【作者】 赖增伟；

【导师】 张洪彬；

【作者基本信息】 云南大学 ， 有机化学， 2011， 硕士

【摘要】 石松生物碱(Lycopodium alkaloids)是从蕨类植物石松及其近缘植物(Lycopodium related plants)中分离得到的结构相似,具有相同生源途径的一类天然生物碱。广泛存在于石松及其类似植物种群,特别是石杉科(Huperziaceae)和石松科(Lycopodiaceae)植物。此类生物碱通常都具有极其独特的骨架和良好的生物活性,因此引起了药学家和有机化学家的广泛关注。1986年,中国科学家刘嘉森从传统中医千层塔分离了石杉碱甲(Huperzine A)并发现其是一种高效的乙酰胆酯酶抑制剂,此后成为药学界备受瞩目的研究热点之一,推动了石松生物碱的研究,包括全合成研究。作为极具挑战的全合成多环分子,有机合成化学家对其表现出浓厚的兴趣,近年来已完成了一些石松生物碱的全合成工作。本论文主要研究了对Fawcettimine型石松生物碱合成方法研究,最终通过高效、简洁的途径成功完成了(-)-8-deoxyserratinine的首次不对称合成。本论文共分三章,第一章主要介绍了石松生物碱在天然产物化学、药物化学和有机合成化学中的重要地位及研究进展。重点介绍了Fawcettimine型石松生物碱的合成研究进展,对fawcettimine、sieboldine A、Paniculate、Magellanine和Magellaninone等分子的合成研究进行综述。第二章首先介绍Inubushi小组对Serratinine和8-Deoxyserratinine的合成工作,然后开始介绍我们对(-)-8-D eoxyserratinine的不对称全合成研究工作。从(+)-pulegone 202大量制备的烯酮化合物(-)-187作为起始原料,通过15步反应以7%的总收率,高效地完成了(-)-8-Deoxyserratinine的不对称全合成。我们的核心策略包括三个方面：1.通过高效的Helquist环化方法来构建顺式6/5双环；2.通过氮双烷基化策略简洁地构筑氮杂9元环；3.运用不对称Shi氧化立体专一性地制备β-环氧化合物。第三章为论文中相关化合物的合成实验操作及其谱图数据。更多还原

【Abstract】 Lycopodium alkaloids are isolated from the pteridophyta lycopodium and related plants with similar biogenesis. These compounds present in lycopodium and related species, especially plants of Huperziaceae and Lycopodiaceae. The Lycopodium alkaloids often possess unusual skeletons and promising bioactivity, which attract the attention of numerous organic chemists and medicinal chemists. In 1986, Jiasen-Liu, a Chinese scientist, isolated Huperzine A from Huperzia serrata, a traditional Chinese medicine. Huperzine A has been shown to be a potent, reversible inhibitor of acetylcholine esterase and significantly impacts the investigate of Lycopodium alkaloids. Owing to their appealing biological activities as well as synthetically challenging polycyclic systems, a number of total syntheses of Lycopodium alkaloids have been conducted and documented in the literature.This thesis describes the synthetic studies on Lycopodium alkaloids of fawcettimine class, the first asymmetric total synthesis of (-)-8-Deoxyserratinine was successfully realized and summarized in this thesis.Three chapters are included in this thesis. In the first chapter, we summarized the synthesis of fawcettimine class alkaloids, including fawcettimine、sieboldine A、paniculate、Magellanine and magellaninone.In chapter 2, studies towards the first asymmetric total synthesis of (-)-8-Deoxyserratinine was described. We completed the first enantioselective total synthesis of (-)-8-Deoxyserratinine in 15 steps from enone (-)-187 with 7% overall yield. The key features include a highly efficient Helquist annulation to furnish the cis-fused 6/5 bicycle, construction of the aza nine-membered ring system employing double N-alkylation strategy and asymmetric Shi epoxidation to secure the desiredβ-epoxide stereospecifically.Experiment procedure, physical and spectrum data for compounds described in Chapter 2 are recorded in Chapter 3.更多还原