The pyrethrins and related compounds. XIX Geometrical and optical isomers of 2,2-dimethyl-3-(2,2-dichlorovinyl)-cyclopropanecarboxylic acid and insecticidal esters with 5-benzyi-3-furylmethyi and 3-phenoxybenzyl alcohols

Esters of 2,2-dimethyl-3-(2,2-dichlorovinyl)-cyclopropanecarboxylic acid with appropriate alcohols are more active insecticides than the corresponding 3-isobutenyl compounds (chrysanthemates). (±)-Cis and (±)-trans forms of the dichloro acid are obtained by fractional crystallisation of the mixed acids or by hydrolysis of the ethyl esters separated by fractional distillation. The (±)-cis and (±)-trans acids are resolved into their (+)- and (-)-forms with α-methyl-benzylamine and threo-l-p-nitrophenyl-2-N,N-dimethyiamino-propane-1,3-diol respectively. As for the corresponding chrysanthemates, the (+)-cis and (+)-trans acids give esters more active as insecticides than their enantiomers.     

Toxicity of some pyrethroids to the adult desert locust,Schistocerca gregaria forsk

The toxicity of a number of topically applied pyrethroids has been tested against adult male desert locusts, Schistocerca gregaria: the most potent proved to be 5-benzyl-3-furylmethyl (+)-trans-chrysanthemate (bioresmethrin) with a weighted mean LD₅₀ of 4.0 μg/g. The remaining compounds may be ranked in order of toxicity as follows: 5-benzyl-3-furylmethyl (±)-cis-trans-chrysanthemate (resmethrin) > 4-allyl-2,6-dimethyl-benzyl(+)-trans-chrysanthemate > 4-allylbenzyl (+)-trans-chrysanthemate > 2,4,6-trimethylbenzyl (+)-cis-trans-chrysanthemate > 2,3,4-trimethylbenzyl (+)-cis-trans-chrysanthemate > 2,4-dimethylbenzyl (±)-cis-trans-chrysanthemate; 2-methylbenzyl (±)-cis-trans-chrysanthemate. A small factor of synergism (4.2) was obtained with bioresmethrin following pre-treatment with sesamex, but with resmethrin the synergistic ratio (1.6) was of little practical significance.     

Independent and joint biological activity of isomeric forms of synthetic pyrethroids

Various isomeric mixtures of pyrethroids were examined in topical application tests against houseflies, Musca domestica. On the basis of the activities of the separate isomers of 5-benzyl-3-furylmethyl (±)-cis,trans-chrysanthemate, it was shown that when combined in pairs to give the (±)-trans or (±)-cis or (+)-cis,trans mixtures the observed mortalities did not differ from those expected by simple additive action calculated by the harmonic mean. In contrast the (±)-cis,trans mixture showed considerable antagonism with a mortality only 60% of that expected. Similar evaluations using the separate and combined isomers of bioallethrin [(R,S)-3-allyl-2-methyl-4-oxocyclopent-2-enyl (allethronyl) ( + )-trans-[(1R,3R)-chrysanthemate] and the corresponding (+)-cis-(1R,3S)-chrysanthemate indicate antagonism calculated to be correlated with the content of the (R)-isomer of the alcoholic moiety. Hence the activity of the most active isomer of the “allethrin” series, (S)-3-allyl-2-methyl-4-oxocyclopent-2-enyl ( + )-trans-(1R,3R)-chrysanthemate, (S)-bioallethrin, is not fully realised unless it is present in pure form and a substantial part of the value of bioresmethrin (5-benzyl-3-furylmethyl ( + )-trans-chrysanthemate] as a killing agent is lost when the racemic form is used. In racemic mixtures there is mutual antagonism between pairs of isomers so that considerable masking of activity occurs.     

Insecticidal activity of the pyrethrins and related compounds V. toxicity of the methylbenzyl chrysanthemates to houseflies (Musca domestica) and mustard beetles (Phaedon cochleariae)

The insecticidal activities to houseflies and to mustard beetles of the 19 methylbenzyl (±)-cis-trans-chrysanthemates were measured to establish the patterns of substitution that produce the greatest toxicities to these insects. The two species of insect differ in their responses to the various compounds in the series. The most active compounds to houseflies and mustard beetles are, respectively, 2,4,6-and 2,3,6-trimethylbenzyl (±)-cis-trans-chrysanthemates.     

