Semisynthesis of Matrinic Acid/Alcohol/Ester Derivatives, Their Pesticidal Activities, and Investigation of Mechanisms of Action against Tetranychus cinnabarinus

To discover new natural-product-based potential pesticides, 85 matrinic acid/alcohol/ester derivatives were synthesized by structural modifications of a quinolizidine alkaloid matrine. N-(4-Methyl)benzylmatrinyl n-decylate (76) and N-(2-chloro)benzylmatrinyl n-undecylate (86) exhibited greater than seven-fold more pronounced acaricidal activity than matrine against Tetranychus cinnabarinus; N-(2-chloro)benzylmatrinyl benzoate (80) showed the most promising insecticidal activity against Mythimna separata. The carboxyl group of matrinic acids and introduction of n-decyl/n-undecylcarbonyl into matrinic alcohols were important for the acaricidal activity; introduction of alkyloxy into the carboxyl of matrinic acids and introduction of the electron-withdrawing groups on the N-benzyl of matrinic esters were necessary for the insecticidal activity. Through RT-PCR and qRT-PCR analysis, it was shown that the lactam ring of matrine was vital for action on VGSC; opening the lactam ring of matrine and the alkylcarbonyl of side-chain were two important factors for acting with α1, α2, and α4 nAChR subunits; α1, α2, α4, and β3 subunits may be the target of action of compound 86 against T. cinnabarinus.