Study On Synthesis And Antifungal Activities Of α-substituted Thiochromone Amides

In order to explore new fungicides for the control of wheat diseases including wheat Take-all,α-substituted thiochromone amides as a new structure were designed based on the structural characteristics of amide antifungal active compounds and Silthiopham.Two synthetic routes were developed,18 α-substituted thiochromone amide derivatives were synthesized,and their biological activities were investigated,and a good progress was made.1.The synthetic route of α-phenyl substituted thiochromone amide derivatives was designed.Using thiosalicylic acid as the raw material,the dimer of 2mercaptobenzaldehyde was obtained by reduction and oxidation.The dimer reacted with ethyl cinnamate in the presence of triphenylphosphine and tetramethylguanidine to give an intermediate.Nine 2-phenyl substituted thiochromone amide derivatives were obtained by oxidation,hydrolysis and amination of the intermediate.Their structures were characterized and confirmed by 1H NMR,13C NMR,and HRMS.2.The synthetic route of α-nitrogen and α-oxygen substituted thiochromone amide derivatives was designed.Using o-chloroacetophenone as the raw material,nine αnitrogen and oxygen substituted thiochromone amides were obtained successively through the reaction with dimethyl carbonate,ester amine exchange,condensation with carbon disulfide,cyclization and oxidation.Their structures were characterized and confirmed by 1H NMR,13C NMR,and HRMS.3.The activities of the synthesized thiochromone derivatives were studied by the mycelial growth rate method.By testing the activities of thiochromone derivatives against Gaeumannomyces graminis var.tritici in vitro,it was found that 10 compounds had EC50 values less than 50 mg/L,and 3 compounds had EC50 values less than 1 mg/L.At the same time,the activities of the compounds against Fusarium graminearum,Rhizoctonia solani and Sclerotinia sclerotiorum in vitro were also investigated.Two compounds were found to have EC50 values less than 100 mg/L against Fusarium graminearum.Four compounds had EC50 values less than 100 mg/L against Rhizoctonia solani.Eight compounds had the EC50 values against Sclerotinia sclerotiorum less than 100 mg/L.Two compounds had the EC50 values against the four pathogens less than 100 mg/L,showed a certain broad spectrum activity.4.The structure-activity relationship of thiochromone amide derivatives were analyzed preliminarily.Through the analysis of the structure-activity relationship,it is found that it had an important impact on the activity whether the carbon atom at the aposition of the thiochromone ring has a conjugate relationship with the amide functional group.Those derivatives with a conjugate relationship had better activities than those without a conjugate relationship.When the α-position substituent was a benzene ring,the substituent on the nitrogen atom of thiochromone amide had a greater impact on the activity.When the substituent on the nitrogen atom was a substituted phenyl,its EC50 value against Gaeumannomyces graminis var.tritici could reach a level of less than 1 mg/L.The α-position substituent also had a greater impact on the active range of the derivatives.When the substituent was aniline,the compounds had certain activities against the four tested pathogens.The scope of activity was expanded.The study on the structure and activity relationship of α-substituted thiochromone amide derivatives provided a certain theoretical surport for the further design and structure optimization of active compounds,and provided some ideas for the discovery of new pesticides.