Electrophysiological and behavioural responses of Pityophthorus pubescens (Coleoptera: Scolytinae) to (E,E)‐α‐farnesene, (R)‐(+)‐limonene and (S)‐(−)‐verbenone in Pinus radiata (Pinaceae) stands in northern Spain

BACKGROUND: Some twig beetles in the genus Pityophthorus (Coleoptera: Scolytinae) may vector pitch canker disease Fusarium circinatum (Niremberg & O'Donnell) of Pinus spp. (Pinaceae). Because Pityophthorus pubescens (Marsh.) has been found to be associated with F. circinatum in the Basque Country (northern Spain), various experiments were conducted to assess the beetle's behavioural responses to (E, E)‐α‐farnesene, (R)‐(+)‐limonene and (S)‐(?)‐verbenone to develop a potential inhibitor to host attraction. These experiments comprise electroantennographic and double‐choice olfactometer tests, as well as field assays in Pinus radiata D. Don stands. RESULTS: Both sexes of P. pubescens showed similar electroantennographic responses to different doses (from 1 ng to 1 µg in decadic steps) of each individual compound, with depolarisations to (S)‐(‐)‐verbenone (100 ng) being similar to those of the aggregation pheromone (+)‐trans‐pityol. In olfactometer assays, both sexes were significantly attracted to (+)‐trans‐pityol, but the attraction was reduced when increasing amounts of the chemicals were added to the pheromone. Particularly relevant was the repellent effect induced by (S)‐(?)‐verbenone at 1 ng dose and higher. In the field, (E, E)‐α‐farnesene, (R)‐(+)‐limonene and (S)‐(?)‐verbenone reduced significantly the number of beetles attracted to (+)‐trans‐pityol and racemic trans‐pityol, with (S)‐(?)‐verbenone being the most effective. CONCLUSIONS: (S)‐(?)‐Verbenone showed an interesting potential for use in the protection of P. radiata stands. A potentially effective strategy, which could be implemented in further, more in‐depth studies, could involve the use of this semiochemical as repellent and (+)‐trans‐pityol‐baited traps as attractant in a ‘push‐pull’ strategy. Copyright © 2012 Society of Chemical Industry     

Stability of cypermethrin and cyfluthrin on wheat in storage

Cypermethrin and cyfluthrin were applied to wheat, which was stored for 52 weeks at 25 or 35°C, and either 12 or 15% moisture content. Total residues and the proportions of the four pairs of enantiomers, cis I [(αR),(1R)-cis + (αS),(1S)-cis], cis II [(αR),(1S)-cis + (αS),(1R)-cis], trans III [(αR),(1R)-trans + (αS),(1S)-trans], and trans IV [(αR),(1S)-trans + (αS),(1R)-trans] for each pyrethroid were determined at five intervals during storage. For all storage conditions, the cis I isomers were the most stable, and the trans IV isomers were the least stable. Calculated half-lives (weeks) for the pairs of enantiomers at 25°C (12% moisture) and 35°C (15% moisture) were: cypermethrin, cis I, 252, 62 and trans IV 66, 27; cyfluthrin, cis I, 114, 52 and trans IV 42, 23. The results suggested that one of the enantiomers of the cypermethrin trans IV pair was degraded faster than the other.     

Synthetic pyrethroids containing a C–C triple bond

The three commercial synthetic pyrethroids containing a carbon–carbon triple bond, α-ethynyl-2-methylpent-2-enyl (1R)-trans-chrysanthemate, (S)-2-methyl-4-oxo-3-(2-propynyl)cyclopent-2-enyl (1R)-trans,cis-chrysanthemate and [2,5-dioxo-3-(2-propynyl)-1-imidazolidinyl]methyl (1R)-trans-chrysanthemate are reviewed with emphasis on their inventive histories. Their chemistry and efficacy are described briefly. The relationship between stereochemistry and the biological activity is also discussed. © 1998 SCI.     

