1,5 - Heterocyclic -1,4 - Pentadiene -3 - Ketones, Synthesis And Biological Activity

As Curcumin the(2E,5E)-hepta-2,5-dien-4-one have a variety of biological activity,such as anti-cancer,anti-inflammatory,anti-oxidation,anti-HIV and so on.Due to these properties,it has gained enormous importance in drug development.In addition,pyridyl and pyrazol compounds have attracted much attation,because of their high efficiency,low toxicity and compatiblity to the environment for research application.We have introduced oxime ester units to curcumin derivatives,and synthesized compounds of 1,5-diphenyl-1,4-pentadiene-3-ketoxime ester with certain antifungal activity.Some compounds have the similar antifungal activities compared with Hymexazol on Gibberella zeae at the concentration of 50 mg·L^-1.In order to find novel and highly biologically active curcumin derivatives,we designed and synthesized two series of new compounds by considering the principle of combination of bioactivity substructure and bioisoteric relationship.There are three 1,5-dipyridyl(substited) -penta-1,4-dien-3-ones(Ⅰ) and thirteen 1,5-dipyrazolyl(substited)-penta-1,4-dien-3-one(Ⅱ) respectively.Structures of all compounds were identified by ¹H NMR,¹³C NMR,IR and elemental analysis.To optimize the reactions,the synthesis ofⅠandⅡwere carried out under several conditions. The more viable condition was achieved in dichloromethane and 10%NaOH.Compounds(Ⅰ) were synthesized in low yields(14.7～27.3%) at room temperature for 1～2 days.However,when the solvent was changed to ethanol,using similar methodology,compounds(Ⅱ) with yields between 29.0～84.6%were obtained.The yield was however influenced by the steric bulk in the molecule.These two methods had several advantages such as mild conditions,green technology and fewer byproducts.However,the former series afforded low yield while the later one was influenced by steric hindrance.The title compounds were tested against pathogenic fungi and Tobacco mosaic virus(TMV). The result of bioassay showed that the antifungal activity of all compounds was far less than the Hymexazol which served as the control.Some compounds of(Ⅱ) showed moderate anti-TMV activity,compared with Ningnanmycin.In terms of protective effect,compoundⅡk had the best anti-TMV activity which accounted for 50.1%,although it was lower than Ningnanmycin (66.5%).