Hydantocidin及其立体异构体的合成和生物活性研究进展

在前文总结了Hydantocidin新型类似物研究进展的基础上,对Hydantocidin及其15个立体异构体、硫代Hydantocidin和碳环衍生物的合成,以及它们的除草活性等方面的研究进展进行了综述。     

海藻糖酶结构及其抑制剂的农用活性研究进展

海藻糖是一种非还原性二糖,在昆虫、真菌等有害生物体内参与能量代谢、逆境恢复、几丁质合成等过程。海藻糖酶 (EC 3.2.1.28) 由于其对海藻糖代谢及其含量调控具有重要作用,且在农业有害生物和哺乳动物体内存在功能差异,已成为开发新型农用化学品的安全型候选靶标。本文对海藻糖酶的晶体结构、海藻糖酶与底物/抑制剂的互作机制研究进展进行了综述;同时对具有农用活性的海藻糖酶抑制剂,如井冈霉素、天然产物salbostatin和trehazolin及其合成类似物、脱氧野尻霉素及其合成类似物、天然生物碱及其合成类似物以及胡椒碱及其类似物的研究进展进行了概述,并重点论述了以胡椒碱为骨架的化合物在农业有害生物防治上的应用。本综述可为靶向海藻糖酶结构进行新型胡椒碱类结构的农用化学品设计与发现提供参考。     

赤霉素及其功能类似物与赤霉素受体的研究进展

赤霉素是一类以贝壳杉烯为骨架的植物激素,现已鉴定出136种赤霉素结构,但仅有少部分具有调节植物生长和发育的生理功能。近年来,赤霉素受体的研究取得了重大突破,尤其是最近成功鉴定了拟南芥Arabidopsis thaliana中GA3/GA4-GID1A-DELLA复合物的晶体结构,这为基于受体蛋白结构进行新型赤霉素功能类似物的生物合理设计奠定了重要基础。主要针对赤霉素及其功能类似物的化学结构与合成、赤霉素受体蛋白的结构特征及其与赤霉素类化合物分子间的相互识别规律进行归纳和总结,以期能够为以生物靶标蛋白为导向,开发新型骨架的赤霉素功能类似物提供参考。     

3-氯-1-(2-吡啶基)-3,5-二甲基-吡唑-4-乙酰胺基-5-三氟甲基-苯基-1,3,4-噻二唑的合成研究

寻找具有较高活性的含1,3,4-噻二唑杂环衍生物。根据活性拼接原理,分别将吡唑,1,3,4-噻二唑引入到同一分子中,用1H NMR 13C NMR将其结构进行表征。所合成的化合物首次被报道。试验表明,该化合物显示出显著的除草活性。可以将其作为先导化合物,设计合成更多的类似物来探索新型、高效低毒和对非靶标生物安全的新型除草剂。     

防治柑桔螨类试验

应用昆虫保幼激素类似物防治害虫颇有前途。近年来美、苏等国对40余种害虫进行直接杀虫和导致不育的试验,对蚜、蚧、蚊、蝇和一些蛾类有较好的效果。国内应用防治农林害虫,也取得了可喜的进展。 昆虫保幼激素类似物具有很高的生物活性,有明显的选择     

昆虫蜕皮激素类似物的定量构效关系及其受体三维结构研究进展

蜕皮激素及其类似物具有调节昆虫蜕皮、变态和繁殖的功能。蜕皮激素类似物在农业生产,尤其是鳞翅目害虫的防治中发挥着重要作用。总结近期的文献,同时结合课题组的工作,综述了蜕皮激素类似物的定量构效关系、蜕皮激素受体三维结构的研究进展。     

