全连续流反应技术在药物合成中的新进展(2019~2022)  

New Progress of Fully Continuous Flow Reaction Technologies in Pharmaceutical Synthesis(2019~2022)

作　　者：冯康博 陈炯 古双喜 王海峰[1,2,3] 陈芬儿 Feng Kangbo;Chen Jiong;GuShuangxi;Wang Haifeng;Chen;Fen'er(Key Laboratory for Green Chemical Process of Ministry of Education,School of Chemical Engineering and Pharmacy,Wuhan Institute of Technology,Wuhan 430205;Pharmaceutical Research Institute,Wuhan Institute of Technology,Wuhan 430205;Hubei Key Laboratory of Novel Reactor and Green Chemical Technology,Wuhan Institute of Technology,Wuhan 430205;Department of Chemistry,Fudan University,Shanghai 200433)

机构地区：[1]武汉工程大学化工与制药学院,绿色化工过程教育部重点实验室,武汉430205 [2]武汉工程大学药物研究院,武汉430205 [3]武汉工程大学新型反应器与绿色化学工艺湖北省重点实验室,武汉430205 [4]复旦大学化学系手性分子催化与合成工程中心,上海200433

出　　处：《有机化学》2024年第2期378-397,共20页Chinese Journal of Organic Chemistry

基　　金：国家自然科学基金(Nos.22377097,21877087);湖北省自然科学基金(Nos.2021CFB556,2022CFB156);绿色化工过程教育部重点实验室开放基金(No.GCP20200201);新型反应器与绿色化学工艺湖北省重点实验室(武汉工程大学)开放基金(No.40201002)资助项目.

摘　　要：连续流动化学作为化学制药行业的一项新兴技术,相较于传统的间歇釜式反应,连续流反应具有快速传质传热的优势,改进反应过程的可控性和安全性,也可以将在线分析和纯化步骤集成到柔性的操作序列中.主要介绍了2019~2022年连续流反应技术在实现从起始原料到最终活性药物成分(API)的全连续流合成工艺方面的新进展,从连续流反应的流程图着手,阐述了其制备工艺及技术优势,同时指出全连续流反应技术在各单步合成转化的工艺衔接和耦合处理仍存在一定挑战,有待进一步提升发展.Continuous flow chemistry is an emerging technology in the chemical pharmaceutical industry.Compared with the traditional batch kettle reaction,continuous flow reaction has the advantages of rapid mass and heat transfer,improves the controllability and safety of the reaction process,and can also integrate the online analysis and purification steps into the flexible operation sequence.The new progress of continuous flow reaction technology in the continuous synthesis process from starting raw material to final active pharmaceutical ingredient(API)from 2019 to 2022 is introduced.Starting from the flow chart of continuous flow reaction,the preparation process and technical advantages of continuous flow reaction are described.At the same time,it is pointed out that the fully continuous flow reaction technology still has some challenges in the process connection and coupling treatment of each single step synthesis transformation,which needs to be further improved.

关 键 词：流动化学 药物 全连续流 合成工艺 

分 类 号：TQ460.6[化学工程—制药化工]