The discovery of SYP‐10913 and SYP‐11277: novel strobilurin acaricides

BACKGROUND: As previously reported, methyl (E)‐2‐[2‐(2‐phenylamino‐6‐trifluoromethylpyrimidin‐4‐yloxymethyl)phenyl]‐3‐methoxyacrylate has proven to be a new lead with highly acaricidal activity. Following on from this, in an effort to discover new strobilurin analogues with improved activity, a series of substituted pyrimidines were synthesised and bioassayed. RESULTS: All compounds were characterised by ¹H NMR, IR, MS and elemental analysis. Preliminary bioassays demonstrated that some of the title compounds exhibited notable control of Tetranychus cinnabarinus (Boisd.) at 1.25 mg L^?1. The relationship between structure and acaricidal activity is discussed. CONCLUSION: Two compounds of particular interest, 6j (SYP‐10913) and 6k (SYP‐11277), exhibited potent acaricidal activity. The acaricidal potencies of these analogues are higher than that of fluacrypyrim in greenhouse applications, and are comparable with those of commercial acaricides such as spirodiclofen and propargite in field trials. Copyright © 2011 Society of Chemical Industry     

Design,synthesis and biological activities of new strobilurin derivatives containing substituted pyrazoles

BACKGROUND: Strobilurins are one of the most important classes of agricultural fungicides. To discover new strobilurin analogues with high activity, a series of new strobilurin derivatives containing substituted pyrazoles in the side chain were synthesised and bioassayed. RESULTS: The compounds were identified by ¹H NMR, IR, MS and elemental analysis. Preliminary bioassays indicated that some title compounds exhibited excellent fungicidal activities against Pseudoperonospora cubensis (Burk. & Curt.) Rostovsev and Erysiphe graminis DC f. sp. tritici Marchal, protecting cucumber and wheat at 6.25 and 1.56 mg L^?1 respectively, and showed a moderately high acaricidal activity against Tetranychus cinnabarinus (Boisd.) at 20 mg L^?1. The relationship between structure and biological activity is discussed in terms of effects of the substituent of the pyrazole ring. CONCLUSION: The present work demonstrates that strobilurin analogues with substituted phenylpyrazolylmethoxymethyl side chains can be used as possible lead compounds for further developing novel fungicides and acaricides. Copyright © 2009 Society of Chemical Industry     

Design, synthesis and structure-activity relationship of novel coumarin derivatives

BACKGROUND: The lead coumarin derivative (E)‐methyl 3‐methoxy‐2‐[2‐(4‐methylcoumarin‐7‐yloxymethyl)phenyl]acrylate was discovered by using an intermediate derivatisation method. To discover new coumarin derivatives with improved activity, a series of substituted coumarins were synthesised and bioassayed. RESULTS: The compounds were identified by ¹H NMR, IR, MS and elemental analysis. Bioassays demonstrated that some of the title compounds exhibited excellent fungicidal activity against cucumber downy mildew at 25 mg L^?1. The relationship between structure and fungicidal activity is reported. CONCLUSION: The present work demonstrates that coumarin derivatives containing methoxyacrylate moieties can be used as possible lead compounds for developing novel fungicides. Copyright © 2011 Society of Chemical Industry     

姜黄素嘧啶酮衍生物的合成及杀螨活性

在明确姜黄素具有杀螨活性,且其结构中的双羰基并非是起杀螨作用的关键基团的基础上,设计、合成了4个新颖的姜黄素嘧啶酮衍生物,其结构经红外光谱、核磁共振氢谱和质谱分析确认。生物活性测定结果表明:4个目标化合物均表现出优于母体化合物姜黄素的杀螨活性,处理48 h后,活性最好的4,6-二 -2-嘧啶酮(3a)对朱砂叶螨Tetranychus cinnabarinus和柑橘全爪螨Panoychus cotri的LC50值分别为487.5和200.3 mg/L,其毒力约为姜黄素的4倍;而处理72 h后,化合物 3a 对朱砂叶螨的LC50值为40.7 mg/L,其毒力约为姜黄素的14倍。     

含取代2-苯基吡啶基团的甲氧基氨基甲酸酯类化合物的合成及杀螨活性

以取代2-溴吡啶和羟基苯硼酸为原料,经Suzuki偶联和亲核取代两步反应合成了9个未见报道的含取代2-苯基吡啶基团的甲氧基氨基甲酸酯类化合物,其结构均经红外光谱、核磁共振氢谱及质谱(ESI-MS)表征。初步生物活性测定结果表明:在500 mg/L下,部分化合物对朱砂叶螨Tetranychus cinnabarinus的致死率达100%,具有作为杀螨剂先导结构的潜力。     

