Synthesis And Antifungalactivities Of ?-keto Enamines

Recently,phytopathogenic fungi have become deadly diseases in agriculture because of their strong infection,high incidence,and hard control.Therefore,developing new structure novel fungicide is urgent and inevitable.Some complicated enamine ketones showed high antifungal activities and medical activities.Retaining the reactive groups,enamine and ketocarbonyl group,and introducing different substituents may be a new way to screen efficient and low toxicity pesticide,fungicide,and herbicide.Therefore,we designed and synthesized different kinds of ?-keto enamines with varies substituent groups and tested their antifungal activities.The conclusions were as follows:1.Twenty six ?-keto enamines with varies substituent groups were prepared(thirteen new compounds),and their structures were characterized by HRMS,1H NMR and 13 C NMR.2.At the concentration of 50 ?g/mL,their antifungal activities were evaluated against twelve phytopathogenic fungi.The results documented that,for each of the test fungi,all the compounds displayed antifungal activities in varying degrees.The antifungal activities of most compounds were same to azoxystrobin or higher than the positive control.Twelve compounds of them showed stronger antifungal activities and their inhibition rates were higher than 80%.3.The range of EC50 values of tested compounds were 2.15–90.7 ?g/mL.EC50 values of most compounds(20/29)were less than those of azoxystrobin,and the most of EC50 values(23/29)were less than 30 ?g/mL.In order to fully reflected the comprehensive toxicity of the compounds,we introduced CA(k/EC50*1000)as the comprehensive activity.It's showed that most compounds(23/29)exhibited better comprehensive activity,whose CA values were above 50.4.Preliminary structure-activity relationships disclosed that the antifungal activities were mainly related to the compounds' structure.For Curvularia lunata,Colletot tichum gloeosporioides,Fusarium graminearum,Alternaria solani and Alternaria alternate,introduction of electron-donating groups on the benzene ring reduced the antifungal activities,on the contrary,introduction of electron-withdrawing groups increased the antifungal activities.When one substituent was introduced to different positions of benzene ring,there would be different antifungal activities against Curvularia lunata,Pyricularia oryzac Cavgra,Colletot tichum gloeosporioides,Fusarium graminearum and Fusarium ox ysporum f.sp.Niveum.For example,the order of antifungal activities of methyl-substituted compounds wasortho>meta>para;the order of antifungal activities of fluoro-substituted compounds was para>meta>ortho.The ?-keto enamines designed by us showed good to excellent antifungal activities.It was worth noting that compounds 9,10,13,14,15 and 17 exhibited broad-spectrum activities,which worth further exploring and developing.This study is the first systematic investigation on the antifungal activities and structure-activity relationships of ?-keto enamines.The results will provide a theoretical base and methodological reference for their future structural optimization and future development of new antifungal agent with ?-keto enamine skeleton.