Studies On Synthesis And Antifungal Activities Of 1-(N-methyl-N-benzylmethyl)amino-3,3-dimethyl-2-(1,2,4-triazol-1-yl)methyl-2-butanols

Ergosterol biosynthesis inhibitor is a type of fungicides which could inhibit the process of ergosterol biosynthesis in fungi.Ergosterol is the typical sterol in fungi,whose structure is different from that of sterol in plants and animals.Therefore,because of its efficiency,broad spetrum,low toxicity and environmental compatibility,ergosterol biosynthesis inhibitor had been concerned extensively since it appeared for the first time.As a class of C-14 demethylase inhibitor,triazole fungicides could effectively inhibit the biosynthesis of ergosterol through hindering C-14 demethylation in the process of ergosterol biosynthesis.However,intensive application for a long time has caused the appearance of resistant strains against triazole fungicides.In order to search for novel antifungal agents for the more effective control of phytopathogenic fungi,especially against resistant fungi,the study used intermediate derivatization method?IDM?to design and synthesize 19 novel target compounds containing 1,2,4-triazole and tertiary amine moiety through combining the active structure of triazole fungicides with the active structure of ?14-reductase/?8??7 isomerase inhibitors.All target compounds were elucidated by means of 1H-NMR,13C-NMR,ESI-MS and IR analysis.The antifungal activities in vitro of all target compounds against six phytopathogenic fungi?M.grisea,A.solani,F.solani,C.lunata,A.alternata,F.graminearum?were assayed using mycelium growth rate inhibition method.The results displayed that most of target compounds exhibited antifungal activities against almost all the tested fungi at the concentration of 50 ?g/mL,surperior to their key intermediate 5 in varying degree.Furthermore,EC₅₀ values of compounds 7c,7j and 7l against A.alternata,F.graminearum and A.solani were 15.11 ?g/mL,11.60 ?g/mL and 8.201 ?g/mL respectively.Among them,compound 7l showed excellent activity against A.solani with EC₅₀ value of8.201 ?g/mL,which was in the same order of that of tebuconazole(EC₅₀ = 2.031 ?g/mL),the positive control.The preliminary analysis of structure-activity relationship?SAR?demonstrated that the activities of target compounds against different species of the tested fungi depend on the type and position of the substituents on benzene ring to some extent.The presence of 2,4-diCl or 3,4-diCl improved activities against most of test fungi in varying degree,while the introduction of OMe decreased the activities of almost all the target compounds against almost all the tested fungi.