Design and Synthesis of Structurally Novel Acridospiroisoxazole Derivatives and Their Antifungal Activity Study

ABSTRACT The persistent threat posed by phytopathogenic fungi to agricultural systems underscores the critical need for novel fungicides. Here, we synthesized and characterized a series of novel acridospiroisoxazole derivatives ( H1 – H36 ) using 1 H/ 13 C NMR and mass spectrometry. The absolute configuration of compound H23 was confirmed using single‐crystal x‐ray diffraction analysis. Integrated in vitro evaluations—including microdilution assays, mycelial growth inhibition, and cellular viability assessments—demonstrated the superior antifungal potency of H35 against Botrytis cinerea . At 25 µg/mL, H35 achieved 93.41 ± 1.4% mycelial suppression, doubling the efficacy of carbendazim (46.90 ± 2.6%) under identical conditions. H35 (EC 50 : 5.0 ± 0.4 µg/mL) exhibited 2.3‐fold greater potency compared to chlorothalonil. In vivo studies demonstrated that H35 had both protective and therapeutic efficacy on corn leaves, with 80.00% prevention and 83.90% cure rates observed at 100 µg/mL. These findings establish the acridospiroisoxazole scaffold as a promising candidate for the development of antifungal agents for crop protection.