Synthesis of Piperine Analogs Containing Isoxazoline/Pyrazoline Scaffold and Their Pesticidal Bioactivities.

In continuation of our program to discover new potential pesticidal agents, thirty-one piperine analogs containing isoxazoline/pyrazoline scaffold were prepared, and confirmed by infrared spectra, proton/carbon-13 nuclear magnetic resonance spectra, and high-resolution mass spectra. The structures of compounds VIIb and VIIIc were further determined by 1H-1H COSY spectra. Especially the configuration of compound VIIIc was unambiguously confirmed by single-crystal X-ray diffraction. Their pesticidal activities were evaluated against three serious and typically crop-threatening agricultural pests, Tetranychus cinnabarinus Boisduval (spider mite), Mythimna separata Walker (Oriental armyworm), and Plutella xylostella Linnaeus (diamondback moth). Compounds VIIIb and VIIIc exhibited greater than 40-fold more potent acaricidal activity than the lead compound piperine against T. cinnabarinus. Notably, compounds VIa-c exhibited more pronounced oral toxicity against P. xylostella than toosendanin; compounds VIb and VIc displayed more promising growth inhibitory activity against M. separata than toosendanin. It demonstrated that the methylenedioxy and isoxazoline scaffolds were important for the oral toxicity and growth inhibitory activity against P. xylostella and M. separata, respectively; the ethylenedioxy and isoxazoline scaffolds were vital for the acaricidal activity against T. cinnabarinus. Moreover, compounds VIb, VIIf, and VIIIc showed very low toxicity against NRK-52E cells.