含1,2,4-三唑基和肟醚基的N-甲氧基氨基甲酸酯类化合物的合成及杀菌活性

通过(Z)-1-(取代苯基)-2-(1H-1,2,4-三唑-1-基)乙酮肟与N-甲氧基-N-(2-溴甲基苯基)氨基甲酸甲酯反应,合成了11个新的含有三唑基和肟醚基的N-甲氧基氨基甲酸酯类化合物( V1 ~ V11 ),其结构均经1H NMR、IR、LC/MS及元素分析确证。对合成的化合物进行了离体抑菌活性实验,结果表明:在50 mg/L下,所有化合物对小麦赤霉病菌Gibberella zeae (Schw.)Petch、稻瘟病菌Pyricularia oryzae Cav.和黄瓜灰霉病菌Botrytis cinerea Pers.都有一定的抑菌活性,其中 V4 、 V11 对稻瘟病菌的抑菌活性分别达96.5%和96.7%,对黄瓜灰霉病菌的抑菌活性分别达到95.9%和90%。     

N-取代苯基-1-(2,4-二氟苯基)-2-(1H-1,2,4-三唑-1-基)乙基氨基甲酸酯的合成及生物活性

为了寻找高活性的三唑类苯基氨基甲酸酯衍生物,以 1,2,4-三氮唑、2-氯-2,4-二氟苯乙酮为原料,采用活性亚结构拼接的策略,设计并合成了18个未见文献报道的N-取代苯基-1-(2,4-二氟苯基)-2-(1H-1,2,4-三唑-1-基)乙基氨基甲酸酯衍生物 6a ~ 6r 。其结构均通过 1H NMR、13C NMR和高分辨质谱（HRMS）的确证。抑菌活性测定结果显示:在100 μmol/L下,化合物 6m 对6种供试真菌具有良好的抑制作用,抑制率均达到50%以上。化合物 6p 对油菜菌核病菌Sclerotinia sclerotiorum的EC₅₀值为7.1 μmol/L,抑菌活性高于对照药剂烯唑醇（EC₅₀值9.1 μmol/L）。杀螨活性测定结果显示,在150 μmol/L时,化合物 6h 、 6k 和 6o 在48 h时对朱砂叶螨Tetranychus cinnabarinus的致死率分别为67.7%、74.9%和57.5%,杀螨活性低于对照药剂阿维菌素B1a(致死率100%)。本研究所合成的化合物 6o 兼具一定杀菌和杀螨活性,可为新型三唑类杀菌杀螨化合物的设计与研究提供参考。     

1-吡唑甲酰基-2-芳基酰肼类化合物的合成及生物活性

为了寻求新的含吡唑双酰肼类先导化合物,用4-取代-1-甲基-3-乙基-5-吡唑甲酰肼与取代苯甲(乙)酰氯进行缩合反应得到了10个1-吡唑甲酰基-2-芳基酰肼类化合物,其中9个是新化合物,其结构经IR,1H NMR,MS和元素分析确证。初步生物活性实验结果表明,在25 μg/mL浓度下, 3b 和 3j 对稻瘟病菌Pyricularia oryzae的抑制率分别为51.3%和56.1%;在1 000 μg/mL下, 3b 对粘虫Mythimna separata的致死率达到100%。     

(Z)-2-(1H-1,2,4-三唑-1-基)-1-(2,3,4-三甲氧基苯)乙酮肟酯的合成和结构表征

合成了8个(Z)-2-(1H-1,2,4-三唑-1-基)-1-(2,3,4-三甲氧基苯)乙酮肟酯新化合物,经元素分析、IR、1H NMR、MS对其结构进行了表征。讨论了目标化合物的合成方法和立体化学结果。     

1-(3-氯吡啶-2-基)-5-二氟甲基-1H-4-吡唑酰胺类化合物的合成及杀菌活性

以2,3-二氯吡啶(1)为起始原料,经肼基化、环合、水解和酰氯化反应,生成1-(3-氯-2-吡啶)-5-二氟甲基-1H-吡唑-4-甲酰氯(6),(6)与取代基苯胺(7) 反应,制得13个未见文献报道的1-吡啶基吡唑酰胺类目标化合物。利用核磁共振氢谱、质谱(LC-MS)和元素分析对目标化合物的结构进行了表征。初步杀菌活性测定结果表明,在 50 mg/L下,大部分目标化合物对瓜类炭疽病菌Gibberella zeae、瓜类灰霉病菌Botrytis cinerea和水稻纹枯病菌Rhizoctonia solani的抑制活性均不高,仅ZJ-10对瓜类灰霉病菌的抑制率达76.03%。     

