Synthesis And Antifungal Activities Of Substituted Aromatic Aldehyde Thiosemicarbazone Derivatives(Ⅱ)

Thiosemicarbazones have attracted much attention due to their strong coordination ability and extensive biological properties such as insecticidal,bactericidal,antiviral and antitumor activities.Therefore,researche on the synthesis and bioactivities of these compounds is still one of the focuses in the field of medicinal chemistry.In our previous study,20 substituted aldehyde thiosemicarbazones were synthesized as antifungal agents,and it found that introduction of a double bond between aromatic ring and aldehyde group could improve the antifungal activities.Based on these results,a series of substituted aromatic aldehyde thiosemicarbazones（including aromatic allyl aldehyde thiosemicarbazones）were designed and synthesized,and their antifungal activities were evaluated in order to find potential antifungal agents.The main results were as follows:1.Target compounds 7d and 7i were directly obtained by condensation of thiosemicarbazide with substituted aromatic aldehydes（1d and 1i）.Aromatic allyl aldehydes（5a-e,g,h）were prepared from aromatic aldehydes（1a-e,g,h）by Perkin reaction,esterification,reduction,and oxidation reactions;then target compounds 8a-e,g,h were further obtained by condensation of thiosemicarbazide with 5a-e,g,h.37 compounds（including 9 target compounds,and 28 intermediates）were prepared.The target compounds were identified by IR,melting point and ¹H NMR.Especially the steric structure of compound 8c was further confirmed by X-ray diffraction analysis.2.At the concentration of 100μg/m L,19 target compounds（including the previous 10compounds in our lab）against six phytopathogenic fungi,such as Valsa mali,Fusarium graminearum,Fusarium solani,Botrytis cinerea,Alternaria alternate and Curvularia lunata.The results showed that compounds 8a-8c、7a-7c and 8e had good inhibitory activities against six pathogenic fungi,and their inhibitory rates were all greater than 85%.3.Further bioassay results showed that compounds 8a-h exhibited higher inhibitory activities than those of 7a-h.In particular,compound 8b showed the highest inhibitory activity against three pathogenic fungi,such as F.graminearum、A.alternate and B.cinerea,and the corresponding EC₅₀ values were 6.30,1.61 and 2.05μg/m L respectively;the inhibitory activities of 7a-h and 8a-h were higher than those of the positive control carbendazim against A.alternate and C.lunata.4.The control efficiency of compounds 7b、8b、7e and 8e against B.cinerea on tomato at100μg/m L were investigated.The results showed that the protective effect was little higher than that of therapeutical effect,and the control efficiency of 8b and 8e were better than that of 7b and 7e.5.Based on QSAR,it found that the activities of compounds containing unsubstituted aromatic ring were better than those containing unsubstituted heterocyclic ring（e.g.,8a Vs.8e and 8f）;the activities of compounds containing substituted aromatic ring were better than those containing unsubstituted aromatic ring（e.g.,8b and 8h Vs.8a）;the activities of compounds containing aromatic allyl aldehydes were better than those containing aromatic aldehydes（e.g.,8a-h Vs.7a-h）.