育亨宾d、e环中间体6-甲氧基-5-氰基异喹啉合成的研究.pdf

人连理工大学硕士学位论文摘要本文所述内容属于天然生物碱育亨宾合成研究课题的一部分。育亨宾(yohimbine) 属于吲跺类生物碱的一种,存在于许多茜草科植物的根茎之中,最早发现于原产于非洲的一种叫做育亨宾树(yohimba)的树皮中,因此得名育亨宾。非洲土著在古代常通过食用育亨宾树的树皮达到催情的作用,现代研究发现育亨宾及其某些异构体的药用价值比较广泛,不但在治疗男性功能障碍作用明显,而且在降低血压治疗心脏疾病以及减肥等方面也有明显的功效。育亨宾的分离和结构鉴定已经有50多年的历史,自从结构一经确认,合成研究的工作也随之进行。。本课题组在参照国外文献报道的基础上,确定育亨宾合成研究课题,并设计了整体的合成路线。根据育亨宾整体的合成路线,本文对育亨宾D、E环中间体6一甲氧基一 5一氰基异喹啉的合成方法作了比较深入的研究。目标产物及中间体经过1HNMP、MS和取的结构验证。以苯甲醛为起始原料,经过硝化、还原、Shift碱缩合、Pictet--Spengler环化、溴代、氰解等11步反应,最终合成目标产物,总体收率26%。该路线设计较合理,原料易得,反应简单易操作。课题研究后期,有了该路线中间体问甲氧基苯乙胺的商品原料的出现,,收率可达到60%以卜。关键词:育亨宾生物碱6一甲氧基_5一澳异喹啉6一甲氧基一5_氰基异喹啉育亨宾D、 Synthesis ofintermediate ofyohimbine D、Epart一 6-methoxyisoquinoline-5-carbonitrile Abstract Thispaperbelongs to one part ofresearch ofyohimbine is one ofthe most plex indolealkaloidtypes,which occurs natrually inthebarkofmany rubiaceous was firstisolatedfrom akindof treenamed yohimba inAfrica, which isthename yohimbine came hasextensivepharmacological properties. Inancient times theAfrican natives,who eaten thebark of trees thatcontain yohimbine, regarded it as apotent medicinal researchrevealed thatyohimbine has notonly notableeffect on curing male erectiledysfimction,but alsoremarkable effect on heart diseaseand even ondiet. Yohimbine hasbeen isolatedand characterized over acentury,sincethen,many research work ofsynthesis plex indolealkaloid ,there Was rio paper about itssynthesis reference totherelated foreign literatures,we decided toput thesynthesis ofyohimbine on our schedule anddesign tothe whole designed routine,in thispaper,we synthesized theintermediate——6一 methoxyisoquinoline-5-carbonitrile ofD、E part finalproduct Was characterized with1HNMR,MS andIR. We synthesized pounds starting undergoes 11 stepsincluding nitration,reduction,Shift basereaction,Pict