Ugi反应与Micheal反应联用构建2,5-二羰基哌嗪类化合物的合成研究

发布时间：2018-03-25 14:15

  本文选题：2　切入点：5-二羰基哌嗪　出处：《天津科技大学》2014年硕士论文

【摘要】：2,5-二羰基哌嗪类化合物(2,5-DKPs)是一类非常重要杂环化合物,广泛存在于天然产物和药物分子中,具有诸多良好的生物活性,例如PDE5抑制剂活性,抗肿瘤活性,抗菌抗病毒活性,催产素受体拮抗剂活性以及消炎酶抑制剂活性等。目前合成2,5-二羰基哌嗪类化合物的常用方法有二肽缩合法,Ugi合成法,氨基酸缩合法,Diels-Alder合成法以及Wittig合成法等,但是如何快速大量制备该类化合物仍是药物化学领域亟待解决的问题。 多样性导向合成能够解决待合成化合物数量庞大、结构复杂的问题,是快速构建各类有机小分子化合物库的有效途径,受到学术界的广泛关注。近年来,Ugi反应在多样性导向合成中展示出独特的魅力,因其反应快速,条件温和,原料易得,产物结构多样性等优点越来越受到有机合成工作者的青睐,成为当今有机合成领域的研究热点之一。 近期,Santra等运用Ugi反应与aza-Micheal反应联用的策略快速有效地合成出一系列2,5-二羰基哌嗪类化合物。但反应需要微波辅助加热且条件较为苛刻(300W，200℃, and18bar),同时大位阻取代基异腈作为反应物时,未能得到预期的产物。这就为反应条件的优化留下了巨大的空间。 本文利用多样性导向合成,通过Ugi反应与aza-Micheal反应联用的策略,构建出一系列的2,5-二羰基哌嗪类化合物。反应所使用的醛是p位为杂原子(氮或氧)的芳香杂环醛,Ugi产物分子中的酰胺能与杂原子形成氢键,有利于分子内Micheal反应的进行。从而实现反应“一锅煮”,条件温和,底物适用性好的目的。通过该策略合成了14个新的并具有潜在药理活性的2,5-二羰基哌嗪类化合物,所有的化合物都通过核磁氢谱、碳谱和质谱进行结构确证。
[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，

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