The activity of some pyrethroids against Periplaneta americana and Blattella germanica

The knockdown and contact killing actions of various pyrethroids were compared using Blattella germanica and Periplaneta americana. A wide range of knockdown activity was found; 5-benzyl-3-furylmethyl (1R)-cis-3-(dihydro-2-oxo-3-thienylidenemethyl)-2,2-dimethylcyclopropanecarboxylate (RU 15525) acted fastest, more rapidly than pyrethrins, against B. germanica as well as having a low LD₅₀ value. Topical application and direct spray tests showed that (S)-α-cyano-3-phenoxybenzyl (1R)-cir-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropanecarboxylate (NRDC 161) was more active as a killing agent, by an order of magnitude, than cismethrin, the next most active compound, and also had considerable knockdown activity. Piperonyl butoxide generally had little synergist effect. Female P. americana were over three times more tolerant than males to a range of insecticides applied topically. Residual knockdown action in the WHO resistance test was observed to provide baseline data. There was little overlap in speed of action between pyrethroids and other insecticides among the compounds tested.     

Interaction between optical isomerism and plant pharmacological action,change of modes of action and chirality of 1-(α-methylbenzyl)-3-p-tolylurea

The optical isomers, (R)-1(α-methylbenzyl)-3-p-tolylurea ((R)-MBU) and (S)-1-(α-methylbenzyl)-3-p-tolylurea ((S)MBU), which are analogues of daimuron [1-(α,α-dimethylbenzyl)-3-p-tolylurea], a herbicide for Cyperaceae weeds and a safener for paddy rice, exhibited different biological responses. These two physiological properties of daimuron were observed separately in (R)-MBU and (S)-MBU. Only (R)-MBU had herbicidal activity against Cyperaceae weeds, while the (S)-isomer was a more effective safener against bensulfuron-methyl (BSM) injury of rice seedlings than was (R)-MBU. (S)-MBU promoted root growth of rice seedlings, but the (R)-enantiomer inhibited root growth. (S)-MBU was a more potent inhibitor than (R)-MBU on PS II reaction of spinach broken chloroplasts. Furthermore, (S)-MBU and (R)-MBU showed cross intergenus selective phytotoxicity among the Gramineae plants, Oryza sativa L. (rice, cv. Tsukinohikari, japonica), Triticum aestivum L. (wheat, cv. Norin No. 61) and Echinochloa crusgalli var. frumentacea Wight, on root growth inhibition in the dark.     

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.     

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.     

Actions of pyrethroid insecticides on insect axonal sodium channels

The actions of pyrethroid insecticides were tested on isolated giant axons of the cockroach Periplaneta americana, using oil-gap, single-fibre recording techniques. Current-clamp and voltage-clamp experiments were used to determine the actions of pyrethroids on axonal membrane potentials and ionic currents. Treatment with deltamethrin at micromolar concentrations caused gradual depolarisation of the axon accompanied by a reduction in amplitude of the action potential. This depolarisation was enhanced by an increase in stimulation frequency. Other synthetic pyrethroids: 3,4,5,6-tetrahydrophthalimidomethyl (1RS)-cis-3-[(RS)-2,2-dimethylcyclopropyl]-2,2-dimethylcyclopropanecarboxylate, biopermethrin and its (1S)-enantiomer, (1R)-tetramethrin, S-bioallethrin, bioresmethrin and its (1S)-enantiomer, cismethrin, and 5-benzyl-3-furylmethyl (E)-(1R)-cis-2,2-dimethyl-3-(2-oxothiolan-3-ylidenemethyl)cyclopropanecarboxylate (RU-15525, ‘Kadethrin’) were investigated. The (1S)-enantiomers were inactive, but all the other pyrethroids tested, apart from deltamethrin, induced prolonged negative (depolarising) after-potentials. All the treatments with the active pyrethroids resulted in the appearance of a voltage and time-dependent ‘maintained’ sodium conductance. The duration of this ‘slow’ conductance varied considerably depending on the pyrethroid under test. Clearly, the effectiveness of pyrethroids on whole insects is not determined only by the degree to which they directly modify the properties of sodium channels. Nevertheless, voltage-clamp experiments on isolated axons readily permit direct comparison of the actions of different pyrethroids on the sodium channels of insect neurones.     

