一锅法合成去甲基麻黄素  

Synthesis of Norephedrine in One Pot

作　　者：罗磊 穆晓清[1,2] 吴涛 聂尧 徐岩[1] LUO Lei;MU Xiaoqing;WU Tao;NIE Yao;XU Yan(Key Laboratory of Industrial Biotechnology,Ministry of Education,Jiangnan University,Wuxi 214122,China;Suqian Jiangnan University Institute of Industrial Technology,Suqian 223800,China)

机构地区：[1]江南大学工业生物技术教育部重点实验室,无锡214122 [2]宿迁市江南大学产业技术研究院,宿迁223800

出　　处：《高等学校化学学报》2021年第8期2458-2464,共7页Chemical Journal of Chinese Universities

基　　金：国家自然科学基金(批准号:21336009,21176103);国家“八六三”计划项目(批准号:2015AA021004);高等学校学科创新引智计划(批准号:111-2-06)资助~~。

摘　　要：以廉价底物苯甲醛、丙酮酸和NH_4Cl为原料,通过级联乙醛羟酸合成酶(ASAHⅠ)催化缩合反应和胺脱氢酶(BbAmDH)催化还原胺化反应,构建了去甲基麻黄素的生物合成新途径.通过优化分步法和一锅法的反应条件,使苯甲醛转化率分别达到99%和83%.采用一锅法,利用底物补料策略,有效解除了ASAHⅠ的底物和产物抑制作用,批次反应的苯甲醛浓度从40 mmol/L提高到100 mmol/L,苯甲醛转化率从83%提高到90%,苯甲醛的时空转化率提高了2.7倍.In this study,a new biosynthetic pathway of norephedrine was constructed,through cascading the carboligation reaction catalyzed by acetohydroxyacid synthase Ⅰ(ASAHⅠ) and reductive amination reaction catalysed by amine dehydrogenase(Bb AmDH),the cheap substrate benzaldehyde,pyruvate and NH4Cl used as raw materials. Optimizing the reaction conditions of the two-step and one-pot method,the conversion rate of benzaldehyde was as high as 99% in the two-step and 83% in one-pot. Utilizing the strategy of feeding in one pot,the substrate and production inhibition effect of ASAHⅠ was successfully relieved,and the benzaldehyde loading was increased to 100 mmol/L from 40 mmol/L in the batch reaction;the benzaldehyde conversion rate was increased to 90% from 83%,and the space-time conversion rate of benzaldehyde was increased by 2.7 times.

关 键 词：去甲基麻黄素 一锅法 生物转化 乙醛羟酸合成酶 胺脱氢酶 

分 类 号：O621.2[理学—有机化学]