Design,Synthesis And Biological Activities Of Novel Strobilurin Fungicide

Since the first commercial strobilurin fungicide entering the market,many pesticide companies interested in it and launched their own products.The mode of mechanism of strobilurin fungicides is to inhibit the respiration of the fungus by combining with the complex of cytochrome b and c₁ on the inner cytomembrane.The sale quantity of strobilurin fungicides has been increasing rapidly due to their high efficiency,broad spectrum,low toxicity to mammals and envirmental friendliness.Currently,the strobilurin fungicides including azoxystrobin and kresoxim-methyl have become the most popular products,surpassing the trizole fungicide.As the members of heterocycle fungicides,the triazole and oxadiazole fungicides have occupied a large market share.Compounds containing heterocycle moieties also exhibit various activities including antibacterial,fungicidal,anti-inflammatory,antivirous and antitumor activities.The triazole fungicides could inhibit the biosynthesis of sterol to stop the formation of cell membrane.Many commercial pharmaceutical ingredients containing 1,3,4-oxadiazole group shows excellent fungicidal activity.Meanwhile,amide fungicides still play an active role in the market.Obviously,the 1,2,4-triazole,amide and 1,3,4-oxadiazole moieties could impove their potent fungicidal activity.Thus,introduction of 1,2,4-triazole,amide and1,3,4-oxadiazole moieties into strobilurin structure arouses our interest that these structures might bring us novel,effective and environmental-friendly fungicidesTo further explore potential activity of strobilurin fungicide,we focus on the side chain of strobilurin structure.Based on above viewpoints,six series summing up to 64novel compounds containing 1,2,4-triazole,amide and 1,3,4-oxadiazole moieties were designed,synthesized and evaluated for the fungicidal activity by applying such approaches as computer simulation technology,sub-structure coordination and bioisosterism.All of the title compounds were confirmed by ¹H NMR,¹³C NMR,HRMS or elemental analysis and melting point.Comparative molecular field analysis（CoMFA）calculation was also undertaken.The biological activity results indicated that 1,2,4-triazole could maintain and improve the fungicidal activity against Physalospora piricola,Cercospora arachidicola Hori,Rhizotonia cerealis.It would be benefical to improve the fungicidal activity against Rhizotonia cerealis by introducing short alkyl chain into1,2,4-triazole.As for 1,3,4-oxadiazole structure,the thiophene with electron-donating groups would enhance the fungicidal activity against Rhizotonia cerealis.Using a sulfur or oxygen atom as the leakage could improve fungicidal activity against Sclerotinia sclerotiorum.However,it would recede activity to most common fungi when pulling the amide group into the 4^th position of 1,2,4-triazole.Some title compounds（such as Ib、Ic、In、Ik）could be considered as potential candidates for strobilurin fungicides.The research work could guide further investigation for the new development of strobilurin fungicides.