有机化学 ›› 2006, Vol. 26 ›› Issue (04): 514-517. 上一篇    下一篇

研究论文

D-谷氨酰胺的制备

钱绍松,吴晓燕,李加友,刘毅,陈然,焦庆才*   

  1. (南京大学生命科学院医药生物技术国家重点实验室 南京 210093)
  • 收稿日期:2005-06-14 修回日期:2005-10-31 发布日期:2006-03-31
  • 通讯作者: 焦庆才

Preparation of D-Glutamine from Glutamic Acid

QIAN Shao-Song,WU Xiao-Yan,LI Jia-You,LIU Yi
CHEN Ran,JIAO Qing-Cai*   

  1. (State Key Laboratory of Pharmaceutic Biotechnology, School of Life Science, Nanjing University, Nanjing 210093)
  • Received:2005-06-14 Revised:2005-10-31 Published:2006-03-31
  • Contact: JIAO Qing-Cai

报道了以化学合成和生物转化的方法制备光学纯D-谷氨酰胺. 首先在中试规模上用化学方法合成DL-谷氨酰胺. 即以廉价的DL-谷氨酸为原料, 采用邻苯二甲酰基作为保护基保护L-谷氨酸的α-氨基, 醋酐回流15 min, 使其分子内脱水生成N-邻苯二甲酰-DL-谷氨酸酐, 在常温、常压条件下, 分别与2 mol/L氨水反应生成中间产物N-邻苯二甲酰-DL-谷氨酰胺, 中间产物在室温条件下与0.5 mol/L水合肼反应48 h脱除保护基, 以57%总收率得到DL-谷氨酰胺. 在37 ℃, pH 4.8的条件下, 利用大肠杆菌(E. coli. AS 1.505)脱羧酶将底物浓度30 g/L的DL-谷氨酰胺中L型对映体在8 h内完全转化为4-氨基丁酰胺, 分离得到D-谷氨酰胺.

关键词: DL-谷氨酸, 脱羧酶, D-谷氨酰胺

Optically pure D-glutamine was prepared by biotransformations of DL-glutamine manufactured by chemical synthesis. Firstly, DL-glutamine was synthesized from DL-glutamic acid on larger scale. Protected DL-glutamic acid was prepared by using inexpensive phthaloyl as protecting group. Then N-phthaloyl-DL-glutamic acid anhydride was synthesized with protected DL-glutamic acid and acetic anhydride under reflux for 15 min. Un-der ambient temperature and normal pressure, N-phthaloyl-DL-glutamine was produced by reacting N-phthaloyl-DL-glutamic acid anhydride with 2 mol/L ammonia solution. After the phthaloyl was removed from the intermediate with 0.5 mol/L hydrazine hydrate under ambient temperature for 48 h DL-glutamine mixture was obtained in 57% yields. L-Glutamine in the racemic mixture was selectively decarboxylated to 4-aminobutanamide by the decarboxylase of E. coli AS1.505. Under the following conditions: temperature of 37 ℃, reaction time of 8 h, pH of 4.8, substrate concentration of 30 g/L, D-glutamine was efficiently produced.

Key words: decarboxylase, DL-glutamic acid, D-glutamine