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有机化学
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有机化学 ›› 2009, Vol. 29 ›› Issue (08): 1272-1277. 上一篇    下一篇

研究简报

一种基于共保护策略合成谷胱甘肽的新方法

周佳栋; 曹 飞*; 张小龙; 杨 颖; 应汉杰; 韦 萍   

  1. (南京工业大学生物与制药工程学院 南京 210009)
  • 收稿日期:2008-10-20 修回日期:2009-01-12 发布日期:2009-08-30
  • 通讯作者: 曹 飞

A Novel Method for the Synthesis of Glutathione Based on a Co-protection Strategy

Zhou, Jiadong; Cao, Fei*; Zhang, Xiaolong; Yang, Ying; Ying, Hanjie; Wei, Ping   

  1. (College of Life Science and Pharmaceutical Engineering, Nanjing University of Technology, Nanjing 210009)
  • Received:2008-10-20 Revised:2009-01-12 Published:2009-08-30
  • Contact: Cao, Fei

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被引次数

8 | 3

报道了一种采用谷氨酸席夫碱Ni(II)配合物共保护L-谷氨酸α-氨基和α-羧基合成谷胱甘肽(γ-L-谷氨酰-L-半胱氨酰-甘氨酸)的新方法. 首先由手性助剂——2-[N-(N’-苄基-脯氨酰)氨基]二苯甲酮(1)、六水合氯化镍和L-谷氨酸反应, 得到谷氨酸席夫碱Ni(II)配合物2, 产率为98%; 进而采用二异丙基碳二亚胺(DIC)/1-羟基-苯并三氮唑(HOBt)复合缩合剂法与S-苄基-L-半胱氨酸反应, 得到S-苄基-γ-L-谷氨酰-L-半胱氨酸席夫碱Ni(II)配合物3, 产率为90%; 接着同样采用DIC/HOBt复合缩合剂法与甘氨酸反应, 得到S-苄基-γ-L-谷氨酰-L-半胱氨酰-甘氨酸席夫碱Ni(II)配合物4, 产率为95%; 然后稀酸水解配合物4, 得到S-苄基-γ-L-谷氨酰-L-半胱氨酰-甘氨酸(5), 产率为70%; 最后采用甲酸铵催化转移氢化脱除S-苄基, 得到谷胱甘肽(6), 产率为87%. 中间产物和终产物的结构经由旋光, 1H NMR, 13C NMR和HRMS表征.

关键词: 谷胱甘肽, 席夫碱, 谷氨酸, 甘氨酸, 半胱氨酸, Ni(II)配合物

A novel method for the synthesis of glutathione (γ-L-glutamyl-L-cysteinyl-glycine) via a Ni(II) complex of glutamic acid Schiff base, which has been employed as co-protection of the α-amino and α-carboxyl groups of L-glutamic acid, was described. Firstly, a Ni(II) complex 2 of glutamic acid Schiff base was formed in a 98% yield from chiral auxiliary 2-[N-(N’-benzyl-prolyl)amino]benzopheone (1) with nickel(II) chloride hexahydrate and L-glutamic acid. Then, 2 reacted with S-benzyl-L-cysteine to give Ni(II) complex 3 of S-benzyl-γ-L-glutamyl-L-cysteine Schiff base in a yield of 90% using a N,N’-diisopropylcarbodiimide (DIC)/1-hydroxybenzotrizole (HOBt) coupling method. Thirdly, 3 reacted with glycine to give Ni(II) com-plex 4 of S-benzyl-γ-L-glutamyl-L-cysteinyl-glycine Schiff base in a yield of 95% using the same DIC/HOBt coupling method. Fourthly, after decomposition of 4 with aqueous HCl, S-benzyl-γ-L-glutamyl-L-cysteinyl-glycine (5) was obtained in a 70% yield. Finally, the S-benzyl was re-moved by catalytic transfer hydrogenation with ammonium formate, while glutathione (6) was synthesized in an 87% yield. Structures of intermediates and final products were characterized by optical rotation, 1H NMR, 13C NMR and HRMS techniques.

Key words: glutamic acid, cysteine, glycine, Schiff base, Ni(II) complex, glutathione