【作者】 尹浩；

【导师】 王少仲；

【作者基本信息】 南京大学 ， 有机化学， 2013， 硕士

【摘要】 吡啶并吖啶(Pyridoacridine)生物碱以很强的细胞毒性著称,它们广泛分布在海绵、海鞘、珊瑚等无脊椎海洋生物中。现代生物学评价发现它们还具良好的抗真菌、抗细菌的生理活性,是潜在的抗生素药物的替代物。绝大多数已知的全合成路线一般需要经过多步完成,涉及繁琐的分离和提纯。因此为了能够更深入地开展生物学评价的研究,就迫切需要开发更加有效的合成策略用于大量获取(?)yridoacridine海洋生物碱及其类似物。本文主要探索高效率的串联成环反应合成Pyridoacridine海洋生物碱及其类似物。一、金催化N-炔丙胺基醌6-endo-dig环异构化反应启动的串联成环反应合成五环吡啶并[4,3,2-mn]吖啶-8-酮运用金(Ⅰ)试剂催化串联分子内6-endo-dig环异构化反应／胺-羰基缩合反应,我们发展了新方法从炔端为邻胺基取代的N-炔丙胺基醌合成包括Isoascididemin在内的五环毗啶并[4,3,2-mn]吖啶-8-酮。这种无需银试剂参与的催化体系适合于制备大量衍生物用于构效关系研究。二、]Bronsted酸促进区域选择性炔烃水合反应启动的分子内串联成环反应合成生物碱Ascididemin及其类似物基于Bronsted酸促进炔烃选择性水合反应启动的串联成环反应,我们提出一条从侧链炔基取代的胺基醌合成五环吡啶并[2,3,4-kl]吖啶-6-酮生物碱(?)min、2-Bromoleptoclinidinone的新方法。新方法适合于合成系列(?)min(?)的衍生物及类似物。更多还原

【Abstract】 Pyridoacridine marine alkaloids are well known for their strong cytotoxic activities which are isolated from corals, tunicates, sponges and marine invertebrates. And they also have antimicrobial and antiviral properties, pointing to a possibility of be replacement for today抯antibiotics. The majority of the approaches to construct the pentacyclic system have limitations for multisteps and the tedious separation and purification. Efforts to obtain pyridoacridine alkaloids as well as their relevant nalogs for further biological evaluations are still in urgent need. The thesis focuses (?) methodology establishment based on efficient domino cyclizations.Part Ⅰ:Assembly of pentacyclic pyrido[4,3,2-mn]acridin-8-ones via a domino reaction initiated by Au(I)-catalyzed6-endo-dig cycloisomerization of N-propargylaminoquinonesUsing a domino cyclization consisting of gold-catalyzed6-endo-dig cycleisomerization and condensation between amine and carbonyl of quinone, we have developed a novel methodology to assemble pentacyclic pyrido[4,3,2-mn]acridin-8-one skeleton as well as isoascididemin. The silver-free catalytic system is appropriate for the preparation of an array of pentacyclic pyridoacridine compounds for the investigation of structure-activity relationship.Part Ⅱ:Total synthesis of alkaloid ascididemin and its analogs via a domino reaction initiated by bronsted acid-promoted regioselective hydration of alkyne functionality.Using a domino cyclization initiated by bronsted acid-promoted regioselective hydration of alkyne functionality, we established a new route to synthesize alkaloids ascididemin and2-bromo-ascididemin. The route is also feasible for the preparation (?)ies of derivatives and analogs of alkaloid ascididemin.更多还原