取代苯甲醛肟羧酸酯的合成及生物活性研究(IV)——拟除虫菊酸4-二甲(乙)氨基苯甲醛肟酯的合成及生物活性

设计合成了 1 2个新拟除虫菊酸肟酯类化合物 ,并对其进行了生物活性测试 ,其中化合物 3e、3f对玉米螟致死活性最好 ,LC5 0 分别达 6.6～ 6.9mg/ L和 7.7～ 8.4mg/ L;化合物 3j对苹果轮纹病菌抑制率突出 ,50 mg/ L抑制率达 1 0 0 % ,1 mg/ L抑制率 50 %以上     

Pyrethroid insecticides derived from 2,2′ -bridged biphenyl-3-ylmethanols

The addition of a hydrocarbon bridge between the 2- and 2′-positions in biphenyl constrains the twist angle between the two phenyl rings to fairly small limits. It has been found that the biological activity of a series of pyrethroid esters, of hydrocarbon bridged biphenyl-3-ylmethanols and of heterocyclic hydrocarbonbridged biphenyl analogues, changes with the length of the bridge. The optimum activity and the maximum biological activity spectrum were found for the esters of three-carbon bridged alcohols. The relationship of the activity to the twist angle for these bridged esters was compared with the activity and spectrum of a series of biphenyl and heterocyclic biphenyl analogues previously reported. A parallel exists between the two series. The optimum twist angle between the aromatic rings of the alcohols, in both the bridged and free rotating analogues, is around 50°. Pyrethroid esters showing the highest activity were produced from 6, 7-dihydro-5H-dibenzo-[a,c]cyclohepten-4-ylmethanol. The biological activity of a series of pyrethroid esters of this alcohol is also reported.     

Structure—activity relationships in pyrethroid esters derived from substituted 2-phenoxy-3-methylbutanoic acids

Non-cyclopropane pyrethroid esters of different substituted 2-phenoxy-3-methylbutanoic acids have been synthesised using the three alcohols—3-phenoxybenzyl alcohol, α-cyano-3-phenoxybenzyl alcohol and 3, 4-methylene-dioxybenzyl alcohol. Among the 35 esters synthesised and tested against Culex quinquefasciatus Say, the Bancroftian filariasis vector, for both larvicidal and adulticidal activities, α-cyano-3-phenoxybenzyl 2-(4-fluorophenoxy)-3-methylbu-tanoate, with an LC₅₀ value of 2.5 × 10^?3 mg litre^?1 for larvicidal activity, and α-cyano-3-phenoxybenzyl-2-(4-chlorophenoxy)-3-methylbutanoate, with an LD₅₀ value of 30 times; 10^?4 ug insect^?1 for adulticidal activity, were found to be as effective as fenvalerate, a well-known non-cyclopropane pyrethroid ester. Structure-activity studies showed that the insecticidal activity is dependent on the nature and position of the substituent in the phenyl ring of the acid moiety and also on the type of alcohol moiety.     

Pyrethroid insecticides derived from 2,2-dimethyl-3-(3-phenoxybenzyloxy)propanal

Fourteen oxime ethers and eleven other unsaturated compounds derived from 2,2-dimethyl-3-(3-phenoxybenzyloxy)propanal were synthesised and their insecticidal activity against Musca domestica, Locusta migratoria, Dysdercus cingulatus, Aedes aegypti, Plutella xylostella, Drosophila melanogaster, Tetranychus urticae and Spodoptera littoralis tested. Structural variations including chain length, branching and unsaturation of the oxime ether O-alkyl group and substituent exchange at the carbon-carbon double bond of the unsaturated compounds were made in order to examine the structure-activity relationship. All biological activities were compared with the activity of the ether pyrethroid MTI-500.     

Influence of pyrethroid ester,oxime ether,and other central linkages on insecticidal activity,hydrolytic detoxification,and physicochemical parameters

The relative potency to target and nontarget insects of ester pyrethroids and the analogous oxime ethers, and the degree of synergism of the esters with tributyl phosphorotrithioate, provide a useful guide to the importance of esterase detoxification in species specificity. These criteria indicate that esterase detoxification is a more important component of pyrethroid tolerance in Chrysopa carnea and Cryptolaemus montrouzieri larvae than in Exochomus flavipis larvae and Musca domestica adults. Studies with 3-phenoxybenzyl 2-(4-chlorophenyl)-2-cyclopropylacetate and the corresponding 2,3,4,5,6-pentafluorobenzyl ester, their oxime ether analogs, and permethrin and its thiol ester and amide analogs provide evidence that the high insecticidal activity of some ester and E-oxime ether pyrethroids, relative to that of the corresponding thiol ester and amide, is more closely associated with the dipole moment and polarizability of the central linkage and its resistance to esterase detoxification than with bond lengths or lipophilicities conferred by a specific linkage. Pentafluorobenzyl tetramethylcyclopropanecarboxylate is very effective in the vapor state for house fly control.     

