异海绵烷二萜Kravanhins A-C的全合成及石松生物碱Annotinolide B的合成研究

发布时间：2018-04-16 15:15

本文选题：羟醛反应 + 仿生合成　；参考：《兰州大学》2017年博士论文

【摘要】：本论文叙述了近年来光诱导的烯烃[2+2]环加成反应,并针对异海绵烷二萜kravanhins A-C与石松生物碱annotinolide B开展了合成研究。该论文共包括三章:第一章光诱导的烯烃[2+2]环加成反应(综述)简要综述了近20年内烯烃通过紫外光直接激发或光敏化作用发生[2+2]光环加成反应的进展。本综述按照受激发的烯烃的共轭类型,对非共轭烯烃、芳基共轭的烯烃、α,β-不饱和酮以及α,β-不饱和羧酸衍生物分别进行讨论。第二章异海绵烷二萜Kravanhins A-C的全合成简要介绍了海绵烷二萜的分离与合成研究。我们以结构新颖的异海绵烷四环二萜kravanhins A-C作为合成目标。第一代合成以13步6.2%的总产率完成了(-)-kravanhin B的首次不对称全合成。关键步骤是用分子内aldol环化反应构筑了trans-anti-cis三环骨架并用酸催化的脱水反应串联烯烃异构化反应构筑了丁烯内酯环。第二代合成是以仿生的策略对(-)-kravanhins A和C进行全合成。我们提出了半日花烷二萜转化成异海绵烷二萜的生源假说,并以此对(-)-kravanhins A和C进行了反合成分析。整个合成先通过汇聚的策略合成了呋喃型的半日花烷二萜衍生物,再通过1O2参与的光氧化反应得到γ-羟基丁烯内酯型半日花烷二萜衍生物。然后,用γ-羟基丁烯内酯通过关键的aldol环化串联内酯化反应合成了异海绵烷二萜(-)-kravanhin C,最后通过区域选择性与立体选择性的还原反应得到了(-)-kravanhin A。这部分工作对探索自然界中萜类的生源转化具有参考意义。第三章石松生物碱Annotinolide B的合成研究简要介绍了石松生物碱lycopodine的分离以及一部分代表性的合成研究。我们以结构新颖的五环石松生物碱annotinolide B作为合成目标。关键反应是通过aldol缩合反应构筑A环,并通过光诱导的烯烃[2+2]环加成反应合成四元环与内酯环。目前,我们已经用aldol缩合构筑了A环,实现了ABC三环骨架的构筑。这部分工作正在进行中。
[Abstract]:In this paper, the photoinduced cycloaddition reaction of olefin [22] was described, and the synthesis of isosomonane diterpene kravanhins A-C with pine alkaloid annotinolide B was studied.The thesis consists of three chapters: chapter 1: light induced [22] cycloaddition reaction of olefin (review). The progress of [22] cycloaddition reaction of olefins by direct excitation or Guang Min reaction by ultraviolet light in the last 20 years is briefly reviewed.In this review, the conjugation of unconjugated olefin, aryl conjugated olefin, 伪, 尾 -unsaturated ketone and 伪, 尾 -unsaturated carboxylic acid derivatives are discussed according to the conjugation types of activated olefin.In chapter 2, the isolation and synthesis of Kravanhins A-C from isomonitane diterpene were introduced briefly.Kravanhins A-C, a novel tetracyclic diterpene, was used as the synthesis target.The first asymmetric total synthesis of the first generation was completed with a total yield of 6.2% in 13 steps.The key step is to construct the trans-anti-cis tricyclic skeleton by intramolecular aldol cyclization and to construct the butenolactone ring with the dehydration reaction catalyzed by acid and the series isomerization of olefins.The second generation of synthesis is a bionic strategy for the total synthesis of Con-Kravanhins A and C.We put forward the biogeneration hypothesis of the conversion of diterpene from hemihelianane to isomorphine diterpene, and based on this hypothesis, we have carried out a reverse synthesis analysis of the two diterpenes, I. e., Cran-kravanhins A and C.Firstly, furan type diterpene derivatives were synthesized by convergent strategy, and then 纬 -hydroxybutenolactone diterpene derivatives were synthesized by photooxidation of 1O2.Then, the isosomonane diterpene triterpene -Kramvanhin C was synthesized by using 纬 -hydroxybutene lactone through the key aldol cyclization series esterification reaction. Finally, the regioselectivity and stereoselectivity reduction reaction resulted in the synthesis of the iso-cavernine diterpene and the stereoselectivity reduction reaction.This part of the work has reference significance for exploring the biotransformation of terpenoids in nature.In the third chapter, the synthesis of Annotinolide B alkaloids of Pinus lanceolata was introduced. The separation of lycopodine and the synthesis of some representative alkaloids were briefly introduced.Annotinolide B, a novel alkaloid of Pinus pentacyclic, was used as the synthesis target.The key reaction is to construct A ring by aldol condensation reaction and to synthesize four member ring and lactone ring by photoinduced [22] cycloaddition reaction of olefins.At present, we have constructed A-ring by aldol condensation, and have realized the construction of ABC three-ring skeleton.This part of the work is under way.
【学位授予单位】：兰州大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：O621.3

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