinteractions were the major forces for chiral separation.

关 键 词：氟代巴拉苏酰胺 手性固定相 分子对接 对映体分离 热力学参数 手性识别机理 

分 类 号：R917[医药卫生—药物分析学]