The Design, Synthesis And Biological Activity Of 1,3,4-thiadiazole Derivatives

In this paper,we chosen the newly mesoionic insecticide Triflumezopyrim and Dicloromeoziaz as the lead structure,introducing 1,3,4-thiadiazole skeleton bound to thioether to design and synthesize series of 1,3,4-thiadiazole mesoionic compounds.The insecticidal activity of the target compound against the Sogatella furcifera?Horváth?was tested by spray method.In vitro laboratory bioassay activity test of meloidogyne incongnita by direct contact killing method.The antibacterial activity of the target compound against the Xanthomonas oryzae pv.oryzae?Xoo?,Xanthomonas oryzae pv.oryzicola?Xoc?and Xanthomonas citri pv.citri?Xcc?was tested by turbidity method.The preliminary antibacterial mechanism of the compounds with good antibacterial activity was studied.The main work of this paper is summarized as follows:1.Using Trifluorophenylpyrimidine and Dicloromezotiaz as the lead structure,the active substructure splicing principle was used to introduce the 1,3,4-thiadiazole active skeleton bound with thioether,and 24 new 1,3,4-thiadipines were designed and synthesized,and the title compound was structurally characterized by ¹H NMR,¹³C NMR,¹⁹F NMR,and HRMS.2.The insecticidal activity of the target compound against Sogatella furcifera was tested by spray method.The test results showed that some compounds had insecticidal activity against Sogatella furcifera at 100?g/mL concentration.Among them,the lethal rates of compounds 8c and 8h against Sogatella furcifera were both70%,but lower than the control agent trifluoropyrimidine?100%?.3.The direct-contact killing method was used to test the insecticidal activity of the target compound against meloidogyne incongnita at the concentration of 100?g/mL.The results showed that these compounds have no insecticidal activity against meloidogyne incongnita.4.The antibacterial activity of the target compound was tested by the turbidity method,using Xoo,Xoc and Xcc as test subjects at a concentration of 50?g/mL.The inhibitory rates of compound 8n against Xoo and Xoc were 70.91%and 53.34%,respectively,which were better than the control agents triflumezopyrim?42.85%and51.22%?,bismerthiazol?66.97%and 17.24%?and thiodiazole copper?47.76%and23.25%?;the inhibition rates of compounds 8j,8v and 8w on Xcc were 68.97%,60.66%and 54.28%,respectively,both exceeding the control agents triflumezopyrim,bismerthiazol and thiodiazole copper?bacteriostatic activity:49.55%,35.85%,and37.53%,respectively?;wherein the EC₅₀ of compound 8j against Xcc was 20.3?g/mL.5.The preliminary antibacterial mechanism of compound 8j on Xanthomonas citri pv.citri?Xcc?.The bacterial solution of Xcc treated by the compound 8j grew slowly,and the duration of the lag phase was prolonged;The effect of compound 8j on the extracellular polysaccharide?EPS?of Xcc was studied by shake flask fermentation.At the concentration of 12.5,25,50?g/mL,the inhibition rate of compound 8j on extracellular polysaccharides of Xcc was 56%,51.53%and 40.71%,respectively,this indicates that compound 8j may reduce the pathogenic ability of the cells;Under scanning electron microscopy?SEM?,the Xcc treated with compound 8j were significantly different from the normal cells,and the cells were deformed and shrunk,which indicated that compound 8j could destroy the cell structure of Xcc and change the surface of Xcc.Permeability,thereby destroying the normal physiological metabolism of the cells and inhibiting the growth and reproduction of the cells.