Expedient discovery of novel oxime ester derivatives of piperine/piperine analogs as potent pesticide candidates and their mode of action against Tetranychus cinnabarinus Boisduval

BACKGROUNDNowadays, pest infestation and resistance have appeared as a consequence of repeated and extensive use of pesticides. Thus, development of new effective pesticide candidates in crop protection is highly desirable. Herein, a series of new piperine derivatives containing oxime ester scaffolds were regioselectively and stereoselectively prepared as pesticidal agents. RESULTSSteric configurations of compounds 2, 5z and 13e were definitively determined by single-crystal X-ray diffraction. Against Tetranychus cinnabarinus, notably, compounds 5f [median lethal concentration (LC50) = 0.14 mg mL(-1)] and 5v (LC50 = 0.13 mg mL(-1)) showed >107-fold greater acaricidal activity than piperine (LC50 = 15.02 mg mL(-1)), which were comparable to the commercial acaricide spirodiclofen. Against Aphis citricola, compound 5d (LD50 = 19.12 ng aphid(-1)) exhibited 6.1-fold more potent aphicidal activity than piperine (LD50 = 116.06 ng aphid(-1)). Additionally, through scanning electron microscopy, the toxicology study suggested that the acaricidal activity of piperine derivatives may be related to damage of the cuticle layer crest of T. cinnabarinus. CONCLUSIONThe structure-activity relationships suggested that 3,4-dioxymethylene of piperine was crucial for its acaricidal activity; and introduction of a certain length of aliphatic chain at the C-2 position was beneficial to the aphicidal and acaricidal activities. Compounds 5f and 5v are potential leads for further structural modification as acaricidal agents. (c) 2023 Society of Chemical Industry.