Synthesis And Bioactivities Preliminary Study Of Tralopyril Derivatives

Tralopyril,with the chemical name of 4-bromo-2-（4-chlorophenyl）-5-trifluoromethylpyrrole-3-nitrile,is a 2-arylpyrrole compound modified and synthesized by the natural antibiotic dioxypyrromycin,which has excellent insecticidal and acaricidal activities.However,the application of tralopyril is severely limited due to its phytotoxicity on crops.In this paper,tralopyril was used as the lead compound.Through structural modification,carboxylate esters,amides,amino acids and 1,3,4-oxadiazole structural fragments were introduced into the 1-N position of tralopyril,and three series of new tralopyril derivatives were designed and synthesized.Their fungicidal,insecticidal,acaricidal and nematicidal activities were determined,and their crop safety and phloem mobility were evaluated,It is expected to obtain tralopyril derivatives with high activity and safety to crops.The main results are as follows:1.By introducing carboxylic acid ester and amide structure at 1-N position of tralopyril,28 novel tralopyril carboxylic acid ester and amide derivatives were designed and synthesized.The bioassay results showed that the target compounds showed certain fungicidal,insecticidal,acaricidal and nematicidal activities,among them,the EC₅₀values of compounds 2,3 and 5m against Magnaporthe oryzae were0.0532,0.0470 and 0.0174 mmol/L,respectively,which were better than the control agent fludioxonil（0.0914 mmol/L）;The EC₅₀values of compound 5m against Rhizoctonia solani and Bipolaris sorokiniana were 0.0218 and 0.0420 mmol/L,respectively,which were lower than the control agent fludioxonil（0.0002 and 0.0010mmol/L）;At the concentration of 0.2 mmol/L,the insecticidal and acaricidal activity of compound 6o against Spodoptera litura and adult mite of Tetranychus cinnabarinus was more than 70%,but lower than that of the control agent chlorfenapyr（100%）;The LC₅₀values of compounds 2,3,5b,5g,6n and 6o against Caenorhabditis elegans were 0.0136,0.0214,0.0109,0.0780,0.1370 and 0.1028mmol/L,respectively,which were superior to the control agent fosthiazate（0.2798mmol/L）.The safety test results showed that compounds 2,3,5b,5m,6o were safer to Oryza sativa L and Brassica campestris L than the parent tralopyril.2.By introducing 1,3,4-oxadiazole structure at 1-N position of tralopyril,20novel tralopyril thioether derivatives containing 1,3,4-oxadiazole were designed and synthesized.The bioassay results showed that the target compounds exhibited certain fungicidal,insecticidal,acaricidal and nematicidal activities,but all were lower than the parent tralopyril;Among them,the LC₅₀values of compounds 9k,9r and 9s against Caenorhabditis elegans were 0.0918,0.0733 and 0.0810 mmol/L,respectively,which were better than that of the control agent fosthiazate（0.2798 mmol/L）.The safety test results showed that compound 9r was safer to Oryza sativa L and Brassica campestris L than the parent tralopyril.3.By introducing amino acid structure into 1-N position of tralopyril,40 novel amino acid derivatives of tralopyril were designed and synthesized.The bioassay results showed that the target compounds exhibited certain fungicidal,insecticidal,acaricidal and nematicidal activities;Among them,the EC₅₀values of compounds 11g,11h and 14a against Magnaporthe oryzae were 0.0499,0.0793 and 0.0644 mmol/L,respectively,which were better than the control agent fludioxonil（0.0914 mmol/L）;The LC₅₀values of compounds 11a and 14a against Caenorhabditis elegans were0.0286 and 0.0165 mmol/L,respectively,which were better than that of the control agent fosthiazate（0.2798 mmol/L）.The safety test results showed that compounds11a,11g,14a were safer to Oryza sativa L and Brassica campestris L than the parent tralopyril.The phloem mobility test showed that the introduction of amino acid structure did not endow the phloem mobility of tralopyril.In conclusion,the target compounds synthesized in this paper have certain fungicidal,insecticidal,acaricidal and nematicidal activities.Although the biological activity is lower than that of the parent tralopyril,the highly active target compounds are safer for crops than that of the parent tralopyril,and can be further optimized as a lead compound.This paper provides ideas for the design and modification of tralopyril derivatives,and has reference significance for exploring the biological activity diversity of tralopyril derivatives.