α，β-不饱和酮类化合物的超声波促进合成与抑菌活性

发布时间：2018-01-21 15:38

本文关键词： 吡咯生物碱 α β-不饱和酮合成抑菌活性　出处：《海南大学》2015年硕士论文　论文类型：学位论文

【摘要】：α,β-不饱和酮类化合物在天然产物、药物分子中有着广泛的分布。由于其独特的结构特征,在合成化学中有着极其重要的应用价值。本文总共合成了27个α,β-不饱和酮类化合物。首先以便宜易得的乙酰乙酸乙酯(乙酰乙酸甲酯)为起始原料,通过亚硝化、Knorr缩合获得4个α-甲基吡咯衍生物,经过硝酸铈铵氧化α-甲基吡咯衍生物得到4个吡咯醛,然后在超声波促进下,4个吡咯醛分别与丙酮进行aldol缩合反应,合成了4个新颖吡咯α,β-不饱和酮。此外还采用将强碱催化与超声波相结合的方法,得到了23个α,β-不饱和酮中的查尔酮类化合物。合成后采用薄层色谱(TLC)、红外光谱(IR)、核磁共振(1H NMR)的方法对合成的化合物进行结构鉴定和表征,结果和目标化合物一致。并对合成的27个α,β-不饱和酮类化合物的抑菌活性进行研究,以期得到具有抑菌活性的先导化合物,为新药开发提供有价值的信息。论文主要内容有： 1.通过查阅相关文献,对毗咯类和α,β-不饱和酮类化合物的研究进展进行综述。吡咯类和α,β-不饱和酮类化合物具有独特的结构,从而具有众多优异的生物活性,在农业、食品、医药等方面具有广泛的应用,因此吡咯类和α,β-不饱和酮类化合物的合成一直是药物合成研究的重要领域。 2.以乙酰乙酸乙酯(或乙酰乙酸甲酯)、亚硝酸钠等原料合成吡咯类化合物1a-1d。然后以THF-HAc-H2O为溶剂,硝酸铈铵为氧化剂,将1a-1d氧化成醛,得到吡咯醛2a-2d。再以吡咯醛2a-2d为原料,以氢氧化钾为催化剂,在40KHz的超声波作用下,与丙酮发生缩合反应,得到4个结构新颖的α,β-不饱和酮类化合物。并对合成的目标产物的分子结构进行了表征。 3.在40KHz的超声波作用下,以各种芳香醛酮为原料,乙醇作为溶剂,少量氢氧化钾固体作催化剂,合成一系列的查尔酮类化合物,产率可达80-90%。该方法具有反应产率高、反应时间短等优点。并对合成的目标产物的分子结构进行了红外测定。 4.将上述合成的化合物对溶藻弧菌、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、酵母菌这九种菌种进行体外抗菌实验。实验结果表明大部分α,β-不饱和酮类化合物对于真菌尖孢镰刀菌都具有较强的抑菌活性,部化合物分对于细菌有抑菌活性。其中查尔酮类化合物c9及c14具有广谱抗菌的活性,不仅对真菌尖孢镰刀菌具有较强的抑制作用,对细菌绿脓杆菌和溶藻弧菌也具有很强的抑制作用。而新颖吡咯α,β-不饱和酮类化合物(3a-3d)仅对溶藻弧菌及尖孢镰刀菌有微弱的抑菌活性。 5.总结了本论文的主要工作,研究的意义及展望。
[Abstract]:伪, 尾 -unsaturated ketones are widely distributed in natural products and drug molecules due to their unique structural characteristics. In this paper, 27 伪, 尾 -unsaturated ketones were synthesized. First, the cheap ethyl acetoacetate (methyl acetoacetate) was used as the starting material. Four 伪-methylpyrrole derivatives were obtained by Knorr condensation, and 4 pyrrolides were obtained by cerium ammonium nitrate oxidation. Four novel pyrrole 伪, 尾 -unsaturated ketones were synthesized by aldol condensation of 4 pyrrolidone with acetone, and 23 伪 were obtained by combining strong alkali catalysis with ultrasonic wave. Chalcone compounds in 尾 -unsaturated ketones were synthesized by TLC, IR). The structures of the synthesized compounds were identified and characterized by 1H NMR. The results were in agreement with the target compounds, and 27 伪 were synthesized. The antimicrobial activity of 尾 -unsaturated ketones was studied in order to obtain the leading compounds with bacteriostatic activity and provide valuable information for the development of new drugs. The main contents of this paper are as follows: 1. The research progress of pyrrolides and 伪, 尾 -unsaturated ketones were reviewed. Pyrrole and 伪, 尾 -unsaturated ketones have unique structures. Thus has many excellent biological activities, in agriculture, food, medicine and other aspects of a wide range of applications, so pyrrole and 伪. The synthesis of 尾-unsaturated ketones has been an important field of drug synthesis. 2. Pyrrole compounds were synthesized from ethyl acetoacetate (or methyl acetoacetate) (or methyl acetoacetate), sodium nitrite for 1a-1d. Then, THF-HAc-H2O was used as solvent and ammonium cerium nitrate as oxidant. Pyrrolidene 2a-2d was obtained by oxidation of 1a-1d to aldehydes. Then pyrrolidone 2a-2d was used as raw material and potassium hydroxide as catalyst, and acetone was condensed with acetone under the action of 40kHz ultrasonic. Four novel 伪, 尾 -unsaturated ketones were obtained and their molecular structures were characterized. 3. A series of chalcone compounds were synthesized by using various aromatic aldehydes and ketones as raw materials, ethanol as solvent and a small amount of potassium hydroxide solid as catalyst. The yield can reach 80-90. The method has the advantages of high yield and short reaction time. The molecular structure of the synthesized target product has been determined by IR. 4. The compounds were synthesized against Vibrio alginolyticus, Vibrio parahaemolyticus, Bacillus subtilis, Streptococcus faecalis, Pseudomonas aeruginosa, Pseudomonas fluorescein, Fusarium oxysporum and T. The results showed that most 伪, 尾 -unsaturated ketones had strong antibacterial activity against Fusarium oxysporum. Among them, c9 and c14 have broad-spectrum antimicrobial activity, and not only have strong inhibitory effect on Fusarium oxysporum. The new pyrrole 伪, 尾 -unsaturated ketone compounds (3a-3d) had only weak inhibitory activity against Vibrio alginolyticus and Fusarium oxysporum, but also had a strong inhibitory effect on bacteria Pseudomonas aeruginosa and Vibrio alginolyticus. 5. The main work, significance and prospect of this paper are summarized.
【学位授予单位】：海南大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R914;R96

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