抗血吸虫药物吡喹酮的合成研究  

Study on the synthesis of schistosomiasis drug praziquantel

作　　者：林楚焱 汪坤坤 张坤 李玫桦 张韵 Lin Chuyan;Wang Kunkun;Zhang Kun;Li Meihua;Zhang Yun(School of Pharmacy,Zunyi Medical University,Zunyi Guizhou 563006,China;the First Clinical Institute,Zunyi Medical University,Zunyi Guizhou 563006,China;Guizhou Provincial Key Laboratory of Innovation and Manufacturing for Pharmaceuticals,Zunyi Medical University,Zunyi Guizhou 563006,China)

机构地区：[1]遵义医科大学药学院,贵州遵义563006 [2]遵义医科大学第一临床学院,贵州遵义563006 [3]遵义医科大学贵州省化学药物创制全省重点实验室,贵州遵义563006

出　　处：《遵义医科大学学报》2025年第4期380-385,共6页Journal of Zunyi Medical University

基　　金：贵州省科技计划项目[NO:黔科合基础-ZK(2022)一般621];遵义医科大学大学生创新创业训练计划项目(NO:S202310661152)。

摘　　要：目的研究吡喹酮的合成方法。方法以四氢异喹啉1为起始原料,通过氧化、基于亚胺酰化的三组分反应、还原反应、酰化反应、脱保护反应、酰化反应及环合反应制得吡喹酮。结果合成吡喹酮的总收率为52%,中间体和目标产物吡喹酮的结构经^(1)H-NMR、^(13) C-NMR和HR-MS确证。结论本方法有效避免使用浓硫酸、高毒性氰化钾以及高温高压等严苛反应条件,整个合成路线中反应条件温和、操作便捷,具有较好的成本效益。Objective To study the synthetic method of schistosomiasis drug praziquantel.Methods Praziquantel was synthesized via oxidation,three-component reaction based on imine acylation,reduction,acylation,deprotection,acylation and cyclization reaction by using tetrahydroisoquinoline as starting material.Results The total yield of the praziquantel synthesis was 52%.The structures of praziquantel and intermediates in the process were confirmed by ^(1)H-NMR,^(13) C-NMR and HR-MS.Conclusion This method effectively avoids the use of harsh reaction conditions such as concentrated sulfuric acid,highly toxic potassium cyanide,high temperature and high pressure.This method ensures the mild reaction conditions,convenience and cost-effectiveness of the entire synthesis route,and shows certain industrial application potential.

关 键 词：吡喹酮 血吸虫药物 三组分反应 合成 新工艺 

分 类 号：R698[医药卫生—泌尿科学]