Changes in cross-resistance patterns of houseflies selected with natural pyrethrins or resmethrin (5-benzyl-3-furylmethyl (±)-cis-trans-chrysanthemate)

A pyrethrins-resistant strain of houseflies, 213ab, previously selected with a 1:10 (by wt.) mixture of natural pyrethrins and piperonyl butoxide, was further selected either with natural pyrethrins alone (strain NPR) or with resmethrin (strain 104). After 50 generations the two populations differed in their resistance to the natural and synthetic esters. Both were resistant to all pyrethroids. Part of strain NPR was immune and very much more resistant than strain 104 to the natural pyrethrins and allethrin, but it was only 2–3 times more resistant than strain 104 against the new synthetic esters resmethrin (5-benzyl-3-furylmethyl (±)-cis-trans-chrysanthemate), bio-resmethrin (5-benzyl-3-furylmethyl (+)-trans-chrysanthemate), pyresmethrin (5-benzyl-3-furylmethyl pyrethrate) and 5B2Me3FC (5-benzyl-2-methyl-3-furylmethyl (±)-cis-trans-chrysanthemate). Pretreatment of both strains with sesamex diminished but did not eliminate resistance. Synergism was greater in strain NPR, especially with natural pyrethrins and allethrin. Both strains had great resistance to DDT indicating that resistance to DDT and pyrethroids is linked. Differences in resistance to different compounds suggest that at least three factors can confer resistance, one of which, pen, delays penetration and two others involve detoxication, one py a on the acid side of the ester linkage and the other, py b, on the alcohol side. Natural pyrethrins and resmethrin select for different groupings of these factors. Treatment with resmethrin does not select for py b presumably because this mechanism cannot attack the resmethrin molecule. Similarly when piperonyl butoxide is added to the natural pyrethrins py b is inhibited and so removed from selection pressure. Under these conditions, the strain produced contains the same factors as one selected by resmethrin and so shows the same small resistance to natural pyrethrins alone.     

Stereochemical and chiral aspects in the synthesis of 3-(2,2- dihalovinyl)-2,2-dimethylcyclopropanecarboxylic acids

The synthesis of (1RS)-cis,trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid by dehydrohalogenation of 4,6,6,6-tetrahalohexanoates has been modified to produce stereo-selectively the cis-isomer. A new stereospecific synthesis of cis-3-(2,2-dihalovinyl)-2,2-dimethylcyclopropanecarboxylic acids using a bicyclic lactone and its extension to the preparation of the optically active (1R)-cis acid are described.     

Substrate-specificity and toxicological significance of pyrethroid-hydrolyzing esterases of mouse liver microsomes

An esterase or esterases in acetone powder preparations of mouse liver microsomes hydrolyze the cyclopropanecarboxylate ester linkage of pyrethroid insecticide chemicals derived from primary alcohols. The rate of cleavage of (+)-trans-chrysanthemates with various alcohol moieties decreases in the following order: 5-propargyl-2-furylmethyl; 5-benzyl-3-furylmethyl (bioresmethrin); 3-phenoxybenzyl; tetrahydrophthalimidomethyl esters. The hydrolysis rate of benzylfurylmethyl esters with various acid moieties decreases in the order: (+)- or (?)-trans-chrysanthemate; (+)-trans-ethanochrysanthemate; tetramethylcyclopropanecarboxylate; (+)- or (?)-cis-chrysanthemate or (+)-cis-ethanochrysanthemate. The trans-isomers of chrysanthemates and ethanochrysanthemates are hydrolyzed from 2.6- to more than 50-fold more rapidly than the corresponding cis-isomers. This enzyme system does not hydrolyze secondary alcohol esters, i.e., allethronyl (+)-trans- and (+)-cis-chrysanthemates.On intraperitoneal administration to mice, the (+)-trans-chrysanthemate and -ethanochrysanthemate of benzylfurylmethanol are of very low toxicity relative to the corresponding (+)-cis-isomers and the tetramethylcyclopropanecarboxylate. S,S,S-tributyl phosphorotrithioate (DEF) pretreatment increases the toxicity of these five compounds by 2.6- to more than 188-fold, with the exception of bioresmethrin whose toxicity is not altered. When the toxicity is increased, it is probably the result of esterase inhibition since DEF strongly inhibits the esterase activity of fresh liver microsomes while the mixed-function oxidase system remains active. The oxidase system metabolizes the chrysanthemates more rapidly than the ethanochrysanthemates of benzylfuryl-methanol. Depending upon the pyrethroid involved, the esterase or the mixed-function oxidase system, or both may be responsible for limiting the toxicity of these pyrethroids to mice.     

