Synthesis of substituted benzyl 2-methyl-2-phenylpropyl ethers and their moth-proofing activity on wool against larvae of Anthrenus fasciatus

Synthesis of new moth-proofing agents is necessary to overcome the damage caused by clothes moths and carpet beetles to hosiery and upholstery. In the present paper substituted benzyl 2-methyl-2-phenylpropyl ethers were synthesised and evaluated for moth-proofing activity. Two compounds were found to provide protection against larvae of Anthrenus fasciatus at levels of 1.0 and 10 g kg⁻¹ respectively. The introduction of a methyl group in the para position of the benzene ring attached to C₂ of the 2-methylpropyl chain (ring A) increased moth-proofing activity. The introduction of a phenoxy ring at the meta position of the benzyl nucleus (ring B) also increased activity, while the presence of a nitro group on the benzyl nucleus (ring B) decreased activity. © 1999 Society of Chemical Industry     

Correlations of the electrophysiological activity of neonicotinoids with their binding and insecticidal activities

The electrophysiological actions of various neonicotinoids, including substituted benzyl derivatives, against recombinant Drosophila SAD/chicken beta2 hybrid nicotinic acetylcholine receptor (nAChR) were measured to analyze the relationships between the in vivo (insecticidal) and in vitro (binding and agonist) activities. Most of the neonicotinoids tested were capable of inducing inward currents by activating the hybrid nAChRs expressed in Xenopus laevis oocytes, whereas some compounds had no agonist activity and only blocked the acetylcholine-induced currents. Variations in the agonist activity were well correlated with those in the binding potency evaluated using [3H]imidacloprid as well as insecticidal activities.     

Effects of organosilicon pyrethroid‐like insecticides on nerve preparations of American cockroaches and crayfish

Quaternary organosilicon pyrethroid‐like ethers (five compounds) and alkanes (three compounds) were used for neurophysiological tests. Their activities in inducing repetitive firing in the central nervous cord of the American cockroach (Periplaneta americana) were evaluated by an extra‐cellular recording method. The ethers were more active than the corresponding alkanes. The ability of the compounds to cause conduction blockage was also measured using the same nerve preparations, but the effects were too weak to allow definitive activity values to be determined. The compounds prolonged the sodium tail‐current in the crayfish giant axon under voltage clamp conditions. The rate of decay of the tail‐current changed in parallel with the reported insecticidal activity against P americana. These findings indicated that tail‐current activity was the most useful nerve parameter in predicting insecticidal activity. Regression analysis of the numerical data together with those reported for other alkanes revealed that the higher the tail‐current activity, the higher the insecticidal activity when a structural feature and the hydrophobicity were considered separately. The insecticidal activity of the ethers was about seven‐fold higher than that of the alkanes with equivalent tail‐current activity and hydrophobicity. Variations in insecticidal activity were parabolically correlated with the hydrophobicity [(log P)_opt = 9.1] when other factors were similar. © 2001 Society of Chemical Industry     

Quantitative structure-activity study of insecticidal 2-methoxy-5-(substituted-phenyl)-1, 3, 2-oxazaphospholidine 2-sulfides against Musca domestica L. by topical application

The quantitative relationship between the structure of 2-methoxy-5-(substituted-phenyl)-1, 3, 2-oxazaphospholidine 2-sulfides (5-PMOS) and their insecticidal activity against the house fly. Musca domestica L., was analyzed using reported physicochemical parameters and regression analysis. The electronic nature of the substituent on the phenyl group of 5-PMOS has the most significant effect on the activity, followed by hydrophobic and steric effects; the optimum value of Σρ is zero and the more hydrophobic the substituents on the phenyl group, the higher the insecticidal activity. The plots of observed pLD₅₀, values against calculated pLD₅₀ values for compounds having substituents in the ortho-position deviated downwards from those of compounds having substituents at the meta and/or para positions. This ortho-effect, which reduces the insecticidal activity of compounds having substituents at the ortho-position, was expressed by a dummy parameter D, which has the value 2 for di-ortho-substituted derivatives, 1 for mono-ortho-substituted derivatives and zero for others. Thus, the highest activity was obtained for 2-methoxy-5-phenyl-1, 3, 2-oxazaphospholidine 2-sulfide, and the activity was decreased by the introduction of any substituents on the phenyl group.     

