L-羧乙基海因与其衍生物的合成研究.pdfVIP

L-羧乙基海因及其衍生物的合成研究 王月霞 曹飞 周佳栋 林欢 杨颖 韦萍 (南京工业大学制药与生命科学学院, 江苏 南京 210009) 摘要: 本文首先采用 Read 合成法，由 L-谷氨酸与氰酸钠在碱性条件下加热反应，得到N- 氨甲酰-L-谷氨酸，进而在盐酸中回流反应，得到 L-羧乙基海因，产率为 79.5% ；接着采用 DIC/HOBt 复合缩合剂法，分别与S-苄基-L-半胱氨酸、乙胺和牛磺酸进行γ-谷氨酰基化反 应，得到三种L-羧乙基海因衍生物——N-海因丙酰-S-苄基-L-半胱氨酸、N- 乙基海因丙酰胺 和N-海因丙酰牛磺酸，产率分别为91.2%、91.9%和90.5% 。中间产物和终产物的结构经由 熔点，1H NMR 和MS 表征。 关键词: L-羧乙基海因；γ-谷氨酰；L-谷氨酸；乙胺；牛磺酸；S-苄基-L-半胱氨酸 Synthesis of L-Carboxyethyl Hydantoin and Its Derivatives WANG Yuexia ，CAO Fei，ZHOU Jiadong ，LIN Huan ，YANG Ying ，WEI Ping (College of Life Science and Pharmaceutical Engineering，Nanjing University of Technology ，Nanjing 210009 ， Jiangsu ，China) Abstract ：Under basic condition, L-glutamic acid and sodium cyanate were heated to form N-carbamyl-L-glutamic acid, then the reaction mixture was refluxed with hydrochloric acid to abtained carboxyethyl hydantoin, the yield was 79.5 ％. In addition, L-carboxyethyl hydantoin was reacted separately with S-benzyl-L-cysteine, ethylamine and taurine by the use of DIC/HOBt as composite condensing agent, the corresponding products were 2-(3-(2,5-dioxoimidazolidin-4-yl) propanamido)-3-(benzylthio)- propanoic acid , N-ethyl-3-(2,5-dioxoimidazolidin-4-yl)propanamide and 2-(3-(2,5-dioxoimidazolidin-4-yl)propanamido)ethanesulfonic acid in yields of 91.2 ％, 91.9% and 90.5% respectively. The structures of intermediate products and final products were characterized 1 by melting point, H NMR and MS spectra. Key Words: L-carboxyethyl hydantoin ；L-glutamic acid ；S-benzyl-L-cysteine；ethylamine ； taurine 联系人：曹飞. 第一作者：王月霞（1986—），女，硕士研究生. 基金项目: 江苏省普通高校研究生创新计划资助项目(CX08B_115Z). Corresponding author: Associate Prof. CAO Fei. E-mail: csaofeiw@njut.edu.cn Foundation item: supported by the Graduate Student Innovation of Jiangsu Province (CX08B_115Z). 引 言 海因类化合物是指含有各种取代基的五元杂环化合