Activity of some new pyrethroids against Blattella germanica L.

The activities of natural and synthetic pyrethroids against male German cockroaches (Blattella germanica) were examined by means of dusting and direct spraying techniques. NRDC 107 (5-benzyl-3-furylmethyl (+)-trans-chrysanthemate) was the most active compound in killing cockroaches. Pyrethrins gave the most rapid knockdown and were 60% as active as NRDC 107 (Bioresmethrin) in killing power. Tetramethrin and the corresponding (+)-trans-ester gave rapid knockdown. Only (+)-trans-allethrin [(+)-trans-chrysan-themate of (±)-allethrolone] provided useful knockdown and killing power together. Piperonyl butoxide had a relatively stronger synergistic action with less active killing agents. The rate of knockdown during the first few minutes of exposure was not altered greatly by piperonyl butoxide.     

铜绿丽金龟对寄主植物挥发物的触角电生理及行为反应

为深入了解铜绿丽金龟的取食行为,探索开发安全高效的植物源引诱剂,应用昆虫触角电位反应仪和Y型嗅觉仪测试其对不同寄主植物挥发物的趋向行为差异,并根据室内行为结果配制诱剂进行大田试验。结果表明:铜绿丽金龟雄虫对水杨酸甲酯和(1,1’-联环戊基)-2-酮的触角电位反应(electroantennography,EAG)值显著高于其它试剂;石竹烯和水杨酸甲酯能引起雌虫触角较强的电位反应;乙酸顺式-3-己烯酯和石竹烯分别对雄虫和雌虫有较高的嗅觉选择反应率,分别达0.95和0.94。综合EAG和嗅觉试验结果,选择对雌、雄虫均有较好引诱效果的反式-2-己烯醛、乙酸顺式-3-己烯酯、石竹烯、(1,1’-联环戊基)-2-酮和水杨酸甲酯进行田间试验,最终筛选到铜绿丽金龟雄虫的最适引诱剂为每诱芯360 mg乙酸顺式-3-己烯酯,雌虫的最适引诱剂为每诱芯360 mg石竹烯,日诱虫量分别可达33.00±1.53头和29.33±1.45头。     

Decreased nerve sensitivity and decreased cuticular penetration as mechanisms of resistance to pyrethroids in a (1R)-trans-permethrin-selected strain of the house fly

A fenthion-resistant strain of the house fly (Musca domestica L.) was selected with bioresmethrin resulting in ca. 90-fold resistance to the selecting agent. This strain was subsequently selected with (1R)-trans-permethrin producing ca. 140-fold resistance to this latter insecticide. The permethrin-resistant (147-R) strain was highly cross-resistant to several other pyrethroids and demonstrated resistance to knockdown by these insecticides as well as by DDT. The sensitivity of the central nervous system to four pyrethroids was investigated. The 147-R strain was 2.6-fold less sensitive to (1R)-trans-ethanoresmethrin than the susceptible (NAIDM-S) strain, and >43-fold and >67-fold less sensitive to (1R,S)-cis, trans-tetramethrin and (1R)-trans-permethrin, respectively. It also displayed decreased penetration of (1R,S)-trans-[¹⁴C]permethrin when compared to the NAIDM-S strain. Lower nerve sensitivity and decreased cuticular penetration are potential mechanisms of resistance to pyrethroids in house flies in the United States.     

