Insecticidal activities stereoisomers

In contrast to the case of HMPC, most lipases hydrolyze the racemic acetate of CPBA 9 to give a mixture of the insecticidally active (S)-CPBA 2 and the (R)-acetate 1J). Thus, the desired (S)-CPBA J2 could be separated from the (R)-acetate 10 by means of a continuous counter-current extraction using n-heptane solvent at 80°C. However, it is important to utilize the recovered (R)-acetate W for an efficient process. Fortunately, since the proton of the asymmetric carbon of the cyanohydrin acetate is labile, the antipodal (R)-acetate is easily racemized by treatment with weak organic base such as triethylamine without any side reactions. The racemized acetate J9 thus obtained was recycled as shown in Figure 6. Therefore, all of the racemic acetate 9 was converted to the desired (S)-CPBA 2 in this recycling process. The (S)-CPBA 2 obtained was esterified with (S)-2-(4-chlorophenyl)-3-methylbutyryl chloride to produce the most insecticidally active stereoisomer V2 of fenvalerate, namely esfenvalerate. The relative biocidal activities between... 

Fenvalerate (XXI, Hg. 7) (Pydrin, Sumicidin, Belmark) is an effective broad-spectrum synthetic pyrethroid insecticide. Fenvalerate exhibits improved photolytic stability and extended field residual activity compared to other pyrethroids. The most insecticidally active stereoisomer is of the 2S,(xS[S,S] conflguration. The racemic mixture and the pure effective insecticide were investigated... 

The residual activity of the racemic mixture and the most insecticidally active stereoisomers [S,S] were investigated on soil samples. Before application the isomer separation of the C-fenvaler-ate was carried out by six consecutive developments in hexane-ether (20 1). The [S,S] and [R,R] isomers were located at R/0.46 and the [R,S] and [S,R] stereoisomers at R/0.49 (Table 9). The isonter pairs were finally resolved in HPLC using a chiral stationary phase. Soil extracts were analyzed in order to investigate the degradation processes and persistence of C-fenvalerate (Table 9) (115). The parent compound and its degradation products were separated by two-dimensional TLC (Table 9)... 

Chrysanthemumic acid may exist in four stereoisomers, because of the two asymmetric carbon atoms in the cyclopropane ring. The natural acid has the D-trans configuration and this has been shown to be more insecticidally active than any of the other isomers or the racemic form. Harper et al, (4,18) have synthesized, separated, and optically resolved all of the isomers of this acid. 

Chrysanthemum dicarboxylic acid or pyrethric acid may exist in eight stereoisomers, owing to the trans or cis configuration on the side chain of the double bond as well as that of the cyclopropane. The natural acid has been shown to be the trans-trans acid. As in the case of the chrysanthemum monocarboxylic acid, the naturally occurring configuration is more insecticidally active than the racemic form or any of the three isomers synthesized. 

Chlorination of benzene gives an addition product that is a mixture of stereoisomers known collectively as hexachlorocyclohexane (HCH). At one time, this was incorrectly termed benzene hexachloride. The mixtnre has insecticidal activity, though activity was found to reside in only one isomer, the so-called gamma isomer, y-HCH. y-HCH, sometimes under its generic name lindane, has been a mainstay insecticide for many years, and is about the only example of the chlorinated hydrocarbons that has not been banned and is still available for general use. Although chlorinated hydrocarbons have proved very effective insecticides, they are not readily degraded in the environment, they accumulate and persist in animal tissues, and have proved toxic to many bird and animal species. 

Synthetic pyrethroids are a group of ester compounds having excellent insecticidal activities. After the discovery of allethrin (1), a variety of useful synthetic pyrethroids have been produced mainly by structural modification of an alcohol having an asymmetric center. The insecticidal activities greatly depend upon the stereoisomers. Therefore, much effort has been expended to develop technologies for obtaining optically active isomers. However, contrary to the case of chrysanthemic acid, chemical methods of optical resolution were not very effective for these alcohols. 

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. 

Table IV. Insecticidal Activities of Stereoisomers of Prallethrin against Housefly and Cockroach (Topical Application)...

The most remarkable compound listed is probably permethrin, a rebuilt chemical with much higher stability and insecticidal activity than the natural pyrethroid. Not much later the difference in activity between the various stereoisomers was taken into account. Permethrin is a racemic mixture, but in the products called bio-, as in bioallethrin and bioresmethrin, as well as in deltamethrin and several other newer pyrethroids, the inactive stereoisomers have been removed. Deltamethrin has a cyano group, making mirror-image isomerism possible. The one shown is the most potent. Substances without the cyclopropane moiety were also found. Fenvalerate was developed by Sumitomo Chemical Co. Ltd. and described in 1974, whereas its most active isomer was found and described in 1979. 

