Synthesis And Activity Of Hydrogenated Acridinedione Derivatives Derived From Cyclohexanedione As Blocks

Several studies show the derivatives with acridone groups have the very obvious biological and pharmacological activities, such as antibacterial, resistance to dysplasia, allergy effect and anticancer. It attracted much attention of the chemists and the biologists.The application of 1,3-cyclohexanedione in the synthesis of heterocyclic compounds was summarized systematically in the first chapter of the thesis. At the first part of second chapter, a series three rings pyridine derivatives were synthesized in TFE by mixing 1,3-cyclohexanedione, acetyl acetone, ammonium acetate, and various kinds of aromatic aldehyde. This method formed pyridine derivatives in one-step with higher yields, and avoided by-production lower yield of multistep reactions. Target compound can be easily purified by using recrystallization in the ethanol, and the desired products were obtained with relatively short reaction times. This method was considered as a "green synthesis", offers the following advantages:simplicity in process and handling, high products yield, easily solvent separation and reusable. The next part of second chapter deals with the synthesis of acridone derivatives from 1,3-cyclohexanedione. Three synthesis routes were used to achieved our purpose. The acridone derivatives synthesized by aniline compounds and pyran derivatives were our first route. In the second route, decahydroacridin-1,8-dione derivatives were prepared by a mixture of aromatic aldehydes and enaminone compounds in acetic acid. Target derivatives were prepared by the equivalent ratios of enaminone, aromatic aldehyde and 1,3-cyclohexanedione under reflux in acetic acid, which is on improvement of second route. The last method enables the formation of acridines in one-step with higher yields (95%) than the previously two ones. In conclusion, the method we developed provides a new convenient way for the synthesis of acridone type derivativesFinally, topoisomeraseâ…¡(topoâ…¡) and antitumor against HL-60, SMMC-7721, A-549, MCF-7, SW480 and HT29 activities of some compounds prepared in chapter two were tested. The representative of compounds are choiced to teste various biological activities. It revealed that the acridine derivatives exhibited a high inhibition activity against the topoisomeraseâ…¡. But for against antitumor activity, there were no obvious biological activities. The possible reason was discussed in the thesis.