Synthesis And Biological Activities Of Strobilurin Derivatives Containing The Moiety Tetramic Acid

The strobilurin fungicides are one of the most important classes of agricultural fungicides in the protection and control of plant disease caused by Oomycete, Aseomycete and Basidiomycete pathogen. The strobilurin derivatives have been one of hot spots of fungicide developing because of their unique mechanism of action, high activity, wide fungicidal spectrum, lower toxicity and environmentally benign characteristics. Up to now, more than ten strobilurin fungicides have been commercialized. Tetramic acids widely present in the natural products, they usually exhibit a broad range of biological activities, including antitumor, antiviral, antibacterial and herbicidal activities. This attract the interest of the majority of chemists, biologists and physicians, a lot of tetramic acid derivatives were synthesized and reported, many of them exhibited good biological activities. In order to find novel lead compounds with better biological activities, tetramic acids were connected with pharmacophore structural unit of strobilurin fungicides through the group of methylene, oxime ether, hydrazone or hydrazine by the means of the active structural stitching. Four series of twenty four novel strobilurin derivatives containing the moiety tetramic acid were synthesized, and their herbicidal and fungicidal activities were also evaluated.First, the key intermediate (E)-methyl-2-(2-bromomethyl)phenyl-3-methoxyacrylate was synthesized by o-tolylacetic acid, four 1-acetyl-5-alkyl-tetramic acids and six 3-(1-hydroxyethlidene)-5-alkyl-tetramic acids were synthesized by natural amino acids, four 1-substituted-3-(1-hydroxyethlidene)tetramic acids were synthesized by substituted anilines and ethyl bromoacetate. Then, the tetramic acids were reacted with (E)-3-methyl-2-(2-(bromomethyl)phenyl methoxyacrylate to give three series of methoxyacrylate derivatives of tetramic acid, including four (â… ) bridged with methylene, four (â…¡) bridged with oxime ether and ten (â…¢) bridged with hydrazone, and a series of six dihydroisoquinolin derivatives of tetramic acid (â…£) bridged with aminoethylidene. The structures of these title compounds were confirmed by IR, 1H NMR, MS and elemental analysis.The fungicidal activities of all title compounds against Rhizoctonia solani, Botrytis cinerea, Fusarium gramineaum and Colletotrichum capsici were evaluated by mycelial growth rate method. The antifungal bioassay results demonstrated that these title compounds showed different fungicidal activities at the concentration of 100 mg/L. The compounds I exhibited lower fungicidal activites against above four fungi, the inhibitory rates were under 40%. The compounds â…¡ exhibited certain fungicidal activites against Rhizoctonia solani with the inhibitory rates of 49.8%-65.2%. The compounds â…¢ showed highest inhibition activities, the inhibitory rates of compounds â…¢c-â…¢g against Rhizoctonia solani and Fusarium gramineaum were 68.4%-76.3% and 50.9%-62.2%, respectively. The compounds â…£ exhibited certain fungicidal activites against Rhizoctonia solani, the inhibitory rates of the compounds â…£c-â…£f were above 50%.The herbicidal activities of all title compounds against Echinochloa crusgalli and Brassica napus were evaluated using the plate procedure. The result showed that the target compounds did not exhibited obviously herbicidal activity at the concentration of 100 mg/L, only two compounds showed certain herbicidal activity, the compound â…  a showed a inhibitory rate of 57.5% against the root of Brassica napus, and the compound â…¡ c showed a inhibitory rate of 57.5% against the stalk of Echinochloa crusgalli.