Design, Synthesis, and Anti-Oomycete and Antifungal Activities of Novel Paeonol Derivatives Containing a Pyrazole Ring

Abstract

Paeonol is the main active ingredient in the Chinese medicinal herb peony root bark. To discover biorational natural product-based fungicides, 25 paeonol derivatives (5a–y) containing a pyrazole ring were designed and synthesized by ingeniously introducing a pyrazole five-membered heterocyclic ring, and their structures were well characterized by ¹H NMR, ¹³C NMR, high-resolution mass spectrometer (HRMS), and m.p. The stereochemical configurations of six target compounds, 5c, 5f, 5g, 5o, 5s, and 5v, were unambiguously subjected to single-crystal X-ray diffraction. Furthermore, we evaluated the bioactivities of these target compounds as anti-oomycete and antifungal agents against two serious agricultural diseases, Phytophthora capsici and Fusarium graminearum. Among all tested compounds, (1) nine compounds 5b–d, 5f, 5g, 5r, 5s, 5u, 5w displayed promising anti-oomycete against P. capsici, with EC₅₀ values ranging from 22.1 to 34.5 mg/L, and the protective effect of the target compounds against P. capsici in vivo further confirmed the above results. (2) Six compounds 5g, 5k, 5m, 5t, 5w, 5x displayed promising antifungal against F. graminearum, with EC₅₀ values ranging from 38.2 to 86.0 mg/L. Moreover, some interesting results of structure–activity relationships were also observed. The results of this study pave the way for further design, synthesis, and development of paeonol derivatives as potential botanical anti-oomycete and antifungal agents in crop protection.