Green Synthesis And Study Of Quinoline Derivatives With Biological Activities

Malignant tumour is one of the most common human diseases,and its incidence is very high worldwide.Nowadays,drug therapy has become the first choice for patients,therefore the development of novel antitumor drugs with high efficiency and low toxicity is a hot topic.Nitrogen-containing heterocyclic compounds widely exist in natural products and drug molecules,and quinoline derivatives,as an important class of nitrogen-containing heterocyclic compounds,are also the basic framework of many drug molecules.A large number of studies have shown that the quinoline containing drug molecules have good antitumor activity,and the application of organic selenium drugs in antitumor has also received great attention in recent years.Therefore,the combination of quinoline parent structure and organic selenium may improve the physiological activity and enhance the efficacy of the drug.The effective combination of the two in drug molecules can improve the physiological activity and enhance the efficacy of drugs.In addition,quinoline olefin fragments are also widely found in some natural products and drug molecules.The structural modification of quinoline olefins will be beneficial to the development of new anti-tumor drugs.At present,the synthesis of quinoline derivatives mainly uses acid anhydride promoted cyclization and transition metal catalyzed cyclization.There are two problems in this method: firstly,the reaction conditions are more intense,which will increase the cost of the reaction;secondly,the functional group tolerance of the reaction is poor,which is very detrimental to the follow-up structure-activity relationship.In view of the existing problems in the synthesis of quinoline derivatives,environmentally friendly electrochemical synthesis and transition metal-free catalysis synthesis methods have been developed,and two novel quinoline derivatives were constructed.The new synthesis method developed in this paper has the advantages of low cost and easy access of raw materials,low pollution emission and green economy in the reaction process.Then,we applied our method to the gram scale synthesis of molecular skeleton with antitumor activity.The successful implementation of this project will contribute to the development of new lead compounds.The main contents of this paper include:1.The electrochemical synthesis of quinoline imidazole derivativesA simple,mild,efficient and environmentally friendly electrochemical synthesis method was developed to prepare imidazo[1,5-a]quinolines containing selenium.The method was carried out in a single room cell at room temperature.The effects of supporting electrolytes,electrode materials,reaction solvents,electricity and additives on the reaction were investigated.This method avoids the transition metals,strong acids and alkalis needed in traditional methods,and uses cheap electrodes to react without chemical oxidation.The method is suitable for aryl-substituted imidazo[1,5-a]quinoline derivatives and alkylsubstituted imidazo[1,5-a]quinoline derivatives,and has been successfully tested in gram scale,which proves the potential application value of the electrochemical selenification method.2.Synthesis of functionalized 2-alkenyl bisquinoline compoundsA green,economical and efficient heating method for the synthesis of 2-alkenyl bisquinolines was established.The method was carried out in pure oxygen.The effects of alkali,additive,reaction solvent,oxidant and temperature on the reaction were investigated.The method avoids the transition metals used in traditional reactions,uses non-toxic reagents,and uses molecular oxygen as oxidant.The reaction conditions are mild and environmentally friendly.This method is suitable for homodimerization and cross-dimerization substrates.A series of symmetric 2-alkenyl bisquinolines and asymmetric 2-alkenyl bisquinolines were obtained.Therefore,this method has potential application prospects in the field of drug synthesis.