关键词: γ-L-谷氨酰二肽, 共保护, 谷氨酸, 席夫碱, Ni(II)配合物

A novel method for the synthesis of γ-L-glutamyl dipeptides 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 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 γ-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 HCl, γ-L-glutamyl dipeptides 5a～5h 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.

Key words: γ-L-glutamyl dipeptide, co-protection, glutamic acid, Schiff base, Ni(II) complex