Research On The Synthesis,Bioactivity Against Influenza A Virus And Application As CMC Paper Of Aza-heterocyclic Compounds

Aza-heterocyclic compounds represent a class of ubiquitous bioactive molecules in natural products and pharmaceuticals.Morever,they are frequently used as intermediates in organic synthesis.Herein,this dissertation is mainly focused on the synthesis,bioactivity or application as fluorescent probes for critical micelle concentration(CMC)determination of pyrrole,pyridine and quinoxaline skeletons.Research content is divided into three parts as following:The first part is on the synthesis methodology of aza-heterocyclic compounds,pyrrolo[1,2-a]quinoxalines.Pyrrolo[1,2-a]quinoxalines possess various bioactivities.Nevertheless,reported methods for preparation suffered from many drawbacks such as poor substrate applicability,strong oxidant and high temperature.Herein,we disclose a new copper/iron catalyzed cyclization reaction of 2-(1H-pyrrol-1-yl)anilines(with 2-methylpyridine/quinoline),under oxygen condition,for synthesis of pyrrolo[1,2-a]quinoxalines.Fifteen compounds were synthesized with high yields,which provided better synthesis method for further research on bioactivities and other application.The second part is on the design,synthesis and structure-activity relationship of dihydropyrroles(DHPs)as a series of novel inhibitors against influenza A virus.Dihydropyrroles are the products of a four-component reaction(4CR)that we have developed before.In high throughput screening,their activities against influenza A virus were discovered.Influenza A virus is a highly contagious virus with global outbreaks and high mortality.We designed and synthesized 37 dihydropyrrole derivatives for investigation into structure-activity relationship.Consequently,their activity against influenza A virus was increased by 60 times,with EC50 of 3.108±0.234 μM similar to those of most reported inhibitors.Preliminary research of anti-influenza mechanism showed dihydropyrroles could significantly decrease the expression of HA mRNA,NP protein,and Nox1 mRNA,with increasing the expression of antiviral factor Mx1 mRNA and IFN-β mRNA.The third part is on fast CMC determination.Surfactants show sharp changes in properties at a particular concentration,called CMC,which can be influenced significantly by many environment factors,including pH,solvent,temperature and salt.Therefore,fast determination of CMC is important in practical applications.Different methods for CMC determination have been developed.However,a series of surfactant solution of different concentrations have to be preprared for getting corresponding physcial quantities.These methods are lack of advantages of efficiency and convenience.Herein,we developed CMC paper to solve this problem.In 2011,we developed an efficient five-component reaction for the synthesis of a new series of C6-unsubstituted tetrahydropyrimidines(THPs)and found that THPs possess strong aggregation-induced emission(AIE).In addition,THPs are unusually no emssive in surfactant micelles.Based on these paticular properties,THPs were developed as a series of unique fluorescence-turn-on probes for CMC determination.In this thesis,THPs were further developed as cheap CMC papers for fast determination of the CMC values of different kinds of surfactants.These CMC values determined by CMC papers are in accordance with those determined by reported methods.In view of accuracy and convenience,CMC paper is promising for broad application prospect.