Design, Synthesis And Nematicidal Activity Of Novel Oxazole-containing Amide Derivative

To find green nematicides with high efficiency,low toxicity,and novel mechanisms of action,60 novel amides containing oxazole were designed and synthesized by introducing 1,2,4-oxadiazole or isoxazole structures into the fluopyram framework,using fluopyram and tioxazafen as lead compounds.The nematicide activity of all target compounds was determined via the dipping method,and the mechanism of nematicide action of highly active compounds was preliminarily studied.The main work is as follows:（1）Two series of 60 novel oxazole-containing（1,2,4-oxadiazole,isoxazole）amide compounds were designed and synthesized,and the structures of all target compounds were confirmed by ¹H NMR,¹³C NMR,and HRMS,and their nematicide activity was tested.（2）The results of biological activity test showed that some of the target compounds showed excellent in vivo nematicide activity against the three plant pathogenic nematodes tested.Among them,compounds A7,A26,A28～A30 had LC₅₀values of 1.39～3.09 mg/L against pine wood nematodes（Bursaphelenchus xylophilus）,rice dry tip nematode（Aphelenchoides besseyi）and sweet potato stem nematode（Ditylenchus destructor）,which were significantly better than the control agent tioxazafen（105.53,48.95 and 74.95 mg/L）.（3）Compound A7 can not only significantly affect the hatching of nematode eggs at high concentrations,but also effectively inhibit the feeding and reproduction of nematodes.Staining experiments related to oxidative stress and intestinal damage indicate that compound A7 could significantly promote the production of reactive oxygen species（ROS）and the accumulation of lipofuscin and lipids in B.xylophilus.The test results of malondialdehyde（MDA）and glutathione（GSH）levels and defensive enzyme activities showed that compound A7 can weaken the antioxidant capacity of B.xylophilus,thereby reducing the pathogenicity of nematodes.Compound A7 can effectively inhibit the activity of succinate dehydrogenase（SDH）in B.xylophilus at a certain concentration,which in turn affects the mitochondrial respiration process of nematodes.Molecular docking experiments showed that A7 and SDH of B.xylophilus had extremely strong binding ability,which indicated that SDH might be the potential target of compound A7.