Synthesisof 1,2,3-triazole Derivaties And Their Activity Against Plant Pathogenic Fungi

1,2,3-triazole has broad application prospects in the fields of agriculture,medicine,and polymer materials due to its biological activity such as antibacterial,anti-tubercular,anti-HIV,anti-alphaglycosidase and antifungal.The early 1,2,3-triazole synthesis conditions are harsh and the reaction yield is low,which limits the development and application of such compounds.Until 2002,the Meldal Research Group of Denmark and the Sharpless Research Group of the United States independently found that under mild conditions,Cu(I)can catalyze the reaction of terminal alkynes with organic azides to obtain a single 1,4-disubstituted 1,2,3-triazole compound(Click Chemistry)have led to rapid development of 1,2,3-triazole studies."Click chemistry" plays an important role in organic synthesis,with high reaction yields,no by-products or harmless by-products,cheap and easy to obtain,simple conditions,good regional selectivity,etc.It has become an important green chemical synthesis method for drug development and biomedical research.Boscalid is a broad-spectrum SDHI bactericide developed by BASF.The bactericide uses succinate dehydrogenase as a molecular target and is mainly used to prevent botrytis,sclerotinia,powdery mildew,and brown rot disease.This article describes the use of boscalid as a template to introduce 1,2,3-triazole groups into the field of SDHIs,based on active substructure combination and bioisosterism,two series of 42 novel 1,2,3-triazole derivatives have been designed and synthesized by modifying the pyridine and biphenyl rings.The structure of each compound was characterized by 1H-NMR?MS(ESI),the crystal structure of compound 5r was confirmed by X-ray single crystal diffraction.Mycelial growth inhibition assay was used to test the antibacterial activity of all target compounds against six plant pathogenic fungi including Sclerotinia sclerotiorum,Rhizoctonia solani,Fusarium graminearum,Gaeu-mannomyces graminsis,Botrytis cinerea and Magnaporthe oryza.The results of bioassay showed that some compounds had good inhibitory activity against S.sclerotiorum,R.solani,B.cinerea and Ggraminsis.The EC50 values of A series compound 6a against S.sclerotiorum and R.solani were 2.97 ?g/mL and 5.38 ?g/mL,the in vivo protective effect of 6a against rape sclerotinia rot could reach 54.68%at a concentration of 200?g/mL,the positive control effect of boscalid reached 51.44%at a concentration of 100 ?g/mL.The B series compound 12a also showed good antifungal activity against S.sclerotiorum and R.solani,with ECso values of 3.72 ?g/mL and 3.63?g/mL,respectively.Compound 12b showed good antifungal activity against B.cinerea,with ECso values of 2.41?g/mL,which is comparable to that of the positive control.Finally,using molecular docking technology,compounds 6a,12a and protein 2FBW were predicted by SYBYL-X2.0 software,demonstrating possible modes of action of compounds 6a and 12a with target receptors.The result showed that compound 6a forms hydrogen bonds with the hydroxyl group at 173-position tryptophan and the hydroxy group at the 58-position tyrosine,compound 12a except for these two hydrogen bonds,the nitrogen atoms at the 2-position of the 1,2,3-trizole ring forms a hydrogen bond with the hydroxyl group at the 58-position tyrosine.The nitrogen atom at the 3-position of the 1,2,3-triazole ring forms hydrogen bonds with the hydroxyl group at the 173-position tryptophan and the 58-position tyrosine.It further elucidated the mode of action of active compounds with molecular targets.