Lewis acid催化1 双酯基环丙烷与碳氧双键分子内32环加成及天然产物Englerin A的全合成.docx

摘要摘 摘要 摘 要 生物活性的天然产物是药物先导发现的重要源泉。很多具有优秀生物活性 的天然产物含有共同的活性骨架(优势结构，活性官能团等)。氧桥双环[n．2．1】骨 架就是这样一类活性骨架，它广泛存在于各种活性化合物及天然产物中。由于 它们结构复杂多样，缺乏简单高效的合成方法构建，发展高效构筑氧桥[n．2．1】 骨架的方法就显得尤为重要，并逐渐成为当今有机化学研究的热点。 构筑氧桥双环【n．2．1]骨架的方法主要可分为四大类：环加成反应，串联反应， 关环反应，扩环反应。其中环加成反应具有极高的成键效率、良好的原子经济 性和优异的立体选择性。 Lewis acid催化下，作为3一碳合成子的1，1一双酯基环丙烷参与的分子间 f3+n1环加成反应的报道很多，且环合产物多为并环骨架，而分子内环加成反应 的相关报道却比较少。 本文首次发展了一种：在Lewis acid催化下，1，1．双酯基环丙烷与碳氧双键 分子内[3+2】环加成反应，通用高效的构筑了氧桥双环[n．2．1】骨架分子，并将该策 略应用到天然产物Englerin A的全合成中。 关键词：Lewis acid 1，1一双酯基环丙烷环加成反应 EnglerinA AbstractAbstract Abstract Abstract Natural products-based strategy for lead discovery provides all efficient access to new medicines and agrochemicals．Many biologically active natural products have similar skeletons．The structurally diverse and interesting family of bridged OXfl- 【n．2．1】skeletons is widely distributes in natural products，and exhibits broad·ranging biological activity．Thus it is very important to develop novel methods and strategies for HECCS(highly efficient construction of complex skeletons)． The main method for construction of the bridged oxa—In．2．1】skeletons Call be divided into four categories：cycloaddtion reaction,tandem reaction,ring·closing reaction,ring-expansion reaction．The merits of cycloaddition reactions ale efficiency, good atom-economy and excellent in stereoselectivity． While Lewis acid—catalyzed intermolecular【3+n】cycloaddition of cyclopropane 1，1-diesters has been well studied，their intramoleeular variants have been got few attentions． The first Lewis acid-catalyzed intramolecular【3+2】cycloaddition of cyclopropane 1,1一diesters wim carbonyl groups has been developed and reported in this thesis．The described method supplied a general and efficient strategy for construction of the bridged oxa-[n．2．1】skeletons．The strategy has also been applied to the total synthesis ofnatural products Englerin A． Key words：Lewis acid 1，1-Cyclopropane diesters Cycloaddition reaction Englerin A II 第一章前言第一章前言 第一章前言 第一章前言 1．1引言 药物先导的发现是新药创制的重要环节，药物先导