6-N-取代的2,4,8,10-四氯-6-硫-12H-双苯并[d,g][1,3,2]-二氧磷杂八环的合成及杀菌活性

通过2,4,6,8,10-五氯-6-硫-12H-双苯并[1,3,2]二氧磷杂八环分别与四氢吡咯、六氢吡啶、吗啉、吡咯、咪唑和1,2,4-三唑反应,得到了6个收率良好的标题新化合物.其结构经1H、13C、31P NMR和元素分析确认.初步杀菌活性测定表明,化合物3c和3d在500 μg/mL浓度下对水稻纹枯病菌Pellicularia sasakii的抑制率为48%～50%,其他化合物对供试菌的活性微弱.     

1,2,3-噻二唑联-1,2,4-三唑衍生物的合成及抑菌活性

以4-氨基-3-(4-甲基-1,2,3-噻二唑)-1,2,4-三唑-5-硫酮为原料,与醛在冰乙酸中回流制得15个新型4-取代亚氨基-3-(4-甲基-1,2,3-噻二唑)-1,2,4-三唑-5-硫酮化合物,其结构经IR、1H NMR 及元素分析表征,其中,化合物 5c 的结构经单晶测试确证,该晶体属单斜晶系,P2(1)/c空间群,晶胞参数a=1.403 7(3) nm,b=1.570 5(3) nm,c=0.686 4(14) nm,β=102.06(3)°,V = 1.479 8(5) nm3,Z=4,F(000)=656。初步的抑菌活性测试结果表明;所有化合物对黄瓜灰霉病菌Botrytis cinerea都有较好的抑制作用,化合物 5l 的抑制率达87%, 5c、5d和5f 的抑制率在78%左右; 5a 对小麦赤霉病菌Gibberella zeae的抑制率为78.7%; 5m 对西瓜炭疽病菌Colletotrichum lagenarium的抑制率为65.6%。     

4-甲基-2-(1H-吡唑-1-基)-噻唑-5-甲酰胺类化合物的合成及杀菌活性

以4-甲基-2-(1H-吡唑-1-基)-噻唑-5-甲酰氯为原料,与取代胺作用制得10个结构新颖的4-甲基-2-吡唑基-噻唑甲酰胺类化合物,利用1H NMR和MS对其结构进行了表征。盆栽法试验结果表明,在500 mg/L质量浓度下,部分化合物对黄瓜霜霉病和黄瓜白粉病的相对防效达100%,对黄瓜灰霉病的防效达85%。     

3-二氟甲基-1-甲基吡唑-4-羧酸肟酯衍生物的合成及抑菌活性

为发现具有高抑菌活性的先导化合物,结合本课题组前期研究,设计并合成了18个新型3-二氟甲基-1-甲基吡唑-4-羧酸肟酯衍生物,其结构均经核磁共振氢谱、碳谱及高分辨质谱分析确证,化合物 9g 的单晶衍射结果证明肟酯的构型为E式。离体生物活性测定结果表明,目标化合物在50 μg/mL下对番茄灰霉病菌 Botrytis cinerea、苹果树腐烂病菌Valsa mali 和小麦全蚀病菌Gaeumannomyces graminis均表现出一定的抑制活性,其中化合物 9d 对苹果树腐烂病菌、 9r 对小麦全蚀病菌的EC₅₀值分别为0.89 μg/mL和3.34 μg/mL,表现出比先导化合物 L1 (E-2-氯-6-氟苯甲醛-O-(1-甲基-3-苯基-1H-吡唑-5-羰基)肟)和肟菌酯更优或相似的抑菌活性。     

