Pyrethroid insecticides isomers

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. 

Giddings, J.M., Barber, I. and Warren-Hicks, W. (2009) Comparative aquatic toxicity of the pyrethroid insecticide lambda-cyhalothrin and its resolved isomer gamma-cyhalothrin. Ecotoxicology, 18, 239-249. 

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-... 

During studies on pyrethroid insecticides methyl permethrate 1 (a mixture of cis and trans isomers) was pyrolysed at 260-270°C in the expectation that a vinylcyclopropane-to-cyclopentene rearrangement would occur. The product, however, was found to be methyl o-toluate (78%). 

It is known that the (S)-forms are the essential stereoisomers for the insecticidal activities of both alcohols (4,5). Chemico-enzymatic processes are also reported in this article on the preparation of the optically active pyrethroid insecticides having the (S)-isomers of the two alcohols. Processes were developed that use enantioselective hydrolysis with a lipase. 

Pyrethroid insecticides can exist as enantiomers because they have two chiral centers, i.e., asymmetric carbons at C-l and C-3. An enantiomer exhibits optical activity and R/S configuration. Thus, a pyrethroid can show as either dextrorotatory (+) or levorotatory (-) isomer. A pyrethoid also can exist as either R or S form. However, only C-l is important to the biological activity of these compounds, and, for activity, it must be in the R position. As shown next, to be the 1R form, the -COOR group must be below the page. The IS form, which has -COOR group above the page, is nontoxic. Therefore, the active isomer of deltamethrin is expressed as (+)-ris-(lR) deltamethrin. The active isomer of permethrin is (lR)-ds-permethrin. 

S-Bioallethrin (Fig. 5 ]9a]) is a S)mthetic pyrethroid insecticide with three asymmetric centers. The S designation refers to the l-K, 3-R, 4 -S isomer and is not a true designation of stereochemistry. Conversion of the terminal allylic group to —CHjCHjCHjOH, formation of hemisuccinate. 

Some veterans were exposed to these pesticides by intentional application, but because many exposures were accidental, it has been difficult to assess pesticide exposure accurately and therefore a topical dose in exposed veterans. Permethrin was intentionally impregnated into the soldier s uniform fabric at a concentration of 0.125 mg/cm to help control insect infestation while in the dessert. This pyrethroid insecticide consists of four different isomers (Figure 9.1), with the cis isomer more toxic than the trans isomer. Permethrin is a large moleeule (MW = 391.3) and has a log octanol-water partition coefficient of 6.5, which suggests that it could readily partition from the uniform into the lipophilic stratum comeum layer of the soldier s skin. With a transfer rate of 0.49% per day of permethrin from the fabric to skin, the daily dose was estimated to be 6.8 x 10" mg/kg/day (National Research Council... 

In this review, we have concentrated on the development of (1) in vivo metabolic data (i.e., and K, etc.), (2) QSAR, and (3) mechanistic models and their application for building PBPK/PD models. The development of the pyrethroid insecticides for agricultural and home use is complicated by their chemistry, in that they each possess one to four chiral centers, increasing the number of isomeric forms by a factor of 2 (where = the number of chiral centers). Isomer mixtures and individual isomers are commonly both subjected to testing for insecticidal activity. The fewer the number of active forms, the easier it is to test them for insecticidal activity, toxicity, and to buUd PBPK/PD models for them. The pyrethroids on which we focus in this review are presented in Table 2, along with their trivial and CAS names and their structures. Table Al (Appendix A) defines the acronyms and abbreviations used in the text, while Table A2 (Appendix A) defines the chemical and mathematical expressions that are presented in this review. 

Resmethrin was the first synthetic pyrethroid insecticide that possessed insecticidal activity approaching the potency of pyrethrin I. In resmethrin, the furan ring replaced the cyclopentenone ring of pyrethrin I, and the benzene ring replaced the diene side chain of pyrethrin I. The success of resmethrin (four isomers, two cis-and two trans-) led to the synthesis of a form that was less toxic to mammals, bioresmethrin (lR-tra s isomer). Unfortunately, bioresmethrin per se was not more photostable than were the earlier synthetic pyrethroids, because both the furan ring and isobutenyl side chain were sites vulnerable to degradation. 

