Synthesis And Biological Activities Of Novel Tetramic Acid Derivatives Incorporating A Moiety Of Hydrazino Pyrimidine

Tetramic acid derivations is an important class of heterocyclic compounds, they can be extracted from some natural products, and often show a variety of bioactivities. Tenuzonic acid (TeA) was a natural tetramic acid, which can be isolated from the culture filtrate of Alternaria alternate. It was found to exhibit bactericidal, herbicidal and antitumor activity. Pyrimidine derivalives have the features of efficiency, broad spectrum, low toxicity and residue, They have been applied as fungicides, herbicides and pesticides. In this paper, natural tetramic acid compounds were acted as the leading molecule. The structures of tetramic acids were modified in3-and5-position, A moiety pyrimidine was introduced to3-position of acetyl in tetramic acid through the group hydrazine, and two series of new tetramic acid derivatives containing pyrimidine were designed and synthesized. The biological activities concluding the herbicidal, fungicidal and insecticidal activities of all the title compounds were evaluated.Firstly, four tetramic acids were synthesized with methyl2-aminoacetate and other raw materials by esterification, acetylation, cyclization and acidification. Then other four N-substituted tetramic acids were synthesized with substitute amines by substitution, acidification, acylation and cyclization. After2-hydrazino-4,6-dimethoxy pyrimidine,4-hydrazino-6-methyl pyrimidin-2-ylamine and4,6-dimethyl pyrimidine-2-yl-thio acetyl hydrazine were synthesized by thiourea or guanidine nitrate through cyclization, substitution and acidification. They were introduced to3-position of tetramic acid to synthesize seven1-(2,4-dioxo-pyrrolidin-3-ylidene)ethyl-4,6-dimethyl pyrimidine-2-ylmethyl hydrazide derivatives hydrazone and thirteen3-hydrazino pyrimidine ethylidene pyrrolidine-2,4-dione derivatives. The structures of these twenty title compounds were characterized by IR,1H NMR, MS and elemental analysis.The herbicidal activities of the title compounds were determined with Brassica campestris and Echinochloa crusgalli. At the concentration of100μg/mL, Some title compounds exhibited certain herbicidal activities. The inhibitory rates of the compounds17c,22b,22c,22d and26f were43.9%to64.4%against the root of B. campestris. All the compounds have low inhibitory rate against the root and the bud of the E. crusgalli.The assay of fungicidal activities indicated most title compounds exhibited wead fungicidal activities against Rhizoctonia cerealis, Botrytis cinera and Fusarium gramineaum at a concentration of100μg/mL. Only four compounds17c,17d,22f and22g showed some inhibitory activity against tenuazonic acid, their inhibitory rates were about40%.