Design,Synthesis And Biological Activity Of 3-phenyl-5-pyridyl-1,2,4-oxadiazole Derivatives And Waltherione A Analogues

The root-knot nematode（RKN）,as one of the most harmful plant parasitic nematodes,cause huge economic losses to crops every year,which is also a worldwide problem.Compared with fungicides and insecticides,the development of nematicides is relatively slow and there are few varieties.In addition to the adjustment of agricultural planting patterns in recent years,the occurrence of root-knot nematode disease has become more and more serious,so the research and development of new nematicides have also attracted more and more attention from researchers.Based on the design strategies for pesticide lead compounds and the ideas for pesticide creation,two types of 30 target compounds and 9intermediate compounds were designed and synthesized,targeting Meloidogyne incognita.All the compounds have been confirmed by ¹H NMR,¹³C NMR and HRMS,and the biological activities of the target compounds were tested.In the first part,using nematicide tioxazafen as the lead compound,a total of 183-phenyl-5-pyridyl-1,2,4-oxadiazole derivatives were designed and synthesized and their structure-activity relationships were discussed.Some of the target compounds had a good inhibitory activity against Meloidogyne incognita at a concentration of 200 mg/L.Among them,the inhibition rates of compounds 11,13,14 and 17 against nematodes reached more than 90%,especially that of compounds 1 and 4 against nematodes,the rates reached even100%,and the LC₅₀ values of these 6 compounds were calculated.The results showed that when the pyridine ring was attached to the oxadiazole ring at the 2-position,the nematicidal activity was better than that at the 3-position;When the substitution site of a single substituent was at the ortho position of the pyridine ring,the nematicidal activity would be higher than that of the same substituent substituted at other positions;The electron-withdrawing groups were more beneficial to the improvement of nematicidal activity compared with the electron-donating groups,and the effect of the substitution site on the nematicidal activity of the compounds would be greater than its electronic effect.In addition,during the exploration of the broad spectrum of biological activity of the target compounds,it was also found that the compound also had a certain degree of inhibitory activity against Plutella xylostella.Among them,the inhibitory activities of compounds 1,13,and 14 on Plutella xylostella at the concentration of 250 mg/L reached 64%,48%,and48%respectively,which were significantly better than tioxazafen（6.7%）.It is expected to be further optimized to discover new compounds that have both high nematicidal and insecticidal activities.In the second part,using the natural product waltherione A as the lead compound,a total of 12 analogues of waltherione A were designed and synthesized through seven steps of reaction by using“the intermediate derivatization method”,and based on the previous work of our group,the structure-activity relationship was further studied.The technological innovations in the optimization of synthetic routes showed that in the first reaction,by changing the reaction substrate,the use of the expensive Grubbs’catalyst was eliminated,which not only reduced the cost,but also increased the product yield by more than 20%compared to the literature;In the sixth step of the reaction,on the basis of literature experimental schemes,the product yield was increased by more than 40%compared with the literature through controlling the reaction conditions strictly,which was conducive to the subsequent reaction.The results of the nematicidal activity test showed that the structure of 5,8-epoxybenzocycloheptanone or alcohol alone could not effectively improve the nematicidal activity of the compound against Meloidogyne incognita.But when it became a substituted alcohol by nucleophilic addition reaction,the nematicidal activities of the compounds were improved to a certain extent,especially with the aromatic hydrocarbon structural substituents.In addition,the nematicidal activity of compound A-12（69.7%）was much greater than that of other compounds,which indicated that substituents containing both aromatic hydrocarbons and aliphatic hydrocarbons might be more conducive to the improvement of activity,and is worth further exploration.