Design, Synthesis And Anti-citrus Huanglongbing Activity Of 1,2,4-triazolo[4,3-a]pyridine Sulfone Compound

To establish a method for rapid screening of fungicides against Citrus Huanglongbing（HLB）,the Candidatus Liberobacter asiaticus（CLas）contents in leaves of different citrus branches,different leaves of the same citrus branch and two half leaves of the same citrus leaf were detected.A screening method for resistance to HLB was designed based on the results of CLas content detection.The stability and reliability of the test method were verified by using hexachloropurine nucleoside as the test agent.To find effective agents for controlling HLB,a series of novel 1,2,4-triazolo[4,3-a]pyridylsulfones were designed and synthesized by introducing sulfone structures into the structure of 1,2,4-triazolo[4,3-a]pyridine using the principle of active splicing.The anti-HLB activities of all the compounds were tested by the half-leaf method.The preliminary structure-activity relationship（SAR）analysis was carried out according to the activity test results.Transcriptomic techniques were used to study the anti-HLB mechanism of highly active compounds.The work is summarized as follows:1.Compared with the leaves on different branches and different leaves on the same branch,the difference of CLas content in the left and right half leaves of the same leaf was small,the difference was basically between 0.7-1.3 times.The results of the repeatability test showed that there was a small deviation in the activity data of 45groups of hexachloropurine nucleosides against HLB,indicating that the test method had a good repeatability and reliability.Nine leaves from three susceptible branches could be used as test plants to test the activity of fungicide against HLB.2.Forty sulfone compounds of 1,2,4-triazolo[4,3-a]pyridine were synthesized,and their structures were characterized by ¹H NMR、¹³C NMR and HRMS.3.At the concentration of 200 mg/L,some of the target compounds had good anti-HLB activity,among which compounds 13 had the best anti-HLB activity of 84.1%.Moreover,when the concentration was reduced to 100 mg/L,it still has 67.2%anti-HLB activity.4.Preliminary mechanism of action study based on the activity of compound 13against HLB showed that the defense enzyme activity and chlorophyll content in citrus leaves were significantly increased after treatment with compound 13,the genes related to disease resistance were up-regulated.The results indicated that compound 13 could enhance the disease resistance of citrus by mediating plant immune response.