本文選題：二氫香豆素 + 2-取代手性喹啉��； 參考：《華東理工大學》2017年碩士論文

【摘要】：含氮、含氧類雜環(huán)化合物廣泛存在于天然產(chǎn)物和藥物中,在藥物化學研究領域具有非常高的重要性和應用價值。二氫香豆素和喹啉化合物是兩類較為常見的含氮、含氧類雜環(huán)化合物,許多以二氫香豆素或喹啉為核心結構的分子具有許多獨特的藥理、生理活性,例如抗高血壓藥物奧美沙坦酯、抗丙肝病毒藥物索非布韋等。本論文利用有機小分子化合物作為催化劑,對二氫香豆素及喹啉的合成進行研究,發(fā)展出高效的二氫香豆素及喹啉的合成方法。本論文分為兩個部分,第一部分介紹我們發(fā)展的3-取代二氫香豆素合成方法,而第二部分介紹我們發(fā)展的手性2-取代喹啉不對稱合成方法。在第一部分,我們利用二級胺為有機小分子催化劑,促進了醛與即時生成的高活性中間體鄰甲亞基環(huán)己二烯酮發(fā)生[4+2]環(huán)化反應,通過進一步氧化,以較高效率合成了一系列3-取代的二氫香豆素。我們進一步使用脯氨酸衍生物作為手性催化劑,初步實現(xiàn)了手性3-取代二氫香豆素的不對稱合成,最高的對映選擇性可以達到92%ee。在第二部分,我們應用BINOL衍生的手性磷酸為布朗斯特酸催化劑,促進N取代-2-(1-羥基-2-苯烯丙基)苯胺發(fā)生環(huán)化反應,實現(xiàn)了2-取代喹啉的不對稱合成。在本論文研究中,我們合成了4種不同類型基于鄰二萘酚或類似物為骨架的手性磷酸,并對其在本反應中的催化活性進行篩選,最高的對映選擇性可以達到68%ee。本論文研究工作為2-取代喹啉今后的不對稱合成研究奠定了一定的基礎。
[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.
【學位授予單位】：華東理工大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R914.5

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本文編號：1910189