Quantitative structure–activity studies of insect growth regulators: XVI. Substituent effects of dibenzoylhydrazines on the insecticidal activity to Colorado potato beetle Leptinotarsa decemlineata

Insecticidal activity against the Colorado potato beetle, Leptinotarsa decemlineata, was measured for a series of substituted N-tert-butyl-dibenzoylhydrazines, in which one of the benzoyl moieties closer to the tert-butyl group was fixed as being 2-chloro-substitued and the other variously substituted singly or doubly. The effects of substituents on the activity were quantitatively analysed using the classical quantitative structure–activity relationship (QSAR) procedure. The activity against the Colorado potato beetle increases with the molecular hydrophobicity. In addition, various types of steric effect are at work, depending upon the positions. Hydrogen-bonding acceptor substituents at the para position enhance the activity. There seem to be threshold (or optimum) values, albeit position-dependent, in the molecular hydrophobicity, above which the activity starts to decrease. This biphasic contribution of the molecular hydrophobicity to activity against coleopterous larvae is the most conspicuous difference in substituent effects from those found for similar compounds against lepidopterous pest insects, and may be the basis of the variations in the activity spectrum for certain compounds in this series. The introduction of bulkier substituents into the meta- and para-positions of the benzene ring, apart from the tert-butyl group, is unfavorable to activity. LD₅₀ values against Colorado potato beetle larvae of methoxyfenozide (RH-2485) and tebufenozide (RH-5992) were in the order of 10⁻⁷ mol per insect, whereas those of RH-5849, and halofenozide (RH-0345) were very low, 10⁻⁹–10⁻¹⁰ mol per insect being selective to the coleopterous larvae. © 1999 Society of Chemical Industry     

The antifungal activity of some sulphonyl derivatives of isoxazole,pyrazole, thiazole and thiophene

Fifty-three heterocyclic sulphonyl derivatives including eight sulphonamides, three sulphonyl azides, nine sulphonohydrazides and twenty sulphonohydrazones of substituted thiophenes, and a smaller range of analogous isoxazoles pryazoles and thiazoles, were tested as potential fungicides in a simple screening procedure against Mucor mucedo, Septoria nodorum, Trichoderma viride, Chaetomium globosum and Aspergillus niger. Several thiophene-2-sulphonyl based compounds exhibited a high level of antifungal activity at 100 mg litre^?1 against the five test species, especially the mono-halogen-substituted sulphonamides and sulphonohydrazines, in which a single chlorine or bromine atom was substituted in the para position of an attached phenyl ring. The most active compound, against all five species of fungus was N-(4-chlorophenyl)-N-(trichloromethylthio) thiophene-2-sulphonamide which had average MIC₅₀ and MIC₁₀₀ values of 86 and 180 μmol respectively. (MIC₅₀ and MIC₁₀₀ values are, respectively, the concentrations required to inhibit fungal growth by 50% and to inhibit it totally.) In general, the isoxazole analogues of the thiophene-2-sulphonyl compounds exhibited a much lower fungitoxic activity, whilst the pyrazole and thiazole based compounds had little or no activity. Compared with the other results, the considerable activity shown by 4-[2′-(3,4-dichlorobenzylidene)hydrazinosulphonyl]thiophene-2-carboxylic acid was unexpected.     

A new pyrethroid of high insecticidal activity

New pyrethroids containing heterocyclic rings in the alcohol moieties were synthesised and their insecticidal activities were studied. Of these new pyrethroids, 3-benzylpyrrol-1-ylmethyl (1RS-cis, trans-3(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate was found to be the most effective, having higher activity than permethrin against Musca domestica by a topical application method. In addition, para-substituted analogues of the 3-benzylpyrrol-1-ylmethyl ester were also synthesised to study the substituent effects on insecticidal activities; the residual effects of these compounds against Blattella germanica were also examined.     

Comparison of the activity of non‐steroidal ecdysone agonists between dipteran and lepidopteran insects,using cell‐based EcR reporter assays

