Synthesis And Preliminary Antitumor Activity Of Triazolopiperidine Derivatives

Fused heterocyclic compounds are the key structure of many drugs and natural products.1,2,3-Triazole fused heterocyclic compounds are very important skeleton structure,which play an important role in drug discovery,biological chemistry and material science.1,2,3-triazole fused heterocyclic compounds have found some antitumor,antifungal and other bioactivities.Therefore,the synthesis of these compounds has attracted extensive researcher’s interest.Huisgen [3 + 2]cycloaddition of azide and alkyne(AAC reaction)is a classic reaction for the construction of five-membered 1,2,3-triazoles.A series of tandem or multi-component reactions have been developed for the synthesis of triazolo-fused heterocycles by improving the Huisgen [3 + 2] cycloaddition reaction process.A highly active organic copper intermediate will be produced in copper catalyzed azide-alkyne cycloaddition reaction,using some electrophilic reagents to capture it can be a simple and efficient way for the construction of a series of 1,2,3-triazole fused heterocyclic compounds.In this paper,we take the acetylene amide alkenyl halide as substrate,realized the reaction of copper catalyst [3 + 2] cycloaddition/C-N coupling.This strategy can build a series of triazolopiperidine derivatives.Besides,preliminary antitumor activity tests were performed on some of these compounds.The whole paper is divided into the following parts.Chapter 1: This part mainly introduces the development of organic copper chemistry and the methods of the construction of fused heterocyclic compounds based on the capture of organic copper intermediates.Besides,we also developed a series of methods for the construction of fused heterocyclic compounds based on this strategy.These methods use copper salt as catalyst,which has the characteristics of economic,green and environmental protection,and can easily and efficiently synthesize a series of fused heterocyclic compounds,it provides the necessary synthesis foundation for drug research and development,and promotes the development of organic synthesis and pharmaceutical chemistry greatly.Chapter 2: A series of triazolo-fused-piperidine derivatives were constructed by copper [3 + 2] cycloaddition/alkenyl C-N coupling reaction,and the reaction were carried out on a gram scale and product transformation,and we proposed a possible reaction mechanism.This method has good adaptability,and can construct triazole fused piperidine skeleton simply and efficiently with good yield.Moreover,the transformation of product shows the potential application of this skeleton.Chapter 3: The antitumor activity and therapeutic effect of some drugs with fused heterocyclic compounds as parent nucleus structure were introduced.The preliminary antitumor activity test of some compounds synthesized by us has been carried out,which obtained some beneficial preliminary research information.