1(R)-(2,6-cis-dimethylmorpholino)- 3(S)-(p-tert-butylphenyl)cyclopentane: A representative of a novel,potent class of bio-rationally designed fungicides

Inhibition of the Δ⁸-Δ⁷ sterol isomerase in the ergosterol biosynthesis pathway is known to lead to fungistatic or even fungicidal effects. Our approach to the rational design of new putative inhibitors of the enzyme was based on the assumed mechanism of the enzymic transformation and in particular on the structure of the unstable carbocationic intermediate, i.e. the ‘transition-state-analogue’ principle. The synthesis and the biological properties of 1(R)-(2,6-cis- dimethylmorpholino)-3(S)-(p-tert-butylphenyl)cyclopentane, a representative of a novel, potent class of rationally designed fungicides, as well as the synthesis and biological activities of several other related compounds are described and discussed.     

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.     

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.     

The optical isomers of α-cyano-3-phenoxybenzyl 3-(1,2-dibromo-2,2-dichloroethyl)-2,2-dimethylcyclo-propanecarboxylate and their insecticidal activities

Bromination of the dichlorovinyl group of cypermethrin yielded a new compound which is a highly potent insecticide. This dibromo adduct has four asymmetric centres and therefore can exist as a mixture of 16 stereoisomers. To establish the influence of the absolute configuration at the chiral centres on the biological activities of these isomers, each of the isomers was isolated; their insecticidal activities against larvae of Heliothis virescens, and adult Calliphora erythrocephala and Blattella germanica were then determined and compared with those of (S)-α-cyano-3-phenoxybenzyl (1R)-cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropanecarboxylate (deltamethrin NRDC 161), of fenvalerate, and of the eight stereoisomers of cyper methrin.     

The metabolism of fenvalerate in plants: The conjugation of the acid moiety

The metabolism of the pyrethroid insecticide fenvalerate [(RS)-α-cyano-3-phenoxybenzyl (RS)-2-(4-chlorophenyl)-3-methylbutyrate] ( I ), and of its most insecticidal (αS,2S) isomer ( II ), has been examined in cabbage plants grown and treated under laboratory conditions with [¹⁴C]chlorophenyl- and [ring-¹⁴C]benzyllabelled preparations of the two compounds. Both insecticides disappeared from the treated leaves with similar half-lives of approximately 12–14 days; they underwent ester cleavage to a significant extent, together with some hydroxylation at the 2- or 4-position of the phenoxy ring, and hydrolysis of the nitrile group to amide and carboxyl groups. Most of the carboxylic acids and phenols thus produced occurred as glycoside conjugates. In separate experiments, the uptake and metabolism of 2-(4-chlorophenyl)-3-methylbutyric acid ( X ), the acidic half of the molecule, were examined in the laboratory, using abscised leaves of kidney bean, cabbage, cotton, cucumber and tomato plants. The acid X was found to be readily converted, mainly into glucose and 6-O-malonylglucose esters in kidney bean, cabbage and cucumber plants, into glucosylxylose, sophorose and gentiobiose esters in cotton, and into two types of triglucose esters with differing isomerism in tomato. One of the acetyl derivatives of the trisaccharide conjugates was identical with the synthetic deca-acetyl derivative of the [1 → 6]-triglucose ester.     

