Synthesis and fungicidal activity of 1,4-dithiino[2,3-b]quinoxaline-2,3-dicarbonitriles

A series of eleven 1,4-dithiino[2,3-b]quinoxaline-2,3-dicarbonitriles was prepared by reaction of 2,3-dichloroquinoxalines with disodium (2)-2,3-dimercapto-2-butenedinitrile in N,N-dimethylformamide. These products were tested for in-vitro fungicidal activity by a Minimum Inhibitory Concentration (MIC) method. Several of these compounds showed broad-spectrum fungicidal activity. The activity exhibited by these compounds was greatly dependent upon the substituents of the quinoxaline ring, with the nitro-substituted derivatives showing the highest levels of antifungal activity. None of the compounds prepared, however, showed fungicidal activity comparable to that of the commercial fungicides screened.     

Synthesis and Anthelmintic Activity of 7-Hydroxy- 5-oxo-5H-thieno[3,2-b]pyran-6-carboxanilides and -6-thiocarboxanilides

7-Hydroxy-5-oxo-5H-thieno[3,2-b]pyran-6-carboxanilides and -6-thio-carboxanilides represent a novel series of anthelmintic compounds, with broad-spectrum activity against important parasitic nematodes in sheep and dogs. In particular, an improved efficacy against Trichostrongylus colubriformis in sheep over the related 3-carbamoyl-4-hydroxycoumarins has been noted. New synthetic routes to the key intermediate, 7-hydroxythieno[3,2-b]pyran-5-one, have been developed.     

Chitin biosynthesis inhibition and fungicidal effect of thiosemicarbazones of 2-formyl- and 2-acetylpyridine,their hydrogenated derivatives and copper complexes thereof

Several thiosemicarbazones of 2-formyl- and 2-acetylpyridine dialkylated on N⁴ and non-alkylated on N² were found to be broad-spectrum protectant fungicides with activity particularly against oomycetes. The effect of some of the compounds on chitin biosynthesis was studied, but the low inhibitory activity observed combined with the fungicidal activity spectrum—particularly the high activity against oomycetes—excludes this as their main mode of action. Attempts at enhancing the systemic properties of the compounds by chemical modifications failed.     

含酰腙结构的新型吡唑酰胺衍生物对小菜蛾的生物活性

采用浸虫法、夹毒叶片法和叶碟法分别测定了13个含酰腙结构的新型吡唑酰胺衍生物对小菜蛾3龄幼虫的触杀、胃毒和拒食活性。结果表明:该类化合物对小菜蛾3龄幼虫具有较高的胃毒和拒食活性,其中苯环上含有氯原子、且酰腙一端的取代基含有杂原子且体积较小的化合物 H7的胃毒和拒食活性最好,明显高于对照药剂毒死蜱。H7 72 h胃毒作用LC50值为0.6 mg/L(毒死蜱的LC50值为7.4 mg/L);有10个化合物的拒食活性高于毒死蜱,其中 H7 48 h的拒食中浓度(AFC50) 最低,为0.6 mg/L,明显低于毒死蜱(AFC50=6.5 mg/L)。供试化合物对小菜蛾3龄幼虫均无触杀活性。     

Organic pesticides. XV. Synthesis and insecticidal activity of some compounds containing phosphorus and fluorine

Forty new organofluorine compounds, containing phosphorus, have been synthesised as potential pesticides. The compounds include esters of O,O-dialkyl phosphoramidic acids of the type (RO)₂P(O)NHAr; thioesters of O,O-dialkyl thiophosphoramidic acids of the type (RO)₂P(S)NHAr; esters of O,O-dialkyl phosphonic acid of the type (RO)₂P(O)Ar and esters of O,O-dialkyl thiophosphonic acid (RO)₂P(S)OAr. All the compounds have been screened for their insecticidal activity against adult cockroaches (Periplanata americana) and a few show appreciable activity.     

