Abstract: To discover and exploit novel fungicidal compounds, twenty two novel strobilurin derivatives were designed and synthesized by sub-structural combination method using azoxystrobin as the lead compound. Their structures were characterized by ¹H NMR, ¹³C NMR and HRMS. Some compounds exhibited high fungicidal activity against Sphaerotheca fuliginea. In greenhouse tests, compound 7b displayed 85% fungicidal activity against cucumber powdery mildew at 50 mg/L. In field trials, compound 7b (281.25 g a.i./hm²) for cucumber powdery mildew proved to be approximately equivalent to commercial products azoxystrobin (281.25 g a.i./hm²) and ethirimol (300.00 g a.i./hm²).