天然产物 gregatin A 的全合成研究

	天然产物 gregatin A 的全合成研究
	赵晓利
导师	邓军
关键词	聚酮 Polyketide Gregatin A Gregatin A 1, 3-偶极环加成 1, 3-Dipole cycloaddition 全合成 Total synthesis
摘要	Gregatin A 和 nivefuranones A 是一类具有烷基化呋喃酮母核结构的聚酮类化合物，该家族主要来源于真菌的次级代谢产物，具有显著的抑菌活性。本文以反式-2-戊烯醛为底物，通过 Wittig 反应、1, 3-偶极环加成反应等关键步骤，共计 6 步 14%的总收率完成了天然产物 gregatin A 的消旋合成。本研究通过关键步骤 1,3-偶极环加成反应构建异噁唑环后经氮氧键裂解完成分子内的关环构建了呋喃酮母核骨架，该条路线设计巧妙，可行性强，经优化后的路线可大量制备(±)- gregatin A。同时，基于本文的第一条路线，得到了天然产物 gregatin A 的类似物。本研究还对 1, 3-偶极环加成反应的区域选择性进行了深入探讨，系统地研究了调控其区域选择性的关键因素。此外，本文在合成天然产物 nivefuranones A 时，对甲酯的水解进行了广泛的探讨。文中巧妙构建呋喃酮母核结构的方法对 gregatin A 家族分子的合成具有很大的指导意义。本文共分为三章，第一章第主要介绍了异噁唑类化合物及其合成研究进展。第二章展示了我们对 gregatin A 全合成研究。第三章主要阐述了具体实验操作步骤和相关化合物的数据与谱图。; Gregatin A and nivefuranones A，having significant antibacterial activity, are a class of polyketides with an alkylated furanone core structure, and gregatins mostly drived from secondary metabolites of fungi. In this paper, gregatin A was racemically synthesized with a total yield of 14% in 6 steps, starting from the commercially available trans-2-pentenal, which went through key steps of Wittig reaction、1, 3-dipole Cycloaddition reaction. The key step in this study is construction of isoxazole ring though a 1, 3-dipole cycloaddition reaction followed by cleaveage of the N-O bond to obtain furanone skeleton self-assembly, which is strongly clever and feasible. Massive preparation of gregatin A could be completed by optimal route. Meanwhile, gregatin A analogue was unexpectedly synthesized based on the first route in this paper, and some explorations with regard to the regioselectivity of 1, 3-dipole cycloaddition reaction were accomplished, and the key factors of the regioselectivity were systematically studied. In addition, during the attempt to synthesis of nivefuranones A, the hydrolysis of methyl esters was extensively explored. The ingenious method of constructing the core structure of furanone in this paper has great guiding significance for the synthesis of gregatins. This paper is divided into three chapters. The first chapter mainly introduces isoxazole-containing compounds and their research progress in synthesis. The second chapter mainly introduces our total systhesis of gregatin A. The third chapter mainly introduces the specific experimental steps and the NMR data of the compounds.
语种	中文
	2022-05
学位授予单位	中国科学院大学
文献类型	学位论文
条目标识符	http://ir.kib.ac.cn/handle/151853/75145
专题	昆明植物所硕博研究生毕业学位论文
推荐引用方式 GB/T 7714	赵晓利. 天然产物 gregatin A 的全合成研究[D]. 中国科学院大学,2022.

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