基于配合共保护策略合成γ-L-谷氨酰二肽的新方法  

A Novel Method for the Synthesis of γ-L-Glutamyl Dipeptides Based on a Complexing Co-protection Strategy

作　　者：周佳栋[1] 曹飞[1] 王月霞[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12期1956-1962,共7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：提出了一种采用谷氨酸席夫碱Ni(Ⅱ)配合物共保护L-谷氨酸的α-氨基和α-羧基合成γ-L-谷氨酰二肽的新方法.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98.2%;进而采用二异丙基碳二亚胺(DIC)/1-羟基-苯并三唑(HOBt)复合缩合剂法分别与L-氨基酸3a～3h反应,得到相应的γ-L-谷氨酰二肽席夫碱Ni(Ⅱ)配合物4a～4h,产率为93.1%～99.0%;最后稀酸水解配合物,得到γ-L-谷氨酰二肽5a～5h,产率为73.0%～86.4%,高收率(92.2%～97.4%)回收手性助剂.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 y-L-glutamyl dipeptides via a Ni（Ⅱ） complex of glutamic acid Schiff base, which has been employed as co-protection of the a-amino and a-carboxyl groups of L-glutamic acid, was described. Firstly, a Ni（Ⅱ） complex 2 of glutamic acid Schiff base was formed in a yield of 98.2% from chiral auxiliary 2-[N-（N-benzyl-prolyl）amino]benzopheone （1） with nickel（Ⅱ） chloride hexahydrate and L-glutamic acid. Then, 2 was reacted separately with L-amino acids 3a-3h to give Ni（Ⅱ） complexes 4a-4h of y-L-glutamyl dipeptide Schiff base in yields of 93.1%-99.0% using a DIC/HOBt coupling method. Finally, after decomposition of the complexes 4a-4h with aqueous HC1, y-L-glutamyl dipeptides 5a^Sh were obtained in yields of 73.0%-86.4% and the chiral auxiliary 1 was recovered in high yields of 92.2%-97.4%, respectively. The structures of intermediates and final products were characterized by optical rotation, ^1H NMR, ^13C NMR and HRMS techniques.

关 键 词：γ-L-谷氨酰二肽 共保护 谷氨酸 席夫碱 Ni(Ⅱ)配合物 

分 类 号：TQ464.7[化学工程—制药化工]