The Design, Synthesis And Mechanism Of Heterocyclic Substituted Thioether (sulfone) Derivatives Based On Nematicidal Activity

Thioether ?sulfone? compounds have attracted much attention because of the broad-spectrum biological activity.The sulfide?sulfone?compounds have been found to exhibit good nematicidal activity by many researchers in recently.A new generation of excellent sulfone nematicide fluensulfone among them has been put on the market for the prevention and control of diseases caused by nematodes.With the expectation of finding high-efficiency,low-toxic,environmentally friendly and ecologically safe green nematicide,five series of new heterocyclic substituted sulfides?sulfone?compounds were designed and synthesized by introducing a thioether?sulfone?structure with nematicidal activity into the parent structure containing heterocycles.The nematicidal activity of the target compounds was evaluated by the contact killing or the root-drenching method,and the Co MFA and Co MSIA models of the compounds were established for three-dimensional quantitative structure-activity relationship analysis?3D-QSAR?.Finally,the effect of highly active compounds on the partial physiology and biochemistry of nematodes was tested.The main work is summarized as follows:1.The thioether ?sulfone? moiety with nematicidal activity was introduced into the parent structure containing 1,3,4-oxdiazole?thidiazole?heterocycle,a total of 149target derivatives of 1,3,4-oxdiazole?thidiazole?substituted with new thioether?sulfone?in 5 series were designed and synthesized.The structures of all target compounds were characterized by ¹H NMR,¹³C NMR,and HRMS.2.All compounds containing heterocyclic substituents were tested for nematicidal activity against nematodes in vitro by contact killing method,and nematicidal activity of highly active compounds was tested by root-drenching method in vivo.The results of nematicidal activity in vitro test showed that some of the target compounds exhibited good inhibitory activity against citrus nematodes?Tylenchulus semipenetrans?.Compound A21 showed excellent nematicidal activity,the LC₅₀value was 11.7 mg/L,which was better than the control agent avermectin?24.8 mg/L?.In addition,the inhibition rates of compounds B34 and B35 on Meloidogyne incognita were both 100%when the concentration was 50 mg/L and treated for 48 h.The LC₅₀values were 6.5 and 7.6 mg/L,respectively,and the activities were 83.3%and 79.2% in vivo.3.The Co MFA and Co MSIA models of 1,3,4-oxadiazole substituted thioether containing phenoxy group and 1,3,4-thiadiazole substituted sulfide?sulfone?amide compound were established.Among them,the q²and r² of the Co MFA model of1,3,4-oxdiazole?thidiazole?-substituted thioether compounds containing phenoxy groups are 0.722 and 0.985,respectively.The q² and r² values of the Co MSIA model are 0.634 and 0.988,respectively.The nematicidal activity is mainly affected by the hydrophobic effect,electrostatic effect and spatial effect in this model.Compound A33 with higher nematicidal activity was designed and synthesized based on the models.The LC₅₀ value was 9.8 mg/L,and the control effect in vivo was 70.7%,which was better than the control agent avermectin.The 3D-QSAR model of amide compounds containing 1,3,4-thiadiazole-substituted sulfide?sulfone?indicates that a small,hydrophobic and electronegative group is introduced near the ethyl group of this series of compounds beneficial for increasing nematicidal activity.4.Citrus nematodes and M.incognita showed certain phobotaxis to compounds A33 and B34,respectively.Compound B34 had a significant effect on the apparent morphology of M.incognita.When the treatment time is constant,the degree of surface deformation and the destruction of the nematode body wall increase with the increase of the treatment concentration.when the treatment concentration is unchangge,the degree of surface deformation and the destruction of the nematode body wall increase with the treatment time.