新型含1,2,4-噻二唑环的甲氧丙烯酸酯类化合物的合成及抑菌活性

设计合成了14个含1,2,4-噻二唑环的甲氧丙烯酸酯类新化合物,其结构经红外、电喷雾串联质谱(ESI-MS)和核磁共振氢谱确证。生物活性测定结果表明,化合物 7j、7k、7m、7n 在 100 mg/L质量浓度下对小麦赤霉病菌等6种供试病原菌均有较高抑菌活性, 其中7i 对小麦赤霉病菌Fusarium graminearum的抑菌率为100%。     

米尔贝霉素类似物的合成及杀螨杀蚜活性

为寻找高活性的米尔贝霉素衍生物,以伊维菌素为原料,经脱糖、羟基保护、氧化、还原胺化、脱保护等将其转变为13-氨基米尔贝霉素类似物,通过三组分反应设计合成了一系列米尔贝霉素磺酰脒类化合物(7a~7i),并初步测定了其对朱砂叶螨Tetranychus cinnabarinus和豆蚜Aphis craccivora的室内活性。结果表明:各衍生物对朱砂叶螨和豆蚜均有较好的触杀活性,其中7f、7h和7i对朱砂叶螨24 h的LC50值分别为1.04×10–2、9.60×10–4和1.44×10–2 mg/L;7i对豆蚜24 h的LC50值为7.81 mg/L。米尔贝霉素13位氨基上磺酰化的结构修饰有助于提高米尔贝霉素类化合物的杀螨、杀蚜活性。     

天维菌素酰化衍生物的合成及杀虫杀螨活性

以天维菌素B、天维菌素B单糖苷和天维菌素B苷元为原料,经选择性C-5羟基保护,在C-13、C-4′和C-4″位引入不同酰基基团,合成了3个系列共23个天维菌素B酰化衍生物,并通过1H NMR、13C NMR和高分辨质谱对所有目标化合物的结构进行了表征。生物活性测定结果表明,所有衍生物对小菜蛾Plutella xylostella、朱砂叶螨Tetranychus cinnabarinus以及松材线虫Bursaphelenchus xylophilus均表现出不同程度的毒杀活性,其中天维菌素B C-4″位衍生物的活性优于C-4′位衍生物及13位衍生物。化合物8e对小菜蛾和松材线虫的毒杀活性最优,LC50值分别为9.2 mg/L和0.42 mg/L,化合物8b对朱砂叶螨的毒性最高,LC50值为0.0019 mg/L,均优于对照药天维菌素B。     

新化合物天维菌素的杀虫杀螨活性

为明确天维菌素(tenvermectin)的杀虫杀螨活性,分别测定了其对小菜蛾Plutellaxylostella (药膜法)、粘虫Mythimna separate Walker (小叶碟添加法)、棉铃虫Helicoverpaarmigera Hübner (饲料混药法)、松材线虫Bursaphelenchus xylophilus (浸渍法)和朱砂叶螨Tetranychus cinnabarinus (叶片浸渍法和玻片浸渍法)的室内毒力,并采用叶碟喷雾法测定了其对朱砂叶螨的盆栽药效。结果表明:天维菌素对鳞翅目害虫小菜蛾、粘虫和棉铃虫的LC50值分别为22.21、19.66和22.09 mg/L,对松材线虫的LC50值为1.94 mg/L,毒力显著高于米尔贝霉素(P50值分别为0.0051和0.0089 mg/L。盆栽试验结果表明:0.2 mg/L的天维菌素药后5 d对朱砂叶螨的防效最高,达97.42%;药后7 d,尽管天维菌素与阿维菌素的防治效果均有所下降,但天维菌素不同浓度(0.0125~0.2 mg/L)处理防效仍保持在80.23%~91.96%之间。研究表明,天维菌素对供试的有害生物均具有较高活性,具有研究开发潜力。     

新型含2(1H)-喹啉酮的甲氧基丙烯酸酯类

以(E)-2-[2'-(bromo-methyl)phenyl]3-甲氧基丙烯酸甲酯和2(1H)-喹啉酮类化合物为原料,通过醚化等反应,合成了11个新型含2(1H)-喹啉酮结构的甲氧基丙烯酸酯类化合物,其结构经红外、电喷雾串联质谱(ESI-MS)和核磁共振氢谱确证。初步生物活性测试结果表明:在100 mg/L质量浓度下,部分目标化合物对烟草赤星病菌Alternaria alternata等6种病原菌具有一定的抑菌活性,其中5a对水稻稻瘟病菌Pyricularia grisea的抑菌率达100%。     