Escherichia coli dihydrodipicolinate synthase and dihydrodipicolinate reductase: kinetic and inhibition studies of two putative herbicide targets

Dihydrodipicolinate synthase (DHDPS) (EC 4.2.1.52) and dihydrodipicolinate reductase (DHDPR) (EC 1.3.1.26) have attracted much recent attention as potential herbicide targets. DHDPS was feedback-inhibited by (S)-lysine; inhibition was reversible and uncompetitive with respect to both (S)-ASA and pyruvate. Homoserine lactone was a reversible non-competitive inhibitor of DHDPS with respect to both (S)-ASA and pyruvate. (R)-Cysteine sulfinic acid and (S)-glutamic acid were reversible uncompetitive inhibitors of DHDPS with respect to (S)-ASA. (S)-Aspartic acid was a reversible mixed-type inhibitor. Dipicolinic acid was a reversible competitive inhibitor of DHDPR with respect to the substrate (4S)-4-hydroxy-2,3,4,5-tetrahydro-(2S)-dipicolinic acid, as was isophthalic acid. Δ³-Tetrahydroisophthalic acid was a moderate inhibitor of both DHDPS and DHDPR. These compounds represent possible leads in the development of novel herbicides. © 1999 Society of Chemical Industry     

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.     

Acifluorfen metabolism in soybean: Diphenylether bond cleavage and the formation of homoglutathione, cysteine, and glucose conjugates

Metabolism of the substituted diphenylether herbicide, acifluorfen [sodium 5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzoate], was studied in excised leaf tissues of soybean [Glycine max (L.) Merr. ‘Evans’]. Studies with [chlorophenyl-¹⁴C]- and [nitrophenyl-¹⁴C]acifluorfen showed that the diphenylether bond was rapidly cleaved. From 85 to 95% of the absorbed [¹⁴C]acifluorfen was metabolized in less than 24 hr. Major polar metabolites were isolated and purified by solvent partitioning, adsorption, thin layer, and high-performance liquid chromatography. The major [chlorophenyl-¹⁴C]-labeled metabolite was identified as a malonyl-β- -glucoside (I) of 2-chloro-4-trifluoromethylphenol. Major [nitrophenyl-¹⁴C]-labeled metabolites were identified as a homoglutathione conjugate [S-(3-carboxy-4-nitrophenyl) γ-glutamyl-cysteinyl-β-alanine] (II), and a cysteine conjugate [S-(3-carboxy-4-nitrophenyl)cysteine] (III).     

Biological Activity of Two Stereoisomers of the N-Thienyl Chloroacetamide Herbicide Dimethenamid

Due to the presence of an asymmetrically substituted C atom, dimethenamid [2-chloro-N-(2,4-dimethyl-3-thienyl)-N-(2-methoxy-1-methylethyl)acetamide], a recently introduced N-thienyl chloroacetamide herbicide, exists as two stereoisomers (S and R) having differing herbicidal activities as demonstrated with a selection of weeds and Lemna minor. The activity of the two isomers was investigated in greater detail with the green alga Scenedesmus acutus and compared to that of alachlor [2-chloro-N-(2,6-diethylphenyl)-N-(methoxymethyl)acetamide]. As with alachlor, the S isomer (5 μM ) strongly inhibited algal growth and fatty acid desaturation while the R isomer had no effect. In short-term experiments (up to 5·5 h), the S isomer and alachlor (100 μM ) inhibited [¹⁴C]acetate uptake and its incorporation into fatty acids in the same manner, while the R isomer did not. Incorporation of [¹⁴C]acetate into a non-lipid fraction of the algae was strongly inhibited by alachlor and the S isomer (100 μM ) and only slightly by the R isomer. A 50% inhibition of incorporation of [¹⁴C]oleic acid into the same non-lipid fraction was attained with less than 10^-7 M of the S isomer while 10^-5 M of the R form of dimethenamid achieved only a 40% inhibition. The same stereospecificity of the compound on growth, fatty acid desaturation, acetate uptake and oleic acid incorporation provides strong evidence that dimethenamid may act upon a primary, specific target in lipid metabolism. Furthermore, the comparable biological activities of dimethenamid and alachlor indicate that this target is common to both N-phenyl and N-thienyl chloroacetamide herbicides. © 1997 SCI.     

