Synthetic pyrethroid modeled

Figure 7. Synthetic Pyrethroid modeled on pyrethrin natural insecticide found in Chrysanthemum cinerariaefli...

These chemorational techniques have generated great interest in, and high expectations for, the acceleration of development of innovative pesticides. However, many purportedly successful appHcations of QSAR procedures have reHed on the quaHtative insights traditionally associated with art-based pesticide development programs. Retrospective QSAR analyses have, however, been helpful in identifying the best compounds for specific uses (17). Chemorational techniques have also found some appHcations in the development of pesticides from natural product lead compounds, the best known examples being the synthetic pyrethroid insecticides (19) modeled on the plant natural product, pyrethmm. 

Many pesticides are not as novel as they may seem. Some, such as the pyre-throid and neonicotinoid insecticides, are modeled on natural insecticides. Synthetic pyrethroids are related to the natural pyrethrins (see Chapter 12), whereas the neo-nicotinoids share structural features with nicotine. In both cases, the synthetic compounds have the same mode of action as the natural products they resemble. Also, the synthetic pyrethroids are subject to similar mechanisms of metabolic detoxication as natural pyrethrins (Chapter 12). More widely, many detoxication mechanisms are relatively nonspecific, operating against a wide range of compounds that... 

The compounds featured in Table 1.1 are considered briefly here. Pyrethrins are lipophilic esters that occur in Chrysanthemum spp. Extracts of flower heads of Chrysanthemum spp. contain six different pyrethrins and have been used for insect control (Chapter 12). Pyrethrins act upon sodium channels in a manner similar to p,p -DDT. The highly successful synthetic pyrethroid insecticides were modeled on natural pyrethrins. 

Maund SJ, Van Wijngaarden R, Roessink I et al (2008) Aquatic fate and effects of lambda-cyhalothrin in model ecosystem experiments. In Gan J, Spurlock F, Hendley P et al (eds) Synthetic pyrethroids occurrence and behavior in aquatic environments. ACS Symposium Series 991, American Chemical Society, Washington DC... 

Mirfazaelian A, Kim K-B, Anand SS, Kim HI, Tomero-Velez R, Bruckner JV, Fisher JW (2006) Development of a physiologically based pharmacokinetic model for deltamethrin in the adult male Sprague-Dawley rat. Toxicol Sci 93 432-442 Miyamoto J (1976) Degradation, metabolism and toxicity of synthetic pyrethroids. Environ Health Perspect 14 15-28... 

In the middle of the 20th century, the synthetic development of DDT and other chlorinated hydrocarbons (C.H.), increased insecticidal activity well beyond that of most natural products. Problems arose with bioaccumulation of C.H. residues in the food chain, human fat tissue, mother s milk, as well as the development of insecticide resistance. It became obvious there were limitations to synthetic technology as well. The modification of a natural product, for example, from chrysanthemum flowers and their pyrethrum extracts (7) to pyrethroids such as allethrin, resmethrin, permethrin (2), and deltamethrin created a model in which insecticides are created from the skeleton of insecticidally active natural molecules. Thus, the avermectin, abamectin, ivermectin family of pesticides originated from compounds produced by the soil bacterium, Streptomyces avermitilis (5), and the commercially successful chloronicotinyl insecticides, though not derived from nicotine, are chemically related 4). Both pyrethroids and chloronicotinyls are currently used commercially as termiticides. We have previously provided a detailed review of natural products as pesticidal agents for control of the Formosan subterranean termites, Coptotermes formosanus Shiraki (5). 

The development of the pyrethroids from the pyrethrins serves as an example of the most successful development of a commercially important synthetic insecticide from a natural precursor. The commercial pyrethroids are among the most active insecticides known and they control a wider range of insect and acarid pests at lower application rates than most other insecticides. Their high toxicity to insects and low mammalian toxicity make these compounds a role model for all present and future insecticides. 

---