| Tetramic acid derivatives represent an important class of nitrogen-containing heterocycles with a pyrrolidine-2,4-dione moiety.They can be isolated from many marine and terrestrial lives,and often exhibit a wide range of biological activities including antioxidant,antitumor,antiviral,herbicidal and antifungal activity.Besides,pyridazinones are useful compounds with a broad-spectrum biologically activities.In this paper,substituted phenylhydrazine and pyridazinone moieties were introduced to 3-position of pyrrolidine-2,4-dione respectively to synthesize eleven series of ninety-six novel tetramic acid derivatives.Their herbicidal and fungicidal activities were also evaluated.5-Substitued pyrrolidine-2,4-diones 6 were prepared by the reactions of esterification,acylation,Dieckmann cyclization and decarboxylation starting from glycine,L-alanine and L-isoleucine.4-(2,4-Dioxopyrrolidin-3-ylidene)-4-hydroxybutanoic acids 7 were prepared by acylation of 5-substitued-pyrrolidine-2,4-diones 6 with ethyl succinyl chloride.Ethyl 4-(2,4-dioxopyrrolidin-3-ylidene)-4-hydroxybutanoate 8 were given by esterification.And ethyl 4-(1-acyl-2,4-dioxopyrrolidin-3-ylidene)-4-hydroxybutanoates 9 were obtained by acylation of the compound 8 with different acylchlorides.These intermediates 7,8 and 9 were reacted with substituted phenylhydrazines respectively to give twenty-seven 4-(2,4-dioxopyrrolidin-3-ylidene)-4-(2-(substituted phenyl)hydrazinyl)butanoic acids 10 and twenty-three ethyl 4-(2,4-dioxopyrrolidin-3-ylidene)-4-(2-(substituted phenylhydrazinyl))butanoates 11.Nineteen 3-(6-substituted-4-oxo-1-(substituted phenyl)-1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazol-3-yl)propanoic acids 12 and twenty-seven 3-(1-(substituted phenyl)-6-oxotetrahydropyridazin-3(2H)-ylidene)pyrrolidine-2,4-diones 13 were given by cyclization of the acids 10.Their structures were characterized by IR,1H NMR,13C NMR,MS and elemental analysis.The fungicidal activities of the target compounds againstFusarium graminearum,Botrytis cinerea,Rhizoctonia solani and Colletotrichum capsici were evaluated in vitro by mycelial growth rate method.The results showed that the compounds 10 and 11 exhibited remarkable fungicidal activities against the tested fungi.The EC50 values of some selected compounds were determined.The compound 11s showed highest activity against F.graminearum with the EC50 value of 0.3046 ?g/mL,lower than that of carbendazin(0.4947?g/mL).The compound 10f showed highest activity against B.cinerea with the EC50 value of 0.1796 ?g/mL,lower than that of procymidone(0.3577 ?g/mL).The compound 11c showed highest activity against R.solani with the EC50 value of 0.0424 ?g/mL,lower than that of carbendazin(0.5417 ?g/mL).And the compound 10h showed highest activity against C.capsici with the EC50 value of 0.2164 ?g/mL,lower than that of azoxystrobin(0.3325?g/mL).Moreover,the compounds 12 and 13 were screened for activities in vitro against selected phytopathogenic fungi at the concentration of 50 ?g/mL,more or less,but their fungicidal activities were far lower than those of the compounds 10 and 11.In addition,the 3D-QSAR of the compounds 11 was studied.The CoMFA and CoMSIA were applied to research the relationship between target compound structure and their antifungal activities against B.cinerea.The models indicated that the bulky hydrophobic group with negative charge at phenyl ring played an importan role in improving antifungal activity against B.cinerea.The herbicidal activities of target compounds 13 against Brassia campestris and Echinochloa crusgalli was evaluated by small glass method at the concentration of 100?g/mL.The results showed that some of compounds possessed certain herbicidal activities.Thereinto,the compound 13p showed highest inhibitory rate of 58.1%against the root of E.crusgalli.The compound 13z showed highest inhibitory rate of 57.1%against the stem of E.crusgalli.And the compound 13q showed highest inhibitory rate of 32.5%against the root of B.campestris. |
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