Design and Synthesis of Novel 3,4-Dihydro-2H-1,2,4-benzothiadiazine 1,1-Dioxides-based Strobilurins as Potent Fungicide Candidates

Abstract

To discover novel strobilurins analogues with good and broad spectrum activity, a series of novel 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides-based strobilurins was designed, synthesized, and tested against various phytopathogenic fungi. Compounds 7b, 7c, and 7k exhibited substantial and broad spectrum antifungal activities against the tested phytopathogenic fungi, especially compound 7b, which showed 100%, 80%, 90%, and 90% antifungal activity(in virto) against Erysiphe graminis(E. graminis), Puccinia sorghi Schw.(P. sorghi Schw.), Colletotrichum lagenarium(C. lagenarium), and Pseudoperonospora cubensis(P. cubensis) at 300 µg/mL, respectively, better or comparable to the positive control azoxystrobin. Moreover, compound 7b exhibited 85% greenhouse inhibition activity(in vivo) against E. graminis even at 0.2 µg/mL, equal to azoxystrobin(90%) and trifloxystrobin(90%). Meanwhile, compound 7b against P. cubensis displayed 70% and 55% greenhouse inhibition activity(in vivo) at 1.56 and 0.2 µg/mL, respectively, much better than those of azoxystrobin and trifloxystrobin(both 0% at 1.56 and 0.2 µg/mL). Therefore, compound 7b could be considered as the most promising fungicidal candidate for further study. Furthermore, based on the effective concentration(EC50) against C. arachidicola, the built CoMSIA model provided the useful reference for the further structural optimization design.