Synthesis Of Carabrone Hydrazone Derivatives And Research On Their Antifungal Activities

Recently,biogenic pesticide is a focus on the research and development about new pesticide.As an important branch of which,searching lead compounds from plants and structural modification on them is an important way to develop plant source biological fungicide.On the research about antifungal activities of Carpesium macrocephalum,Research&Development Center of Biorational Pesticide attached to Northwest A&F University found that carabrone isolated from the fruits of Carpesium macrocephalum,a known sesquiterpene containning cyclopropane and sesquiterpene lactone moieties,exhibited high and a relatively broad spectrum antifungal activities.It was also found that the groups of α-methylene-γ-lactone and the double bonds between C-11 and C-13 were the main antifungal activity groups on the subsequent research,meantime,the change of C-4 site showed signally difference on antifungal activities about their derivatives.In order to gain two to three derivatives about carabrone which showed higher antifungal activities and give a guideline for further research,31 carabrone hydrazone derivatives were synthesized and their antifungal activities were tested in vitro and in vivo.The analysis on the relationship between structures and antifungal activeties of carabrone hydrazone derivatives and comparation with carabrone ester derivatives and carabrone oximesate derivatives were also taken.The main results showed as follows:31 carabrone hydrazone derivatives were synthesized by structure modification on C-4 site of carabrone,such as carabryl trichlorophenyl hydrazone,carabryl 4-trifluoromethyl phenyl hydrazone,carabryl 2,3,5,6-tetrafluorophenyl hydrazone,carabryl isoniazone and so on.All these derivatives were characterized with 1H NMR,13C NMR,DEPT135,HSQC,HMBC and HR-ESI-MS.Besides,query through the CA system,the results showed that 30 of them were new compounds.Most of these hydrazone derivatives showed higher antifungal activities than that of carabrone,not only in vitro but also in vivo.Among which,27 exhibited higher antifungal activities than carabrone against C.Lagenarium in the spore germination assay.The EC50 value of carabryl 3-methoxy phenyl hydrazone was 0.77 mg/L,whose antifungal activity against C.Lagenarium was nearly as high as that of chlorothalonil,a commercial fungicide used as positive control.26 derivatives showed higher antifungal activities than carabrone against B.Cinerea in the spore germination assay,among which carabryl trichlorophenyl hydrazone(EC50 1.51 mg/L),carabryl 4-trifluoromethyl phenyl hydrazone(EC50 1.99 mg/L),carabryl 2,3,5,6-tetrafluorophenyl hydrazone(EC50 0.77 mg/L)exhibited septuple higher antifungal activity than carabrone.The protective effect of carabrone derivatives against B.cinerea showed that 23 derivatives had higher protective effect than carabrone.Besides,all the 8 derivatives tested in live plant showed certain protective effect and curative effect against Erysiphe graminis.From the research of the relationship between the structure and antifungal activity,it can be found that when introduced halogen especially chlorine and bromine atoms or cyano and other unsaturated group,the antifungal activities of these derivatives can be significantly improved.When the two kinds of groups were introduced simultaneously,their antifungal activities can be improved more significantly.Since carabryl trichlorophenyl hydrazone,carabryl 4-trifluoromethyl phenyl hydrazone and carabryl 2,3,5,6-tetrafluorophenyl hydrazone showed higher antifungal activities not only in vitro but also in vivo,they may have more potential to development as new fungicide for sustainable agricultural production.In conclusion:The substituent group on C-4 position had important effect on the activity of carabrone and its derivatives.When changed C-4 position from carbonyl to C=N groups,their antifungal activity improved significantly.In addition,it was found that when introduced halogen especially chlorine and bromine atoms or cyano and other unsaturated group,the antifungal activities of these derivatives can be significantly improved.Besides,carabryl trichlorophenyl hydrazone,carabryl 4-trifluoromethyl phenyl hydrazone and carabryl 2,3,5,6-tetrafluorophenyl hydrazone have the potential to further research and development.