Synthesis and insecticidal activity of benzoheterocyclic analogues of N'-benzoyl-N-(tert-butyl)benzohydrazide: Part 1. Design of benzoheterocyclic analogues

The N'-benzoyl group of N-tert-butyl-N'-benzoyl-3,5-dimethylbenzohydrazide (1) was converted to a series of benzoheterocyclecarbonyl groups in order to investigate the potential usefulness of superimposing a hydrazine insecticide on 20-hydroxyecdysone. A series of analogues with benzodioxole, benzodioxane, benzodioxapine, indole, benzoxazole, benzoxazine or benzothiazole instead of the phenyl group of (1) were synthesized and tested for their insecticidal activity against the common cutworm (Spodoptera litura F). N-tert-Butyl-N'-(3,5-dimethylbenzoyl)-1,3-benzodioxole-5-carbohydrazide and N-tert-butyl-N'-(3,5-dimethylbenzoyl)-2,3-dihydro-1,4-benzodioxine-6-carbohydrazide showed high insecticidal activities, superior to that of (1) and equal to that of the commercial insecticide tebufenozide (RH-5992).     

Synthesis and insecticidal activity of benzoheterocyclic analogues of N'-benzoyl-N-(tert-butyl)benzohydrazide: Part 2. Introduction of substituents on the benzene rings of the benzoheterocycle moiety

A series of N'-benzoheterocyclecarbonyl-N-tert-butyl-3,5-dimethylbenzohydrazide analogues possessing a variety of substituents on the benzene rings of the benzoheterocyle moieties were synthesized and tested for their insecticidal activity. The introduction of a methyl group at the R1 position of the benzoheterocycle moiety strongly increased the insecticidal activity. Among the analogues synthesized, N'-tert-butyl-N'-(3,5-dimethylbenzoyl)-5-methyl-6-chromanecarbohydrazide showed the highest insecticidal activity (LC50 = 0.89 mg litre(-1)).     

Assessment of species specificity of moulting accelerating compounds in Lepidoptera: comparison of activity between Bombyx mori and Spodoptera littoralis by in vitro reporter and in vivo toxicity assays

BACKGROUND: Dibenzoylhydrazine analogues have been developed successfully as a new group of insect growth regulators, called ecdysone agonists or moulting accelerating compounds. A notable feature is their high activity against lepidopteran insects, raising the question as to whether species‐specific analogues can be isolated. In this study, the specificity of ecdysone agonists was addressed through a comparative analysis in two important lepidopterans, the silkworm Bombyx mori L. and the cotton leafworm Spodoptera littoralis (Boisd.). RESULTS: When collections of non‐steroidal ecdysone agonists containing different mother structures (dibenzoylhydrazine, acylaminoketone, tetrahydroquinoline) were tested, in vitro reporter assays showed minor differences using cell lines derived from both species. However, when compounds with high ecdysone agonist activity were examined in toxicity assays, larvicidal activity differed considerably. Of note was the identification of three dibenzoylhydrazine analogues with > 100‐fold higher activity against Bombyx than against Spodoptera larvae. CONCLUSION: The present study demonstrated that species‐specific ecdysone‐agonist‐based insecticides can be developed, but their species specificity is not based on differences in the activation of the ecdysone receptor but rather on unidentified in vivo parameters such as permeability of the cuticle, uptake/excretion by the gut or metabolic detoxification. Copyright © 2010 Society of Chemical Industry     

4"-脱氧阿维菌素脲类及硫脲类衍生物的合成与杀虫活性

以构效关系为线索,根据类同合成法和活性官能团拼接策略,以阿维菌素为先导分子,在其4"-位引入硫脲或脲活性结构单元,合成了一系列酰基硫脲（9a~9o）和芳基脲（10a~10i）阿维菌素衍生物,所有目标化合物均经1H NMR、MS和元素分析确证。室内杀虫活性测定结果表明:所有衍生物对朱砂叶螨Tetranychus cinnabarinus和甘蓝蚜Brevicoryne brassicae均表现出不同程度的毒杀活性,大部分化合物对甘蓝蚜的杀虫活性优于阿维菌素B1a,其中化合物9h对朱砂叶螨和甘蓝蚜的LC50值分别为0.100和1.71 μmol/L,表现出很高的毒杀活性,化合物9o对甘蓝蚜的毒性最高,LC50值为1.13 μmol/L。     