氯康唑类似物的合成及抑菌活性

为了发现更多抑菌活性优于抗菌药物盐酸氯康唑的化合物,在盐酸氯康唑的结构基础上,设计、合成了其类似物,并进行了抑菌活性测定。以芝麻酚为原料,经过酰化、1,2,4-三氮唑基团的引入以及醚化3步反应,合成了19个新型氯康唑类似物4a~4s。所有目标化合物的结构均经过1H NMR、13C NMR和ESI-MS等确认。采用抑制菌丝生长速率法测定了目标化合物对水稻稻瘟病菌、番茄早疫病菌、马铃薯干腐病菌、玉米弯孢病菌、烟草赤星病菌、小麦赤霉病菌和棉花枯萎病菌7种植物源病原真菌的抑制活性,并进一步测定了部分化合物的EC50值。结果显示,在50 μg/mL时,大多数目标化合物对供试菌株表现出不同程度的抑制作用。其中,化合物4d和4m对番茄早疫病菌的EC50值分别为6.28和4.61 μg/mL,4m对烟草赤星病菌的EC50值3.58 μg/mL,与对照药剂腈菌唑（对番茄早疫病菌和烟草赤星病菌的EC50值分别为1.63和1.05 μg/mL）在同一数量级,具有开发为新型抗菌药物的潜能。     

天然产物曲地酸及其类似物研究进展

曲地酸(asterric acid)及其类似物是从一些曲霉和青霉等真菌的发酵液中提取分离得到的一类含二苯醚结构的化合物,具有抗菌、抗肿瘤等医药活性以及杀菌、杀线虫及抑制水芹种子萌芽等农药活性,其中曲地酸作为血管内皮生长因子(VEGF)抑制剂和抗生素已被制成为商品化的生物试剂,应用于生物和医学相关领域的研究。对曲地酸及其类似物的来源、结构及物理性质、生物合成及代谢机理,以及其医用和农用活性方面的研究进展进行了综述,对其化学合成及结构改造的前景进行了展望。     

昆虫性信息素及其类似物干扰昆虫行为的机理和应用研究进展

昆虫性信息素及其类似物在有害生物综合治理中起到了越来越重要的作用,如可以对目标昆虫进行监测、诱捕和迷向等。干扰昆虫行为是一种环境友好型的植物保护策略,近年来已在害虫防治领域广泛使用。干扰昆虫行为的机理一直是科学家研究的主要方向,明确其机理能使之得到更有效合理的应用。本文主要对昆虫性信息素及其类似物干扰昆虫行为的机理,以及缓释材料、施用剂量及密度、与其他挥发性物质在田间混合应用等方面的研究进展进行简要综述。     

保幼激素类似物对白蚁的作用研究进展

本文介绍了保幼激素类似物对白蚁的影响,包括诱导前兵蚁、兵蚁和一些中间品级(形态畸形)的产生、抑制白蚁的取食、减少或消除白蚁的共生原生动物群、对白蚁产生不同水平的急性和慢性毒性、抑制工蚁蜕皮以及繁殖蚁建立新群体等方面的影响,其中最主要影响是诱导前兵、兵蚁和一些中间品级的产生破坏了白蚁群体品级比例的平衡性或完整性。因此,保幼激素类似物可用于白蚁的防治,并在田间防治散白蚁和乳白蚁均取得了较好的防治效果,并探讨了应用保幼激素类似物防治白蚁的潜力与前景。     

Natural products as pesticides: Two examples of stereoselective synthesis

The strategy and synthetic efforts leading to efficient stereoselective syntheses of thiangazole, a tris-thiazolinyl-oxazole metabolite isolated from Polyangium spp., and of hydantocidin, a spironucleoside metabolite isolated from Streptomyces hygroscopicus, are discussed.     

Synthesis of anthelmintically active N-methylated amidoxime analogues of the cyclic octadepsipeptide PF1022A

The N-methylated amidoxime analogues of the cyclic octadepsipeptide PF1022A represent novel derivatives with activity against Trichinella spiralis Owen and Nippostrongylus brasiliensis Lane in vitro and against parasitic nematodes in mice and sheep. Some of them show better activity against Hymenolepis nana Siebold, Heterakis spumosa Schneider and Heligmosomoides polygyrus Dujardin in mice than the natural product PF1022A. In particular an improved efficacy against Haemonchus contortus Rudolphi and Trichostrongylus colubriformis Giles in sheep compared to the potent cyclic octadepsipeptide PF1022A and its mono-thionated derivative has been observed. Here we report on a specific modification at the N-methyl amide linkage by using the mono-thionated PF1022A, resulting in novel anthelmintically active backbone analogues of PF 1022A.     

