DL-苯丙氨酸类似物的合成及其拆分  

Synthesis and resolution of DL-phenylalanine analogues

作　　者：刘金春[1] 宋博文[1] 马玉[1] 蔡俊[1] 厉廷有[1] 

机构地区：[1]南京医科大学药学院,江苏南京210029

出　　处：《南京医科大学学报（自然科学版）》2013年第3期412-415,共4页Journal of Nanjing Medical University(Natural Sciences)

基　　金：江苏省高校自然科学基础研究项目(08EJB-350002);南京医科大学科技发展基金重点项目(08NMUZ-011)

摘　　要：目的:采用酶拆分法合成L-2,6-二甲基苯丙氨酸和L-2,4,6-三甲基苯丙氨酸。方法:通过乙酰氨基丙二酸二乙酯氨基酸合成法合成外消旋N-乙酰-2,6-二甲基苯丙氨酸和N-乙酰-2,4,6-三甲基苯丙氨酸,再以L-氨基酰化酶拆分,制备L-2,6-二甲基苯丙氨酸和L-2,4,6-三甲基苯丙氨酸。结果:以乙酰氨基丙二酸二乙酯为起始原料,分别以87.9%和86.0%的收率合成了外消旋的2,6-二甲基苯丙氨酸和2,4,6-三甲基苯丙氨酸。氨基酰化酶能拆分DL-N-乙酰-2,6-二甲基苯丙氨酸得到L-2,6-二甲基苯丙氨酸,但对N-乙酰-2,4,6-三甲基苯丙氨酸没有水解活性。结论:L-氨基酰化酶能用于2,6-二甲基苯丙氨酸的拆分,不能用于2,4,6-三甲基苯丙氨酸的拆分。Objective：Synthesis of L-2,6-dimethylphenylalanine and L-2,4,6-trimethylphenylalanine through enzymatic resolution. Methods： Racemie 2,6-dimethylphenylalanine and 2,4,6-trimethylphenylalanine were synthesized through reaction of diethyl acetamidomalonate with 2,6-dimethylbenzyl bromide or 2,4,6-trimethylbenzyl bromide,respectively. The DL-amino acids were then enzymatically resoluted by L-amino acylase. Results： Racemic 2,6-dimethylphenylalanine and 2,4,6-trimethylphenylalanine were synthesized through reaction of diethyl acetamidomalonate with 2,6-dimethylbenzyl bromide and 2,4,6-trimethylhenzyl bromide in yield of 87.9% and 86.0% respectively;DL-2,6-dimethylphenylalanine was successfully resoluted by L-amino aeylase,but it was failed in the resolution of 2,4,6-trimethylphenylalanine. Conclusion：L-amino acylase can be used in the resolution of DL-2,6- dimethylphenylalanine, but it is ineffective in the resolution of 2,4,6-trimethylphenylalanine.

关 键 词：2 6-二甲基苯丙氨酸 2 4 6-三甲基苯丙氨酸 氨基酰化酶 

分 类 号：R962[医药卫生—药理学]