具有潜在生物活性的含氮、含氧杂环化合物的合成研究

发布时间：2018-05-19 12:58

本文选题：二氢香豆素 + 2-取代手性喹啉　；参考：《华东理工大学》2017年硕士论文

【摘要】：含氮、含氧类杂环化合物广泛存在于天然产物和药物中,在药物化学研究领域具有非常高的重要性和应用价值。二氢香豆素和喹啉化合物是两类较为常见的含氮、含氧类杂环化合物,许多以二氢香豆素或喹啉为核心结构的分子具有许多独特的药理、生理活性,例如抗高血压药物奥美沙坦酯、抗丙肝病毒药物索非布韦等。本论文利用有机小分子化合物作为催化剂,对二氢香豆素及喹啉的合成进行研究,发展出高效的二氢香豆素及喹啉的合成方法。本论文分为两个部分,第一部分介绍我们发展的3-取代二氢香豆素合成方法,而第二部分介绍我们发展的手性2-取代喹啉不对称合成方法。在第一部分,我们利用二级胺为有机小分子催化剂,促进了醛与即时生成的高活性中间体邻甲亚基环己二烯酮发生[4+2]环化反应,通过进一步氧化,以较高效率合成了一系列3-取代的二氢香豆素。我们进一步使用脯氨酸衍生物作为手性催化剂,初步实现了手性3-取代二氢香豆素的不对称合成,最高的对映选择性可以达到92%ee。在第二部分,我们应用BINOL衍生的手性磷酸为布朗斯特酸催化剂,促进N取代-2-(1-羟基-2-苯烯丙基)苯胺发生环化反应,实现了2-取代喹啉的不对称合成。在本论文研究中,我们合成了4种不同类型基于邻二萘酚或类似物为骨架的手性磷酸,并对其在本反应中的催化活性进行筛选,最高的对映选择性可以达到68%ee。本论文研究工作为2-取代喹啉今后的不对称合成研究奠定了一定的基础。
[Abstract]:Nitrogenous and oxygen containing heterocyclic compounds are widely used in natural products and drugs, and are of great importance and application in the field of pharmaceutical chemistry. Two hydrogen coumarin and quinoline compounds are two common types of nitrogen containing, oxygenated heterocyclic compounds and many molecules with two hydrogen coumarin or quinoline as the core structure. Unique pharmacological, physiological activities, such as the antihypertensive drug ormesartan ester, anti HCV drug suopvir, and so on. In this paper, the synthesis of two hydrogen coumarin and quinoline was studied by using organic small molecule compounds as a catalyst. The synthesis method of high efficient two hydrogen coumarin and quinoline was developed. This paper is divided into two parts. Part one introduces the synthesis of 3- substituted two hydrogen coumarin, and the second part introduces the asymmetric synthesis method of chiral 2- substituted quinoline. In the first part, we use two grade amine as an organic small molecular catalyst to promote the occurrence of [4+2] ring of aldehyde and the highly active intermediate, adjacent methylamine cyclohexadienone. By further oxidation, a series of 3- substituted two hydrogen coumarins are synthesized at high efficiency. We have further used proline derivatives as chiral catalysts to realize asymmetric synthesis of chiral 3- substituted two hydrogen coumarin. The highest enantioselectivity can reach 92%ee. in the second part, and we apply BINOL derivative. Chiral phosphoric acid is a catalyst for brunditic acid, which promotes the cyclization of N substituted -2- (1- hydroxyl -2- phenyl allyl) aniline and realizes asymmetric synthesis of 2- substituted quinoline. In this study, we synthesized 4 different types of chiral phosphoric acid based on the skeleton of adjacent two naphthol or analogues, and the catalytic activity in this reaction Screening, the highest enantioselectivity can reach 68%ee.. This work lays a solid foundation for the future asymmetric synthesis of 2- substituted quinoline.
【学位授予单位】：华东理工大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R914.5

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