苯并二氮杂酮酸的合成及其在肽模拟中的应用Synthesisof.PDF

2010 年第 30 卷 有 机 化 学 Vol. 30, 2010 第 7 期, 1010～1016 Chinese Journal of Organic Chemistry No. 7, 1010～1016 ·研究论文· 苯并二氮杂酮酸的合成及其在肽模拟中的应用 * 袁建海 杨潇骁 林 浩 王德心 (北京协和医学院 中国医学科学院药物研究所 北京 100050) 摘要 采用两种方法以靛红酸酐为起始原料, 分别与谷氨酸(L-Glu)和亚氨基二乙酸(Ida)反应制备两种含有游离羧基的 1,4-苯并二氮杂-2,5-二酮类中间体 2a 和 2b; 同时, 由 2a 或 2b 与氨基组分 3c～3f, 3h, 3j 进行缩合制备了含有 1,4-苯 并二氮杂-2,5-二酮环的肽模拟物 4c～4f, 4h, 4j, 5c～5f, 5h, 5j. 另外, 讨论了溶剂对微波辅助法合成 1,4-苯并二氮杂 -2,5-二酮酸的影响. 所合成新化合物均经 MS, 1H NMR 证明其结构. 关键词 靛红酸酐; 1,4-苯并二氮杂-2,5-二酮酸; 肽模拟; 微波 Synthesis of Benzodiazepinonic Acid and Application in Peptide Mimetics Yuan, Jianhai Yang, Xiaoxiao Lin, Hao Wang, Dexin* (Institute of Materia Medica, Peking Union Medical College, Chinese Academy of Medical Science, Beijing 100050) Abstract To synthesize two 1,4-benzodiazepine-2,5-dione intermediates 2a and 2b with free carboxyl, two methods were applied in this paper, in which isatoic acid was used as starting material and reacted with glu- tamic acid (L-Glu) and imino diacetic acid (Ida), respectively. Meanwhile, peptide mimetics 4c～4f, 4h, 4j, 5c～5f, 5h, 5j with 1,4-benzodiazepine-2,5-dione cycle were prepared by condensation of 2a or 2b with amino components 3c ～3f, 3h and 3j. In addition, effect on the microwave-assisted synthesis of 1,4-benzodiazepine-2,5-dionic acid by solvent was discussed. All the new compounds were characterized by 1 MS and H NMR techniques. Keywords isatoic acid; 1,4-benzodiazepine-2,5-