【作者】 汤丽娜；

【导师】 赵康；

【作者基本信息】 天津大学 ， 应用化学， 2011， 博士

【摘要】 Coumestan,又叫6H-苯并呋喃[3, 2-c]苯并吡喃-6-酮,是一类具有四个环的重要天然产物,具有抗菌、止血、雌激素作用等重要的生理活性。目前关于它的合成有很多种。本文通过4-羟基-3-芳基香豆素在单电子氧化剂FeCl₃作用下氧化成环合成Coumestan化合物,为Coumestan类化合物的合成提供了一个有效的新方法。根据文献,4-羟基-3-芳基香豆素由以下三种方法合成:1.水杨酸酯和取代的苯乙酸通过缩合成酯、酯分子内缩合成环形成;2.间苯二酚与取代的苯乙酸缩合,酚羟基单甲基化,再与碳酸二甲酯缩合成环形成;3.间苯三酚与取代苯乙腈缩合,酚羟基甲基化,再与碳酸二甲酯缩合成环形成。由以上方法合成了一系列带有不同取代基的4-羟基-3-芳基香豆素。4-羟基-3-芳基香豆素在FeCl₃/SiO₂作用下氧化成环生成Coumestan类化合物。利用FeCl₃/SiO₂取代FeCl₃使反应更加温和,后处理简单。研究了带有不同取代基（如甲氧基、甲基、卤素、CF3等）的4-羟基-3-芳基香豆素的分子内氧化成环反应,当苯环上取代基为甲氧基、甲基、卤素或者没有取代基时,4-羟基-3-芳基香豆素可以顺利成环,共合成了16个Coumestan化合物。当环合苯环上有强吸电基CF3、甲氧基位于环合苯环间位、或甲基位于环合苯环的邻位时,4-羟基-3-芳基香豆素不能氧化成环。根据以上实验结果,推测了4-羟基-3-芳基香豆素在单电子氧化剂FeCl₃作用下氧化成环形成Coumestan化合物的可能机理。由于大多数Coumestan天然产物分子内含有羟基取代基,且羟基对Coumestan化合物的活性具有重要的作用。因此我们以合成的9-甲氧基-4-甲基-6H-苯并吡喃[3, 2-c]苯并吡喃-6-酮为底物,在BBr3作用下脱去甲基,顺利得到了目标产物。9-甲氧基香豆雌酚是一个Coumestan天然产物,将该方法运用到此化合物的全合成中,以间苯二酚,对甲氧基苯乙酸为原料,在三氟化硼乙醚作用下缩合,异丙基保护羟基,与碳酸二甲酯缩合,FeCl₃/SiO₂下氧化成环,最后利用AlCl3脱去异丙基顺利得到了目标产物。更多还原

【Abstract】 Coumestan, known as 6H-benzofuran [3, 2-c] benzopyran-6-one, is a class of important natural products with significant pharmaceutical activities, such as antibacterial, hemostatic, phytoestrogenic effects and so on. Therfore, many organic chemists focus on their synthesis. This paper is mainly about its facile synthesis by FeCl₃-mediated oxidative cyclization of 4-hydroxy-3-aryl coumarin.According to the reference, 4-hydroxy-3-aryl coumarins were synthesized by the following methods: 1. First condensation of methyl salicylate with substituted phenyl acetic acids to form the intermediate ester, then the intramolecular condensation of the ester to form the targets. 2. Condensation of resorcin with substituted phenyl acetic acids, methylation, and then condensation with dimethyl carbonate （DMC） to form the coumarin. 3. Condensation of phloroglucinol with substituted phenylacetonitrile, methylation, and then condensation with DMC to form the coumarin. A series of coumarins with different substituents were formed by the above methods.A series of coumestan were obtained by FeCl₃-mediated oxidative cyclization of 4-hydroxy-3-aryl coumarin under the optimized conditions. The workup was more convenient and the yield was improved by using FeCl₃/SiO₂ instead of FeCl₃. We found that the substrates with different substituents such as methoxy, methyl, halogen, or no substituent could provide the corresponding products. However, when the substrates with strong electron-withdrawing group CF3, methoxy on the meta position, or methyl on the ortho site, no products were obtained.As many natural coumestan possess hydroxyl group, and hydroxyl group has something important with the activities of coumestan. When the synthesized 9-Methoxy-4-methyl-6H-benzofuro [3, 2-c] chromen-6-one was subjected to BBr3, the corresbonding hydroxylated coumestan was obtained.9-Methoxy coumestrol is a natural coumestan. We also applied our method to its synthesis by using a protection– deprotection protocol.更多还原