固相合成胸腺五肽(TP5)有机化学.pdfVIP

2007 年第 27 卷 有 机 化 学 Vol. 27, 2007 第 12 期, 1525～1529 Chinese Journal of Organic Chemistry No. 12, 1525～1529 ·研究论文· 固相合成胸腺五肽(TP5) 宓鹏程 朱颐申* 张 琪 韦 萍 (南京工业大学制药与生命科学学院 南京 210009) 摘要 采用 Fmoc 固相多肽合成中的活化酯方法和2,6-二氯苯甲酰氯(DCB)混合酸酐法, 对 Fmoc-Tyr(t-Bu)-OH 与 Wang 树脂反应中的反应级数和表观活化能进行了研究, 并采用常规方法和微波强化方法分别进行了胸腺五肽的合成. 实验 结果表明, 活化酯方法的反应级数为 1.855, 表观活化能 15.24 kJ/mol, 混合酸酐法的表观活化能为 35.14 kJ/mol. 与传 统方法相比, 微波将缩合反应速率提高了 30 倍以上, 氨基酸过量倍数也从传统的三倍降低到两倍. 关键词 微波强化; 固相多肽合成; 胸腺五肽; 反应级数; 表观活化能 Solid-Phase Synthesis of Thymopentin (TP5) MI, Peng-Cheng ZHU, Yi-Shen* ZHANG, Qi WEI, Ping (College of Life Science and Pharmaceutical Engineering, Nanjing University of Technology, Nanjing 210009) Abstract The reaction order and apparent activation energy of esterification reaction of Fmoc-Tyr- (t-Bu)-OH and Wang resin were studied using the active ester method and 2,6-dichlorobenzoyl chloride method (DCB mixed anhydride method). Microwave-irradiation technique was applied to synthesize the thymopentin. Experiment results showed that the reaction order by the active ester method was 1.855 and the apparent activation energies by the active ester method and mixed anhydride method were 15.24 and 35.14 kJ/mol, respectively. Compared with the classical method, the reaction rate of forming peptide bond was in- creased by over 30 times, and the excessive amount of amino acid was reduced to twice from 3 times of that in the classical method. Keywords microwave enhancement; solid-ph