Synthesis and fungicidal activity of N-2-(3-methoxy-4-propargyloxy) phenethyl amides. Part 3: stretched and heterocyclic mandelamide oomyceticides

Novel analogues of mandipropamid have been designed and prepared. The synthetic approach to these stretched and heterocyclic mandelamides is outlined. Biological data demonstrate their high efficacy against important plant diseases like tomato and potato late blight (Phytophthora infestans De Bary) and grape downy mildew (Plasmopara viticola Berliner & de Toni). Structure-activity relationship studies are discussed.     

N-(3,5-二甲氧基-4-烷氧基苯乙基)扁桃酰胺类杀菌剂的设计合成及杀菌活性

以第一个扁桃酰胺类杀菌剂双炔酰菌胺为模板,在炔丙氧基的邻位引入第二个甲氧基,设计合成了15个未见文献报道的 N-(3,5-二甲氧基-4-烷氧基苯乙基)扁桃酰胺类化合物(8a～8o),其结构通过核磁共振氢谱和高分辨质谱确认。初步的离体和活体杀菌试验结果表明,化合物 8e、8h和8o 对辣椒疫霉 Phytophthora capsici 具有较好的杀菌活性,其中 8h和8o 在62.5 mg/L下对辣椒疫霉活体抑制率达100%。     

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 insecticidal activity of lipophilic amides. Part 3: Influence of chain length and terminal group in N-(2-methylpropyl)-2,4-dienamides

Increasing the alkylene chain length in N-(2-methylpropyl)-ω-phenylalka-2,4-dienamides revealed in addition to the active compounds reported earlier a second peak of activity, but only against mustard beetles, with the tridecadienamide. Similar extension in the methyl-terminated series gave much weaker peaks, at different lengths for the two test species. Results with terminal vinyl compounds were intermediate, and indicated a specific functional role in the lethal process for the terminal unsaturation, with a possible contribution to steric flexibility and physical property optimisation from the longer chains. Synthetic samples of pellitorine and pipercide, natural products to which insecticidal activity has been ascribed, were only very weakly active in the present tests, but compounds with other groups on the ends of chains nearer the optimum length were more active.     

2-[4-(对氟苯基)噻唑-2-基]-3-羟基-3-烃氧基丙烯腈的合成及杀菌活性

为了寻找生物活性良好的噻唑基丙烯腈类化合物,利用2-氰甲基-4-(对氟苯基)噻唑( 3 )与取代氯甲酸酯( 4 )在碱存在下反应,合成了15个未见文献报道的2- -3-羟基-3-烃氧基丙烯腈化合物( 5 ),其结构经核磁共振氢谱、质谱和元素分析表征。初步杀菌活性测试结果表明:所有化合物在试验浓度下均具有一定的抑菌活性,尤其对炭疽病菌Colletotrichum gossypii表现出较好的抑制活性,在质量浓度25 mg/L下,所有化合物的抑制率均在50%以上,其中化合物 5a、5e、5g、5k、5n和5o 的抑制率在80%以上。     

5-(2-乙基亚环己基)-2-取代氨基咪唑啉酮类化合物的合成及其杀菌活性

以2-乙基环己酮和2-硫代乙内酰脲为起始原料,经Knoevenagel缩合反应制得5-(2-乙基亚环己基)-2-硫代咪唑啉-4-酮(1),化合物1在乙醇钠-乙醇体系中与碘甲烷反应得到5-(2-乙基亚环己基)-2-甲硫基咪唑啉-4-酮(2),化合物2再与相应的取代苄胺在冰醋酸体系中回流制得新化合物3a～3f,其化学结构均经1H NMR、IR和MS确证。初步生物活性测定结果表明:在50 μg/mL下,部分目标化合物对油菜菌核病菌Sclerotinia scleotiorum显示出良好的抑制活性,其中3a、3c、3e和3f的EC50值分别为12.10、8.73、10.11和7.67 μg/mL。     

