Studies On HDAC Inhibitors Belinostat Analogs And Synthesis Of Spirotetrahydrofuran Oxidized Indole Derivatives

Cancer is a serious disease that directly affects human life and health.In recent years,histone deacetylase inhibitors are clinically proven of the ideal treatment of cancer drugs.Therefore,the development of good anti-cancer effects and small side effects of new histone deacetylase inhibitors drugs has great significance in drug research and clinical medicine.In this paper,a histone deacetylase inhibitor with anti-tumor activity was designed and synthesized.The procedure was easy and the raw materials were cheap and easy to obtain with good broad-spectrum inhibitory activity.Of the various natural and known drugs,the heterocyclic compound accounts for one third of the organic compound.Since the oxidized indole spiro compounds are the core skeleton of many natural products,they also has a very good biological activity.Therefore,the synthesis of oxidized indole spiro compounds in a green and environmentally friendly manner has great importance in the field of natural product chemistry and pharmaceutical chemistry.In this paper,a series of compounds were synthesized by oxidative indole spirocyclofuran as the core ske leton.The method is not only simple,but also environmentally friendly,and no organic solvent was involved in the reaction.In the first section of this article,the histone deacetylase inhibitors were briefly introduced,and the research status of the s tructure design and activity exploration of these compounds were expounded,and the interaction between the structure and activity of these compounds was summarized.We also draw on the previous research to provide the innovative ideas for the route design of this article.Simultaneously,this chapter summarizes the natural products and chemical drugs of oxygen-containing spiro,and summarizes the research methods of the synthesis of indole-spiro-tetrahydrofuran ring derivatives.The pros and cons of this kind of reaction are analyzed,which provide reference for the content of this article.In the second chapter of this paper,the synthetic route of the histone deacetylase inhibitor is described.The target compounds are synthesized by a few steps through cheap and readily available starting materials and lists its antitumor activity.The third chapter describes one-step synthesis of oxidized indole spiro tetrahydrofuran ring derivatives reaction with the ?-isopentenyl indigo derivatives as the substrate.In this reaction,the green and non-toxic water to replace other organic solvents as the reaction solvent,catalyzed by methanesulfonic acid to form indole spiro derivatives,and we also put forward the possible mechanism.All of the compounds obtained by the above mentioned reactions were characterized by 1H NMR,13 C NMR and HRMS.Some compounds were characterized by X-ray.