Synthesis Of 3-position (iso)quinoline-substituted Flavonoids And Quinolone Compounds

4-Chromenone and 4-quinolone are core backbones commonly found in bioactive natural products and pharmaceutical molecules.For example,the 4-chromenone derivatives ipriflavone and flavoperate are an anti-asthma and anti-spasmodic drug,respectively.Quinolone compounds are the core frameworks of a large number of antibacterial drugs such as norfloxacin and ofloxacin.On the other hand,quinoline and isoquinoline structures are important core structure units of many biologically active natural products and drug molecules,showing significant physiological activities.Recent studies have shown that 3-quinolinyl 4-quinolone,which combines 4-quinolone and quinoline units,shows excellent antibacterial activity.However,only two example compounds have been reported,due to the limited synthetic methods.The existing methods require transition metals and quinoline boronic acid reagents,which are costly,harsh,and have limited substrate expansion.Therefore,a metal-free,green and efficient method for synthesizing such compounds is of great significance.In the first part of this thesis,the application of flavonoids and quinolones in medicine and their synthesis methods are introduced firstly.Secondly,the physiological activities and applications of quinoline and isoquinoline alkaloids,the classical methods of synthesis 3-(iso)quinoline substituted flavonoids and quinolones,and the reactions of alkynes and(iso)quinoline nitroxide compounds in the absence of metal catalysts are introduced.Finally,the background and research contents of this thesis are briefly described.In the second part,a metal-free synthesis of 3-(iso)quinoline substituted flavones was established.Using the reaction of o-hydroxyphenylpropanone and isoquinoline as model reaction,we firstly optimized the reaction conditions.After that we investigated the reaction scope and the reaction mechanism by isolation of the intermediate.In the third part,the synthesis of 3-(iso)quinoline substituted quinolones under metal-free conditions was described.The reaction condition which was used for the synthesis of 3-(iso)quinoline substituted flavones was also used for the synthesis of 3(iso)quinoline substituted quinolones.The substrate scope was also examined.All newly synthesized compounds were characterized by 1H NMR,13C NMR,and HRMS to confirm their structures.In this thesis,3-(iso)quinoline substituted flavonoids and 3-(iso)quinoline substituted quinolones were synthesized by the reactions of o-hydroxy alkynone and oamino alkynone compounds with(iso)quinoline N-oxides,respectively.Compared with literature reportes,the method described in this thesis shows the following advantages:(1)metal-free;(2)broad substrate scope;(3)simple operation;(4)environmentally friendly.The reaction is a green and efficient method for the synthesis of 3(iso)quinoline substituted flavonoids and 3-(iso)quinoline substituted quinolones,which provides a material basis for the study of their biological activities.