Synthesis And Antifungal Activities Of Coumarin-3-carboxamides/Hydrazides

Plant diseases cause severe crop yield reduction and result in significant economic losses every year.How to control them in modern agriculture is still a big challenge.Although many chemical agents were developed and applied to control these diseases,most of them cannot fully protect the crops or completely cure the crops’ tissues from fungal infection under field conditions.Because of richness in species,diverse biological activities and unique mechanisms,the botanical fungicide is one of the plant protection alternatives,generally considered safe to the environment and health.The development of botanical fungicide is important.The natural product coumarins and amide fungicides have unique fungicidal activity,which gives us cue during the searching of lead structure for designing novel fungicides.Based on our previous work on structural modification and bioscreening of coumarin based fungicides,we envisioned that the combination of the coumarin framework with carboxamides/hydrazide units may afford the desired high performance fungicides.We thus designed and synthesized a series of coumarin amides/hydrazides.The target compounds were evaluated in vitro for their antifungal activity against some common agricultural phytopathogeic fungi.In this thesis,we employed different substituted benzaldehyde and Michaelis acid as the raw materials to generate two kinds of coumarin-3-carboxylic acid,and 37 coumarin carboxamide/hydrazide compounds were synthesized from coumarin-3-carboxylic acid and different amines/phenylhydrazines.The target compounds were confirmed by IR,NMR and HRMS.The target compounds were evaluated against six phytopathogenic fungi.For the purposes of the structure-activity relationship analysis,the antifungal activity of all target compounds were compared with the positive controls,including Osthole,and Boscalid,a broad spectrum fungicide used for protecting plants and food crops from fungal diseases.It was determined that the EC50 values of compounds 4a,4d,4e and 4f were as low as 1.8034μg/mL,2.4977 μg/mL,2.2468 μg/mL and 2.0961 μg/mL,respectively,against Rhizoctorzia solani,which suggested that they exhibited much more effective activity than the control Boscalid.Meanwhile,compounds 4a and 4e were equivalent to Boscalid against Botrytis cinerea.Further structural optimization of coumarin analogues is well under way,aiming to prepare analogues with improved antifungal activity.