Cantharidin and its anhydride-modified derivatives: relation of structure to insecticidal activity

Cantharidin is a natural compound of novel structure with ideal insecticidal activity. However, the relationship of structure to insecticidal activity of cantharidin and its derivatives has not been ever clarified. To explore what determines the insecticidal activity structurally of cantharidin-related compounds, two series target compounds 6 and 7 were synthesized by replacing the anhydride ring of norcantharidin with an aromatic amine or fatty amine with different electron density, respectively. The structures of these compounds were characterized by 1H NMR, 13C NMR and HRMS-ESI. A bioassay showed that compounds 6 (a-m) lacked any larvicidal activity against Plutella xylostella; whereas their ring-opened partners 7 (a-m) provided a variety of larvicidal activities against P. xylostella, and compound 7f indicated the highest larvicidal activity with LC(50) value of 0.43 mM. The present work demonstrated that the form of the compound (cyclic or ring-opened) or their ability to hydrolyze facilely was the key to determine whether it exhibits larvicidal activity. Moreover, it revealed that the improvement of insecticidal activity required a reasonable combination of both aliphatic amide and aromatic amide moieties, and the type of substituent Y on the aniline ring was critical.