Pyrethroid esters activity

Our search for a new lead in the pyrethroid area started with a simple proposition It has been suggested that for a pyrethroid ester to be active it must have an alcohol with the specific feature of two centers of unsaturation separated by a bridging group (1, ) (Figure 4). In the case of allethrin and res-methrin the bridging atom is a methylene group. In permethrin it is an oxygen atom. If this is a requirement, one should be able to express it with some physicochemical parameter or set of parameters. 

Replacement of the normal pyrethroid ester by alternative linkages usually leads to diminution of biological activity. One important exception to this general phenomena is several oxime ether derivatives, in particular, 3-phenoxybenzyl derivatives of various alkyl aryl ketones. Pyrethroid esters derived from certain 2-substituted-[1,1 -biphenyl]-3-methanols have been shown to possess initial and residual activity surpassing that of esters derived from 3-phenoxybenzyl alcohol. Now it has been demonstrated that the same enhancement of activity was observed for alkyl aryl oxime ethers of certain [1,1 -biphenyl]-3-methanols compared to the corresponding 3-phenoxybenzyl alcohol derived oximes. The synthesis, biological activity, including soil activity, structure-activity relationships and toxicity of several of these biphenylmethyl oxime ethers are described. 

Many synthetic pyrethroids with excellent insecticidal activity have been discovered through modification of the acid and alcohol moieties of the natural pyrethrins. However, replacement of the pyrethroid ester linkage with an alternative linkage usually leads to compounds of diminished biological activity(D. One exception to this trend of lower activity is the class of compounds wherein the oxime linkage is introduced in place of the ester linkage in the fenvalerate series. Additionally, only the E-isomer of the alkyl aryl oxime ethers is reported to be insecticidal< 2-4). 

Pyrethroid esters derived from [1,1 -biphenyl]-3-methanol have been of interest at FMC(5-7). It has been reported that [1,1 -biphenyl]-3-methanol esterified with both cis-3-(2-chloro-3,3,3-trifluoro-l-propenyl)-2,2-dimethylcyclopropanecarboxylic acid and cis-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylic acid produced esters which have initial and residual activity surpassing that of permethrin against a number of insects. It occurred to us that this same enhancement of activity might be observed with alkyl... 

The replacement of the ester linkage of pyrethroids by alternatives was known to lead to compounds of diminished biological activity. Thiol esters and amides are two such isosteric replacements that lead to a loss in biological activitv(13.14). The exception to this trend was the replacement by the oxime function-alitv(2.3). The alkyl aryl oxime ethers are not susceptible to alkaline hydrolysis and esteric attack as are the pyrethroid esters(15). The present study details our investigation of the biological activity of [1,1 -biphenyl]-3-methanols when combined with alkyl aryl methanone oximes. 

The breakthrough for pyrethroids as agricultural insecticides became possible when the high activity of its pyrethroid ester in connection with the photostabihty of 3-dichlorovinyl-2,2-dimethyl cyclopropane carboxyhc acid 91 was found. This acid, synthesized first by Farkas, Sorm and Kurim in 1957 [127], was rediscovered during a straight forward search for higher stabihty by Elhott and Janes in 1969 and tested as the photostable ester permethrin. 

The stereospecific synthesis of the cis-norisopyrethrinic acid 231 deserves particular interest. This is an acid component for highly active pyrethroid esters with a very interesting biological spectrum (Reaction scheme 156). Usually the Horner olefmation gives Z/E-mixtures [455], but by applying cyclic phosphonic esters 232, one obtains only the Z-isomers [456, 922]. 

Resolution of 262, using phenethyl amine [532], phenyl-tolyl-ethylamin [534] or cinchonidin [535] produces the S-enantiomer [529, 530, 533], essential for insecticidal activity of its pyrethroid ester esfenvalerate. Flucythrinate acid is resolved by phenethyl amine [531]. 

One fluorine atom in position 4 of 3-phenoxy benzaldehyde improves the insecticidal activity of its ensuing pyrethroid esters (cyfluthrin and flumethrin) and nonesters by a factor of at least two (see p. 42, Vol. 4 of this series). Production of this aldehyde 288 certainly is more expensive. An essential step is also the Ullmann-reaction with a fluorine atom in the nucleus of one component 289 (Reaction scheme 206) [599-604]. 

This alcohol 312 was the first one conveying very high insecticidal activity to its pyrethroid esters, and must be regarded as the direct forerunner of modem pyrethroid alcohols. The technical process for resmethrin 315 (Reaction scheme 219) builds up a furane ring in a classical manner [676, 677]. 

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). 

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. 

The first significant success in creating a photostabilized pyrethroid with high insecticidal activity was achieved through use of the 3-phenoxybenzyl alcohol moiety. A further step was the finding that 2-aryl-3-methylbutyric acid esters of pyrethroid alcohols were both photostable and... 

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. 

In 1958, Barthel et al. [25] reported dimethrin (15), which was the first substituted benzyl alcohol ester of chrysanthemic acid. This compound was not put into practical use due to its low insecticidal activities. Phenothrin (16), one of the m-phenoxybenzyl alcohol esters developed by Fujimoto et al. [26], was found to have superior chemical stability as well as safety, and has been the sole pyrethroid used as a lice control agent for humans. Further improvement was made by Matsuo et al. [27] who introduced a cyano function at the a position of the benzyl part of phenothrin, leading to a-cyano-m-phenoxybenzyl alcohol esters (17). Thereafter, this alcohol moiety has been used as a component for a number of photostable pyrethroids for agricultural purposes however, the development of cross-resistance can be seen in some pests. 

A. aegypti colonies were found to have developed cross-resistance to even polyfluoro benzylalcohol ester pyrethroids with potent insecticidal activity. Mosquito coils of these compounds were effective against allethrin-susceptible A. aegypti colonies at ultra-low concentration, but needed several times higher concentrations for A. aegypti colonies in Group III in Table 8 (unpublished). 

Hirano M, Itaya N, Ohno I, Fujita Y, Yoshioka FI (1979) A new pyrethroid-type ester with strong knockdown activity. Pestic Sci 10 291-294... 

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