Quantitative structure-activity relationships of pyrethroid insecticides

The structure-activity relationships of two congeneric series of pyrethroid insecticides, the methylbenzyl (1RS)-cis,trans-chrysanthemates tested against Musca domestica (houseflies) and Phaedon cochleariae (mustard beetles), and the (E)-4-aryl-3-chlorobut-2-enyl chrysanthemates and their corresponding 2,2,3,3-tetramethylcyclo-propanecarboxylates tested against M. domestica only, have been examined using multiple regression analyses and substituent constants. With M. domestica, different optimum partition values (π) were indicated for knockdown and toxicity; with P. cochleariae, an optimum π value for toxicity, similar to that for M. domestica, was obtained 24 h after application, but at later times the more lipophilic compounds were more effective. For the methylbenzyl chrysanthemates, a steric constraint associated with 3,5-dimethyl substitution reduced toxicity approximately five-fold. The influence on toxicity of geometrical isomerism and electronic effects are briefly discussed. Differences between the required polarities for knockdown and toxicity are attributed to variations in the binding affinities of pyrethroid molecules at the sites of action.     

The pyrethrins and related compounds. Part XXII. Preparation of isomeric cyano-substituted 3-phenoxybenzyl esters

Preparation of 3-phenoxybenzyl chrysanthemates and their dihalovinyl analogues substituted with a cyano group at the 2-, 6-, (R)-α-, or (S)-α- positions is described. The (R)- and (S)- isomers of α-cyano-3-phenoxybenzyl esters of 2,2-difluoro-, -dichloro-, and -dibromo-vinyl analogues of cis- and trans- chrysanthemic acid are separated chromatographically, as are the separate pairs of enantiomers of fenvalerate, (RS)-α- cyano-3-phenoxybenzyl (RS)-2-(4-chlorophenyl)-3-methylbutyrate. An optically active ester of α-cyano-3-phenoxybenzyl alcohol (obtained using D -oxynitrilase) with 2,2,3,3-tetramethylcyclopropanecarboxylic acid is synthesised.     

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.     

Insecticidal activity of the pyrethrins and related compounds. Part XI. Relative potencies of isomeric cyano-substituted 3-phenoxybenzyl esters

The insecticidal activities to Musca domestica L. and Phaedon cochleariae Fab. of a series of 3-phenoxybenzyl pyrethroid esters with a cyano substituent at the 2-, 6-. (R)-α-, or (S)-α-position are compared with those of the unsubstituted analogues. Only an (S)-α-substituent enhances activity; others diminish or almost eliminate it. (RS)-α-mixtures are generally less active than would be predicted from the potencies of their separate constituents.     

Response of susceptible and resistant peach-potato aphids Myzus persicae (Sulz.) to insecticides in leaf-dip bioassays

The response of susceptible (S), moderately resistant (R₁) and strongly resistant (R₂) peach-potato aphids, Myzus persicae (Sulz.) to organophosphorus, carbamate and pyrethroid insecticides was tested by a leaf-dip bioassay. The aphids were placed on potato leaves (dipped in insecticide solutions 1–2 or 24 h before infestation) and their mortality examined 48 h later. R₁ aphids were virtually susceptible to most of the carbamates, demephion and acephate, but were slightly to moderately resistant (2.1–9.4 times) to permethrin, cypermethrin and (S)-α-cyano-3-phenoxybenzyl (1R)-cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropanecarboxylate (I), (NRDC 161), to 5,6,7,8-tetrahydro-2-methylquinolin-4-yl dimethylcarbamate (II), (Hoechst 25 682) and demeton-S-methyl. R₂ aphids resisted more strongly or very strongly (between 65 and 1280 times) the pyrethroids, demeton-S-methyl (×94), II (×83) and demephion (×9), and were slightly to moderately (2–5 times) resistant to acephate, pirimicarb, ethiofencarb and 2-(dimethylcarbamoyloxyimino)-3-methoxyimino-N,N- dimethylbutyramide (III), (DPX 3853). Both resistant strains were susceptible to nitrilacarb [4,4-dimethyl-5-(methylcarbamoyloxyimino)pentanenitrile] complex (1:1) with zinc chloride (IV), (AC 85 258). The implications of these results in terms of practical aphid control are discussed.     

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。