The same synthetic approach (i.e., varying the acid, alcohol, or both) resulted in the development of the coirnnercially successful active pyrethroid insecticides covered in this review this same approach also produced a host of relatively inactive isomers. The most potent constituent of resmethrin is the IR, 3R isomer (bioresmethrin), and is formed during the esterification of (-r) cis-, trans-chrysanthemic acid with 5-benzyl-3-furyImethyl alcohol to produce bioresmethrin and three other stereoisomers. Of greater interest to most chemists/biologists is the... 

In the past, industry sold most pyrethroids as isomer mixtures however, in recent years the active isomer or isomers are being made and sold under different, but similar product names (e.g., biopermethim, cismethrin, bioresmethrin, and deltamethrin). This reflects the fact that the manufactures were able to economically produce one, or primarily one isomer. It is, therefore, reasonable to now develop PBPK models for these active isomers, rather than to try to construct them to only reflect the metabolism of mixtures. As a result of our having reviewed the metabolism of the 15 pyrethroids of interest in this paper, we have attempted to point out the isomers of each product that were studied (e.g., labeled with " C), and to provide their relative insecticidal activities. In Appendix D, Tables D1-D15, we... 

The sections on the metabolism and neurotoxicity of the pyrethroids in this review provide a starting point that feeds into the physiological and biochemical parameters that are needed to develop PBPK/PD models for assessing risks to the pyrethroids. The development of such pyrethroid model parameters requires knowledge of their discovery, chemistry, chirality, their isomers, and their chromatographic separation. To this end. Sect. 2 above (viz.. Nature of Pyrethroid Insecticides) was developed with a listing of 15 of the most important pyrethroids... 

Hutson DH, Logan CJ (1986) The metabolic fate in rats of the pyrethroid insecticide WL85871,a mixture of two isomers of cypmnethrin. Pestic Sci 17 548-558 lARC (1991) Occupational exposures in insecticide application and some pesticides. lARC, Lyon Inoue S, Howgate EM, Rowland-Yeo K, Shimada T, Yamazaki H, Tucker GT, Rostami-Hodjegan A (2006) Prediction of in vivo drug clearance from in vitro data. D Potential inter-ethnic differences. Xenobiotica 36 499-513... 

Oi N, Horiba M, Kitahara H (1981) Gas chromatographic separation of optical isomers of chrysanthemic acid on an optically active stationary phase. Agric Biol Chem 45(6) 1509-1510 Oi N, Kitahara H, Kira R (1990) Enantiomer separation of pyrethroid insecticides by high-performance liquid chromatography with chiral stationary phases. J Chromatogr A 515 441 50... 

Pyrethroid Esters of Benzene Acetate. These insecticides have more extensive stmctural optimization in both acid and alcohol moieties. Fenvalerate [51630-58-17, a-cyano-(3-phenoxyphenyl)methyl (+)-(2R,5)"Ct"isoprop5i-4-chlorophenylacetate (24) d 1.17, vp 1.4 p.Pa at 25°C), a mixture of four isomers, is soluble in water to 0.3 mg/L The rat oral LD q is 450 mg/kg. Esfenvalerate [66230-04-4] is the (+)-2-(i, 5)-isomer (mp 59°C). The rat LD qS are 75, 458 (oral), and the rabbit dermal LD q is 2000 mg/kg. These pyrethroids are widely used general-purpose insecticides for field, vegetable, and fmit crops. 

Synthetic pyrethroids is one of the group of modern insecticides of cyclopropancai bonic acid derivate. The pyrethroids prepai ation is the racemic mixture of optical isomers or mixture of cis- or tran.s-isomers. 

Pyrethrins and pyrethroids are probably the best known and safest classes of natural or synthetic insecticides, widely used in domestic and agricultural applications (1-7). Pyrethrins are natural insecticides derived from the Chrysanthemum cineraria flowers the plant extract, called pyrethrum, is a mixture of six isomers (pyrethrin I and II, cinerin I and II, jasmolin I and II) which was first used in China in the century AD, during the Chou Dinasty. The world pyrethrum market is worth half a billion US dollars [main producers are East Africa highlands (Kenia, Tanzania and Rwanda) and Australia] however, its availability is subject to cyclical trends, due to rains and relations with farmers, who face high harvest costs also due to the fact that the flowers have to be... 

Pyrethroids are commercially important insecticides that usually contain a cyclopropyl unit that is m-substituted and a cyanohydrin derivative. They are usually sold as a mixture of isomers. However, asymmetric routes have been developed, especially because these compounds are related to chrysanthemic esters (Chapter 12).251 The pyrethroids can be resolved through salt formation or by enzymatic hydrolysis.252... 

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