Non-food bioactive products: Design and semisynthesis of novel (+)-nootkatone derivatives containing isoxazoline moiety as insecticide candidates

Abstract

(+)-Nootkatone, isolated from the heartwood of Alaska yellow cedar, Citrus Rutaceae and Alpinia Zingiberaceae, is a natural bicyclic sesquiterpene. Toward the discovery of new natural products-based insecticides, twenty-five novel (+)-nootkatone derivatives containing isoxazoline moiety were designed and prepared by [3 + 2] cycloaddition. Structures of all (+)-nootkatone derivatives were confirmed by different spectral analyses, in which compound 2 h was further identified by X-ray diffraction. Compounds 2 g, 2i, 2q, 2 u, 2 w and 2y displayed more effective insecticidal activities against both Mythimna separata Walker and Plutella xylostella Linnaeus than the botanical insecticide, toosendanin. Especially, derivatives 2i and 2 w showed significant growth inhibitory (GI) activity with the final mortality rates (FMRs) both of 73.3%. Derivative 2 r exhibited pronounced larvicidal activity with LC50 values of 0.23 μmol mL−1. In addition, the structure–activity relationships (SARs) of these (+)-nootkatone derivatives were also observed. Moreover, the potent compounds 2 h, 2 l, 2p, 2 r and 2 w exhibited relative low toxicity to mammalian cells (RAW 264.7).