Absorption and metabolism of permethrin and cypermethrin in the cockroach and the cotton-leafworm larvae

Permethrin was metabolised by attack at the ester bond, in vivo by adult cockroaches, Periplaneta americana and in vitro by esterase preparations. Metabolites retaining the ester linkage could not be detected. In all cases, the (1RS)-trans-isomer (transpermethrin) was more labile than the (1RS)-cis-isomer. Cypermethrin was metabolised at one-fifth the rate for permethrin. In-vitro and in-vivo studies with synergists indicated that cleavage of the ester bond in permethrin can be both oxidative for the (1RS)-cis-isomer and hydrolytic for the (1RS)-trans-isomer. The penetration of permethrin through the cuticle of the cockroach was significantly greater than that of cypermethrin. The penetration and metabolism of permethrin and cypermethrin in sixth-instar larvae of susceptible and resistant strains of the Egyptian cotton-leafworm, Spodoptera littoralis, were studied as possible factors in resistance. No significant differences were found. It is suggested that the major resistance factor to permethrin in S. littoralis is probably non-metabolic.     

Metabolism of four resmethrin isomers by liver microsomes

Microsomal esterases of mouse and rat liver readily cleave the trans- but not the cis-isomers of resmethrin (5-benzyl-3-furylmethyl chrysanthemate). The ester linkage also appears to undergo oxidative cleavage when esterase attack is minimal, i.e., with (+)-cis- and particularly (?)-cis-resmethrin in microsome-NADPH systems and with any of the isomers when NADPH is added to microsomes pretreated with TEPP. Metabolites retaining the ester linkage are detected in significant amounts only with (+)-cis-resmethrin in which case they are formed by oxidation at either the trans(E)- or cis(Z)-methyl group of the isobutenyl moiety with or without oxidation of the benzylfurylmethyl group. Metabolites of each acid moiety include chrysanthemic acid and up to six derivatives of this acid formed by oxidation at the trans(E)- or cis(Z)-methyl group yielding the corresponding alcohol, aldehyde, or acid, with chrysanthemate isomer and enzyme source variations in the preferred site of oxidation. The major identified metabolite of the alcohol moiety is either benzylfurylmethanol or the corresponding carboxylic acid depending on the enzyme system used. In the course of microsomal oxidation, a fragment from the alcohol but not the acid moiety of (+)-trans- and (+)-cis-resmethrin is strongly bound to microsomal components. These findings confirm in vivo studies on the isomeric variations in metabolism of the resmethrin components.     

Cross-resistance spectrum in pyrethroid-resistant Culex quinquefasciatus

Strains of Culex quinquefasciatus Say, selected with biopermethrin [(1R)-trans-permethrin] or with (1R)-cis-permethrin, were examined in the larval stage for crossresistance to 30 pyrethroids, DDT, dieldrin, temephos, propoxur, and two organotin compounds. The (1R)-trans-Permethrin-R strain [resistance factor (RF) = 4100-fold] and the (1R)-cis-Permethrin-R strain (RF= 450-fold) of C. quinquefasciutus were cross-resistant to all pyrethroids tested [RF= 12-fold for an allethrin isomer to about 6000-fold for (RS,RS)-fenvalerate] as well as to DDT (RF= about 2000-fold). However, they were not significantly Cross-resistant to dieldrin, temephos, propoxur, and the two organotin compounds. Changes in the alcohol moiety, structural isomerism, and susceptibility of the cyclopropane C-3 side chain to oxidative attack are important factors in determining the level of cross-resistance to various pyrethroids. Limited synergism of the pyrethroids by S,S,S-tributyl phosphorotrithioate and piperonyl butoxide (PB), and of DDT by chlorfenethol and PB, suggested that some non-metabolic mechanism, such as kdr, may be an important component of resistance to pyrethroids as well as to DDT in this mosquito.     

