一种基于共保护策略合成谷胱甘肽的新方法  

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

作　　者：周佳栋[1] 曹飞[1] 张小龙[1] 杨颖[1] 应汉杰[1] 韦萍[1] 

机构地区：[1]南京工业大学生物与制药工程学院,南京210009

出　　处：《有机化学》2009年第8期1272-1277,共6页Chinese Journal of Organic Chemistry

基　　金：国家重点基础研究发展计划(973计划)(No.2009CB724700);江苏省普通高校研究生创新计划(No.CX08B_115Z)资助项目

摘　　要：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,1HNMR,13CNMR和HRMS表征.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 Schiffbase 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） complex 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 HC1, 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.

关 键 词：谷胱甘肽 谷氨酸 半胱氨酸 甘氨酸 席夫碱 NI(II)配合物 

分 类 号：TQ464.7[化学工程—制药化工] TQ224.125