2-(3-羟基金刚烷-1-基)六氢吡咯[1,2-a]哌嗪-1,4-二酮的合成及其优化  

Synthesis of 2-(3-hydroxyadamantan-1-yl)hexahydropyrrolo[1,2-a]pyrazine-1,4-dione and its optimization

作　　者：张立 江澜 蔡林宏 官晓书 胡湘南[1] ZHANG Li;JIANG Lan;CAI Lin-hong;GUAN Xiao-shu;HU Xiang-nan(School of Pharmacy,Chongqing Medical University,Chongqing 400016,China;College of Environment and Resources,Chongqing Technology and Business University,Chongqing 400067,China)

机构地区：[1]重庆医科大学药学院,重庆400016 [2]重庆工商大学环境与资源学院,重庆400067

出　　处：《化学研究与应用》2020年第12期2240-2244,共5页Chemical Research and Application

基　　金：重庆市科委项目(cstc2019jscx-msxmX0096)资助;重庆医科大学药学院大学生众创空间项目(DXSZCXM201905)资助。

摘　　要：为了对降糖药物维格列汀进行质量控制,以L-脯氨酸和盐酸金刚烷胺为原料,经仲N-氯乙酰化,羟基化,氨基取代和分子内环合4步反应合成其相关物质:2-(3-羟基金刚烷-1-基)六氢吡咯[1,2-a]哌嗪-1,4-二酮(4),合成的物质其结构经IR、1 H NMR、13 C NMR和MS确证。应用星点设计-效应面法优化4的合成工艺,使得整个工艺路线具有实际应用价值,可以作为维格列汀原料药质量控制的对照品。To conduct the quality control of an antidiabetic vildagliptin,the related material of vildagliptin 2-(3-hydroxyadamantan-1-yl)hexahydropyrrolo[1,2-a]pyrazine-1,4-dione(4)was synthesized in this paper.The related substance of vildagliptin was syn-thesized from L-proline and amantadine hydrochloride through chloroacetylation,hydroxylation,amino substitution and intramolecular cyclization.Finally,the structure was confirmed by IR,1 H NMR and 13 C NMR and MS.Preparation process gained the application value after it was optimized by the central composite design-response surface methodology.The synthesized relate substance could be used as the standard substances in the quality control of vildagliptin.

关 键 词：糖尿病 维格列汀 相关物质 星点设计-效应面法 工艺优化 

分 类 号：O626[理学—有机化学]