新型1H-吡唑-5-甲酰基氨基脲类化合物的合成及生物活性

采用活性亚结构拼接和生物合理设计的方法,将4-氯-1-甲基-3-乙基-5-吡唑甲酰肼与取代苯基异氰酸酯反应得到14个新的含氨基脲的吡唑类化合物。其结构经IR、1H NMR、质谱和元素分析确证。初步生物活性实验结果表明, 化合物1-( 4-氯-3-乙基-1-甲基-1H-吡唑-5-甲酰基) -4-(2-甲基苯基)氨基脲( 4g) , 1-( 4-氯-3-乙基-1-甲基-1H-吡唑-5-甲酰基) -4-( 4-氯苯基)氨基脲( 4b)在500μg /mL 剂量下对小麦白粉病菌Bumeria graminis和粘虫Mythimna separata 的抑制率和致死率分别达到90%和100%。     

Structural studies in azolylmethanes

The crystal structures of a number of fungicidal azolylmethanes are compared. In the benzyl compounds [1-aryl-4,4-dimethyl-2-(1,2,4-triazol-1-yl)pentan-3-ones, the corresponding pentan-3-ols, and 1-(4-chlorophenyl)-3-(2-fluorophenyl)-2-(1,2,4-triazol-1-yl)propan-1-one], the benzyl and tert-butyl groups (or 4-chlorophenyl group) are trans, whereas in the analogous phenoxy compounds [1-(4-chlorophenoxy)-3,3-dimethyl-1-(1,2,4-triazol-1-yl)butan-2-one and the corresponding butan-2-ol], the tert-butyl groups are trans to the triazole and gauche to the phenoxy group. Coupling constants, determined by nuclear magnetic resonance (n.m.r.) spectroscopy, suggest that for some compounds there is one dominant solution conformation. Intramolecular hydrogen bonding, observed by infrared spectroscopy in two of the compounds, supports the findings by n.m.r. For some compounds, the crystal and solution conformations appear to be very similar, whereas in others they are quite different. Published data on the relative activity of the enantiomers of the benzyl- and phenoxy-compounds are discussed, but differences in the relative activity of enantiomers in the two series cannot be readily rationalised. It is concluded that different enantiomers may have different modes of binding at the active site.     

Phototransformation of Triadimefon on Glass and Soil Surfaces

Photodegradation of triadimefon has been studied on glass and soil surfaces. A number of photoproducts have been isolated and characterised by NMR, IR and MS. Photolysis resulted in considerable amounts of 1-(4-chlorophenoxymethyl)-1,2,4-triazole, 1-(4-chlorophenoxy)-2,2-dimethyl-1-(1,2,4-triazol-1-yl)propane, 1-(1,2,4-triazol-1-yl)-3,3-dimethylbutan-2-one and 1-(4-chlorophenoxy)-3,3-dimethyl-1-(1,2,4-triazol-1-yl)butan-2-ol. Rates of photodegradation on glass and soil surfaces under UV and sunlight followed first-order kinetics with a significant correlation coefficient. Photodegradation was greater on alluvial soil than on laterite soil.     

Photolysis of Diniconazole-M under Sunlight

The photodegradation of diniconazole-M [(E)-(R)-1-(2,4-dichlorophenyl)-4,4-dimethyl-2-(1,2,4-triazol-1-yl)-1-pentene-3-ol] was studied as thin film on glass surface under sunlight. Photoproducts were separated and identified by NMR, IR, UV and mass spectroscopy. They were characterised as the (Z)-isomer of diniconazole-M, a cyclic alcohol and its corresponding ketone and an isoquinoline derivative. © 1997 SCI.     

Synthesis and fungicidal activity against Pyricularia oryzae of 6-(1,2,4-triazol-4-yl) chromone and -1-thiochromone derivatives

