Preliminary Study On Synthesis And Biological Activity Of Phenylthiazole-1,3,4-oxadiazole Thiones (Ketones) Derivatives

To discover green,efficient,and low toxicity antifungal natural product antifungal pesticides.In our previous work,we first screened the agricultural activity of natural product thiasporine A and its derivatives found that exhibited promising antifungal activity.The aforementioned findings inspired us to develop novel fungicides based on phenylthiazole skeleton.In this study,we designed and synthesized 56 phenylthiazole-1,3,4-oxadiazole thiones（ketones）based on the active skeleton structure of phenylthiazole.All target compounds were characterized by ¹H NMR,¹³C NMR and HRMS.Compounds E series——phenylthiazole-1,3,4-oxadiazole ketones（E1-E26）.We designed and synthesized a total of 26 compounds E,and tested EC₅₀ activity against C.camelliae.The results showed that the EC₅₀values of the tested compounds E3（33.76μg/m L）,E7（16.62μg/m L）,E14（17.29μg/m L）,E22（13.33μg/m L）were better than hymexazol（82.88μg/m L）among which the inhibitory effect of the best compound E22is 2.2 times that of hymexazol.Compounds F series——phenylthiazole-1,3,4-oxadiazole thione（F1-F30）.We designed and synthesized a total of 30 compounds F,The series of compounds have significant antifungal activity against S.sclerotiorum,and the EC₅₀ value of the optimal compound F1 against S.sclerotiorum is 0.22μg/m L,which is significantly better than the commercial fungicides hymexazol（5.78μg/m L）and carbendazim（0.70μg/m L）.Subsequently,we established 3D-QSRA model based on antifungal activity and analyzed the structure-activity relationship between stereoelectric and electrostatic fields.Based on the EC₅₀ experimental results,we selected some compounds to determine activity of rape sclerotinia stem rot in vivo.The results showed that compound F1 was better than carbendazim in the protective effect and curative effect of rape sclerotinia stem rot at different concentrations.The results of sclerotinia formation and sclerotinia germination inhibition showed that the inhibition effect of compounds F1 and F5 on sclerotinia formation were significantly better than that of carbendazim at the same concentration;Compound F1 was equal to inhibitory effect on sclerotia germination as carbendazim at10.0 and 5.0μg/m L concentrations.