α-甲硫基环十二酮肟醚的合成及杀菌活性

以环十二酮为原料,经α-甲硫基环十二酮制得中间体α-甲硫基环十二酮肟后,经烷基(芳基)化反应合成了10个α-甲硫基环十二酮肟醚,其结构经元素分析、1H NMR、13C NMR和IR的确证。初步生测结果表明,部分化合物对立枯丝核菌Rhizoctonia solani、褐孢霉菌Fulvia fulva(cooke)cifer 、灰霉病菌Botrytis cinerea等病原菌具有较好的杀菌活性,其中 F3和 F8 对立枯丝核菌的EC50值为11.22和13.38 μg/mL, 对褐孢霉菌的EC50值为37.12和48.41 μg/mL, F9 对灰霉病菌的EC50值为17.96 μg/mL。     

Synthesis,insecticidal activity and pyrethroidal mode of action of new tin ether derivatives

A novel range of trimethylstanniomethyl ethers of well known pyrethroid alcohols were synthesised, and their insecticidal activities and modes of action as insecticides were investigated. Among them, ethers from three types of alcohol (3-phenoxybenzyl, 4-fluoro-3-phenoxybenzyl and 6-phenoxy-2-pyridylmethyl) showed remarkable insecticidal activities against rice stem borers, houseflies and German cockroaches. According to electrophysiological studies on the abdominal nerve cords of German cockroaches, trimethylstanniomethyl 6-phenoxy-2-pyridylmethyl ether induced a rapid decline in spontaneous firing similar to that from tetramethrin. However, insecticidal trimethyltin chloride caused an entirely different response. These observations suggest that the present tin ether derivatives resemble pyrethroids, rather than the insecticidal tin compounds known so far.     

Research into fluorinated pyrethroid alcohols—an episode in the history of pyrethroid discovery

An account of pyrethroid research from 1975 to 1985 at Bayer AG is given. The exploitation of fluorine chemistry for this purpose led to increased activity of known 3-phenoxybenzyl pyrethroid esters and to the commercialisation of the broad-spectrum insecticide cyfluthrin, the particularly tick-toxic flumethrin and the rapid-acting household insecticides fenfluthrin and transfluthrin. The last two constituted in 1976 a novel type of pyrethroid, based on polyfluorinated benzyl alcohols, off the mainstream of published pyrethroid research. Transfluthrin, the single isomer (1R)trans-permethric acid ester of 2,3,5,6-tetrafluorobenzyl alcohol has just been introduced to the market. The history of its discovery and structure–activity data as well as resistance considerations regarding cyfluthrin, are presented. © 1998 SCI.     

State-dependent modification of voltage-gated sodium channels by pyrethroids

Pyrethroids disrupt nerve function by altering the rapid kinetic transitions between conducting and nonconducting states of voltage-gated sodium channels that underlie the generation of nerve action potentials. Recent studies of pyrethroid action on cloned insect and mammalian sodium channel isoforms expressed in Xenopus laevis oocytes show that in some cases pyrethroid modification is either absolutely dependent on or significantly enhanced by repeated channel activation. These use-dependent effects have been interpreted as evidence of preferential binding of at least some pyrethroids to the open, rather than resting, state of the sodium channel. This paper reviews the evidence for state-dependent modification of insect and mammalian sodium channels expressed in oocytes by pyrethroids and considers the implications of state-dependent effects for understanding the molecular mechanism of pyrethroid action and the development and testing of models of the pyrethroid receptor.     

Sodium channel mutations (T929I and F1534S) found in pyrethroid-resistant strains of the cigarette beetle,Lasioderma serricorne (Coleoptera: Anobiidae)

RNA-seq data analysis of cigarette beetle (Lasioderma serricorne) strains having different sensitivities to pyrethroids identified sodium channel mutations in strains showing pyrethroid resistance: the T929I and F1534S mutations. These results suggest that reduced sensitivity of the sodium channel confers the pyrethroid resistance of L. serricorne. Results also showed that the F1534S mutation mostly occurred concurrently with the T929I mutation. The functional relation between both mutations for pyrethroid resistance is discussed.     

The pyrethrins and related compounds. Part xxxi: Alkoxyimino-substituted esters

Esters derived from pyrethroidal acids and benzyl and furylmethyl alcohols bearing a wide range of side-chains each containing at least one oxime ether group, and related derivatives of allethrin and benzylnorthrin, were synthesised and tested for insecticidal activity. Of the benzyl esters, the most insecticidal were those with the methoxyimino-methyl or -ethyl side-chains at C-3 or C-4, and with E configuration. Changing the alkoxy group, the configuration or the chain length resulted in lower activity. Introducing an occyano group increased activity if the side-chain was at C-3, but lowered it drastically if the substituent was at C-4. In the case of allethrin, the methoxime derivative was less active than the parent ketone, but with benzylnorthrin conversion to the methoxime markedly increased activity against one of the test species.     

