Natural products as insecticides: the biology, biochemistry, and quantitative structure-activity relationships of spinosyns and spinosoids

The spinosyns, a novel family of insecticidal macrocyclic lactones, are act ive on a wide variety of insect pests, especially lepidopterans and diptera ns. The biological activity of a mixture (spinosad; Tracer (R), Spin-Tor (R ) Success (R)) of the two most abundant spinosyns (spinosyns A and D) again st pest insects, is on a par with that of many pyrethroid insecticides. The spinosyns also exhibit a very favorable environmental and toxicological pr ofile, and possess a mode of action that appears unique, with studies to da te suggesting that both nicotinic and gamma-aminobutryic acid receptor func tions. are altered in a novel manner. Compared to pyrethroids such as cyper methrin, spinosyn A is slow to penetrate into insect larvae such as tobacco budworm larvae (Heliothis virescens); however, once inside the insect, spi nosyn A is not readily metabolized. To date, more than 20 spinosyns and mor e than 800 spinosoids, (semi-synthetic analogs) have been isolated or synth esized, respectively. Artificial neural network-based quantitative structur e activity relationship (QSAR) studies for the spinosyns suggested that mod ification of the 2',3',4'-tri-0-methylrhamnosyl moiety could improve activi ty and several spinosoids incorporating these modifications exhibited marke dly improved lepidopteran activity compared to spinosad. Multiple linear re gression-based QSAR studies also suggest that whole molecule properties suc h as CLogP and MOPAC dipole moment can explain much of the biological activ ity observed for the spinosyns and closely related spinosoids. (C) 2001 Soc iety of Chemical Industry.