海洋生物碱Aaptamine的全合成  

Total synthesis of Aaptamine

作　　者：张佳[1] 卞长昊 薛海涛 廖洪泽 林厚文[1] ZHANG Jia;BIAN Changhao;XUE Haitao;LIAO Hongze;LIN Houwen(Research Center for Marine Drugs,Department of Pharmacy,Renji Hospital,School of Medicine,Shanghai Jiao Tong University,Shanghai 200127,China)

机构地区：[1]上海交通大学医学院附属仁济医院海洋药物研究中心,上海200127

出　　处：《沈阳药科大学学报》2024年第5期544-550,共7页Journal of Shenyang Pharmaceutical University

基　　金：国家重点研发计划(2022YFC2804100);国家自然科学基金资助项目(81903499);上海高水平地方高校创新团队(SHSMU-ZDCX20212702)。

摘　　要：目的设计了一条高效的海洋生物碱Aaptamine的合成路线。方法该合成路线使用廉价易得的6,7-二甲氧基四氢异喹啉为原料,经过六步反应成功合成目标天然产物,总产率约为21%。全合成中的关键步骤包括甲基化反应和在布朗斯特酸的作用下,Vilsmeier试剂促进关环生成苯并[de][1,6]萘啶骨架结构。结论关键中间体和产物结构经~1H-NMR、~(13)C-NMR和HR-MS(ESI)进行了确证。本文所提供的合成路线简单易行、合成步骤相对较短,为Aaptamine类生物碱的开发应用奠定了基础。Objective To develop an efficient synthetic route of Aaptamine,a marine alkaloid in this study.Methods Starting from readily available 6,7⁃dimethoxytetrahydroisoquinoline,the target natural product can be synthesized successfully in six steps with an overall yield of approximately 21%.The key steps in the synthesis involved a methylation and a cyclization promoted by Vilsmeier reagent in the presence of Brønsted acid,leading to the formation of a benzo[de][1,6]naphthyridine skeleton.Conclusion The structures of all intermediates and target product are confirmed by 1H⁃NMR,13C⁃NMR and HR⁃MS(ESI).The synthetic route is straightforward and efficient,with relatively short steps,laying a foundation for the development and application of Aaptamine⁃type alkaloids.

关 键 词：Vilsmeier试剂 天然产物 Aaptamine 全合成 

分 类 号：O629[理学—有机化学]