6-硫-6-烷硫基-12H-氯代双苯并[d,g][1,3,2]-二氧磷杂八环的合成

通过双- (2 -羟基 -氯代苯基 )甲烷 2与 P4S10 在三乙胺存在下的关环反应 ,得到了6 -硫 - 6巯基 - 12 H-氯代双苯并 [d,g][1,3,2 ]-二氧磷杂八环三乙胺盐 3,后者与卤代烷酯化得到了一系列 6 -硫 - 6 -烷硫基 - 12 H-氯代双苯并 [d,g][1,3,2 ]-二氧磷杂八环 4 ,测试并讨论了它们的1H和31P NMR数据。初步生物试验结果表明化合物 4对黄瓜霜霉病菌具有较好的抑制活性。     

糖醋酒液对韭菜迟眼蕈蚊的诱杀效果及其挥发物活性成分分析

为了明确糖醋酒液诱集韭菜迟眼蕈蚊的作用机制,比较了4种糖醋酒液配方对该虫的田间诱杀效果,并采用动态顶空吸附法、气相色谱与质谱联用技术（GC-MS）、气相色谱及触角电位仪联用技术（GC-EAD）测定了最优配比对该虫的电生理反应。绵白糖、乙酸、无水乙醇及自来水的比例为3∶3∶1∶80的糖醋酒液A为最优配比,该配比与其它各处理诱虫效果差异显著（P〈0.05）。糖醋酒液A的挥发物有33种,其中酮类化合物7种、醛类化合物8种、醇类化合物2种、烷烃类化合物12种、酯类化合物3种、酚类化合物1种,但4种配比液的挥发性成分之间差异较大。糖醋酒液A挥发物中的对乙基苯乙酮（16.119%）和1,4-二乙酰苯（4.996%）能引起韭菜迟眼蕈蚊的电生理反应。     

Alkyl aryl ketone oxime O-ethers: A novel group of pyrethroids

The alkyl phenyl ketone oxime O-benzyl ethers are a new group of insecticidal compounds. Although they lack the ester linkage, they resemble the pyrethroids in general, and the esters of 2-phenylalkanoic acids, in particular fenvalerate, because they show similar physiological effects on isolated nerve preparations and on whole insects; they also show a similar pattern of change of biological activity in response to structural change. The compounds may exist as two geometric isomers, of which only the (E) series shows significant biological activity; this observation appears to have some bearing on the relationship between conformation and activity in the pyrethroid series as a whole.     

两种挥发性拟除虫菊酯杀虫剂对伊蚊的驱避作用研究

拟除虫菊酯杀虫剂广泛应用于蚊香及其他驱蚊产品,不仅对蚊子有杀虫作用,而且具有驱避效应,然而拟除虫菊酯杀虫剂对蚊子驱避作用的机理尚不清楚.本研究发现两种挥发性拟除虫菊酯杀虫剂四氟甲醚菊酯和氯氟醚菊酯对白纹伊蚊和埃及伊蚊具有非接触驱避作用.触角电位(EAG)试验表明除四氟甲醚菊酯有微弱EAG响应外,其他拟除虫菊酯杀虫剂均没...     

Genetics of Pyrethroid Resistance in a Strain (ALHF) of House Flies (Diptera: Muscidae)

Five house fly lines were derived from crosses of the pyrethroid-resistant ALHF (wildtype) and the susceptible aabys (bearing recessive morphological markers on each of five autosomes) strains. Each line was homozygous for one mutant-type marker from aabys. The level of resistance to permethrin was measured for each line to determine the genetic linkage of pyrethroid resistance in ALHF. Permethrin resistance in ALHF was 6600-fold compared with that in aabys. Resistance in flies bearing a mutant-type marker on autosome 4 was similar to that in ALHF. Flies with mutant-type markers on autosomes 1 and 2 had relatively lower resistance than ALHF; flies with mutant-type markers on autosomes 3 and 5 had much lower levels of resistance. These results demonstrated that factors on autosomes 3 and 5 play very important roles in pyrethroid resistance, whereas factors on autosomes 1 and 2 may have relatively small roles in resistance. Piperonyl butoxide (PBO) increased toxicity of permethrin in strains with mutant-type markers on autosomes 3 and 4 similar to that in ALHF. Slightly decreased synergism ratios in strains with autosomes 1 and 2 mutant-type markers compared with ALHF indicated that factors on autosomes 1 and 2 might make a small contribution in P450 monooxygenase-mediated resistance. However, when the autosome 5 mutant-type marker was present, PBO did not substantially decrease resistance, suggesting that the factor(s) on autosome 5 plays the most important role in P450 monooxygenase-mediated resistance. The resistance ratios of permethrin + PBO in strains with mutant-type markers on autosomes 1, 2, and 5 were significantly lower than those in ALHF, suggesting that factors on autosomes 1, 2, and 5 might be involved in pyrethroid resistance mechanisms other than P450-mediated detoxication. Injection did not change levels of resistance in the house flies tested, revealing that decreased rate of cuticular penetration (pen) probably does not play an important role in pyrethroid resistance in ALHF. The interaction and regulation of different mechanisms and/or factors involved in pyrethroid resistance in house flies are discussed.     

