New Class of 2‑Aryl-6-chloro-3,4-dihydroisoquinolinium Salts as Potential Antifungal Agents for Plant Protection: Synthesis, Bioactivity and Structure–Activity Relationships

Thirty-four new 2-aryl-6-chloro-3,4-dihydroisoquinolin-2-ium bromides were synthesized, and their structures were elucidated by spectroscopic analysis. Antifungal activities against <i>Alternaria alternate</i>, <i>Curvularia lunata</i> and <i>Valsa mali</i> were evaluated by the mycelium linear growth rate method. SAR was discussed also. All compounds showed some activity against each of the fungi at 25 μg/mL. Compared to azoxystrobin, a commercial fungicide, 31 out of 34 test compounds showed higher inhibition rates against <i>C. lunata</i> and 10 were more effective against <i>A. alternate</i> and <i>V. mali</i>. Compounds <b>5</b>-<b>4</b>, <b>5</b>-<b>2</b> and <b>5</b>-<b>34</b> showed the highest activity against <i>A. alternate</i> (EC₅₀ = 10.3 μg/mL), <i>C. lunata</i> (EC₅₀ = 4.6 μg/mL) and <i>V. mali</i> (EC₅₀ = 3.9 μg/mL), respectively, superior to azoxystrobin (EC₅₀ = 12.8, 71.9, 37.2 μg/mL). Compound <b>5</b>-<b>4</b> displayed good activities against each of the fungi with EC₅₀ of 10.3, 4.7, and 18.0 μg/mL while <b>5</b>-<b>34</b> displayed excellent activities against <i>V. mali</i> (EC₅₀ = 3.9 μg/mL) and <i>C. lunata</i> (EC₅₀ = 5.8 μg/mL). The SAR showed that the type and position of substituents on the C-ring had significant effects on the activity. Generally, the presence of 2′-F, 4′-F or 2′-CH₃ could significantly improve the activities, whereas OH, OMe, NO₂ or CF₃ groups decreased the activities. Thus, it was concluded that the present research provided a new series of 2-aryl-6-chloro-3,4-dihydroisoquinolin-2-iums with excellent antifungal potency, and the results were of importance for the structure optimization design, synthesis and development of more potent isoquinoline antifungal agents