Design, Synthesis And Biological Activity Of Ferulic Acid And Sesquiterpene Derivative

In this thesis,a series of ferulic acid derivatives and two series of sesquiterpene derivatives were designed and synthesized by introducing the active substructures such asβ-amino alcohols,oxadiazoles and hydrazide-hydrazone from the natural products ferulic acid and sclareolide,respectively.The structures of the compounds were identified by ¹H NMR,¹³C NMR,¹⁹F NMR,and HRMS.Target compounds were tested against plant viruses such as tobacco mosaic virus（TMV）,plant bacteria such as Xanthomonas oryzae pv.oryzae（Xoo）and Xanthomonas axonopodis pv.citri（Xac）as research objects,looking for highly active candidate compounds with potential antiviral and bactericidal properties.For the compounds with high activity against plant viruses,the interaction between the active compounds and the tobacco mosaic virus coat protein（TMV-CP）was investigated by molecular docking and molecular dynamics simulation,and the mechanism of action was preliminarily explored.The results are as follows:1.Twenty-four ferulic acid derivatives containingβ-amino alcohols were designed and synthesized,and the biological activity test results illustrated that the EC₅₀ values of compounds D22 and D23 for Xoo were 16.2μg/mL and 19.5μg/mL,respectively,which were higher than those of thiodiazole copper.(EC₅₀=44.5μg/mL).Especially compound D24(EC₅₀=14.5μg/mL)showed 50.5%and 50.1%of the curative and protective activities against Xoo,respectively.The EC₅₀ values of compounds D2 and D4 for the inactivation activity of TMV were 56.8μg/mL and 52.5μg/mL,respectively,with compound D3(EC₅₀=38.1μg/mL)in particular showing significantly higher activity than ningnanmycin(EC₅₀=39.2μg/mL).Autodocking and molecular dynamics simulation results indicated that compound D3 interacts with the active site of TMV-CP through amino acid residues,and its binding energy is-7.54 kcal/mol,which is better than that of ningnanmycin（-6.88 kcal/mol）,and it is consistent with the results of the target compound tested for inactivation activity against TMV.2.Twenty-three sesquiterpene derivatives containing 1,3,4-oxadiazole and thirty hydrazide-hydrazone-containing sesquiterpene derivatives were designed and synthesized,and the biological activities of the two series of compounds were evaluated.The results demonstrated that the protective and curative activities of compound H8(EC₅₀=43.3μg/mL)against Xoo were 49.3%and 51.9%,respectively.And the protective and curative activities of compound Z22(EC₅₀=16.1μg/mL)were 50.8%and 51.3%,respectively.In addition,the EC₅₀ values of the inactivation activities of compounds H5 and H16 were 58.9μg/mL and 60.5μg/mL,respectively.Especially compound H10(EC₅₀=43.9μg/mL)was higher than that of ningnanmycin(EC₅₀=44.8μg/mL),and the EC₅₀ values of compounds Z17 and Z18 on TMV inactivation activity were 57.2μg/mL and 52.2μg/mL,respectively.Among which compound Z28(EC₅₀=38.7μg/mL)was superior to ningnanmycin(EC₅₀=39.2μg/mL).Autodocking,molecular dynamics simulation and transmission electron microscopy（TEM）revealed that the amino acid residues of compounds H10 and Z28 bind to the active site of TMV-CP(the binding energies are-8.88 kcal/mol and-8.25 kcal/mol,respectively,resulting in the difference in energy characteristics to obtain a stable conformation.