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 Xanthomonas oryzae pv. oryzae (Xoo.),and Xanthomonas oryzae pv. oryzicola (Xoc.), 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 Xoo.; EC50 = 162.95 μg/mL against Xoc.) and thiadiazole copper (EC50 = 175.78 μg/mL against Xoo.; EC50 = 171.44 μg/mL against Xoc.). This work provides valuable references for the application of thiasporine A derivatives containing heterocyclic amide structures in plant protection.