3-取代苯基-4-酰氧基-2(1H)-喹啉酮的合成及抑菌活性

以5-甲基-2-氨基苯甲酸和2-氨基苯甲酸为原料,通过酯化、酰化、环合再酯化的路线,合成了15个新型喹啉酮类衍生物(5a~5o),其结构均经红外、电喷雾串联质谱(ESI-MS)和核磁共振氢谱确证。初步的生物活性测定结果表明:在 100 mg/L质量浓度下,化合物 5c 对6种供试病原菌均具有较好活性,抑制率在61.7% ~92.9%之间;同时,化合物 5i 对棉花枯萎病菌Fusarium oxysporum f.sp.Vasinfectum的抑制率达96.1%,接近对照药剂嘧菌酯。     

Synthesis and fungicidal activity of N-(p-sulfonylphenyl)-N1 -carbamoylureas

A series of 11 N-(p-sulfonylphenyl)-N¹-carbamoylureas was prepared by reaction of 1,6-diphenyl-2,4-dioxohexahydro-s-triazine with chlorosulfonic acid and thionyl chloride. The resultant N-(p-chlorosulfonylphenyl)-N¹-carbamoylurea was subsequently condensed with amines, butanol, hydrazine and sodium azide. The hydrazide was reacted with carbonyl compounds and the azide with trimethyl phosphite. The products were tested for in-vivo fungicidal activity against barley powdery mildew (Erysiphe graminis); the acetone hydrazone derivative showed the highest activity. © 1998 SCI.     

N-(2-三氟甲基-4-氯苯基)-2-吡唑酰氨基环己烷基磺酰胺类化合物的合成与杀菌活性

吡唑酰胺类杀菌剂是近年新农药开发的热点。本研究采用EDCI/HOBt酰胺化法合成了14个结构新颖的N-(2-三氟甲基-4-氯苯基)-2-吡唑酰氨基环己烷基磺酰胺类化合物 ( 3a ~ 3n ),其结构均经1H NMR、13C NMR、质谱和元素分析确认,并用X-射线衍射法确定了化合物 3g 的单晶结构和立体构型。菌丝生长速率法试验结果表明,化合物 3a 、 3e 和 3j 对番茄灰霉病菌Botrytis cinerea KZ-9的EC₅₀值分别为4.28、10.08和11.31 mg/L,抑菌活性不及对照药剂啶酰菌胺和腐霉利;但在孢子萌发试验中,目标化合物表现出与对照药剂相近的抑菌活性,在10 mg/L下有7个化合物对灰霉病菌孢子萌发的抑制率超过了85%;在番茄活体盆栽试验中,化合物 3e 在200 mg/L下对番茄叶片及其花上灰霉病菌的防治效果分别为77.5%和65.2%,高于对照药剂啶酰菌胺 (防效分别为59.8%和30.3%),有进一步研究的价值。     

Synthesis and insecticidal activity of lipophilic amides. Part 6: 6-(disubstituted-phenyl)hexa-2,4-dienamides

By using a phosphonate containing an N-(2,2-dimethylpropyl) instead of an N-(2-methylpropyl) group, rearrangement during the Wadsworth-Emmons condensation step was restricted to an acceptable level even with products from disubstituted phenylacetaldehydes. Previous results had shown that this change in N-group did not alter insecticidal activity drastically, so structure-activity relationship conclusions could be drawn from both series in combination. The presence of methyl groups on the phenyl lowered activity, confirming results in the mono-substituted series, so attention was directed primarily to the numerous possible di-halo combinations. Many were active, especialty those with 3,4 or 3,5 substitution patterns, but beyond this no simple correlations could be detected relating position or nature of substituents to activity. Varying both the phenyl substituents and amine group gave results approximately in agreement with additivity principles.     

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%。     

2-(2-氨基噻唑-4-基)-(Z)-甲氧亚氨基乙酸酯的酰胺及亚胺衍生物的合成及抑菌活性

以乙酰乙酸甲(乙)酯为原料,合成了2-(2-氨基噻唑-4-基)-(Z)-甲氧亚氨基乙酸酯的酰胺和亚胺两类共13个衍生物,其中10个化合物未见文献报道,所有化合物的结构均经核磁共振氢谱(1H NMR)、红外光谱(IR)和电喷雾电离质谱(ESI-MS)确证。初步杀菌活性测试结果表明,所有化合物在质量浓度200 mg/L下对6种供试植物病原菌均有不同程度的抑制作用,其中化合物 mk-1 在200 mg/L下对小麦赤霉病菌Fusarium graminearum的抑制率达81.4%。     

