Design, synthesis and herbicidal activity of 5-cyclopropyl-N-phenylisoxazole-4-carboxamides

Abstract

4-Hydroxyphenylpyruvate dioxygenase (HPPD) inhibitors are a type of important herbicides, and they cause bleaching symptoms by indirectly inhibiting the biosynthesis of carotenoids. In this study, thirty isoxazolamide compounds were designed based on the structure of Isoxaflutole, a commercial HPPD herbicide. Starting from 1,1-dimethoxy-N,N-dimethyl-methanamine and methyl 3-cyclopropyl-3-oxo-propanoate, the title compounds were readily prepared and their structures were determined by MS and NMR analysis. In Petri dish tests, most of the title compounds showed strong inhibitory effect on the root and stem growth of both monocotyledon and dicotyledon weeds, and it was clearly different from the symptoms caused by HPPD inhibitors. However, several of them, especially I-17, showed characteristic bleaching symptoms of HPPD herbicides and good post-emergence herbicidal activity on tested weeds in glasshouse assay. These compounds are prodrugs, and compounds undergo conversion to the active entity diketonitrile (DKN) in plant and soil. The result of molecular docking analysis revealed that the DKN moiety of I-17 excellently binds to the active sites of HPPD. The 1,3-diketone can form bidentate interaction with FeII, and the benzene ring can form π-π interaction with Phe 360 and Phe 403. These results indicated that the title compounds bears other herbicidal mechanism except for HPPD inhibitor. Therefore, a lead compound for the discovery of novel multi-target herbicides is provided.