Synthesis And Biological Activities Of1-[1-(Pyrrolin-2-one-3-yl)Ethylidene]-4-alkyl Semicarbazides

Tenuazonic acid (TeA), named3-acetyl-4-hydroxy-5-sec-butylpyrrolin-2-one, was a secondary metabolite of Alternaria alternate. It was found that TeA exhibited medical activities against cancer, tumor and bacteria. In recent years, it was also found that TeA presented a certain degree of herbicidal and insecticidal activities. The compounds possessing the moiety of semicarbazone which displayed the activities of antifungal, anticancer and anti-HIV. In order to find novel and low-toxic compounds with better biological activities, thirty one1-[1-(pyrrolin-2-one-3-yl)ethylidene]-4-alkylsemicarbazides were designed and synthesized using TeA as leading compound.Firstly,3aryl ureas were synthesized using aryl amine and potassium cyanate as starting materials, which were reacted with hydrazine hydrate to give aryl semicarbazides respectively. Then, aryl semicarbazides were reacted with3-acetyl-4-hydroxylpyrrolin-2-ones to give twenty one semicarbazone derivatives respectively1-[1-(pyrrolin-2-one-3-yl)ethylidene]-4-arylsemicarbazides4. Furthermore, N-alkyl phenyl carbamates were synthesized using alkyl amine and phenyl chloroformate as starting material, which were reacted with hydrazine hydrate to give alkyl semicarbazides, then they were reacted with3-acetyl-4-hydroxylpyrrolin-2-ones to give ten semicarbazone derivatives1-[1-(pyrrolin-2-one-3-yl)ethylidene]-4-alkylsemicarbazides5respectively. The structures of all title compounds were confirmed by1H NMR, MS, IR spectra and elemental analysis.The herbicidal activities of the title compounds were evaluated by the Petri dish test method with Brassica napus (as a sample of annual dicotyledonous plant) and Echinochloa crusgalli (as a sample of annual monocotyledonous plant). The antifungal activities were tested by the mycelial growth Petri dish test method against3kinds of plant fungi Rhizoctonia cerealis, Colletotrichum orbiculare and Fusarium graminearum. At concentration of100μg/mL, the tested results indicated that all the compounds exhibited certain herbicidal activity and weak antifungal activity. The inhibitive rates of the compound4m,4n,4o,4r,4s and4u against root of Brassica napus, were67%to86%, the EC50values were13.37μg/mL to55.89μg/mL. And the inhibitive rates of4q,4r and4s against the root of Echinochloa crusgalli, were67%to86%, the EC50values were35.12μg/mLto87.84μg/mL.The DFT-B3LYP methods with6-31G*basis set was used to optimize the geometry structure of title compounds by Gaussian03. The structure activity relationships of selected22title compounds were studied based on the frontier molecular orbital levels and charges distribution. When R1was alkyl or aryl, the herbicidal activities of the corresponding title compounds against the root of Brassica napus were better than that of the unsubstituted compounds. R2had no significant impact to the activities. When R3was aryl, the activities were higher than alkyl.