Flavumounes B、Calodenin A和Calodenin B的关键中间体的合成研究

发布时间：2018-08-21 19:57

【摘要】：黄酮类化合物具有广谱的药理作用,因而越来越引人瞩目。然而某些黄酮类化合物在天然植物中的含量普遍偏低,且分离提取困难,严重阻碍了对这些化合物后续的活性研究。FlavumounesB、CalodeninA、CalodeninB是类含有苯并呋喃结构的黄酮类化合物,在自然界中分布均较少,且无文献报道相关的化学合成路线。本文共尝试了三种合成策略来合成这三种天然黄酮类化合物的关键中间体。第一种合成策略尝试是以芹菜素为起始原料,经选择性保护、碘代、sonogashira反应、选择性脱保护、羰基插入、氢化等一系列反应,以及数次的保护基调整以后,成功得到了侧环未氢化的FlavumounesB合成中间体。第二种合成策略尝试合成CalodeninB,本文成功得到了2-取代-3-羰基苯并呋喃结构的合成中间体。第三种合成策略采用1, 3-二羰基化合物与2, 4, 6-三羟基苯乙酮为底物,通过氧化加成反应一步构建了 2-取代-3-羰基苯并呋喃结构,经过多次尝试,我们最终得到了 CalodeninB的同分异构体。此外本论文还研究了保护基对羰基插入反应的影响以及不同底物脱乙酰基保护基的反应条件。本文成功合成目标天然黄酮类化合物Flavumounes B、Calodenin A、CalodeninB的数个关键中间体化合物,且通过对这三种不同的合成策略的尝试,提示我们要避免使用空间位阻比较大的保护基,同时又要考虑底物的结构对氢化反应的影响,这部分工作为将来合成该类化合物提供参考。
[Abstract]:Flavonoids have attracted more and more attention because of their broad-spectrum pharmacological effects. However, the content of some flavonoids in natural plants is generally low, and it is difficult to separate and extract them. FlavumounesB, Calodenin A, Calodenin B are flavonoids containing benzofuran structure. Three synthetic strategies have been tried to synthesize the key intermediates of these three natural flavonoids. The first synthetic strategy is based on apigenin as the starting material, selective protection, iodide, Sonogashira reaction, and selective deactivation. A series of reactions, such as protection, carbonyl insertion, hydrogenation, and several modifications of the protective groups, were successfully used to synthesize flavumounesB. The second synthetic strategy was to synthesize CalodeninB, and the 2-substituted-3-carbonyl benzofurans were successfully synthesized. The structure of 2-substituted-3-carbonyl benzofurans was constructed by one-step oxidation-addition reaction of carbonyl compounds with 2,4,6-trihydroxyacetophenone. After several attempts, the isomers of Calodenin B were obtained. In addition, the effect of protective groups on carbonyl insertion reaction and deacetylation protection of different substrates were also studied. Several key intermediates of target natural flavonoids Flavumounes B, Calodenin A and Calodenin B have been successfully synthesized in this paper. Attempts to synthesize these three key intermediates suggest that we should avoid using a protective radical with large steric hindrance and consider the structure of substrates for hydrogenation. This work will provide references for the future synthesis of the compounds.
【学位授予单位】：天津科技大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R914

【参考文献】