Design, Synthesis And Biological Activity Study Of Novel Spirocyclic Derivative

In this thesis,49 pyridine spiro derivatives were designed and synthesized from methyl 1-aminocyclohexyl formate and pyridine acetic acid,and then active substructures such as benzyl,acyl and sulfonyl were introduced into the hydroxyl group of the intermediate.The structures of the compounds were determined by ¹H NMR,¹³C NMR,¹⁹F NMR and HRMS.Taking two kinds of pests and two kinds of plant viruses as the research objects,the insecticidal and antiviral activities of the target compounds were tested,and the mechanism of the active compounds against Tobacco mosaic virus（TMV）was preliminarily studied.The results are as follows:1.The antiviral activities of the target compounds against TMV and Cucumber Mosaic Virus（CMV）were tested by half-leaf spot method.Most of the target compounds showed moderate to excellent inhibitory activity against TMV at 500 mg/L,among which compounds E20 and F4 showed the most excellent anti-TMV inactivation activity,and their EC₅₀ values were 63.68 mg/L and 47.81 mg/L,respectively,which were similar to that of Ningnanmycin(EC₅₀=58.01mg/L).The mechanism of the two compounds was explored,and the results were as follows:Molecular docking showed that compounds E20 and F4 exhibited higher affinities for the TMV coat protein（TMV-CP）than Ningnanmycin.Molecular dynamics analysis showed that compounds E20 and F4 were more stable in binding with TMV-CP than Ningnanmycin.Microscale thermophoresis revealed that compounds E20（K_d=0.053±0.016μM）and F4（K_d=0.045±0.022μM）bound more strongly to TMV-CP than Ningnanmycin（K_d=0.10±0.029μM）.The results of transmission electron microscopy showed that these two compounds hindered the growth of TMV.In addition,we also found that compounds with obvious anti-TMV activities also have good anti-CMV curative activity.2.The insecticidal activity of the target compound against Plutella xylostella and acaricidal activity against Tetranychus urticae were tested by leaf dipping method.The results showed that the acaricidal activities of compounds E1,E2,E8,E14,E15 and E23 against Tetranychus urticae were as high as 90%at 200 mg/L.In particular,compound E23 showed 3-4 times stronger acaricidal activity than spirodiclofen.At the same time,we also found that most compounds also showed good insecticidal activity against Plutella xylostella,especially compound F2,whose insecticidal activity against Plutella xylostella was 93.33%at 200 mg/L.