本文關鍵詞：以環(huán)己二酮為砌塊的氫化吖啶二酮類衍生物的合成及活性研究　出處：《云南大學》2016年碩士論文　論文類型：學位論文

  更多相關文章： 1 3-環(huán)己二酮 噠嗪類衍生物 吡啶類化合物 氫化吖啶二酮衍生物

【摘要】：由于許多含吖啶酮結(jié)構的衍生物具有很好的生物和藥理活性,如抗菌活性、抗發(fā)育不良、抗過敏作用及抗癌作用等,這吸引了研究人士的關注。本論文在第一章中概述了1,3-環(huán)己二酮在雜環(huán)化合物合成中的重要應用。本論文主要概述了1,3-環(huán)己二酮用于吡啶類、吡咯類、吡喃類、吖啶酮等類衍生物的合成及活性測定。第二章中,首先,本文以1,3-環(huán)己二酮為合成模塊與乙酰丙酮、醋酸銨和各種芳香醛于三氟乙醇中反應制得8個未見報道的含多環(huán)結(jié)構的吡啶類衍生物。該合成只經(jīng)歷一步反應,避免了多步反應可能造成產(chǎn)率降低及副產(chǎn)物多的缺點,采用在乙醇中重結(jié)晶的方法純化,產(chǎn)率可達90%。反應過程中,操作簡便、產(chǎn)率高、并且溶劑可回收重復利用,這個過程符合當前所提倡的綠色化學的宗旨。其次,本文還以1,3-環(huán)己二酮為切塊共合成氫化吖啶二酮衍生物32個,同時還合成了2個噠嗪類衍生物。對于氫化吖啶二酮衍生物,本文采用了三種路線進行合成,方法一是通過優(yōu)先合成吡喃環(huán)類氧雜蒽衍生物,再與苯胺類化合物反應制備氫化吖啶酮衍生物；方法二是通過優(yōu)先合成中間體烯胺化合物,再與芳香醛反應合成目標化合物；方法三在方法二的基礎上進行了改進,利用中間體烯胺化合物、芳香醛與1,3-環(huán)己二酮反應制備氫化吖啶二酮衍生物。經(jīng)對比不難發(fā)現(xiàn)方法三最為合適,它既結(jié)合了前兩條路線的優(yōu)點,又避免了其缺點和不足,以極高的產(chǎn)率得到了產(chǎn)物產(chǎn)率,可達95%以上,同時該方法也為類似化合物的合成提供了新的便捷的方法。由于氫化吖啶酮衍生物具有多種生物和藥理活性,本文第三章在所合成的化合物中選擇了具代表性的部分化合物進行了活性測試和分析,經(jīng)過拓撲異構酶Ⅱ抑制活性測試,絕大部分對拓撲異構酶Ⅱ的抑制活性十分理想,說明該類化合物可能具有一定抑制活性或成藥的可能性。但是在進行細胞株活性測試中,對HL-60(白血病)、SMMC-7721(肝癌)、A-549(肺癌)、MCF-7(乳腺癌)、SW480(結(jié)腸癌)、HT29(人結(jié)腸癌細胞)六個細胞株進行體外抗腫瘤活性的篩選時,活性結(jié)果并不顯著。原因可能是樣品沒有嵌入細胞體內(nèi),或嵌入的量較少,因此沒有發(fā)揮抑制作用。
[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，

本文編號：1414121