BACKGROUND: Diacylhydrazine (DAH) analogues have been developed successfully as a new group of insect growth regulators, called ecdysone agonists or moulting accelerating compounds. These DAHs have been shown to manifest their toxicity via interaction with the ecdysone receptor (EcR) in susceptible insects, as does the natural insect moulting hormone 20‐hydroxyecdysone (20E). A notable feature is their high activity and specificity, particularly against lepidopteran insects, raising the question as to whether non‐lepidopteran‐specific analogues can be isolated. However, for the discovery of ecdysone agonists that target other important insect groups such as Diptera, efficient screening systems that are based on the activation of the EcR are needed. RESULTS: In this study, a dipteran‐specific reporter‐based screening system with transfected S2 cells of Drosophila melanogaster Meig. was developed in order to discover and evaluate compounds that have ecdysone agonistic or antagonistic activity. A library of non‐steroidal ecdysone agonists containing different mother structures with DAH and other related analogues such as acylaminoketone (AAK) and tetrahydroquinoline (THQ) was tested. None of the compounds tested was as active as 20E. This is in contrast to the very high activity of several DAH and AAK congeners in lepidopteran cells (Bombyx mori L.‐derived Bm5 cells). The latter agrees with a successful docking of a DAH, tebufenozide, in the binding pocket of the lepidopteran EcR (B. mori), while this was not the case with the dipteran EcR (D. melanogaster). Of note was the identification of two THQ compounds with activity in S2 but not in Bm5 cells. Although marked differences in activity exist with respect to the activation of EcR between dipterans and lepidopterans, there exists a positive correlation (R = 0.724) between the pLC₅₀ values in S2 and Bm5 cells. In addition, it was found through protein modelling that a second lobe was present in the ligand‐binding pocket of lepidopteran BmEcR but was lacking in the dipteran DmEcR protein, suggesting that this difference in structure of the binding pocket is a major factor for preferential activation of the lepidopteran over the dipteran receptors by DAH ligands. CONCLUSIONS: The present study confirmed the marked specificity of DAH and AAK analogues towards EcRs from lepidopteran insects. THQ compounds did not show this specificity, indicating that dipteran‐specific ecdysone‐agonist‐based insecticides based on the THQ mother structure can be developed. The differences in activity of ecdysone agonists in dipteran and lepidopteran ecdysone‐reporter‐based screening systems are discussed. Copyright © 2010 Society of Chemical Industry     

Synthesis and fungicidal activity of tubulin polymerisation promoters. Part 1: pyrido[2,3‐b]pyrazines

BACKGROUND: The excellent fungicidal activity of [1,2,4]triazolo[1,5‐a]pyrimidines suggested the search for further analogues with improved properties. RESULTS: A series of novel trisubstituted pyrido[2,3‐b]pyrazines has been designed and prepared as 6,6‐biheterocyclic analogues of related 5,6‐bicyclic [1,2,4]triazolo[1,5‐a]pyrimidines. Their fungicidal activity was evaluated against the plant pathogens Puccinia recondita Rob. ex Desm. f. sp. tritici (Eriks.) CO Johnston (wheat brown rust), Mycosphaerella graminicola (Fuckel) Schroter (Septoria tritici Rob., leaf spot of wheat) and Magnaporthe grisea (Hebert) Barr (Pyricularia oryzae Cav., rice blast). Structure–activity relationship studies revealed the advantage of a fluoro substituent in position 6 and of a secondary amine in position 8. CONCLUSION: 8‐Amino‐7‐aryl‐6‐halogen‐substituted pyrido[2,3‐b]pyrazines have been prepared as 6,6‐biheterocyclic analogues of similarly substituted triazolopyrimidine fungicides. A concise four‐step synthesis route has been worked out to prepare these novel compounds from commercially available starting materials. [(R)‐(1,2‐Dimethylpropyl)]‐[6‐fluoro‐7‐(2,4,6‐trifluorophenyl)pyrido[2,3‐b]pyrazin‐8‐yl]amine showed excellent activity against three economically important phytopathogens. Copyright © 2009 Society of Chemical Industry     

Nicotinic acetylcholine receptor binding of imidacloprid-related diaza compounds with various ring sizes and their insecticidal activity against Musca domestica

Fifteen 5-substituted 1-(6-chloro-3-pyridylmethyl)-2-nitromethylene-1,3- diazacyclohexanes and three other related compounds having a five- or seven-membered ring were synthesized and their biological activities were measured in vivo and in vitro. The insecticidal (in vivo) activity was evaluated against houseflies Musca domestica L under synergistic conditions with propargyl propyl phenyl phosphonate and piperonyl butoxide. The binding activity of each compound to nicotinic acetylcholine receptor in vitro was measured using [125I] alpha-bungarotoxin. The insecticidal activities of the unsubstituted diazacyclohexane analogues were slightly higher than those of the imidazolidine analogues, but the enlargement of ring size to diazacycloheptane lowered the activity. Substitution of 1,3-diazacyclohexane or imidazolidine rings was not generally favourable for the activity, but the unsubstituted 1,3-diazacyclohexane analogue showed the highest binding activity. Ring substitutions and ring enlargement decreased the activity 100-30,000-fold.     

