Preparation And Antibacterial Activity Of Novel Fludioxonil Structural Analogs

In order to develop a new type of high-efficiency and broad-spectrum pyrrole fungicides,based on the structure of fludioxonil,we designed and synthesized the new compounds 1a(4-(2-Cl-3-fluorophenyl)-1H-pyrrole-3-nitrile)and the N-position Meth-yl-substituted pyrrole compound 1b(4-(2-Cl-3-fluorophenyl)-1-methyl-pyrrole-3-carb-onitrile),and the structures of two new pyrrole compounds were characterized and con-firmed.The results show that the difference of the substituents on the benzene ring leads to a significant change in the chemical shift of the C atom.The single crystal X-ray diffraction results show that the molecular formula of the target compound 1b is C₁₂H₈Cl FN₂,the molecular weight is M_r=234.65,and the monoclinic system is P 21/n space group.The antibacterial effects of 19 new pyrrole compounds synthesized in the early stage of this research group and the two newly synthesized compounds in this paper were studied.The result is as follows:This paper studied the antibacterial effects of 21 new structural analogues of fludioxonil against Rhizoctonia solani and calculated the IC₅₀ value.The results showed that compound 1a,3a,4a,6a and 8a,had strong antibacterial effects,with IC₅₀values of 0.5 mg/L.Then a 3D-QSAR study was conducted on 21 compounds using computer-aided drug design,and an effective CoMFA model(q²=0.503,r²=0.974)was established.The model's significance test value F was 81.35 and the standard estimated deviation S was 0.219,which showed that the model had good predictive ability,and it provided theoretical guidance for the further optimization of the series of compounds.In order to further study the broad-spectrum bactericidal activity of the four compounds 1a,3a,4a,and 6a,which have good bactericidal activity Rhizoctonia solani,we tested the compounds against Fusarium graminearum,Alternaria brassicae(Berk.)Sace,Helminthosporium maydis,Fusarium oxysporum f.sp.,Colletotrichum capsici(syd.)Butl antibacterial activity.The results showed that when the concentration was below 1mg/L,compound 1a,3a,4a,and 6a exhibited extremely strong inhibitory effects on Fusarium graminearum Schw,and the inhibitory rates reached percent of 84.13,85.29,69.23,and 88.45,respectively;and compound 3a showed high bacteriostasis against Alternaria brassicae(Berk.)Sace and Fusarium oxysporum.F.s p.cucmrium,with IC₅₀ of 8.15 mg/L and 7.7 mg/L,respectively.This article has certain reference significance and guidance for the development and application of new broad-spectrum fungicides.