3-((1R,3aS,3aS,10aR)-十氢-(1H,4H)-吡啶并[1,6]萘啶-1-基)丙-1-胺的合成  

Synthesis of 3-((1R,3aS,3aS,10aR)-decahydro-(1H,4H)-pyrido[1,6]naphthyridin-1-yl)propan-1-amine

作　　者：江欣育 胡莉娟 芦昕 赵帅[1] 钱明成 陈新[1] JIANG Xin-yu;HU Li-juan;LU Xin;ZHAO Shuai;QIAN Ming-cheng;CHEN Xin(School of Pharmacy, Changzhou University, Changzhou 213164, China)

机构地区：[1]常州大学药学院,江苏常州213164

出　　处：《合成化学》2021年第1期1-6,共6页Chinese Journal of Synthetic Chemistry

基　　金：国家自然科学基金资助项目(21272029);国家自然科学基金青年基金资助项目(21602018)。

摘　　要：以廉价易得的苦参碱为起始原料,经开环、酯化、水解等步骤,得到4-((3aS,3aS,10aR)-2-(叔丁氧基羰基)十氢-(1H,4H)-吡啶并[1,6]萘啶-1-基)丁酸(5)。5再经过Curtius重排反应,得到叔丁基(1R,3aS,3aS,10aR)-1-(3-(((苄氧基)羰基)氨基)丙基)八氢-(1H,4H)-吡啶并[1,6]萘啶-2(3H)-羧酸叔丁酯(6)。然后,6脱去Cbz基团得到(1R,3aS,3aS,10aR)-1-(3-氨基丙基)八氢-(1H,4H)-吡啶并[1,6]二氮杂萘-2(3H)-羧酸叔丁酯(7),最后,7脱去Boc基团成功得到苦参碱衍生物的重要中间体3-((1R,3aS,3aS,10aR)-十氢-(1H,4H)-吡啶并[1,6]萘啶-1-基)丙-1-胺(8),总收率28%。目标化合物和中间体的结构经1H NMR,13C NMR和HR-MS(ESI)确证。Employing matrine as starting material,4-((3aS,3aS,10aR)-2-(tert-butoxycarbonyl)decahydro-(1H,4H)-pyrido[1,6]naphthyridin-1-yl)butanoic acid(5)was prepared through ring-opening,esterification,and hydrolysis.5 underwent Curtius rearrangement reaction to give tert-butyl(1R,3aS,3aS,10aR)-1-(3-(((benzyloxy)carbonyl)amino)propyl)octahydro-(1H,4H)-pyridine tert-butyl[1,6]naphthyridin-2(3H)-carboxylic acid(6).Then,the CBZ group in 6 was removed to obtain(1R,3aS,3aS,10aR)-1-(3-aminopropyl)octahydro-(1H,4H)-pyrido[1,6]diazanaphthalene-2(3H)-tert-butyl carboxylic acid(7).Finally,deprotection of the Boc group in 7 successfully afforded 3-((1R,3aS,3aS,10aR)-decahydro-(1H,4H)-pyrido[1,6]naphthyridin-1-yl)propan-1-amine(8),an important intermediate of the matrine derivative.The overall yield was 28%,the structures of the final product and the intermediates were confirmed by their 1H NMR,13C NMR and HR-MS(ESI)spectral properties.

关 键 词：苦参碱 Curtius重排 开环 酯化 水解 合成 

分 类 号：O623.6[理学—有机化学] O626[理学—化学]