Synthetic pyrethroids, insecticidal

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. 

Synthetic Pyrethroid Insecticides. Elucidation of the chemical stmctures of the naturally occurring pyrethmm esters, their rapid and selective insecticidal action, and their high cost stimulated the search for effective synthetic derivatives (13,17,21). Since the 1940s, stmctural optimisation has produced an array of broad-spectmm insecticides with activity 10- to 20-fold greater than other types of insecticides, and with extended residual action. These synthetic pyrethroids have become one of the most important classes of insecticides with world aimual production estimated at 6000 t (21). 

K. Naumaim, Synthetic Pyrethroid Insecticides Structures and Properties, Sptinger-Verlag, Berlin, 1990. 

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. 

Detailed information on ecological and toxicological aspects of fenvalerate and other synthetic pyrethroid insecticides is provided in reviews by Elliott (1977), Elliott and Janes (1978), Wouters and Bercken (1978), Glickman and Casida (1982), Vijverberg and Bercken (1982), Gray and Soderlund (1985), Leahey (1985), Smith and Stratton (1986), Coats et al. (1989), Bradbury and Coats (1989a), and Eisler (1992). 

Synthetic pyrethroids now account for at least 30% of the world insecticide market and are rapidly replacing other agricultural chemicals for control of insect pests. Fenvalerate is one of the more widely used synthetic pyrethroid insecticides. It is derived from a combination of a-cyano-3-phenoxybenzyl alcohol and a-isopropyl phenylacetate ester. Technical fenvalerate is a mixture of four optical isomers, each occurring in equal amounts but with different efficacies against insect pests. Fenvalerate does not usually persist in the environment for >10 weeks, and it does not accumulate readily in the biosphere. Time for 50% loss (Tb 1/2) in fenvalerate-exposed amphibians, birds, and mammals was 6 to 14 h for reptiles, terrestrial insects, aquatic snails, and fish it was >14 h to <2 days and for various species of crop plants, it was 2 to 28 days. Fenvalerate degradation in water is due primarily to photoactivity, and in soils to microbial activity. Half-time persistence in nonbiological materials is variable, but may range up to 6 days in freshwater, 34 days in seawater, 6 weeks in estuarine sediments, and 9 weeks in soils. 

Pyrethroids are used primarily for the control of household and agricultural insect pests, and secondarily in industrial, stored product, and veterinary applications. They are especially advantageous for use in northern climates because their toxicity is enhanced at low temperatures (Smith and Stratton 1986). Synthetic pyrethroid insecticides, including fenvalerate, are used as alternatives... 

The sodium channel in the nerve membrane is the major target site for all synthetic pyrethroid insecticides (and many other neurotoxicants)... 

Coats, J.R. and N.L. O Donnell-Jeffery. 1979. Toxicity of four synthetic pyrethroid insecticides to rainbow trout. Bull. Environ. Contam. Toxicol. 23 250-255. 

Flannigan, S.A., S.B. Tucker, M.M. Key, C.E. Ross, E.J. Fairchild II, B.A. Grimes, and R.B. Harrist. 1985. Primary irritant contact dermatitis from synthetic pyrethroid insecticide exposure. Arch. Toxicol. 56 288-294. 

Materna, E.J. 1991. Effects of the Synthetic Pyrethroid Insecticide, Esfenvalerate, on Larval Amphibians. M.S. thesis. Univ. Missouri, Columbia. 96 pp. 

Smith, T.M. and G.W. Stratton. 1986. Effects of synthetic pyrethroid insecticides on nontarget organisms. Residue Rev. 97 93-120. 

Taylor, K.S., G.D. Waller, and L.A. Crowder. 1987. Impairment of a classical conditioned response of the honey bee (Apis mellifera L.) by sublethal doses of synthetic pyrethroid insecticides. Apidologie 18 243-252. Theophilidis, G., M. Benaki, and E. Papadopoulu-Mourkidou. 1997. Neurotoxic action of six pyrethroid insecticides on the isolated sciatic nerve of a frog (Rana ridibunda). Comp. Biochem. Physiol. 118C 97-103. Tippe, A. 1987. Evidence for different mechanisms of action of the three pyrethroids, deltamethrin, cypermethrin, and fenvalerate, on the excitation threshold of myelinated nerve. Pestic. Biochem. Physiol. 28 67-74. 

Webber, E.C., W.G. Deutsch, D.R. Bayne, and W.C. Seesock. 1992. Ecosystem-level testing of a synthetic pyrethroid insecticide in aquatic mesocosms. Environ. Toxicol. Chem. 11 87-105. 

Knox JM, Tucker SB, Flannigan SA (1984) Paresthesia from cutaneous exposure to synthetic pyrethroid insecticide. Arch Dermatol 120 744-746... 

Kavlock R, Chemoff N, Baron R et al (1979) Toxicity studies with decamethrin, a synthetic pyrethroid insecticide. J Environ Pathol Toxicol 2 751-765... 

Zhou JL, Rowland S, Mantoura FC (1995) Partition of synthetic pyrethroid insecticides between dissolved and particulate phases. Water Res 29 1023-1031... 

Liu W, Qin S, Gan J (2005) Chiral stability of synthetic pyrethroid insecticides. J Agric Food Chem 53 3814-3820... 

The pesticides included in this study were fenvalerate, chlordecone (kepone), chlorothalonil, and chlorpyrifos. Fenvalerate is a synthetic pyrethroid insecticide used, for example, for mites on chickens. Its chemical name is cyano(3-phenoxyphenyl)-methyl 4-chloro-alpha-(1-methylethyl)benzeneacetate. Chlordecone is an insecticide, no longer used, and has a chemical name decachloro-octahydro-l,3,4-metheno-2H-cyclobuta(cd)=pentalen-2-one. Chlorothalonil is fungicide used on tomatoes whose chemical name is 2,4,5,6-tetrachloroisophthalonitrile. Chlorpyrifos is an insecticide with a chemical name 0,0-diethyl 0-(3,5,6-trichloro-2-pyridyl)phosphorothioate. Chlorpyrifos is the U. S. Food and Drug Administration chromatographic reference standard since numerous specific detectors (electron capture, flame photometric in both sulfur and phosphorus modes, alkali flame, nitrogen phosphorus, and Hall detectors) are sensitive to it. 

A variety of three-membered carbocycles including cyclopropylcarbonyl and -sulfonyl derivatives, cyclopropylcarbonitriles and -methanols, nitrocyclopropanes, cyclo-propanols and cyclopropylamines have been prepared via the 1,3-elimination of HX. Some representative cyclopropyl derivatives recently prepared by this method are shown in Scheme 116-18 and in equations 8-26. Conversion of chelated homoserine, 5,to chelated 2-amino-4-bromobutyrate and treatment with aqueous base directly affords chelated 1-aminocyclopropane-l-carboxylate (equation 8)19. The 1,3-elimination in 6 interestingly leads to the preferential formation of the cis isomer, from which 7, a key structural element of synthetic pyrethroid insecticides, is obtained (equation 9)20. A sulfur substituent can serve both as an activating group and as a leaving group in this type of reaction and, thus, 1,3-bis(phenylthio)propane affords cyclopropyl phenyl sulfide upon treatment with butyl-... 

K. Naumann, Synthetic pyrethroid insecticides, in Chemistry of Plant Protection, Vol. 5 (Eds. G. Haug and H. Hoffmann), Springer-Verlag Berlin, Heiderberg, New York, 1990. 

---