Studies On Synthesis And Antifungal Activities Of Derivatives Of Kakuol With The Terminal Double Bond Of Carbon To Carbon

Kakuol is the main extracted ingredient from Asarum forbesii Maxim and exhibits significant activity,because of its simple structure,great transformation and modification potential,it is possible to become a natural product model for pharmaceutical synthesis research.On the basis of the results of the report in literature and our team's previous research,the analysis demonstrated that these unsaturated ketones as derivatives of kakuol which possessed the structure bearing a terminal C=C bond conjugated to the C=O group exhibited remarkable antifungal activity.34?,?-unsaturated ketones which possessed the terminal C=C bond,including 21compounds have not been reported before in literature,were synthesized and characterized by means of ¹H-NMR,¹³C-NMR and ESI-MS in this paper.By using the mycelium growth rate method,all the target compounds underwent in vitro antifungal activities evaluation against seven plant pathogenic fungi?A.solani,M.grisea,A.alternate,C.lunata,F.solani,F.graminearum,F.oxysporum?.The preliminary analytical data of antifungal activities indicated that most of all the synthesized compounds displayed the obvious growth inhibition activity against all the tested fungi.Among them,target compounds 9c,9g and 10a displayed excellent activity against A.solani with EC₅₀ values of 6.89–12.33?g/mL,much lower than that of thiabendazole(EC₅₀=24.86?g/mL),a commercial fungicide.In addition,compared with the other target compounds,compounds 9c and 10a showed inhibitory activities against all the tested plant pathogenic fungi with inhibition rates over 60%,which exhibited their broader antifungal spectrum.The preliminary SAR analysis demonstrated that the conjugated terminal C=C bond is necessary for improvement of the activity.Generally,both the length of the alkyl chain and substitution patterns and positions of the benzene ring remarkably impact the activity for most of the test fungi.The above research results provide great reference values to further design,synthesis and SAR research of derivatives of kakuol.