Synthesis And Anti-tumor Activity Of Bicyclic Pyridine And Polycyclic Quinoline Compounds

Nitrogen-containing heterocyclic compounds are widely present in a variety of natural products,because of its diverse structure and unique biological activity,it has an important position in the design and synthesis of drugs.The bicyclic pyridines and quinolines derivatives are widely used in the pharmaceutical field due to their rich biological activity.Due to the special property of fluorine atoms,the organic fluorine compounds enhance the biological activity.In this paper,fluorine-containing bicyclic pyridinium derivatives and polycyclic quinoline derivatives were designed and synthesized.The synthesis process was green,high efficiency and environmental protection.The reaction conditions were mild,highly yield and the simple post-treatment.The first chapter:We describe the use of bicyclic pyridine and quinoline compounds in drugs,the activity of fluorine-containing organic compounds,and the structure and reaction characteristics of the heterocyclic ketene amines as a type of versatile synthetic intermediate.In the second chapter:A concise and eco-friendly route for the synthesis of highly functionalized bicyclic pyridinium derivatives via one-step reaction of the chromone-3-carboxaldehyde(Ⅱ-1)and N-benzyl nitro ketene aminals(Ⅱ-2)in ethanol media has been developed.The targeted compound can efficiently obtain by filter without extra post-treatment.The reaction is particularly attractive due to following features:low-cost and biocompatibility solvent,mild temperature,atom economy,high yields,and potential biological activity product.R = CI,F,H,CH3;Ar=4-NO2Ph,4-CF3Ph,4-CNPh,4-FPh,4-CIPh,Ph,4-MePh,4-MeOPh,3-FPh etc.The third chapter:The polycyclic quinolines Ⅲ-3 and Ⅲ-4 were synthesized by the reaction of 2-fluorobenzaldehyde Ⅲ-1 with HKAs Ⅲ-2 in solvent of 1,4-dioxane while piperidine and CaCl2 as catalyst.The reaction has highly yield,green and mildlyAll the structures of 114 synthetic compounds were confirmed by 1H NMR,13C NMR,and HRMS spectra.One compound that selected from each category was confirmed through the X-Ray analysis.conditions,without column chromatography.Then the obtained compounds were tested for the activity of in vitro tumor cell lines,and some of the compounds were showed good antitumor activity.