新颖吡咯嘧啶酮的合成与抑菌活性研究

发布时间：2018-03-07 10:15

本文选题：吡咯生物碱　切入点：嘧啶酮　出处：《海南大学》2014年硕士论文　论文类型：学位论文

【摘要】：含吡咯环的生物碱广泛存在于海洋天然产物中,有着广泛的生物活性。应用合成的方法合成含吡咯环的生物碱,对保护海洋资源和开发海洋药物有着重要意义。本文论文采用Biginelli反应,应用固相无溶剂多组分的合成方法,共设计合成了32个化合物,且都是首次报道的新化合物。使用薄层色谱(TLC)、核磁共振仪(1HMNR)、红外仪(IR)、质谱仪(LC-MS)等分析测试方法,对合成的所有化合物进行了结构验证和表征。对合成的吡咯二氢嘧啶酮类化合物的生物活性进行初步研究,通过抑菌实验了解这类化合物的抑菌性质。主要内容如下：第一部分：系统的介绍了海洋生物碱,并具体阐述了吡咯和嘧啶两大类化合物的研究现状、发展和活性等情况。同时介绍多组分合成、目标导向合成和绿色合成等合成方法。以此为基础,提出确定本论文课题以及研究的目标。第二部分：通过对文献合成条件进行优化,应用knorr合成法,以THF-HAc-H2O为溶剂,获得了中间体化合物A1-A5。然后,以硝酸铈铵为氧化剂对化合物A1-A5进一步氧化,获得吡咯醛类衍生物B1-B5。最终,对合成的5个吡咯醛类化合物的性质和合成条件进行研究讨论。第三部分：以尿素(硫脲)、乙酰乙酸乙酯(乙酰乙酸甲酯、乙酰丙酮或苯甲酰丙酮)、吡咯醛类化合物B1-B5为原料,磷酸为催化剂,通过Biginelli反应多组分无溶剂缩合反应,获得16个吡咯-氧代二氢嘧啶酮类化合物和16个吡咯-硫代二氢嘧啶酮类化合物,并对其性质和合成条件进行研究讨论。第四部分：对所合成的目标产物进行抑菌活性研究,研究菌种选用溶藻弧菌、副溶血性弧菌、枯草芽孢杆菌、粪链球菌、绿脓假单胞菌、荧光假单胞菌、尖孢镰刀菌、白地霉、酵母菌。实验结果表明,合成的化合物对选取的细菌和真菌没有抑制作用。
[Abstract]:Alkaloids containing pyrrole ring are widely present in marine natural products and have a wide range of biological activities. In this paper, 32 compounds were designed and synthesized by Biginelli reaction and solid phase solvent-free multicomponent synthesis. TLC, 1HMNRX, IR, LC-MS, and so on. The structures of all the synthesized compounds were confirmed and characterized. The biological activities of the synthesized pyrrolidine compounds were preliminarily studied, and the bacteriostatic properties of these compounds were studied by bacteriostasis experiments. The main contents were as follows:. Part one: the marine alkaloids are introduced systematically, and the research status, development and activity of pyrrole and pyrimidine are described in detail. On the basis of the synthesis methods such as goal-oriented synthesis and green synthesis, this paper proposes the subject of this paper and the research objectives. The second part: by optimizing the synthesis conditions of literature, using knorr synthesis method, using THF-HAc-H2O as solvent, the intermediate compound A _ 1-A _ 5 was obtained. Then cerium ammonium nitrate was used as oxidant to further oxidize compound A _ 1-A _ 5. Pyrrolidone derivatives B _ 1-B _ 5 were obtained. Finally, the properties and synthesis conditions of five pyrrolides were studied and discussed. The third part: using urea (thiourea), ethyl acetoacetate (methyl acetoacetate, acetylacetone or benzoyl acetone), pyrrolidone compounds B1-B5 as raw material and phosphoric acid as catalyst, multicomponent solvent-free condensation reaction was carried out through Biginelli reaction. Sixteen pyrrole-oxo-dihydropyrimidinone compounds and 16 pyrrole-thio-dihydropyrimidinone compounds were obtained, and their properties and synthesis conditions were discussed. Part 4th: the bacteriostatic activity of the synthesized target product was studied. The strains of Vibrio alginolyticus, Vibrio parahaemolyticus, Bacillus subtilis, Streptococcus faecalis, Pseudomonas aeruginosa, Pseudomonas fluorescein, Fusarium oxysporum were selected. The experimental results showed that the synthesized compounds had no inhibitory effect on selected bacteria and fungi.
【学位授予单位】：海南大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R914;R96

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