盐酸去氧肾上腺素的合成工艺改进  

Improved Synthetic Process of Phenylephrine Hydrochloride

作　　者：王汉杰 刘甲甲 汤佳伟 陈少欣[2] 张福利[2] 余俊 WANG Hanjie;LIU Jiajia;TANG Jiawei;CHEN Shaoxin;ZHANG Fuli;YU Jun(School of Chemistry and Chemical Engineering,Shanghai University of Engineering Science,Shanghai 201620;Shanghai Institute of Pharmaceutical Industry Co.,Ltd.,China State Institute of Pharmaceutical Industry,Shanghai 201203)

机构地区：[1]上海工程技术大学化学化工学院,上海201620 [2]中国医药工业研究总院上海医药工业研究院有限公司,上海201203

出　　处：《中国医药工业杂志》2025年第1期47-51,共5页Chinese Journal of Pharmaceuticals

基　　金：科技部国家重点研发计划“绿色生物制造”项目(2021YFC2102100);上海启明星培育(扬帆专项)项目(23YF1445800)。

摘　　要：对盐酸去氧肾上腺素(1)的合成工艺进行了改进。以3-羟基苯乙酮(2)为起始原料,与磺酰氯反应得2-氯-1-(3-羟基苯基)乙酮(3)。3和N-甲基苄胺经亲核取代反应得1-(3-羟基苯基)-2-[苄基(甲基)氨基]乙烷-1-酮(4)。4经过含有羰基还原酶A12的工程菌催化还原,得(R)-3-[2-[苄基(甲基)氨基]-1-羟乙基]苯酚(5)。5经钯炭脱苄基、成盐制得1,总收率62.8%(以2计),纯度99.9%,ee值大于99.9%。优化后的工艺操作简便,收率提高,适合工业化生产。In this paper,the synthetic route of phenylephrine hydrochloride(1)was improved.3-Hydroxyacetophenone(2)was used as the starting material to synthesize 2-chloro-1-(3-hydroxyphenyl)ethan-1-one(3)by reacting with sulfonyl chloride.Compound 3 was transformed into 1-(3-hydroxyphenyl)-2-[benzyl(methyl)amino]ethan-1-one(4)through nucleophilic substitution with N-methylbenzylamine.(R)-3-[2-[Benzyl(methyl)amino]-1-hydroxyethyl]phenol(5)was stereoselectively synthesized from 4 via reduction by the engineered bacteria containing carbonyl reductase A12.Compound 1 was obtained from 5 with the purity of 99.9%and ee value of up to 99.9%by palladium carbon debenzylation and salification,and the total yield reached to 62.8%(based on 2).The improved synthetic route had the characteristics of simple operation and high yield,which was suitable for industrial production.

关 键 词：盐酸去氧肾上腺素 升压药 羰基还原酶 合成 工艺改进 

分 类 号：TQ460.6[化学工程—制药化工] R972.5[医药卫生—药品]