Design and Synthesis of Novel Oxathiapiprolin Derivatives as Oxysterol Binding Protein Inhibitors and Their Application in Phytopathogenic Oomycetes.

Oomycetes, particularly those from the genus , are significant threats to global food security and natural ecosystems. Oxathiapiprolin (OXA) is an effective oomycete fungicide that targets an oxysterol binding protein (OSBP), while the binding mechanism of OXA is still unclear, which limits the pesticide design, induced by the low sequence identity of and template models. Herein, we generated the OSBP model of the well-reported using AlphaFold 2 and studied the binding mechanism of OXA. Based on it, a series of OXA analogues were designed. Then, compound , the most potent candidate, was successfully designed and synthesized, showing a control efficiency comparable to that of OXA. Moreover, field trial experiments showed that exhibited nearly the same activity (72.4%) as OXA against cucumber downy mildew at 25 g/ha. The present work indicated that could be used as a leading compound for the discovery of new OSBP fungicides.