Mutations in the sodium channel associated with pyrethroid resistance in the greenhouse whitefly, Trialeurodes vaporariorum

BACKGROUND: Trialeurodes vaporariorum Westwood is an important pest of protected crops in temperate regions of the world. Resistance to pyrethroid insecticides is long established in this species, but the molecular basis of the mechanism(s) responsible has not previously been disclosed. RESULTS: Mortality rates of three European strains of T. vaporariorum to the pyrethroid bifenthrin were calculated, and each possessed significant resistance (up to 662‐fold) when compared with a susceptible reference strain. Direct sequencing revealed three amino acid substitutions in the para‐type voltage‐gated sodium channel (the pyrethroid and DDT target site) of bifenthrin‐resistant T. vaporariorum at positions previously implicated with pyrethroid or DDT resistance (M918L, L925I and T929I) in other related species. CONCLUSION: This study indicates that resistance to bifenthrin in T. vaporariorum is associated with target‐site insensitivity, and that the specific mutations in the sodium channel causing resistance may differ between localities. Copyright © 2012 Society of Chemical Industry     

Pyrethroids, knockdown resistance and sodium channels

Knockdown resistance to DDT and the pyrethrins was first described in 1951 in the housefly (Musca domestica L.). This trait, which confers reduced neuronal sensitivity to these insecticides, was subsequently shown to confer cross-resistance to all synthetic pyrethroid insecticides that have been examined to date. As a consequence, the worldwide commercial development of pyrethroids as a major insecticide class over the past three decades has required constant awareness that pyrethroid overuse has the potential to reselect this powerful resistance mechanism in populations that previously were resistant to DDT. Demonstration of tight genetic linkage between knockdown resistance and the housefly gene encoding voltage-sensitive sodium channels spurred efforts to identify gene mutations associated with knockdown resistance and understand how these mutations confer a reduction in the sensitivity of the pyrethroid target site. This paper summarizes progress in understanding pyrethroid resistance at the molecular level, with particular emphasis on studies in the housefly.     

Frequency detection of pyrethroid resistance allele in Anopheles sinensis populations by real-time PCR amplification of specific allele (rtPASA)

To investigate the level of pyrethroid resistance in Anopheles sinensis Wiedemann 1828 (Diptera: Culicidae), a major malaria vector in Korea, we cloned and sequenced the IIS4-6 transmembrane segments of the sodium channel gene that encompass the most widely known kdr mutation sites. Sequence analysis revealed the presence of the major Leu-Phe mutation and a minor Leu-Cys mutation at the same position in permethrin-resistant field populations of An. sinensis. To establish a routine method for monitoring resistance, we developed a simple and accurate real-time PCR amplification of specific allele (rtPASA) protocol for the estimation of resistance allele frequencies on a population basis. The kdr allele frequency of a field population predicted by the rtPASA method (60.8%) agreed well with that determined by individual genotyping (61.7%), demonstrating the reliability and accuracy of rtPASA in predicting resistance allele frequency. Using the rtPASA method, the kdr allele frequencies in several field populations of An. sinensis were determined to range from 25.0 to 96.6%, suggestive of widespread pyrethroid resistance in Korea.     

板兰根中三种拟除虫菊酯杀虫剂的残留分析

研究了板蓝根中3种拟除虫菊酯杀虫剂残留分析方法。以石油醚为萃取溶剂，分别用索氏抽 提法、浸渍振荡法、超声波法提取。提取液经100 mL丙酮∶0.05 mol/L氯化钙溶液(1∶1)液 -液分配净化后，以弗罗里硅土柱净化，5%乙酸乙酯-石油醚淋洗，气相色谱法电子捕获检 测器测定。结果表明，方法的线性范围为0.4×10-10～4×10-10g，氯氰菊酯 、氰戊菊酯、溴氰菊酯最低检测浓度分别为5×10-3、5×10-3、2×10-3 mg/kg。3种提取方法对板蓝根的添加回收率、变异系数符合农药残留分析的要求。