Non-food bioactive products: Design, synthesis, anti-oomycete, and anti-fungal activities of novel paeonol oxime ether derivatives containing isoxazoline/isoxazole fragments

21 novel hybrid derivatives of paeonol isoxazoline/isoxazole were designed and synthesized. • The stereochemical configurations of target compounds 7 h and 7 n were determined by single-crystal X-ray diffraction, which confirmed that the E configurations of oxime ether fragments. • The discovery of a novel structural framework with good inhibitory activity against plant pathogenic oomycetes provides a new research direction for the application of paeonol in the design of anti-oomycete agents. • Some interesting results of structure-activity relationships were observed. Paeonol is the main active ingredient in the Chinese medicinal herb peony root bark. To discover biorational natural product-based fungicides, twenty-one novel paeonol oxime ether derivatives ( 6a-q and 7a,d,h,n ) containing an isoxazoline/isoxazole ring were designed and synthesized by ingeniously introducing an isoxazoline/isoxazole five membered heterocyclic ring, and their structures were well characterized by 1 H NMR, 13 C NMR, and HRMS. The stereochemical configurations of two title compounds 7 h , and 7 n were determined by single-crystal X-ray diffraction. Particularly, the E configurations of oxime ether fragments at the carbonyl position of title compounds were undoubtedly determined by X-ray crystallography. The bioactivities of these title compounds as anti-fungal and anti-oomycete agents were evaluated. Two pathogenic microorganisms that have a devastating impact on agricultural production were selected as the test subjects, namely Fusarium graminearum and Phytophthora capsici . Amongst evaluated compounds, 1) Compound 6o exhibited good anti-oomycete against the plant pathogen P. capsici , with an EC 50 value of 29.2 mg/L, and the protective effect (pepper leaves and plants) of this compound against P. capsici in vivo further confirmed the above result. 2) Three compounds 6i , 6j , and 6o displayed moderate anti-fungal activities against the plant pathogen F. graminearum . 3) Introducing an isoxazole ring into the structural skeleton of paeonol oxime ether derivatives was beneficial for enhancing their anti-oomycete activity, while introducing an isoxazoline ring was beneficial for enhancing their anti-fungal activity. Some interesting results of structure-activity relationships were also observed. This study provides valuable design ideas and theoretical data for further exploring the preparation and pesticide bioactivity of paeonol oxime ether derivatives. Download: Download high-res image (251KB) Download: Download full-size image