Enhancement of fungicidal and insecticidal activity by reductive alkylation of chitosan

A series of N-alkyl chitosan (NAC) derivatives were synthesized using a reductive alkylation reaction to examine their fungicidal and insecticidal activity. The chemical structures were characterized by IR and (1)H NMR spectroscopy, and the degree of substitution (DS) ranged from 0.02 to 0.37. Their fungicidal activity was evaluated against the grey mould Botrytis cinerea Pers ex Fr (Leotiales: Sclerotiniaceae) and the rice leaf blast pathogen Pyricularia grisea Sacc [Teleomorph: Magnaporthe grisea (Hebert) Barr] by a radial growth bioassay. It was of interest that most of the NAC derivatives were more active against both fungi than chitosan itself. The most active derivative was N-(2,2-diphenylethyl)chitosan with EC50 values of 0.031 and 0.23 g L(-1) against B. cinerea and P. grisea respectively. In addition, some derivatives, at higher concentrations up to 1.0 g L(-1), inhibited the mycelial growth and spore formation of P. grisea. Bioassays against larvae of the cotton leafworm, Spodoptera littoralis (Boisd.) (Lepidoptera: Noctuidae) with the NAC derivatives at a rate of 5.0 g kg(-1) in artificial diet demonstrated that N-(3-phenylbutyl)chitosan was the most active compound. In addition, N-propylchitosan, N-undecanylchitosan and N-(3-phenylpropyl)chitosan derivatives strongly inhibited larval weight gain in S. littoralis, with respective reductions of 76, 66 and 65% after 4 days of feeding on treated diet.     

Synthesis and insecticidal activity of 4-perhaloalkoxy (or thioalkyl) benzophenonehydrazone derivatives

Benzophenonehydrazone derivatives containing a mesylate or triflate substituent are known to exhibit insecticidal activity. In the present study, such substituents have been replaced by perhaloalkoxy groups. High levels of activity against lepidopteran pests were observed in greenhouse trials. For optimum activity, the substituents should be relatively small. In semi-field trials, however, none of the compounds tested showed sufficient persistence to warrant further development.     

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 insecticidal activity of 5-acyloxyimino-5-deoxyavermectin B1 derivatives

Four novel 5-acyloxyimino-5-deoxyavermectin B1 compounds have been synthesized from avermectin B1 by selective oxidization of the hydroxy group at C-5, followed by oximation and convenient esterification. Their structures were confirmed by IR, 1H NMR, 13C NMR and MS. Insecticidal activities of the intermediate oxime and the four new acyl derivatives were evaluated against Helicoverpa armigera, Spodoptera exigua and Musca domestica.     

3-丙烯酰胺类化合物的合成及杀虫活性

以3,4-亚甲二氧基苯酚(芝麻酚)为原料,经醚化、Vilsmeier反应、Horner反应、酰胺化等步骤制备了12个未见文献报道的3-(3,4-亚甲二氧基-6-烷氧基)丙烯酰胺类化合物,所有化合物的结构均经红外光谱、质谱、1H NMR确证。初步的杀虫活性测试结果表明:化合物 5a~5l 对粘虫3龄幼虫均有一定的杀虫活性,其中化合物 5h和5j 在150 mg/L质量浓度下对粘虫3龄幼虫的校正死亡率分别为50.0%和66.7%。     

Synthesis and insecticidal/acaricidal activity of novel 3‐(2,4,6‐trisubstituted phenyl)uracil derivatives

A series of novel 3‐(2,4,6‐trisubstituted phenyl)uracil derivatives has been synthesised and assayed for insecticidal/acaricidal activity. The assay indicated certain requirements for optimal insecticidal activity, which can be summarised as follows: (a) the substituents on the phenyl ring should possess hydrophobicity and electron‐withdrawing properties, and the sum of their volumes determines the level of activity; (b) the substituent at the 6‐position on the uracil ring should also possess electron‐withdrawing properties and hydrophobicity, together with the correct volume; (c) the 1‐position on the uracil ring should be unsubstituted for activity against Nephotettix cincticeps and Epilachna vigintioctopunctata, but substituents with length C3 to C4 may be optimal for activity against Tetranychus urticae; (d) certain substituents at the 5‐position of the uracil ring give activity against E vigintioctopunctata and T urticae, but not against N cincticeps; (e) a thiocarbonyl group at the 2‐position of the uracil ring is less effective than a carbonyl group. Of the compounds assayed, 3‐(2,6‐dichloro‐4‐trifluoromethylphenyl)‐6‐trifluoromethyluracil showed high activity against all the species assayed. © 2000 Society of Chemical Industry     

