Novel Dioxolane Ring Compounds for the Management of Phytopathogen Diseases as Ergosterol Biosynthesis Inhibitors: Synthesis, Biological Activities, and Molecular Docking.

Thirty novel dioxolane ring compounds were designed and synthesized. Their chemical structures were confirmed by H NMR, HRMS, and single crystal X-ray diffraction analysis. Bioassays indicated that these dioxolane ring derivatives exhibited excellent fungicidal activity against , , , , , , and herbicidal activity against lettuce (), bentgrass (), and duckweed (). Among these compounds, 1-((2-(4-chlorophenyl)-5-methyl-1,3-dioxan-2-yl)methyl)-1-1,2,4-triazole (), 1-(((4)-2-(4-chlorophenyl)-4-methyl-1,3-dioxolan-2-yl)methyl)-1-1,2,4-triazole (), 1-((5-methyl-2-(4-(trifluoromethyl)phenyl)-1,3-dioxan-2-yl)methyl)-1-1,2,4-triazole (), and 1-((2-(4-fluorophenyl)-1,3-dioxolan-2-yl)methyl)-1-1,2,4-triazole () had broad spectrum fungicidal and herbicidal activity. The IC values against duckweed were 20.5 ± 9.0, 14.2 ± 6.7, 24.0 ± 11.0, 8.7 ± 3.5, and 8.0 ± 3.1 μM for , , , and and the positive control difenoconazole, respectively. The EC values were 7.31 ± 0.67, 9.74 ± 0.83, 17.32 ± 1.23, 11.96 ± 0.98, and 8.93 ± 0.91 mg/L for , , , and and the positive control difenoconazole against the plant pathogen , respectively. Germination experiments with seeds indicated that the target of these dioxolane ring compounds in plants is brassinosteroid biosynthesis. Molecular simulation docking results of compound and difenoconazole with fungal CYP51 P450 confirmed that they both inhibit this enzyme involved in ergosterol biosynthesis. The structure-activity relationships (SAR) are discussed by substituent effect, molecular docking, and density functional theory analysis, which provided useful information for designing more active compounds.