N-羟基-N-2-[N-(4-氯苯基)-3-吡唑氧基甲基]-苯胺的合成

高效低成本合成N-羟基-N-2-[N-(4-氯苯基)-3-吡唑氧基甲基]-苯胺。以2-[(N-4-氯苯基)-1H-吡唑-3-基氧甲基]硝基苯和碳酸氢钠为原材料,5%Pt/C为催化剂,通入氢气还原得N-羟基-N-2-[N-(4-氯苯基)-3-吡唑氧基甲基]-苯胺,并对不同条件下的试验结果进行了分析。优化条件为氢气进气压力为0.2Mpa,5%Pt/C催化剂与2-[(N-4-氯苯基)-1H-吡唑-3-基氧甲基]硝基苯的配比为5∶60,温度为30℃,反应时间为4h。该反应条件下产物反应收率≥97%,含量≥97%,生产成本低、操作简便非常适合工业化生产。     

3-苄基-5-(1-(2-氧代-1-氧杂螺[4,5]癸-3-烯-3-基)亚乙基)-2-氨基咪唑啉-4-酮类化合物的合成及杀菌活性

为寻找高活性的杀菌化合物,在前期合成5-(1-(4-甲基-2-氧代-1-氧杂螺[4,5]癸-3-烯-3-基) 亚乙基)-2-氨基咪唑啉-4-酮类化合物的基础上进行结构修饰,在咪唑啉-4-酮的3-位引入苄基,设计并合成了一系列未见文献报道的化合物,其结构经过核磁共振氢谱 (1H NMR)、碳谱 (13C NMR) 及高分辨质谱 (HR-ESI-MS) 确证。经高效液相色谱 (HPLC) 分析显示,Z-构型中间体化合物 6 在酸性条件下会发生氮质子化开环再环化,转化为E-构型化合物 7 。离体杀菌活性测定结果表明,3-位苄基的引入改善了该类化合物的杀菌活性,其中化合物 (E)-3-苄基-5-(1-(4-甲基-2-氧代-1-氧杂螺[4,5]癸-3-烯-3-基) 亚乙基)-2-(4-甲氧基苯基) 氨基-咪唑啉-4-酮 ( 9c ) 和 (E)-3-苄基-5-(1-(4-甲基-2-氧代-1-氧杂螺[4,5]癸-3-烯-3-基) 亚乙基)-2-(4-氟苯基) 氨基-咪唑啉-4-酮 ( 9h ) 对油菜菌核病菌的EC₅₀ 值分别为14.3和21.1 mg/L。活体杀菌活性测试结果显示,在400 mg/L下化合物 9c 对于黄瓜霜霉病和小麦白粉病的防治效果分别为 80%和85%。     

(4-亚甲基-5-羰基-3-四氢呋喃基)-苯甲酸甲酯衍生物的合成及其杀菌活性

为了探索天然产物Cedarmycins衍生物的结构与活性关系,以α-亚甲基-β-羟甲基-γ-丁内酯为起始原料,经过与不同取代的羧酸缩合,合成了19个新的(4-亚甲基-5-羰基-3-四氢呋喃基)-苯甲酸甲酯衍生物。杀菌活性测定结果表明,该类衍生物具有广谱的杀菌活性,尤其对水稻纹枯病菌Rhizoctonia solani和辣椒疫霉Phytophthora capsici显示出很强的杀菌活性,其中化合物2e(R=2,4-2Cl)对这2种病菌的EC50值约为1.6 mg/L。     

