Design, synthesis, and biological evaluation of thiasporine A derivatives containing a heterocyclic amide moiety

In this study, to discover new derivatives of the natural product thiasporine A with higher biological activity, 12 thiasporine A derivatives containing a heterocyclic amide structure were designed and synthesised. Their structures were characterised using 1H NMR, 13 C NMR and HRMS. Preliminary bioassays revealed that most of the synthesised compounds exhibited moderate antifungal activity against the five tested fungi. Notably, compound C12 demonstrated significant antibacterial activity against <i>Xanthomonas oryzae</i> pv. <i>oryzae</i> (<i>Xoo</i>.),and <i>Xanthomonas oryzae</i> pv. <i>oryzicola</i> (<i>Xoc</i>.), with EC₅₀ values of 5.09 μg/mL and 34.85 μg/mL, respectively, outperforming both the positive control natural product thiasporine A (EC₅₀ = 128.54 μg/mL against <i>Xoo</i>.; EC₅₀ = 162.95 μg/mL against <i>Xoc</i>.) and thiadiazole copper (EC₅₀ = 175.78 μg/mL against <i>Xoo</i>.; EC₅₀ = 171.44 μg/mL against <i>Xoc</i>.). This work provides valuable references for the application of thiasporine A derivatives containing heterocyclic amide structures in plant protection.