Effects of Cytochrome P450-Interacting Plant Growth Retardants,Fungicides and Related Compounds on Cell Development and Phase-I Biotransformation Capacity of Unicellular Photoautotrophic Green Algae

Fourteen compounds (paclobutrazol, triadimenol, BAS111..W, propiconazole, tetcyclacis, prochloraz, metyrapone, piperonyl butoxide, 1-aminobenzotriazole, fenpropimorph, propham, prohexadione, mepiquat chloride and chlormequat chloride), most of them established inhibitors of cytochrome P450-dependent mixed function oxygenases and used as pesticides, especially plant growth regulators or fungicides, were applied to the non-target organisms Chlorella fusca and Chlorella sorokiniana, two species of photoautotrophic unicellular green algae. The inhibitory properties of these compounds were evaluated by comparing concentration/response relationships for the integral parameters of cell volume growth and cell division with those for the P450-dependent O-dealkylase activity measured in vivo using 7-ethoxycoumarin and 7-ethoxyresorufin as xenobiotic model substrates for phase-I biotransformation. The results obtained indicate a strong algicidal activity for some of these compounds, with differential sensitivity of the order: cell division>O-dealkylation>cell volume increase. EC₅₀ values for cell division of C. fusca ranged from 0·1 to 9·3 μmol litre⁻¹ for prochloraz and paclobutrazol, respectively. Furthermore, in most cases, concentrations around 10 μmol litre⁻¹ limited significantly the capacity for cytochrome P450 O-dealkylase activity.     

Anticoagulant resistance in Europe: Appraisal of the data from the 1992 EPPO questionnaire

Resistance to the first successful anticoagulant rodenticide, warfarin, was detected in the Norway rat (Rattus norvegicus Berk.) in 1958, and it has since expanded to cover other commensal rodent species (R. rattus L., Mus musculus L.) and the majority of later-developed anticoagulant compounds. The purpose of this paper is to give an up-to-date picture of the current distribution of anticoagulant resistance in Europe, as revealed by the questionnaire dispatched by EPPO (European and Mediterranean Plant Protection Organization) to its member countries in 1992. Replies were received from 13 countries (43% of EPPO members), and it was found that broad-spectrum resistance occurred in practically all those countries that reported testing activity. A likely conclusion based on this finding is that true distribution of resistance is certainly more extensive than documented by the questionnaire replies. Another conclusion drawn by the EPPO Rodent Control Panel was that the existing resistance detection protocols were no longer adequate to cover the whole array of existing anticoagulant rodenticides. Consequently, a new guideline including novel methods particularly for detecting resistance to single-dose anticoagulant compounds was urgently needed. This guideline is currently under review.     

Fungicidal activity of N-(2-cyano-2-methoximinoacetyl)amino acids and their derivatives

More than 20 N-(2-cyano-2-methoximinoacetyl)amino acids and derivatives were synthesised and tested for antifungal activity against grape downy mildew, caused by Plasmopara viticola (de Bary) Berl. & de Toni, and rape downy mildew, Peronospora parasitica Fr. Two of the compounds containing a free carboxylic acid group, a moiety which has been shown to confer phloem mobility on compounds, showed high activity, especially against P. parasitica, in protectant tests. These results indicate that there is no incompatibility between the acid function and fungicidal activity. A number of the esters showed activity comparable with that of cymoxanil in the protectant tests, and the tert-butyl esters of the methionine derivative and its sulfone were more than ten times as active as the commercial compound.     

姜黄素异噁唑和吡唑衍生物的合成及杀螨活性

为了寻求和开发新的基于天然产物的杀螨剂,在明确姜黄素具有杀螨活性,且其结构中的双羰基并非杀螨活性关键基团的基础上,设计并合成了15个姜黄素异噁唑和吡唑衍生物,其结构均经红外光谱、核磁共振氢谱和质谱分析确认。生物活性测定结果表明:几乎所有的目标化合物对朱砂叶螨Tetranychus cinnabarinus和柑橘全爪螨Panonychus citri均表现出了比先导化合物姜黄素更优异的触杀活性,其中化合物 4和11 的活性最为突出。处理48 h后,化合物 4 对朱砂叶螨和柑橘全爪螨的LC50值分别为333.0和156.0 mg/L,其毒力是姜黄素的6.35和4.56倍, 11 的LC50值分别为478.4和144.7 mg/L,毒力是姜黄素的4.42和4.92倍;相应地处理72 h后, 4 的LC50值分别为115.0和84.9 mg/L,其毒力是姜黄素的5.02和1.43倍, 11 的LC50值分别为91.0和68.7 mg/L,毒力是姜黄素的6.35和1.77倍。化合物 4和11 可作为进一步开发研究的具有杀螨活性的候选化合物。     

