化学酶法合成(R)-肾上腺素及工艺优化  

Chemo-enzymatic synthesis of(R)-adrenaline and process optimization

作　　者：朱文韬 刘雨晴 彭艳 杨宝兴 陆群[1] 赵昱 ZHU Wen-tao;LIU Yu-qing;PENG Yan;YANG Bao-xing;LU Qun;ZHAO Yu(School of Life Science and Engineering,Southwest Jiaotong University,Chengdu 610031,China;Engineering Laboratory of Development and Utilization of Medicinal Insects and Arachnids Resources in Yunnan Province,Dali 671000,China)

机构地区：[1]西南交通大学生命科学与工程学院,四川成都610031 [2]云南省药用昆虫及蛛形类资源开发利用工程实验室,云南大理671000

出　　处：《化学研究与应用》2023年第10期2431-2439,共9页Chemical Research and Application

基　　金：国家自然科学基金项目(2019G010129)资助;四川省科技支撑计划项目(2015FZ0016)资助。

摘　　要：以氯乙酰儿茶酚为起始原料,在羰基还原酶NsCRsO_(2)的不对称催化下得到(R)-4-(2-氯-1-羟乙基)苯-1,2-二醇,然后和甲胺反应制备了(R)-肾上腺素。本研究对羰基还原酶-葡萄糖脱氢酶双酶(全细胞)催化体系的不对称还原进行了单因素条件优化,优化后的工艺条件为:氯乙酰儿茶酚22.32 g·L^(-1),葡萄糖43.2 g·L^(-1),NsCRs0_(2)、葡萄糖脱氢酶菌体10 g·L^(-1),NADP^(+)0.04 g·L^(-1),二甲亚砜10%,温度35℃,pH 6.0,反应时间12 h。在上述条件下使用5 L体系反应,氯乙酰儿茶酚几乎被完全还原为(R)-4-(2-氯-1-羟乙基)苯-1,2-二醇且e.e._(p)>99.9%,甲胺化反应后得到(R)-肾上腺素,收率84.0%,e,e._(p)>99.9%。The(R)-adrenaline was obtained from(R)-4-(2-chloro-1-hydroxyethyl)benzene-1,2-diol,which was obtained from 2-Chloro-3',4'-dihydroxyacetophenone by carbonyl reductase NsCRsO_(2),and reacted with methylamine.In this study,single-factor con-ditions were optimized for the asymmetric reduction of carbonyl reductase-glucose dehydrogenase dual enzyme catalytic system,the optimized conditions were as follows:2-chloro-3',4'-dihydroxyacetophenone 22.32 g·L^(-1),glucose 43.2 g·L^(-1),NsCRsO_(2)、glucose dehydrogenase 10 g-L^(-1),NADP^(+)0.04 g·L^(-1),DMSO 10%,reaction temperature 35℃,reactionpH 6.0andreactiontime12h.The reaction was carried out using a 5L system under the above conditions,2-chloro-3',4'-dihydroxyacetophenone was almost com-pletely reduced to(R)-4-(2-chloro-1-hydroxyethyl)benzene-1,2-diol,e.e_(p)>99.9%,and(R)-adrenaline was obtained after metamerization reaction,yield 84%,e.e._(p)>99.9%.

关 键 词：(R)-肾上腺素 羰基还原酶 化学酶法合成 工艺优化 

分 类 号：O657.1[理学—分析化学]