發(fā)布時(shí)間：2018-03-25 14:15

  本文選題：2　切入點(diǎn)：5-二羰基哌嗪　出處：《天津科技大學(xué)》2014年碩士論文

【摘要】：2,5-二羰基哌嗪類化合物(2,5-DKPs)是一類非常重要雜環(huán)化合物,廣泛存在于天然產(chǎn)物和藥物分子中,具有諸多良好的生物活性,例如PDE5抑制劑活性,抗腫瘤活性,抗菌抗病毒活性,催產(chǎn)素受體拮抗劑活性以及消炎酶抑制劑活性等。目前合成2,5-二羰基哌嗪類化合物的常用方法有二肽縮合法,Ugi合成法,氨基酸縮合法,Diels-Alder合成法以及Wittig合成法等,但是如何快速大量制備該類化合物仍是藥物化學(xué)領(lǐng)域亟待解決的問題。 多樣性導(dǎo)向合成能夠解決待合成化合物數(shù)量龐大、結(jié)構(gòu)復(fù)雜的問題,是快速構(gòu)建各類有機(jī)小分子化合物庫的有效途徑,受到學(xué)術(shù)界的廣泛關(guān)注。近年來,Ugi反應(yīng)在多樣性導(dǎo)向合成中展示出獨(dú)特的魅力,因其反應(yīng)快速,條件溫和,原料易得,產(chǎn)物結(jié)構(gòu)多樣性等優(yōu)點(diǎn)越來越受到有機(jī)合成工作者的青睞,成為當(dāng)今有機(jī)合成領(lǐng)域的研究熱點(diǎn)之一。 近期,Santra等運(yùn)用Ugi反應(yīng)與aza-Micheal反應(yīng)聯(lián)用的策略快速有效地合成出一系列2,5-二羰基哌嗪類化合物。但反應(yīng)需要微波輔助加熱且條件較為苛刻(300W，200℃, and18bar),同時(shí)大位阻取代基異腈作為反應(yīng)物時(shí),未能得到預(yù)期的產(chǎn)物。這就為反應(yīng)條件的優(yōu)化留下了巨大的空間。 本文利用多樣性導(dǎo)向合成,通過Ugi反應(yīng)與aza-Micheal反應(yīng)聯(lián)用的策略,構(gòu)建出一系列的2,5-二羰基哌嗪類化合物。反應(yīng)所使用的醛是p位為雜原子(氮或氧)的芳香雜環(huán)醛,Ugi產(chǎn)物分子中的酰胺能與雜原子形成氫鍵,有利于分子內(nèi)Micheal反應(yīng)的進(jìn)行。從而實(shí)現(xiàn)反應(yīng)“一鍋煮”,條件溫和,底物適用性好的目的。通過該策略合成了14個(gè)新的并具有潛在藥理活性的2,5-二羰基哌嗪類化合物,所有的化合物都通過核磁氫譜、碳譜和質(zhì)譜進(jìn)行結(jié)構(gòu)確證。
[Abstract]:As a kind of very important heterocyclic compounds, they are widely found in natural products and drug molecules, and have many good biological activities, such as PDE5 inhibitor activity, antitumor activity, antibacterial and antiviral activity. The activity of oxytocin receptor antagonist and the activity of anti-inflammatory enzyme inhibitor, etc. At present, the commonly used methods of synthesizing 2o 5-dicarbonyl piperazine compounds include dipeptide condensation method, amino acid condensation method, Diels-Alder synthesis method and Wittig synthesis method, etc. However, how to prepare these compounds quickly and in large quantities is still an urgent problem in the field of drug chemistry. The diversity oriented synthesis can solve the problem of large quantity and complex structure of the compounds to be synthesized, so it is an effective way to construct various kinds of organic small molecular compounds library quickly. In recent years, the Ugi reaction has shown unique charm in the diversity oriented synthesis, because of its rapid reaction, mild conditions, easy access to raw materials, The advantages of product structure diversity are more and more favored by organic synthesis workers and become one of the research hotspots in the field of organic synthesis. Recently, Ugi reaction combined with aza-Micheal reaction was used to synthesize a series of dicarbonyl piperazine compounds rapidly and effectively. However, the reaction requires microwave assisted heating with more stringent conditions of 300WN 200 鈩，

本文編號：1663505