商陆中三萜皂苷类成分抗烟草花叶病毒活性研究

从垂序商陆中筛选具有抗烟草花叶病毒(Tobacco mosaic virus,TMV)活性的小分子化合物,为开发高效、低毒和环境友好的天然抗病毒剂提供依据。通过现代化分离、纯化技术,采用活性追踪的方法,对采自于贵州省的垂序商陆中的化学成分进行抗TMV活性逐级筛选,获得了两个抗TM V活性较强的三萜皂苷类化合物—商陆皂苷丁和商陆皂苷H,利用光谱解析手段确定了化合物的结构。生物活性测定结果表明:商陆皂苷丁和商陆皂苷H均具有一定的活体钝化与抑制病毒增殖作用,其中活体钝化及病毒增殖抑制作用均强于对照药物宁南霉素。该研究首次发现垂序商陆中的三萜皂苷类化合物具有抗TMV的活性,为下一步系统研究该种植物提供了科学依据。     

嗜线虫致病杆菌对小菜蛾的致死和亚致死效应室内评价

嗜线虫致病杆菌是与昆虫病原线虫共生的细菌,对小菜蛾等多种害虫具有广谱的杀虫活性。为了深入了解该菌的杀虫活性,在室内测定了嗜线虫致病杆菌HB310 ( 简称 Xn HB310)菌株对小菜蛾幼虫的致死和亚致死效应以及持效期。结果表明, Xn HB310菌液对小菜蛾2龄和3龄幼虫72 h的LC50值分别是3.32×104 和8.56×104 CFU/mL,其活性组分主要存在于菌株细胞和经50 kDa超滤膜超滤后的上清液中。此外, Xn HB310菌液对小菜蛾幼虫还表现出明显的拒食活性,其2龄和3龄幼虫的拒食中浓度(AFC50)分别为4.03×105和8.48×105 CFU/mL。将2.24×106 CFU/mL菌液喷施到甘蓝苗上,其在室内的持效期为3~4 d。用亚致死剂量(LC30和LC50)的菌液饲喂小菜蛾2龄幼虫,存活幼虫的生长发育指标、蛹重、雌虫寿命以及成虫产卵量均明显下降,推测这可能导致小菜蛾下一代种群数量减少。研究结果表明,嗜线虫致病杆菌HB310菌株具有开发成为杀虫剂的潜力。     

Fungicidal activity and chemical constitution XXT. The fungitoxicity of aliphatic polyamines

Fifteen polyamines have been prepared and shown to inhibit spore germination of Penicillium expansum and Neurospora crassa in vitro, but not Erysiphe graminis, Sphaerotheca fuliginea or Podosphaera leucotricha; no activity was shown against S. fuliginea on marrow seedlings or P. leucotricha on apple seedlings. Spermine homologues were considerably more active than spermidine homologues, but greatest activity was shown by the two naturally occurring compounds.     

Induced antimicrobial activity in heat-treated woodchips inhibits the activity of the invasive plant pathogen Phytophthora ramorum

The antimicrobial activity of heat-treated woodchips of three woody host species against the invasive oomycete plant pathogen Phytophthora ramorum was investigated to assess the potential of heated woodchips to suppress disease. Results demonstrated that heat-treated woodchips of pine (Pinus sylvestris), Japanese larch (Larix kaempferi) and rhododendron (Rhododendron ponticum) inhibited recovery of P. ramorum spores and mycelium compared with similar material that had only been air-dried. Effects were most evident with pine and larch; inhibition was maintained even when larch woodchips were diluted with soil. In vitro assays using methanol crude extracts from woodchips of the three species showed they all had an inhibitory effect on P. ramorum zoospores and reduced chlamydospore germination compared with air-dried wood extracts. Chemical analysis of the extracts revealed several induced compounds were present but in different concentrations for each species. Coniferaldehyde was the most active inhibitor against spores and mycelium, while the dominant resin acids, dehydroabietic and abietic acid, decreased the minimum inhibitory concentration of phenolic compounds tested against P. ramorum but were ineffective when used alone. An array of compounds, including dehydroabietic acid, methyl abietate, α-pinene and 3-carene, occurred at elevated levels in the living tissue of Japanese larch bark attacked by P. ramorum. These compounds may be part of the induced resistance response of larch to P. ramorum. Results of a field trial using heat-treated and air-dried woodchips were consistent with the crude extract bioassay results, suggesting that heat-treated woody materials have potential to reduce the survival of P. ramorum under natural conditions.     