Quantitative structure-activity studies of insect growth regulators: XIX. Effects of substituents on the aromatic moiety of dibenzoylhydrazines on larvicidal activity against the beet armyworm Spodoptera exigua

Larvicidal activity against the beet armyworm, Spodoptera exigua (Hübner), was measured after topical treatment for a series of N-tert-butyl-dibenzoylhydrazines having various substituents in the benzoyl (A-ring) moiety closer to the tert-butyl group, the other benzoyl (B-ring) moiety being unsubstituted. The effects of substituents on the larvicidal activity were analyzed using the classical quantitative structure-activity relationship (QSAR) procedure. Introduction of hydrophobic substituents with a small volume into any position was favourable to activity. The existence of electron-withdrawing substituents at ortho positions was also favourable to activity. For multi-substituted compounds, physico-chemically unknown unfavourable factors were suggested to remain after separating common substituent effects derived from QSAR for mono-substituted analogues. With the exception of the unsubstituted compound RH-5849, the effect of substituents in the A-ring moiety on the larvicidal activity was similar to those found with the lepidopteran rice stem borer, Chilo suppressalis (Walker). The larvicidal activity of RH-5849 against S exigua was significantly lower than the value predicted from the correlation between activities against S exigua and C suppressalis. Topical treatment with piperonyl butoxide, a synergist inhibiting oxidative metabolism, slightly enhanced the larvicidal activity of RH-5849 against S exigua.     

Synthesis and Insecticidal Activity of Some New 3-[4(3H)-Quinazolinone-2-(yl)thiomethyl]-1,2,4- triazole-5-thiols

A series of 14 new 3-[4(3H)-quinazolinone-2-(yl)thiomethyl]-1,2,4-triazoles were prepared and characterized by elemental analyses, IR, [¹H] NMR and mass spectral data. Four of the compounds showed insecticidal activity equivalent to that of malathion against the adult stage of the blow fly (Chrysomyia albiceps). However, their activity against the larval stages of this insect species was considerably weaker.     

新型七氟异丙基取代2,2-二氟-1,3-苯并二氧-5-乙酰胺衍生物的合成与杀虫活性

为探索环境友好新型农药先导化合物,通过水相中酰胺缩合反应合成了16个未见文献报道的七氟异丙基苯基取代的2,2-二氟-1,3-苯并二氧-5-乙酰胺类目标化合物。其结构通过核磁共振氢谱、氟谱以及高分辨质谱确认。初步生物活性测定表明,部分目标化合物对蚕豆蚜虫和粘虫表现出良好的杀虫活性,初步构效关系显示苯环上取代基的种类和位置在化合物的杀虫活性中起关键作用。     

The pyrethrins and related compounds. Part XXXVIII—optimisation of insecticidal activity in 3-[(alkoxyimino)methyl]-4-fluorobenzyl esters

Optimisation of activity in 3-[(alkoxyimino)methylbenzyl] esters has been investigated by introducing an α-cyano group and a fluorine atom in position 4 of the benzylic moiety in conjunction with varying the length and nature of the side chain. Of the five side-chain variations investigated, the 3-methoxyiminomethyl was more effective than others. Introduction of fluorine in position 4 of the benzylic moiety generally increased activity, particularly against mustard beetles, as in previous instances. Surprisingly, the effect on insecticidal activity of introducing an α-CN group ranged from positive to negative depending upon the nature of the alkoxyimino substituent, an effect not observed previously. The most effective esters were derived from α-cyano-4-fluoro-3-[(methoxyimino)methyl]benzyl alcohol, which was synthesised from 2-{4-fluoro-3-[(hydroxyimino)methyl]phenyl}-1,3-dioxolane.