Excavation Of Flazin/Oridonin Esterification Derivatives For The Active Ingredient Of Chinese Medicine And Optimization Of Cyanomethylation Of Quinoline-2,4-dione Reaction Process

The medicinal chemistry synthesis of dominant skeletons and the study of active ingredient modifications in Chinese medicine are two of the most commonly used tools to obtain important tools for the development of new drugs.This thesis addresses the synthesis of Flazin/Oridonin esterified derivatives and the optimization of cyanomethylation quinoline-2,4-dione reaction process were investigated to find more promising active compounds.Flazin and Oridonin are two types of heterocyclic dominant backbones derived from Chinese medicine with multiple biological activities,and a series of Flazin and Oridonin esterified hetero derivatives were synthesized in this thesis.They were subsequently assayed for antitumor bioactivity at the cellular level,and it was found that the esterified derivatives 2-12,2-13,2-14,and 2-15 exhibited good cytotoxicity against a variety of tumor cells.In particular,compounds 2-13 showed remarkable inhibitory activity against the colon cancer cell line SW480.The advantages of the synthetic method presented here are highlighted by its easy handling,efficient reaction,and mild conditions.Finally,the effect of the subject product on tumor cell growth was examined using a modified MTT method,and esterified geneous derivatives with high antitumor activity were screened to provide a material basis for the development of antitumor agents.In addition,compounds containing cyanomethyl fragments have a wide range of applications and play a critical role in pharmaceuticals,pesticides,and functional materials.To facilitate the development of new drugs,it is critical to explore novel,efficient,mild,and convenient methods for the synthesis of cyanomethylation compounds.Among the many methods to introduce cyanomethyl functional groups,the development of radical cyanomethylation reactions is promising and has become a hot research topic nowadays.In this thesis,a series of cyanomethylated quinoline-2,4-dione compounds were successfully obtained by cyanomethylation of olefins in o-arylacrylamides in the presence of cyanomethyl source acetonitrile under the catalytic conditions of copper perchlorate and based on the radical cyanomethylation reaction.The reaction conditions are almost gentle and have excellent functional group compatibility,and a variety of substituents substrates are suitable.Besides,this thesis utilizing isotope labeling experiments and control experiments and provides an applicable reaction mechanism.