Degradation of the herbicide flamprop-isopropyl in soil under laboratory conditions

The degradation of the wild-oat herbicide flamprop-isopropyl, [isopropyl (±)-N-benzoyl-N-(3-chloro-4-fluorophenyl)alaninate], in four soils has been examined under laboratory conditions with sampling times of up to 45 weeks after treatment. The major degradation product of [¹⁴C]flamprop-isopropyl in all soils at up to 10 weeks after treatment was the carboxylic acid (±)-N-benzoyl-N-(3-chloro-4-fluorophenyl)alanine. This compound in turn underwent degradation by loss of the benzoyl group and the propionic acid moiety, with evolution of [¹⁴C]carbon dioxide to form 3-chloro-4-fluoroaniline (CFA). The CFA was formed slowly in soil and occurred mainly as a bound form. There was evidence to show that the CFA was subsequently converted into other polar products. The time for depletion of 50% of the applied herbicide was approximately 10 weeks in sandy loam and medium loam soils, 11 weeks in a clay loam soil and 23 weeks in a peat soil.     

The pyrethrins and related compounds: X.—The methylbenzyl chrysanthemates

New or improved routes are used to prepare all the nineteen methylbenzyl chrysanthemates, including 2,4,6-trimethylbenzyl (+) and (?)-trans-chrysanthemates, 2,3,4,6-tetramethyl-and 2,3,4,5,6-pentamethyl-benzyl chrysanthemates, and the chrysanthemates of the new alcohols, 2,3,5-and 3,4,5-trimethylbenzyl alcohols.     

Metabolism of the cis- and trans-isomers of cypermethrin in mice

Metabolism in mice of the separated cis- and trans-isomers of the pyrethroid insecticide cypermethrin (NRDC 149), (RS)-α-cyano-3-phenoxybenzyl (1RS)-cis, trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate, was investigated in each case with preparations that were ¹⁴C-labelled in the benzyl and cyclopropyl moieties. Radioactivity from the trans-isomer was mainly excreted in the urine and that from the cis-isomer in the faeces. Elimination of both isomers was rapid except for a small portion (approximately 2%) of the cis-isomer which was released from the fat with a half-life of approximately 13 days. Metabolism of cypermethrin occurred mainly by ester cleavage and elimination of the cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethyl- cyclopropanecarboxylic acid moieties as glucuronide conjugates. The α-cyano-3-phenoxybenzyl alcohol released by ester cleavage was mainly converted to 3-phenoxy-benzoic acid which was partly eliminated unchanged, partly conjugated with aminoacids (mainly taurine) and glucuronic acid, and partly oxidised to 3-(4-hydroxyphenoxy) benzoic acid which was excreted as the sulphate conjugate. Metabolites retaining the ester linkage were formed by hydroxylation at various sites in the molecule with more hydroxylation of the cis- than of the trans-isomer occurring.     

Life-table analyses for the tomato leaf miner,Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae): effects of plant genotype

BACKGROUND

Host plant resistance plays an important role in integrated pest management programs. Crop resistance assessments commonly focus on only a single dependent variable, such as larval survival/plant damage, which limits the ability to appreciate the impact of host plants on pest populations in the full sense. Therefore, we performed life-table analyses for tomato leaf miner Tuta absoluta, on 19 Solanum lycopersicum genotypes and a wild Solanum habrochaites accession. These analyses assess the ability of the pest to attain a high population density on different tomato genotypes. Based on the resulting ranking of tomato resistance at the vegetative stage (45-day-old plants), we tested the resistance of six selected genotypes at the reproductive stage (4-month-old plants).

RESULTS

T. absoluta performance was significantly inferior on vegetative-stage S. habrochaites plants (LA 1777); time taken for the first instars to mine the leaves (5 ± 0.14 days), development time of early- and late-stage larvae (8.8 ± 0.2 and 4.2 ± 0.2 days, respectively), pupal period (11.2 ± 0.58 days), and total developmental time (29.4 ± 0.83 days) were significantly longer, fecundity was significantly lower (18.66 ± 7.24 days), and the highest total mortality (63.33%) also recorded compared with other genotypes, resulting in the lowest net reproductive rate (R₀) (11.20 ± 2.51). For the six selected genotypes, the ranking of plant resistance did not change between plants at the vegetative and reproductive stages.

CONCLUSION

This study suggested that of 20 screened tomato genotypes, LA 1777 and EC-620343 are the least suitable hosts for T. absoluta to establish fast-growing populations, and thus can be employed in integrated T. absoluta management. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.