Bioactivity of compounds from Acmella oleracea against Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae) and selectivity to two non-target species

BACKGROUND: Tropical plants are recognised sources of bioactive compounds that can be used for pest control. The objective of this study was to evaluate the biological activity of compounds present in Acmella oleracea (Asteracea) against Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae), which is the main pest of tomato crops in Latin America. The selectivity of these compounds to the predator Solenopsis saevissima (Smith) (Hymenoptera: Formicidae) and to the pollinator Tetragonisca angustula (Latr.) (Hymenoptera: Apidae: Meliponinae) was also of interest. RESULTS: A bioassay screening with hexane and ethanol extracts from 23 plants was performed. The hexane extract of A. oleraceae was the most active of the extracts and was selected for further study. The following three alkamides were isolated from a hexane extract of the aerial parts of A. oleracea : spilanthol, (E)‐N‐isobutylundeca‐2‐en‐8,10‐diynamide and (R, E)‐N‐(2‐methylbutyl)undeca‐2‐en‐8,10‐diynamide. All of the isolated compounds showed insecticidal activity, with spilanthol being the most active (LD₅₀ = 0.13 µg mg^?1) against T. absoluta . The alkamides were selective to both beneficial species studied. CONCLUSION: The crude hexane extract of A. oleraceae showed high insecticidal activity and can be used to control T. absoluta in organic or conventional crops. Quantification of LD₅₀ values of isolated compounds against T. absoluta showed that alkamides could serve as potent insecticides for T. absoluta control programmes. Spilanthol was the main alkamide active isolated. This alkamide is the most promising as it has the highest insecticidal activity and is selective to non‐target organisms. Copyright © 2011 Society of Chemical Industry     

Quantitative structure–activity studies of optically active 2-methoxy-1,3,2-oxazaphospholidine 2-sulfides against Musca domestica L

The quantitative relationship between the structure of optically active 4-substituted 2-methoxy-1,3,2-oxazaphospholidine 2-sulfides (4-RMOS) and their insecticidal activity on the house fly, Musca domestica L., was analysed using reported physicochemical parameters and regression analysis. The configuration at the C₄ atom was more important for insecticidal activity than that at the phosphorus atom, since the coefficient of the dummy parameter for the C₄- configuration was larger than that for the configuration of the phosphorus atom: (S)c(R)p diastereoisomers showed the highest insecticidal activity, and the activity decreased in the order of (S)c(R)p > (S)c(S)p > (R)c(R)p > (R)c(S)p. The electronic nature of the substituent at the C₄ position was the most important, followed by the steric and hydrophobic effects: the more electron-donating, the less bulky and the more hydrophobic the 4-substituent, the higher the insecticidal activity. Thus the highest activity was obtained for the isopropyl derivatives, and the activity decreased in the order of isopropyl > isobutyl > ethyl > sec-butyl > benzyl > phenyl > methyl > tert-butyl.     

Synthesis and insecticidal activity of lipophilic amides. Part 7. Alternative aromatic groups for phenyl in 6-phenylhexa-2,4-dienamides

Synthesis of a wide range of analogues of the lead compound, N-2-methylpropyl-6-phenylhexa-2,4-dienamide, in which phenyl was replaced by other aromatic systems is reported. In cases where rearrangement rendered the N-2-methylpropyl compound less accessible, N-2,2-dimethylpropyl substitution was used, because rearrangement was then suppressed. Several of the groups examined, for instance 2-naphthyl, enhanced insecticidal activity, and when appropriately substituted, particularly with halogen, led to the most active compounds discovered in this series.     

吡啶联三唑类衍生物的合成及杀虫活性

以3-氨基-2-氯吡啶(1)为起始原料,经重氮化、叠氮化、环合和酰氯化反应,生成1-(2-氯吡啶-3-基)-5-甲基-1H-1,2,3-三唑-4-甲酰氯(5),(5)与取代苯胺反应,制得13个未见文献报道的吡啶联三唑类化合物,其结构通过 1H NMR和LC-MS表征。初步生物活性测定结果表明:在500 mg/L质量浓度下,所有目标化合物对粘虫 Mythimna separate 均有一定的杀虫活性,部分化合物致死率达100%;但在100 mg/L下,除化合物ZJ-7的致死率仍达100%外,其余化合物的活性明显降低,甚至无活性。     

Synthesis and insecticidal activity of lipophilic amides. Part 2: Effect of heteroatom replacements and of introducing methyl groups in the pentadiene system

Following the discovery of insecticidal activity in (2E,4E)-N-(2-methylpropyl)-6-phenylhexa-2,4-dienamide, structural analogues containing variations of the central pentadiene system have been examined. They include the five compounds with extra methyl groups on each of the five carbons in turn, and compounds in which heteroatoms have been introduced instead of, or additional to, the original CH or CH₂ groups. All were insecticidally inactive, indicating for the first time the severe limitations on this group if activity is to be retained.     