C. (25 )-a-cyano-3-phenoxybenzyl (a/ )-2-4-chlorophenyl-3-methylbutyrate. The 25, aR isomer has markedly reduced insecticidal activity when compared with the 25, aS isomer, but is greatly elevated in this respect when compared with fenvalerate stereoisomers with an R configuration in the acid moiety, that is, the 2R, aS, and the 2R, aR isomers. 

Resmethrin possesses excellent insecticidal activity and low toxicity to mammals. It is applied as space spray for fly control in and around dairy facilities. The persistence and metabolism of its stereoisomers were studied in tissues and excreta of lactating cows (Table 9) (124). 

Alkylamines have a variety of applications in the chemical industry as starting materials for the preparation of insecticides and pharmaceuticals. Labetalol, for instance, a so-called /3-blocker used for the treatment of hi h blood pressure, is prepared by SN2 reaction of an epoxide with a primary amine. The substance marketed for drug use is a mixture of all four possible stereoisomers, but the biological activity derives primarily from the (R,R) isomer. 

Pyrethrolone and cinerolone make up the keto alcohol moiety of the pyrethrins. Both of these keto alcohols have one asymmetric carbon at the 4-position and a double bond in the side chain which is capable of cis-trans isomerism in the 2-position. It is possible, therefore, to have four stereoisomers for each keto alcohol. Katsuda et al. (22) show that only the ( + ) form occurs in the natural esters. Elliott (8) has shown recently, by a new procedure developed to obtain pure ( + ) pyrethrolone, that the hitherto unidentified prye-throlone C is in reality pyrethrolone contaminated with thermally isomerized material. (+) Pyrethrolone forms a crystalline monohydrate from which the pure alcohol is obtained. The natural configurations of the keto alcohols in the esters are insecticidally more active, as is the case with the acid moiety. 

The steric structure of the compounds is also of great importance from the activity viewpoint. From the two possible stereoisomers (Biichel et al., 1966), only jS-chlordane (41a) of -exo-2-exo structure has a strong insecticidal effect while its stereoisomer, a-chlordane of -exo-2-endo structure (41b), is considerably weaker (March, 1952). 

The compound is a quick-acting contact and systemic insecticide and, being volatile, it haialso a fumigant action. Both leaves and roots of the plant absorb the compound rapidly. Of its stereoisomers, the Z-isomer (Z-mevinphos, 73a) is a hundred times more active than the -isomer ( -mevinphos, 73b), so that the Z-isomer is virtually the sole carrier of the insecticidal effect. 

Mevinphos (96, Phosdrin ) is prepared from methyl 3-chloroacetoacetate in reaction with trimethyl phosphite. Mevinphos (Phosdrin ) is a mixture of Z and E stereoisomers in which the Z isomer was found to be 100 times more active.54 In contrast to mevinphos, E and Z isomers of bromfenvinphos (92) and chlorfenvinphos (94) show no significant difference for a number of biological properties for insecticides.55 The less toxic Clodrin (98) is synthesized from the 1-phenylethoxy ester of 3-chloracetoacetate 97 which is used for control of ectoparasites in horses, cattle, sheep, and swine.54... 

The synthesis of chrysanthemic acid 1 as mixture of stereoisomers, as racemate of pure stereoisomers or as single optically active isomer was important before the advent of synthetic photostable pyrethroids. Because of the approved and favourable properties of pyrethrin I as a non-toxic and fast-acting contact insecticide, not only pyrethrum, but also other esters of chrysanthemic acids with similar properties are of commercial interest. Therefore cheap methods for the synthesis of this add or even total synthesis of the natural compound deserve the attention of chemists involved in synthesis. Many interesting reactions, involving rearrangements, eliminations and additions were apphed in the synthesis of this archetypical pyrethroid cydopropane carboxyhc acid. 

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... 

Geinoz S, Guy RH, Testa B, Carrupt PA (2004) Quantitative structure-permeation relationships (QSPeRs) to predict skin permeation a critical evaluation. Pharm Res 21 83-92 Ghiasuddin SM, Soderlund DM (1985) Pyrethroid insecticides potent, stereospecific enhancers of mouse brain sodium channel activation. Pestle Biochem Physiol 24 200-206 Girelli AM, Messina A, Sinibaldi M (2002) A study on the separation of synthetic pyrethroid stereoisomers by FIPLC. Ann Chim 92 417-424... 

Pyrethroids are synthetic analogs of derivatives of chrysanthemic acid, 25.6, naturally occurring in plants of the Chrysanthemum genus. The naturally extracted materials, pyrethrin I and II (25.7, 25.8), have been modified for better activity in compounds such as permethrin, 25.9, and deltamethrin, 25.10. They are toxic to cats and to aquatic life but have otherwise generally low toxicity to mammals and are broken down rapidly in the environment. They are widely used as domestic insecticides. You should note that although a single stereoisomer... 

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