Synthetic Methodologies And Product Activities Based On Sodium Sulfinates And 2-methylquinolines As Substrates

Sulfones and quinolines are two kinds of important organic compounds,which are widely used in the field of biomedicine.Sodium sulfinates and 2-methylquinolines are widely used synthons for the synthesis of sulfones and quinolines,respectively.In this paper,the synthetic methodologies of sodium sulfinates and 2-methylquinolines and the bioactivities of their products were studied.The paper is divided into the following three parts:The first part is the synthetic methodologies of sodium sulfinates and the bioactivities of the products.Sodium sulfinates can participate in the reaction to synthesize sulfones.The reported synthesis methods of sulfonylmethyl substituted Nheterocycles have many disadvantages,such as metal catalysts,unavailable raw materials,harsh conditions and so on.In this paper,we synthesized 76 sulfonylmethylated N-heterocycles by using sodium sulfinates as sulfone source and glyoxylic acid as C1 source.The reaction featured high yields and broad substrate scope.Various types of N-heterocycles can participate in the reaction.At the same time,12 products showed preliminary anti-tumor activities and the inhibitory activities of compound 2-8p on cancer cell lines(HeLa,HepG2 and B16-F10)were stronger than that of positive control drug 5-Fu.The second part is the synthetic methodologies of 2-methylquinolines and the bioactivities of the products.Quinoline compounds are the skeleton of a variety of drugs and have anti-tumor,antiviral and antibacterial activities.In this paper,2-methylquinolines were used as substrates and activated into enamine structures with stronger nucleophilic ability under acid catalyst,and then[5+1]-cyclization with dienones to obtain 30 quinolyl substituted cyclohexanones.The reaction further enriched and developed the[5+1]-cyclization reaction participated by dienones,which is of great significance in the synthetic methodologies.In addition,10 products showed preliminary anti-tumor activities and the inhibitory activities of compound 3-3ja on cancer cell lines A549,MCF7 and HCT116)is stronger than that of positive control drug 5-Fu.The third part is the synthesis of alkenylquinolines and the study of structure-activity relationship against influenza A virus.Influenza A virus is prone to mutate and produce drug resistance.Therefore,the development of novel small molecule inhibitors is an important means to treat influenza A virus infection.After preliminary screening,we found that alkenylquinolines have anti-influenza A virus activities.In this part,23 alkenylquinoline compounds were synthesized and their inhibitory activities against influenza A virus were studied.It was found that the inhibitory activities of compounds 4-17 and 4-32 on influenza A virus were better than that of the positive control drug Ribavirin.