Synthesis And Application Of 2,3-Disubstituted Quinolines And 3,8a-Disubstituted Indolinones

Nitrogen containing heterocyclic compounds have a wide range of applications in the fields of organometallic materials and biomedicine due to their abundant reaction sites and easy structural modification.In the previous reports on the synthesis of Nitrogen containing heterocyclic compounds,most of these methods have disadvantages such as the use of noble metal catalyst and organic solvents.Therefore,the development of simple and efficient synthesis methods has been attracting great attention in the field of organic chemistry.This thesis focuses on the synthesis of quinoline compounds and indolinone compounds,and establishes the aqueous synthesis of 2,3-disubstituted quinolines,and uses the copper-catalyzed Domino reaction reported in our research group to synthesize 3,8a-disubstituted indolinone derivatives.According to the structural characteristics of 3,8a-disubstituted indolinone,the ability to specifically recognize DNA c-myc G-quadruplex was evaluated.This disertation is mainly consist of the following two parts:In the first part,we have developed a method for the synthesis of2,3-disubstituted quinoline derivatives using HOAc as catalyst,water as solvent,cheap and readily available aliphatic aldehydes and aniline as substrates.Compared with previous synthesis methods,this method uses cheap and safe water as solvent,and avoids using metal catalysts to participate in the reaction;it has a wide range of functional group toluence.This protocol would be attractive for organic synthesis and medicinal chemistry.In the second part,3,8a-disubstituted indolinones were synthesized by copper catalyzed Domino reaction of pyridyl ketones with terminal alkynes.3,8a-disubstituted indolinones have a distorted "Butterfly" configuration,which can effectively distinguish the different conformations of DNA G-quadruplex.We have studied the ability of 10 different 3,8a-disubstituted indolinone derivatives to target DNA G-quadruplex,and found that indolinone with 3-naphthyl functional group can be used as a probe to recognize DNA G-quadruplex with parallel configuration,especially DNA C-myc G4.In addition,MTT and cell localization experiments were carried out,which showed that indolinone probe could enter into living cells with low cytotoxicity.