Synthesis And Biological Activities Of Novel3-Substituted Tetramic Acid Derivatives

The tetramic acids compounds isolated from natural products usually exhibit some biological activities including antiviral, antibiotic, antifungal cytotoxic, antitumour and herbicidal activity. It was found that these compounds contain important heterocyclic building blocks: tetramic acid (pyrrolidine-2,4-dione). Thus, many scholars used it as a key structural unit, designed and synthesized a large number of tetramic acid derivatives and have seached many biologically active compounds, so it have attracted more and more attention. In this article,1-position,3-position and5-position of tetranic acid were modified by four different routes to design and synthesize four series of novel tetramic acid derivatives containing the group of aromatic base, pyridine, or cyanogroup. The biological activities concluding the herbicidal, fungicidal and insecticidal activities of all the four series title compounds were evaluated.Firstly,1-acetyl-3-H tetramic acids were synthesized by methyl2-aminoacetate through four steps, then they were reacted with (p-nitro) benzyl chloride via alkylation to give five1-acetyl-3-(un) pyrrolidine-2,4-diones6a-f. At the same time, they were reacted with bromo (4-methoxy/F/Cl) acetophenone to obtain tweleve1-acetyl-3-(2-oxo-2-phenylethyl)pyrrolidine-2-ones8a-I, and reacted with2-acetyl pyridine bromide to get three1-acetyl-3-(2-oxo-2-(pyridine-2-base)Ethyl)pyrrolidine-2,4-dione derivatives10a-c. p-Methyl) amiline and isopropylamine was reacted with ethyl bromo-acetate to give the N-substituted glycine ethyl ester, then by the reactions of dehydration condensation, solid phase synthesis Claisen cyclization three kinds of1-aromatic (alkyl)-based-3-cyano-4-hydroxy-pyrrolo-diketone derivatives12a-c were synthesized. All the title compounds were confirmed by IR,1H NMR, MS and elemental analysis.The herbicidal activities of all the title compounds were evaluated. At the concentration of100μg/mL, some of the title compounds exhibited certain herbicidal activities, in which there were nine compounds6e、6f and8c、8d、8e、8f、8g、8h and81 showed inhibitory activity from40.6%to63.8%against the root of the Echinochloa crusgalli, the compound8f showed the highest activity of63.8%. The title compounds inhibited low activity against the root of Brassica campestral L except8f, which inhibitory rate was49.2%. Futhermore, the inhibitory rates of all title compounds against the bud of the E. crusgalli were less than40%except the compunds6e and8g, which inhibitory rates was47.4%and49.0%respectively.At the same time, the fungicidal activities of all the title compounds were evaluated against Fusarium graminearum, Rhizoctonia cerealis and Botrytis cinera. At the concentration of100μg/mL, there were four target compounds exhibited certain fungicidal activity, higher than the compound TeA. The compounds6b,6d and8c showed good activity against B. cinera, their inhibitory rates were over50%, and6d reached67.7%. Moreover, inhibitory rates of the compounds8b and8c were more than40%against F. graminearum, in which8c reached52.4%. All the title compounds showed low activity against R. cerealis, the inhibitory rates were no more than30%.