Design, synthesis, anti-oomycete, anti-fungal, and nematicidal activities of novel eugenol acyloxy/sulfonyloxy derivatives containing an isoxazoline ring.

Abstract

Eugenol is the main component of clove basil oil, mainly extracted from Syzygium aromaticum. In order to discover biorational natural product-based pesticides, 24 novel eugenol acyloxy/sulfonyloxy derivatives (3a-q and 4d,f,j-n) containing an isoxazoline ring were designed and synthesized by simultaneously introducing isoxazoline and acyloxy/sulfonyloxy pharmacophores, and their structures were characterized by 1H NMR, 13C NMR, and HRMS. The single-crystal X-ray diffraction of two titled compounds 3k and 4l usefully established the 5-substituted regiochemistry. Furthermore, we screened the bioactivities of these compounds as anti-oomycete, anti-fungal, and nematicidal agents. Three serious agricultural diseases that have a devastating impact on agricultural production were selected as the test subjects, namely Phytophthora capsici, Fusarium graminearum, and Heterodera glycines. Amongst evaluated derivatives, (1) Compounds 2 and 4f displayed potential anti-oomycete against the plant pathogen P. capsici, with EC50 values of 40.20 and 71.43 mg/L, respectively. (2) Compounds 2 and 4d also exhibited potential anti-fungal against the plant pathogen F. graminearum, with EC50 values of 49.19 and 61.29 mg/L, respectively. (3) Seven compounds (3a, 3i, 3l, 3n, and 4l-n) showed significant nematicidal activity against H. glycines, with LC50 values below 20 mg/L. Especially for compound 3a (R1 = CF3), its LC50 was 11.38 mg/L. It has been proven that the simultaneous introduction of isoxazoline ring and acyloxy/sulfonyloxy pharmacophores into the structural skeleton of eugenol (1) has been successful in enhancing its nematicidal activity.