报道了一种采用谷氨酸席夫碱Ni(Ⅱ)配合物共保护三-谷氨酸α-氨基和α-羧基合成谷胱甘肽(y—L-谷氨酰正-半胱氨酰-甘氨酸)的新方法.首先由手性助剂——2-[N-(NO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,得到譬苄基-γ-L-谷氨酰也-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,得到口苄基-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,得到墨苄基-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.