Synthesis and Pesticidal\nActivities of Ester Derivatives\nof the Labdane Diterpenoid Andrographolide at the C‑3 Position\nContaining the Isoxazoline Fragment and Their Toxicology Study against <i>Tetranychus cinnabarinus</i> Boisduval

Due to the long-term overuse of chemical pesticides,\nserious resistance\nand negative problems on human health and the ecological environment\nhave appeared. To develop plant-product-based pesticide candidates,\na series of novel andrographolide ester derivatives containing the\nisoxazoline skeleton were prepared at the C-3 position. Their pesticidal\nactivities were evaluated against three typical pests such as <i>Mythimna separata</i> Walker, <i>Aphis citricola</i> Van der Goot, and <i>Tetranychus cinnabarinus</i> Boisduval.\nAgainst <i>M</i>. <i>separata</i>, compounds <b>Ik</b>, <b>IIf</b>, <b>IIg</b>, and <b>IIk</b> showed 1.6–1.8 times insecticidal activity compared to that\nof andrographolide; against <i>A</i>. <i>citricola</i>, compounds <b>6</b>, <b>Ih</b>, and <b>IIh</b> possessed 3.7–3.9-fold aphicidal activity compared to that\nof andrographolide; against <i>T</i>. <i>cinnabarinus</i>, compounds <b>Ib</b>, <b>Ig</b>, and <b>IIk</b> exhibited 7.4–9.1-fold promising acaricidal activity compared\nto that of andrographolide. It is worth mentioning that effects of <b>IIk</b> on morphological changes of the treated mite cuticle layer\nstructures were observed by the scanning electron microscope imaging\nmethod. Compound <b>IIk</b> can be studied as a pesticidal lead\nfor further structural modification.