以环己二酮为砌块的氢化吖啶二酮类衍生物的合成及活性研究

发布时间：2018-01-12 11:41

  本文关键词：以环己二酮为砌块的氢化吖啶二酮类衍生物的合成及活性研究　出处：《云南大学》2016年硕士论文　论文类型：学位论文

  更多相关文章： 1 3-环己二酮 哒嗪类衍生物 吡啶类化合物 氢化吖啶二酮衍生物

【摘要】：由于许多含吖啶酮结构的衍生物具有很好的生物和药理活性,如抗菌活性、抗发育不良、抗过敏作用及抗癌作用等,这吸引了研究人士的关注。本论文在第一章中概述了1,3-环己二酮在杂环化合物合成中的重要应用。本论文主要概述了1,3-环己二酮用于吡啶类、吡咯类、吡喃类、吖啶酮等类衍生物的合成及活性测定。第二章中,首先,本文以1,3-环己二酮为合成模块与乙酰丙酮、醋酸铵和各种芳香醛于三氟乙醇中反应制得8个未见报道的含多环结构的吡啶类衍生物。该合成只经历一步反应,避免了多步反应可能造成产率降低及副产物多的缺点,采用在乙醇中重结晶的方法纯化,产率可达90%。反应过程中,操作简便、产率高、并且溶剂可回收重复利用,这个过程符合当前所提倡的绿色化学的宗旨。其次,本文还以1,3-环己二酮为切块共合成氢化吖啶二酮衍生物32个,同时还合成了2个哒嗪类衍生物。对于氢化吖啶二酮衍生物,本文采用了三种路线进行合成,方法一是通过优先合成吡喃环类氧杂蒽衍生物,再与苯胺类化合物反应制备氢化吖啶酮衍生物；方法二是通过优先合成中间体烯胺化合物,再与芳香醛反应合成目标化合物；方法三在方法二的基础上进行了改进,利用中间体烯胺化合物、芳香醛与1,3-环己二酮反应制备氢化吖啶二酮衍生物。经对比不难发现方法三最为合适,它既结合了前两条路线的优点,又避免了其缺点和不足,以极高的产率得到了产物产率,可达95%以上,同时该方法也为类似化合物的合成提供了新的便捷的方法。由于氢化吖啶酮衍生物具有多种生物和药理活性,本文第三章在所合成的化合物中选择了具代表性的部分化合物进行了活性测试和分析,经过拓扑异构酶Ⅱ抑制活性测试,绝大部分对拓扑异构酶Ⅱ的抑制活性十分理想,说明该类化合物可能具有一定抑制活性或成药的可能性。但是在进行细胞株活性测试中,对HL-60(白血病)、SMMC-7721(肝癌)、A-549(肺癌)、MCF-7(乳腺癌)、SW480(结肠癌)、HT29(人结肠癌细胞)六个细胞株进行体外抗肿瘤活性的筛选时,活性结果并不显著。原因可能是样品没有嵌入细胞体内,或嵌入的量较少,因此没有发挥抑制作用。
[Abstract]:Because many derivatives with acridine ketone structure have good biological and pharmacological activities, such as antibacterial activity, anti-dysplasia, anti-allergic and anti-cancer effects, etc. This has attracted the attention of researchers. In the first chapter of this paper, the important applications of 1hexamethanedione in the synthesis of heterocyclic compounds are summarized. In this paper, the application of 1k3- cyclohexanedione to pyridines is summarized. Synthesis and activity determination of pyrrole pyrrolides pyrans acridine ketones and other derivatives. Eight unreported pyridine derivatives with polycyclic structure were synthesized by the reaction of ammonium acetate with various aromatic aldehydes in trifluoroethanol. The method of recrystallization in ethanol was used to purify the yield and the yield was up to 90. During the reaction, the operation was simple and the yield was high. The solvent can be recycled and reused, which is in line with the aim of green chemistry. Secondly, 32 hydroacridine diketone derivatives were synthesized by using 1 ~ (3) -cyclohexanedione as a cutting block. At the same time, two pyridazine derivatives were synthesized. For hydroacridine diketone derivatives, three routes were used to synthesize them. Hydrogenated acridine ketone derivatives were prepared by reaction with aniline compounds. The second method is to give priority to the synthesis of intermediate enamine compounds and then to react with aromatic aldehydes to synthesize the target compounds. Method 3 was improved on the basis of method 2. The reaction of aromatic aldehydes and aromatic aldehydes with 1 ~ (3) -cyclohexanedione was used to prepare hydroacridine diketone derivatives. It was not difficult to find that method 3 was the most suitable method for the synthesis of hydroacridine diketone derivatives. It not only combines the advantages of the first two routes, but also avoids its shortcomings and shortcomings. The yield of the product can reach more than 95% with extremely high yield. At the same time, this method also provides a new and convenient method for the synthesis of similar compounds, because the hydroacridone derivatives have many biological and pharmacological activities. In the third chapter, some representative compounds were selected for activity test and analysis, and the inhibitory activity of topoisomerase 鈪，

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