Miticidal pyrethroids having an isobutyranilidoxime ether skeleton

Isobutyranilidoxime meta-phenoxybenzyl ethers and related compounds were synthesized. Their insecticidal activities measured against Periplaneta americana by injection were lower than that of phenothrin by factors of at least 1/60. However, some compounds were comparable to or only slightly less potent than phenothrin and tetramethrin in miticidal activity tested by a contact method against Dermatophagoides farinae, D. pteronyssinus and Tyrophagus putrescentiae. © 1998 SCI     

辣椒碱类似物的合成及杀虫活性

基于辣椒碱结构,以取代苄胺为原料,经N-酰化反应合成了6个系列204个辣椒碱类似物,其中8个为新化合物。通过核磁共振氢谱 (1H NMR) 对化合物的结构进行了确证。采用叶碟法测定了目标化合物的杀虫活性。结果表明:大部分化合物在10 μg/ 片下对供试的3龄东方黏虫Mythimna separata有较强的毒杀活性,其中化合物 A30 、 D20 、 D30 、 D35 、 E30 和 F30 48 h的致死率达100%,化合物 D19 、 D21 、 D22 、 D23 、 D31 和 E31 48 h的致死率在90%以上。初步构效关系表明,苄胺苯环上氟原子单取代衍生物的杀虫活性优于氟原子双取代衍生物,其中以2-氟苄胺衍生物 ( D 系列) 杀虫活性较好;此外,酰基为2-噻吩甲酰时的杀虫活性明显优于其他取代基,表明酰基对该类化合物的杀虫活性也有显著影响。     

Insecticidal and binding activities of N3-substituted imidacloprid derivatives against the housefly Musca domestica and the alpha-bungarotoxin binding sites of nicotinic acetylcholine receptors

N3-substituted imidacloprid congeners containing C1-C6 alkyl groups or various analogous groups, and their corresponding nitromethylene analogues, were used in this study. Their insecticidal activity against the housefly, Musca domestica, and their binding activity toward the nicotinic acetylcholine receptor were determined. The insecticidal test was conducted using the synergists piperonyl butoxide and propargyl propyl phenylphosphonate. The binding assay was performed with housefly head membrane preparations using radio-labelled alpha-bungarotoxin. Both insecticidal and binding activities were drastically lowered by the introduction of alkyl/allyl groups at the imidazolidine NH sites of both nitroimino and nitromethylene compounds. The binding activity of N3-substituted nitromethylene analogues was much higher than that of the corresponding nitroimino analogues. However, the insecticidal activity of both series of compounds with a given substituent was nearly identical. The insecticidal activity correlated positively with the binding activity after taking into account the structural difference of the nitroimino and nitromethylene moieties and a structural feature of the N3-substituents.     

Insecticidal activity and nicotinic acetylcholine receptor binding of dinotefuran and its analogues in the housefly, Musca domestica

The insecticidal activity of dinotefuran and 23 related compounds against the housefly, Musca domestica (L) was measured by injection with metabolic inhibitors. Dinotefuran was less active than imidacloprid and clothianidin by a factor of 10 in molar concentrations. Their binding activities to the fly-head membrane preparation were measured by using [125I]alpha-bungarotoxin ([125I]alpha-BGTX) and [3H]imidacloprid ([3H]IMI) as radioligands. The activity of some selected compounds measured with [3H]IMI was 10(4)-fold higher than that measured with [125I]alpha-BGTX. With [3H]IMI as a radioligand, dinotefuran was 13-fold less active than imidacloprid. The inhibitory effect of dinotefuran on the binding of [3H]IMI to the membrane preparation was in a competitive manner. Quantitative analysis of the insecticidal activity of the test compounds with the binding activity measured with [3H]IMI showed that the higher the binding activity, the higher was the insecticidal activity.