A series of novel 6-(1,2,4-triazol-4-yl) chromone and -1-thiochromone (benzo[b]thiazin-4-one) derivatives was obtained by cyclisation via thiosemicarbazides which were prepared by reaction of hydrazines and the corresponding isothiocyanates. Their fungicidal activity was evaluated against the rice blast fungus Pyricularia oryzae. Of this series, 2,5,8-trimethyl-6-(1-propyl-5-thioxo-3-trifluoromethyl-1,2,4-triazol-4-yl) chromone, 6-(1-butyl-5-thioxo-3-trifluoromethyl-1,2,4-triazol-4-yl)-2,5,8-trimethylchromone, 6-(1-hexyl-3-methyl-5-thioxo-1,2,4-triazol-4-yl)-2,5,8-trimethylchromone and 6-(1-allyl-5-thioxo-3-trifluoromethyl-1,2,4-triazol-4-yl)-2,5,8-trimethylchromone were highly active (pEC₅₀>6·0). Structure–activity relationship studies using the capacity factor k′ as a hydrophobicity index suggested that the log k′ optimum for 2,5,8-trimethyl-chromone and -1-thiochromone derivatives was around 1·0, equivalent to a log P_ow value of c. 4·4. © 1998 SCI     

Synthesis and biological evaluation of [1-(1H-1,2,4-triazol-1-yl)alkyl]-1-silacyclopentanes

A series of 1-aryl-1-(1H-1,2,4-triazol-1-yl)alkyl-1-silacyclopentanes has been synthesized by four-step reactions starting from 1-chloroalkyltrichlorosilane and tested for fungicidal activities in vitro for ten fungi and in vivo for four fungi occurring in rice, cucumber, tomato etc. Biological activities of the title compounds are strongly dependent upon the p-substituent on the phenyl group in the following order: F>Cl>Ph>OEt>H. Especially, 1-p-fluorophenyl-1-[1-(1H-1,2,4-triazol-1-yl)alkyl]-1-silacyclopentanes (alkyl=methyl or ethyl) showed significant fungicidal activity with a broad spectrum comparable to flusilazole in in-vivo assay. © 1998 SCI.     

吡啶衍生物研究(IV):4-烃基-3-[(2-氯吡啶)-4-基]-1,2,4-三唑啉-5-硫酮的合成及抑制棉花立枯菌活性

越来越多的吡啶衍生物被发现具有各种不同的生物活性。据报道,吡啶环的2位或6位被氯原子取代后的某些化合物能够诱导植物产生抗病机能,如N-氰甲基-2-氯异烟酰胺(NCI)对防治稻瘟病有很好的效果,它不是直接作用于病菌,而是诱导水稻植物体产生抗病机能,这是防治植物病害的新的化学途径[1]。而2,6-二氯异烟酸也是一个能诱导植物系统产生抗病性的有效药剂,能诱导植物产生大量PR蛋白[2]。为此,在前期工作[3]的基础上,我们设计、合成了一系列标题化合物(I),并测定了它们抑制棉花立枯菌的活性。合成路线如下:NCOOHH2O2NOCOOHPCl5POCl3NCl…     

Binding of azole fungicides related to diclobutrazol to cytochrome P-450

Fungicides containing the imidazole and triazole groups are known to block the 14α-demethylation reaction in ergosterol biosynthesis, which is a cytochrome P-450 enzyme system. Fungicides related to diclobutrazol [(2RS, 3RS)-1-(2,4-dichlorophenyl)-4,4-dimethyl-2-(1,2,4-triazol-1-yl)pentan-3-ol] bind to cytochrome P-450 in rat liver microsomes, whole yeast cells, yeast microsomes and to a partially purified cytochrome P-450 from yeast, with Type II spectral changes. The most fungicidally active isomer (2R, 3R) shows greater binding than the less active (2S, 3S)-enantiomer to yeast microsomes; when the cytochrome P-450 was purified, a preparation was obtained to which binding more closely matched the fungicidal activity. Binding to rat liver microsomes does not reflect the fungicidal activity of the compounds.     

含1,3,4-噻二唑的吡啶联吡唑乙酰胺类化合物的合成及除草活性

以乙酰丙酮、溴乙酸乙酯和2,6-二氯吡啶为起始原料,经取代、肼基化、环合、水解、酸化及缩合等反应,得到9个未见文献报道的吡啶联吡唑乙酰基类化合物 B1~B9 。其结构均经核磁共振氢谱和质谱表征。初步生物活性测定表明:在150 g/hm2的处理剂量下,大部分目标化合物表现出一定的除草活性,其中化合物 B2、B3、B6 和 B8 对苘麻Abutilon theophrasti Medicus、反枝苋Amaranthus retroflexus和凹头苋Amaranthus lividus L.生长的抑制率接近100%。