摘要
广谱杀真菌剂恩康唑系比利时杨森公司开发,属二类新兽药,但目前国内无拥有兽药批文的原料药和制剂生产厂家。在系统剖析国内外恩康唑合成路线后,针对传统路线中硝化、高压加氢等高危步骤及总收率≤30%的缺陷,设计绿色新工艺:以廉价咪唑为起始原料,先与3-氯-1-丙烯在离子液体中完成区域选择性N-烷基化,随后与2,2′,4′-三氯苯乙酮经硼氢化钠-三氟化硼乙醚协同还原,避免高压氢化;最后以碳酸钾/PEG-400催化O-烷基化,得到不低于欧洲药典标准的恩康唑原料药。
Enilconazole,a broad-spectrum fungicide originally developed by Janssen Pharmaceutica(Belgium),is classified as a Category II new veterinary drug in China,where there are no manufacturers with either its active pharmaceutical ingredient(API)or formulated products approvals.Based on a systematic analysis of existing synthetic routes,a novel green pathway was designed to overcome the critical limitations of conventional approaches—specifically,the hazardous nitration and high-pressure hydrogenation steps and the low overall yield(≤30%).The synthesis started with commercially available imidazole,which underwent regioselective N-alkylation with 3-chloro-1-propene in an ionic liquid medium.The resulting intermediate was then chemoselectively reduced using a sodium borohydride-boron trifluoride etherate system,thereby eliminating the need for high-pressure hydrogenation.Finally,O-alkylation catalyzed by potassium carbonate/PEG-400 afforded enilconazole API that consistently complied with European Pharmacopoeia specifications.
作者
黎浩
刘一粟
祝宏
张银博
袁航
LI Hao;LIU Yishu;ZHU Hong;ZHANG Yinbo;YUAN Hang(School of Chemical Engineering and Pharmacy,Wuhan Institute of Technology,Wuhan 430205,China)
出处
《武汉工程大学学报》
2025年第6期600-606,共7页
Journal of Wuhan Institute of Technology
基金
武汉工程大学第十六届研究生教育创新基金(CX2024252)。
关键词
恩康唑
原料药
合成工艺
优化
enilconazole
active pharmaceutical ingredient(API)
synthetic process
optimization