新型喹唑啉-4(3H)-酮Schiff碱的合成及生物活性

为探索具有高杀菌活性的新型喹唑啉酮类先导化合物,以4-氯-2-氨基苯甲酸为起始原料,经重氮化、叠氮化、酯化等系列反应,得到17个未见文献报道的喹唑啉-4(3H)-酮Schiff碱类化合物。所有目标化合物的结构均经IR、1H NMR、MS及元素分析确证。初步生物活性测定结果表明,目标化合物表现出一定的杀菌活性,特别是对芒果褐色蒂腐病菌Phomopsis mangiferae Ahmad活性较好。化合物7-氯-3-(2,4-二氯-苯基)亚氨乙基-2-苯氨基喹唑啉-4(3H)-酮 (7e) 在 100 μg/mL 时,对橡胶棒孢霉叶斑病菌Corynespora cassiicola Wei和芒果褐色蒂腐病菌Phomopsis mangiferae Ahmad的抑制率分别为26.21%±1.11%和98.18%±1.07%,与对照药剂百菌清(25.64%±1.31%和100%)相当。初步的构效关系表明,吸电子基团有利于提高目标化合物的杀菌活性。     

The fungicidal activity of substituted 1, 4-naphthoquinones. Part II: Alkoxy,phenoxy and acyloxy derivatives

A representative group of 1, 4-naphthoquinone derivatives, bearing alkoxy, phenoxy and acyloxy substitutents in the 2-position, has been synthesised and assayed against Botrytis cinerea, Cladosporium fulvum and Venturia inaequalis. The alkoxy compounds exhibited moderate activity, which was enhanced by the presence of a 3-chloro and, to a lesser extent, a 3-bromo substituent. 2-Chloro-3-phenoxy derivatives were highly active, but diphenoxy compounds were inactive. Acyloxy derivatives possessed only weak activity unless a halogen atom was present in the 3-position; benzoyloxy compounds, however, were generally poor fungicides.     

氨基甲酸-2-氯吡啶-5-甲酯化合物的合成与抑菌活性

以芳香硝基化合物、2-氯-5-吡啶甲醇和一氧化碳为原料,在Pd-Fe/TiO2催化下进行羰基化反应,合成了11个新型氨基甲酸-2-氯吡啶-5-甲酯化合物,其结构经 1H NMR和MS表征。初步抑菌活性测定结果表明:在50 mg/L下,大多数目标化合物对4种供试病原菌具有一定的抑制活性,其中化合物 3f (4-甲氧基苯基氨基甲酸-2-氯吡啶-5-甲酯、3h (2,4-二氯苯基氨基甲酸-2-氯吡啶-5-甲酯)和 3j (3,4-二氯苯基氨基甲酸-2-氯吡啶-5-甲酯)对小麦赤霉病菌Gibberella zeae的抑制率达77.3%以上, 3f 对苹果轮纹病菌Physalospora piricola的抑制率达82.5%,与对照药多菌灵接近;所有化合物在50 mg/L下对番茄灰霉病菌Botrytis cinerea的抑制活性均优于对照药多菌灵。     

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     

丹皮酚衍生物——3-羟基-1-(2-羟基-4-甲氧基苯)-3-(2'-溴苯)-1-丙酮的合成及其抗菌活性

从牡丹根皮中提取丹皮酚,将丹皮酚精制后与2-溴苯甲醛在室温及碱催化下发生亲核加成反应,生成一种丹皮酚衍生物——3-羟基-1-(2-羟基-4-甲氧基苯)-3-(2'-溴苯)-1-丙酮,产率为78.6%,其结构用紫外光谱(UV)、红外光谱(IR)、质谱(MS)及核磁共振谱(NMR),结合元素分析等进行表征。单晶X-衍射(X-ray diffraction)测定结果表明:该晶体属单斜晶系;P2(1)/n空间群;晶胞参数:a=0.99380(15) nm,b=0.80617(12) nm,c=1.9251(3) nm,α=90.0(2)°,β=103.287(2)°,γ=90(2)°,V=1.5010(4) nm3,Dc=1.554 mg/cm3, μ=2.751 mm-1,F(000)=712,Z=4,R1=0.0290,ωR2=0.0660,R(int)=0.0322。该丹皮酚衍生物具有抗菌活性,对植物源真菌油菜菌核病菌Sclerotinia sclerotiorum和番茄灰霉病菌Botrytis cinerea的最小抑菌浓度(MIC)分别为0.36和0.48 g/L,对病源细菌福氏志贺菌Shigella flexneri 51065和金黄色葡萄球菌Staphylococcus aureus ATTCC25925的MIC分别为0.02和0.06 g/L。