有机化学 ›› 2016, Vol. 36 ›› Issue (1): 191-195.DOI: 10.6023/cjoc201509005 上一篇    下一篇

研究简报

(S)-4-氨基-5-巯基戊酸的简便合成方法

吴平a, 马春华b, 胥森瀚b, 李英霞b, 翟延君a, 张伟b   

  1. a 辽宁中医药大学药学院 大连 116600;
    b 复旦大学药学院 上海 201203
  • 收稿日期:2015-09-05 修回日期:2015-09-28 出版日期:2016-01-25 发布日期:2015-10-08
  • 通讯作者: 翟延君, 张伟 E-mail:zhangw416@fudan.edu.cn
  • 基金资助:

    国家自然科学基金(No. 81573340)和复旦大学卓学人才计划资助项目.

Facile Synthesis of (S)-4-Amino-5-mercaptopentanoic Acid

Wu Pinga, Ma Chunhuab, Xu Senhanb, Li Yingxiab, Zhai Yanjuna, Zhang Weib   

  1. a School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600;
    b School of Pharmacy, Fudan University, Shanghai 201203
  • Received:2015-09-05 Revised:2015-09-28 Online:2016-01-25 Published:2015-10-08
  • Supported by:

    Project supported by the National Natural Science Foundation of China (No. 81573340) and the “Zhuo Xue” Talent Plan of Fudan University.

(S)-4-氨基-5-巯基戊酸(Glutamate thiol, GluSH)是谷氨酸α-羧基被亚甲基巯基取代的衍生物, 也可被视为半胱氨酸的衍生物. 该氨基酸是海洋抗肿瘤环酯肽Apratoxin E及其结构优化物的重要组成片段. 报道(S)-4-氨基-5-巯基戊酸两种简便合成方法. 第一种方法是以巯基和氨基均被保护的D-半胱氨酸为原料, 先与米氏酸缩合生成β-酮酯, 然后还原消除酮羰基、脱羧形成内酰胺, 最后去除巯基和氨基上的保护基以及将内酰胺环打开, 以4步76.0%的总收率得到所需产物. 第二种方法以氨基和γ-羧基被保护的谷氨酸为原料, 先将α-羧基还原为伯醇, 然后借助Mitsunobu反应引入巯基, 最后一锅脱除氨基、巯基和羧基上的保护基得到(S)-4-氨基-5-巯基戊酸.

关键词: (S)-4-氨基-5-巯基戊酸, γ-氨基酸, Mitsunobu反应, 合成

(S)-4-Amino-5-mercaptopentanoic acid (glutamate thiol, GluSH) is a derivative of glutamic acid with α-carboxyl group substituted by methanethiol group. Meanwhile, it could be considered as a derivative of cysteine. This amino acid is an important fragment of marine cytotoxic cyclic depsipeptide apratoxin E. Two facile synthetic methods of (S)-4-amino-5-mercaptopentanoic acid are described. For the first strategy, protected D-cysteine derivate was used as starting material. After coupled with Meldrum's acid, the resulting β-keto ester underwent reductive elimination and thermal decarboxylative ring closure to afford 5-substituted pyrrolidinone (γ-lactam). After removal of protecting groups and ring-open, the target compound was obtained in 76.0% overall yield. For the second method, commercial available Boc-Glu(OBzl)-OH was used as starting material. The thiol group was introduced by Mitsunobu reaction after converting the carboxylic acid to its corresponding alcohol. Then the protecting groups of amino, thiol, and carboxylic acid were removed smoothly in one pot to yield (S)-4-amino-5-mercaptopentanoic acid.

Key words: (S)-4-amino-5-mercaptopentanoic acid, γ-amino acids, Mitsunobu reaction, synthesis