Synthesis And Antifungal Activities Of The Coumarin Ring-opening Derivatives

Because of the repeated,excessive and improper usage of pesticides,the existing pesticides are facing very serious resistance problems.As the agricultural diseases usually caused by fungi,bacteria and viruses,which display the characteristics of reproductive cycle short,bursty,propagation speed fast,the crop growth is inhibited,product deterioration or reduced,and bring a serious threat to the national food security and the food quality for human being.Therefore,it is urgent to study and develop new pesticide varieties with new skeleton structure and novel mechanism to meet the needs of agricultural production.Because of its rich variety of natural products,a variety of biological activity,a unique mechanism has become an important source to develop new pesticides.The natural products coumarin and methoxyacrylate derivatives have unique fungicidal activity,which gives us cue during the searching of lead structure for novel fungicide development.The coumarin compounds can be regarded as O-hydroxyphenyl acrylate lactone,its ring-opening product contain a substructural unit of strobilurin,and many strobilurin compounds have been proved to be very efficient as fungicide.This thesis aimed to furo[3,2-c]coumarin as a precursor,synthesized a series of ring-opening product by hydrolysis,etherification and esterification,and evaluated for their antifungal activities,to search for the lead structures with high antifungal activity.In this thesis,we employed different substituted phenols and Michaelis acid as the raw materials to generate three kinds of 4-hydroxycoumarin derivatives,and eight quinoline[4,3-b]coumarins were synthesized from 4-hydroxycoumarin derivatives and different amines.4-hydroxycoumarin and a-haloketone via the alkylation/molecular aldol reaction to generate 11 kinds of furan[3,2-c]coumarin,and then use furan[3,2-c]coumarin as an intermediate,to give a compound containing the substructure of the strobilurin group by hydrolysis and methylation.The structures of the all target compounds have been confirmed by IR,NMR and HRMS.All ring-opening derivatives were evaluated in vitro for their antifungal activities against Botrytis cinrea,Cucumber anthrax,Alternaria solani,Gibberella zeae,Rhizoctonia solani and Alternaria mali.The results of preliminary bioassay indicated that the synthesized coumarin derivatives exhibited different levels of antifungal activities to the six tested pathogens.Some of these compounds showed better antifungal activities against Rhizoctonia solani and Botrytis cinerea,but less effective to the other four kinds of fungi,or even totally inactive.The inhibition rate of compound 8b on Rhizoctonia solani was 81%,and the inhibition rate of compound 12 on Rhizoctonia solani and Cucumber anthrax were 67.2%and 84.2%.The primary results showed positive antifungal activity,which are worthy of further research.