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

Paeonol is the main active ingredient in the Chinese medicinal herb peony root bark. To discover biorational natural product-based fungicides, 25 paeonol derivatives (<b>5a</b>-<b>y</b>) 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, <b>5c</b>, <b>5f</b>, <b>5g</b>, <b>5o</b>, <b>5s</b>, and <b>5v</b>, 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, <i>Phytophthora capsici</i> and <i>Fusarium graminearum</i>. Among all tested compounds, (1) nine compounds <b>5b</b>-<b>d</b>, <b>5f</b>, <b>5g</b>, <b>5r</b>, <b>5s</b>, <b>5u</b>, <b>5w</b> displayed promising anti-oomycete against <i>P. capsici</i>, with EC₅₀ values ranging from 22.1 to 34.5 mg/L, and the protective effect of the target compounds against <i>P. capsici</i> <i>in vivo</i> further confirmed the above results. (2) Six compounds <b>5g</b>, <b>5k</b>, <b>5m</b>, <b>5t</b>, <b>5w</b>, <b>5x</b> displayed promising antifungal against <i>F. graminearum</i>, 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.