Synthesis and acaricidal activity of phenylpiperazine derivatives

We synthesized 33 new phenylpiperazine derivatives and assessed their acaricidal activity. These derivatives were synthesized through sequential reactions consisting of the sulfonylation of 2-substituted 4-methylaniline with chlorosulfonic acid, reduction with red phosphorus and iodine, alkylation by alkyl halide, cyclization with bis(2-chloroethyl)amine hydrochloride, and N-substitution reaction of phenylpiperazines with various reagents. All phenylpiperazines synthesized were evaluated for acaricidal activity and their structure–activity relationships discussed, it was found that 4-substituted 1-[2-fluoro-4-methyl-5-(2,2,2-trifluoroethylsulfanyl)phenyl]piperazine derivatives exhibited good acaricidal activity. Among them, 1-[2-fluoro-4-methyl-5-(2,2,2-trifluoroethylsulfanyl)phenyl]-4-(trifluoromethylsulfonyl) piperazine showed the highest level of activity against Tetranychus urticae and provided a high level of activity against Tetranychus kanzawai and Panonychus citri. In addition, studies on the effect at various stages of T. urticae exhibited that this compound showed good activity against both adults and eggs.     

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。     

新型含吡唑杂环邻氨基苯甲酰胺类化合物的合成与杀螨活性

以氯虫苯甲酰胺和氟虫腈的结构为基础,通过活性亚结构拼接的方法,设计合成了24个新型含吡唑杂环邻氨基苯甲酰胺类化合物,其结构经1H NM R、IR及APCI-M S表征。初步生物活性测试结果表明:化合物5-溴-N-[4-氯-2-甲基-6-(甲氨基甲酰基)苯基]-1-1-[2,6-二氯-4-(三氟甲基)苯基]-4-三氟甲基亚磺酰基-1H-吡唑-3-甲酰胺(5k)和5-溴-N-[4-溴-2-甲基-6-(甲氨基甲酰基)苯基]-1-[2,6-二氯-4-(三氟甲基)苯基]-4-三氟甲基亚磺酰基-1H-吡唑-3-甲酰胺(5l)在500 mg/L下对朱砂叶螨Tetranychus cinnabarinus的致死率为100%,但在100 mg/L下其致死率则分别降至30%和50%。所得结果可为邻氨基苯甲酰胺类化合物构效关系研究提供参考。     

新型喜树碱类药性分子的合成与杀螨活性

应用三组分“一锅法”合成了一系列新型喜树碱类药性分子 4a~4n、5a~5n 和 7a~7f ,所有目标化合物均经核磁共振氢谱和质谱确证。室内杀螨活性测定结果表明,所有化合物对朱砂叶螨Tetranychus cinnabarinus均有不同程度的杀螨活性,其中化合物 4l （LC₅₀:25.93 mg/L）和 7d （LC₅₀:28.16 mg/L）的杀螨活性与喜树碱（LC₅₀:24.55 mg/L）的相当。该研究为进一步开展喜树碱作为先导的新农药设计与研究提供了基础。     

姜黄素异噁唑和吡唑衍生物的合成及杀螨活性

为了开发基于天然产物的新型杀螨剂,以胡椒碱为先导化合物,设计并合成了26个含1,3,4-噁二唑杂环的胡椒碱类衍生物 8a ~ 8z ,并经核磁共振氢谱 (或碳谱)、红外光谱和高分辨质谱确证其结构。化合物 8g 通过X-射线单晶衍射确定其空间构型。采用玻片浸渍法测定了系列化合物对朱砂叶螨Tetranychus cinnabarinus Boisduval雌成螨的触杀活性。结果表明：化合物 8m (LC₅₀：0.41 mg/mL)、 8r (LC₅₀：0.36 mg/mL) 及 8u (LC₅₀：0.32 mg/mL) 表现出良好的杀螨活性,其活性分别为胡椒碱 (LC₅₀：15.64 mg/mL) 的38.1、43.4及48.9倍,且化合物 8u 在0.3 mg/mL质量浓度下对朱砂叶螨有较好的室内防治效果,施药后第5天的防治效果为61.8%。构效关系分析发现：在胡椒碱C2位引入1,3,4-噁二唑杂环有利于提高其杀螨活性,且杀螨活性与噁二唑苯环上的取代基密切相关。