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     

Organosilane insecticides. Part II: Chemistry and structure—activity relationships

Silicon effectively substitutes for quaternary carbon in etofenpr ox-type insecticides; the resulting dimethyl-4-ethoxyphenyl-3-(4-fluoro-3-phenoxyphenyl)propylsilane is a broad-spectrum insecticide with extremely low toxicity to fish. Four regions of this new silane insecticide have been systematically altered. The methyl groups on silicon appear to be critical for activity. Replacement of the fluorine with hydrogen results in a substantial loss of activity. The aromatic rings of the phenoxyphenyl fragment are best tethered by oxygen or carbonyl, the methylene and nitrogen analogs being of very low toxicity to the test species. The activity ranking of the methylene and carbonyl tethers is opposite to that found for ester pyrethroids. The relationship of insecticidal activity to the aromatic substituent para to the silicon atom has been found to correlate with the molar refractivity of the substituent. Replacement of a tetra-substituted carbon atom with a silicon atom can simplify construction of test compounds and thus be advantageously used in the exploration of structure—activity relationships. A novel method for preparing allylbenzenes from aromatic aldehydes was also developed.     

N-氰基甲基-[(苯甲酰基)(2-氯噻唑-5-基甲基)氨基乙基]砜亚胺类化合物的合成及杀虫活性

为了寻找和发现高效、广谱、低毒、低生态风险并与现有杀虫剂无交互抗性的新型杀虫剂,以2-氯-5-氯甲基噻唑为原料,经多步反应制得10个新型N-氰基甲基 砜亚胺类化合物,其结构均经核磁共振氢谱、元素分析确证。室内生物活性测试结果表明,目标化合物对桃蚜Myzus persicae具有一定的杀虫活性,其中化合物 7-1 在质量浓度为10 mg/L下对桃蚜的致死率达到80%。     

Synergism between fungicides with different mechanisms of action against acylalanine-resistant strains of Phytophthora spp.1

The authors have studied the efficacy of two systemic compounds, cymoxanil and propamocarb, used as partners of acylalanines, in limiting mycelial growth of acylalanine-sensitive and resistant strains of Phytophthora capsici and P. nicotianae var. parasitica. The fungicidal activity of the single components was compared to that of the different mixtures, at various ratios. The degree of synergy was calculated using the method of Wadley. The results obtained indicate synergistic interactions of various intensities: synergistic factors (SF) up to seven were found. The highest synergistic effects were observed in the case of resistant Phytophthora strains.     

The properties of RH 3866, a new triazole fungicide

2-Butyl-2-(4 chlorophenyl)-3-(1H-1,2,4-triazol-1-yl)propanenitrile, RH 3866, a new broad-spectrum fungicide was particularly effective against fungi in the subclass loculoascomycetidae and against powdery mildews and rusts. Some activity against fungi in the genera Fusarium, Monilinia and Rhizoctonia was also observed. The compound was translocated upwards when applied as a soil drench to control wheat-leaf rust caused by Puccinia recondita f.sp. tritici. Fenarimol-resistant Aspergillus nidulans was cross-resistant to RH 3866. Using a cell-free yeast enzyme extract RH 3866 strongly inhibited desmethyl sterol production.     

Antimicrobial activity of some N-(arylalkyl)maleimides

A series of N-(arylalkyl)maleimides was prepared for the reaction of maleic anhydride and N-(arylalkyl) amines, and their antimicrobial activities were examined. All compounds exhibited antibacterial activity against gram-positive bacteria such as Bacillus subtilis and Staphylococcus aureus. Almost all compounds exhibited antibacterial activity against the gram-negative bacterium, Escherichia coli, but were inactive against Pseudomonas aeruginosa. Activities against gram-positive bacteria were independent of the nature of the substituent on the benzene ring or the length of alkyl group, but that against gram-negative bacteria was influenced by these parameters. All N-(arylalkyl)maleimides showed activity against yeasts and mycelial fungi.