Pyrethroid insecticides, structures

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

K. Naumann, Synthetic Pyrethroid Insecticides Structure and Properties Chemistry and Patents, Springer, Berlin 1990. 

The structures of some pyrethroid insecticides are shown in Figure 12.1. They are all lipophilic esters showing some structural resemblance to the natural pyrethrins. They can all exist in a number of different enantiomeric forms. Permethrin, cypermethrin, and deltamethrin, for example, all have three asymmetric carbon atoms... 

Casida, J.E. and LJ. Lawrence. 1985. Structure-activity correlations for interactions of bicyclophosphorus esters and some polychlorocycloalkane and pyrethroid insecticides with the brain-specific t-butylcyclo-phosphorothionate receptor. Environ. Health Perspec. 61 123-132. 

Vijverberg, H.P.M., G.S.F. Ruigt, and J.V.D. Bercken. 1982. Structure-related effects of pyrethroid insecticides on the lateral-line sense organ and on peripheral nerves of the clawed frog, Xenopus laevis. Pestic. Biochem. Physiol. 18 315-324. 

Sawicki RM, Denholm I, Famham AW, Murray AWA (1986) Structure-activity relationship to pyrethroid insecticides in houseflies (Musca domestica L.) with kdr and super-kdr. Sixth International Congress Pesticide Chemistry, Ottawa, Canada, Abstract 3E-25... 

Choi JS, Soderlund DM (2006) Structure-activity relationships for the action of 11 pyrethroid insecticides on rat Nav1.8 sodium channels expressed in Xenopus oocytes. Toxicol Appl Pharmacol 211 233-244... 

Hudson, B. D., George, A. R., Ford, M. G., and Livingstone, D. J. (1992) Structure-activity relation ships of pyrethroid insecticides. Part 2. The use of molecular dynamics for conformation searching and average parameter calculation.. /. Comput-Aided Mol. Design 6, 191-201. 

Some derivatives of 56 have been investigated because they are related to the widely used pyrethroid insecticides. Pure cyhalothric acid (70) forms H-bonded centrosymmetric dimers in the crystal125. Newly discovered clathrates with aromatic molecules may facilitate the separation of isomers126. The structures of the acid 71 and of its 2/1 inclusion compound with benzene have been determined126. 

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-... 

Synthetic Pyrethroid Insecticides. Elucidation of the chemical structures of the naturally occurring pyrethrum esters, their rapid and selective insecticidal action, and their high cost stimulated the search for effective synthetic derivatives (13,17,21). Since the 1940s, structural optimization has produced an array of broad-spectrum 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 annual production estimated at 6000 t (21). 

Pyrethroid insecticides. The natural pyrethrins, which act on the voltage-gated sodium channel, are highly potent insecticides obtained from flowers of the chrysanthemum plant. Though the pyrethrins are highly active insecticides, they are not stable enough for commercial use. However, a number of structural modifications of the early pyrethrin molecule resulted in a wide range of stable commercially useful pyrethroid insectides. 

Pyrethroid insecticides have three basic general structures ... 

Chemical/Pharmaceutical/Other Class Type II synthetic pyrethroid insecticide Chemical Eormula C25H22CINO3 Chemical Structure ... 

Chemical/Pharmaceutical/Other Ceass Type I pyrethroid insecticide Chemicae Structure ... 

The crystal structures of three pyrethroid insecticides have been determined. ... 

Enantioselection can be controlled much more effectively with the appropriate chiral copper, rhodium, and cobalt catalyst.The first major breakthrough in this area was achieved by copper complexes with chiral salicylaldimine ligands that were obtained from salicylaldehyde and amino alcohols derived from a-amino acids (Aratani catalysts ). With bulky diazo esters, both the diastereoselectivity (transicis ratio) and the enantioselectivity can be increased. These facts have been used, inter alia, for the diastereo- and enantioselective synthesis of chrysan-themic and permethrinic acids which are components of pyrethroid insecticides (Table 10). 0-Trimethylsilyl enols can also be cyclopropanated enantioselectively with alkyl diazoacetates in the presence of Aratani catalysts. In detailed studies,the influence of various parameters, such as metal ligands in the catalyst, catalyst concentration, solvent, and alkene structure, on the enantioselectivity has been recorded. Enantiomeric excesses of up to 88% were obtained with catalyst 7 (R = Bz = 2-MeOCgH4). 

Even if the phytoalexins so far isolated have little commercial utility, it is still possible that useful substances may yet appear. But the more exciting possibility is that consideration of the chemical structures of natural phytoalexins and of their modes of action against fungal infections may provide clues for the development of synthetic pesticides. The complexity of the chemical structures of the natural phytoalexins may make them uneconomical to manufacture but a comparison should be made with the synthetic pyrethroid insecticides. The natural pyrethrums have complex chemical structures but simpler compounds, economical to manufacture, have been developed on the basis of the structures of natural pyrethrums and many of these have much more desirable properties for use in agriculture than the natural substances. There would seem to be no reason why simpler compounds based on the structures of natural phytoalexins should not provide synthetic fungicides as important and useful as the synthetic pyrethroids. This is a future challenge for the synthetic organic chemists in this area. 

The pyrethroid insecticide fenvalerate, (a-cyano-3-phenoxybenzyl-2-(4-chlorophenyl)isovalerate, contains two centers of chirality in its structure (designated as the 2 and a positions Fig. 19) and therefore four stereoisomers, two pairs of enantiomers are possible. Initial evaluation of the mixture, by addition to the diet of a number of species, resulted in granulomatous changes in the liver, lymph nodes, and spleen. Separation and evaluation of the individual stereoisomers indicated that the toxidty was associated with one of the four, the 2i ,a5-stereoisomer, and subsequent metabolic studies found the cause to be associated with the formation and disposition of a cholesterol ester of (i )-2-(4-chlorophenyl)isovalerate (Fig. 19). A metabolic transformation shown to be stereospedfic in mice, only the 2i ,a5-stereoisomer yielding the ester both in vitro and in vivo [159]. 

Pyrethroid insecticides are generally recognized as potent neurotoxicants that interfere with nerve membrane function by interaction with the sodium channel. Syntheticpyrethroids are more toxic against insect pests, up to ten times more potent in some cases, than the other insecticides now in general use. However, the stereochemical structure of pyrethroid insecticides greatly influences their toxicity to insects and mammals, and this phenomenon is especially pronounced in fenvsderate. 

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