Design, synthesis, and anti‐oomycete, antifungal and nematicidal activities of novel paeonol ether derivatives containing isoxazoline/isoxazole moiety

Abstract BACKGROUND Paeonol is the main active ingredient in root bark of Paeonia suffruticosa , with broad‐spectrum bioactivity. Additionally, isoxazoline/isoxazole is becoming the core skeleton for creating efficient and green pesticides today owing to its unique structural advantages and bioactivity potential. RESULTS In order to discover biorational natural product‐based pesticides, 26 novel paeonol ether derivatives ( 3a–q and 5a , c , d , f–j , m ) were synthesized by ingeniously introducing an isoxazoline/isoxazole ring, and their structures were well‐characterized by proton and carbon nuclear magnetic resonance (NMR), and high‐resolution mass spectrometry (HRMS). The stereochemical configurations of five target compounds 3a , 3g , 3j , 5a and 5h were unambiguously subjected to single‐crystal X‐ray diffraction (XRD) analysis. Furthermore, we screened the bioactivities of these compounds as anti‐oomycete, antifungal and nematicidal agents. Amongst evaluated derivatives, (1) compounds 2 and 4 displayed promising anti‐oomycete against the plant pathogen Phytophthora capsici , with median effective concentration (EC 50 )values of 28.51 and 42.52 mg L –1 , respectively. (2) Compounds 2 and 4 also exhibited excellent antifungal activity against the plant pathogen Fusarium graminearum , with EC 50 values of 29.11 and 31.23 mg L –1 , respectively. (3) Nine compounds ( 3f–h , j , o–q and 5f , g ) showed significant nematicidal activity against Heterodera glycines , with LC 50 values all <30.00 mg L –1 . Especially for compound 3g , its LC 50 value is the smallest, at 21.78 mg L –1 . CONCLUSION The research results indicate that, on the one hand, introducing an allyl or propargyl group at the hydroxyl position of paeonol can effectively enhance its anti‐oomycete and antifungal activities. On the other hand, further introduction of an isoxazoline/isoxazole ring into the structural skeleton of paeonol can significantly enhance its nematicidal activity. © 2026 Society of Chemical Industry.