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     

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 2-hydroxy-3-alkyl-1,4-naphthoquinones: correlation of inhibition of ubiquinol cytochrome c oxidoreductase (complex III) with insecticidal activity

The insecticidal and in vitro activities of four homologous series of 2-hydroxy and acetoxy-3-substituted-1,4-naphthoquinones have been measured and correlated with their (Log) octanol/water partition coefficients (Log Ko/w). In vitro activity against mitochondrial complex III was only exhibited by 2-hydroxy-3-alkyl-1,4-naphthoquinones, indicating that the 2-acetoxy compounds act as proinsecticides. Good correlation was observed between in vivo activity against the two-spotted spider mite, Tetranychus urticae and inhibition of complex III isolated from blowfly flight muscle. Both hydroxy and acetoxy analogues of individual compounds exhibited similar levels of in vivo activity with optimum activity for analogues with Log Ko/w values of 7-8. In contrast, the acetoxy derivatives showed superior in vivo activity against the tobacco whitefly, Bemisia tabaci. Complex III isolated from whitefly was optimally inhibited by hydroxy analogues with lower Log Ko/w values (6.0-6.5) and was also more sensitive than the blowfly enzyme to all the compounds tested.     

Binding activity of substituted benzyl derivatives of chloronicotinyl insecticides to housefly‐head membranes,and its relationship to insecticidal activity against the housefly Musca domestica

Variously substituted benzyl derivatives of chloronicotinyl insecticides were synthesized with a wide range of substituents including halogens, NO₂, CN, CF₃ and small alkyl and alkoxy groups at the ortho, meta and para positions, as well as multiple‐substituted benzyl analogues. Their binding activity to the α‐bungarotoxin binding site in housefly (Musca domestica) head membrane preparations was measured. Among the compounds tested, the activity of the meta‐CN derivative was the highest, being 20–100 times higher than those of imidacloprid, acetamiprid and nitenpyram. The synergized insecticidal activity against houseflies was also measured for selected compounds with the metabolic inhibitor, NIA16388 (propargyl propyl phenylphosphonate). For the nitromethylene analogues, including both benzyl and pyridylmethyl analogues, higher binding activity usually resulted in higher insecticidal activity. © 2000 Society of Chemical Industry     

Synthesis and fungicidal activity of a series of novel aryloxylepidines

A series of novel (hetero) aryloxylepidine derivatives was devised as hybrid structures of the phenoxyquinoline and phenethoxyquin(az)oline fungicides. Synthesis of these targets required the development of several new routes to derivatised 4-hydroxymethylquinolines, and subsequent coupling with phenols or haloarenes. The aryloxylepidines generally showed moderate broad-spectrum fungicidal activity across several diseases of cereals. Substitution of the quinoline ring with chlorine at the 7- and/or 5-positions gave molecules with high levels of protectant activity against Erysiphe graminis f sp tritici (powdery mildew of wheat), but this did not improve the level of fungicidal activity against other diseases. In vitro activity against mitochondrial electron transport complex I (MET) derived from Ustilago maydis showed that 8-fluorolepidine analogues were moderately active at this target site, while the more fungicidally active 7- and 5,7-substituted compounds were inactive. This indicates that MET is not the primary target of these highly active powdery mildewicides.     

Design,synthesis and acaricidal activity of novel strobilurin derivatives containing pyrimidine moieties

BACKGROUND: The intermediate derivatisation method based on bioisosteric replacement led to the discovery of the lead strobilurin compound 5a. To produce new strobilurin analogues with improved activity, a series of substituted pyrimidines were synthesised and bioassayed. RESULTS: The compounds were identified by ¹H NMR, IR, MS and elemental analysis. The highly active compound 5g was studied by X‐ray diffraction. Preliminary bioassays demonstrated that some of the title compounds exhibited excellent acaricidal activity against Tetranychus cinnabarinus (Boisd.) at 10 mg L^?1. The relationship between structure and acaricidal activity is reported. CONCLUSION: The present work demonstrates that strobilurin derivatives containing pyrimidine moieties can be used as possible lead compounds for developing novel acaricides. Copyright © 2010 Society of Chemical Industry     

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.