2-[4-(2,6-二氟苯基)噻唑-2-基]-3-羟基丙烯腈衍生物的合成及生物活性

为了寻找生物活性良好的噻唑基丙烯腈类化合物, 利用2-[4-(2,6-二氟苯基)噻唑-2-基]乙腈(3)分别与取代氯甲酸酯4和取代苯基异氰酸酯6在碱存在下反应, 合成了8个2-[4-(2,6-二氟苯基)噻唑-2-基]-3-羟基-3-烃氧基丙烯腈化合物5和7个2-[4-(2,6-二氟苯基)噻唑-2-基]-3-羟基-3-取代苯胺基丙烯腈化合物7, 均为首次报道的丙烯腈类化合物. 化合物结构经1H NMR, IR, MS和元素分析表征. 初步生物活性测定结果表明, 在试验浓度下, 目标化合物均具有一定的杀虫和抑菌活性, 其中化合物5f和5h在100 mg/L浓度下对炭疽病菌的抑制率达95%; 化合物5g和7d在250 mg/L浓度下对棉红蜘蛛的致死率达85%.     

1-苯基-3-甲基-5-芳氧基-1H-吡唑-4-甲醛-O-[(2-氯吡啶-5-基)甲基]肟的合成与生物活性

利用1-苯基-3-甲基-5-芳氧基吡唑4-甲醛肟与2-氯-5-氯甲基吡啶发生缩合反应,合成了14个新型含吡啶环的吡唑肟醚衍生物.通过1H NMR,13C NMR和元素分析对所合成的化合物进行了结构表征.初步生物活性测试结果表明,在试验浓度下部分化合物具有一定的杀菌和植物生长调节活性.     

N-[4-氯-2-取代氨基甲酰基-6-甲基苯基]-1-芳基-5-氯-3-三氟甲基-1H-吡唑-4-甲酰胺的合成及生物活性

通过改变传统氯虫酰胺中吡唑环上氨基甲酰基与吡啶环之间的相对位置, 或以其它芳环取代原分子中的吡啶环, 设计合成了24个结构新颖的N-[4-氯-2-取代氨基甲酰基-6-甲基苯基]-1-芳基-5-氯-3-三氟甲基-1H-吡唑-4-甲酰胺类化合物. 所有目标化合物的结构均通过¹H NMR谱、 元素分析或高分辨质谱表征确定. 初步的生物活性测试结果表明, 部分化合物对东方粘虫具有较好的杀虫活性, 其中化合物6m在浓度为50 mg/L时具有80%的杀虫活性. 同时, 在浓度为50 mg/L时目标化合物对5种常见病菌具有明显的抑制作用, 其中化合物6n和6x对苹果轮纹菌的抑菌率达62.1%.     

新型含2,4-咪唑啉二酮的4-甲基-3-苯基-2-酰亚胺噻唑啉的合成及生物活性

通过酰氯制备异硫氰酸酯,与5-(4-氨基苄基)-2,4-咪唑啉二酮反应合成了含2,4-咪唑啉二酮的N-苯甲酰基-N'-苯基硫脲,然后在三乙胺存在下再与溴丙酮发生碱催化缩合反应以中等以上收率合成了新型含2,4-咪唑啉二酮的4-甲基-3-苯基-2-酰亚胺噻唑啉,它们的化学结构经1H NMR,IR,HR-ESI-MS和化合物3g和4g的X-ray单晶衍射表征,硫脲与溴丙酮的反应机理通过化合物3g和4g的晶体结构得到进一步确证.初步生物活性测定结果表明:部分目标化合物对供试昆虫及菌种显现出良好的抑制活性,如在200 mg/L浓度下化合物3i和4q对小菜蛾的死亡率分别为86%和100%,在50 mg/L浓度下化合物4n对油菜菌核菌的抑制率为82.6%,而它们对油菜和稗草显示出微弱但并不特征的除草活性.     

新型4-芳氨基嘧啶类衍生物的合成及其杀虫活性

以取代苯胺为起始原料,经重氮化、Meerwein芳基化、异硫氰化、加成、甲基化、环化等多步反应合成一系列结构新颖的4-芳氨基嘧啶类衍生物,并测试了目标化合物的杀虫活性.初步杀虫活性结果表明,在质量浓度500mg/L时,大部分化合物对粘虫的致死率为100%;当质量浓度降至20 mg/L时, 2-甲基-4-[N-(2-氯-4-氟苯基)氨基]-5-[2-三氟甲基-4-(苯氧基)苯基]-6-甲基嘧啶(6h)对粘虫和小菜蛾的致死率分别为80%和60%.     

8-氮杂双环[3.2.1]辛烷-3-异噁唑肟类衍生物的合成及其杀线虫活性

基于具有潜在杀线虫活性的托烷衍生物结构,通过1,3-偶极环加成反应,设计合成了19个未见报道的8-氮杂双环[3.2.1]辛烷-3-异噁唑肟类衍生物,通过~1H NMR,~(13)C NMR和高分辨质谱对目标化合物的结构进行表征.初步的生物活性测试表明:在浓度25 mg/L下,目标化合物对南方根结线虫表现出良好的抑制活性,活性最好的化合物8-甲基-8-氮杂双环[3.2.1]辛烷-3-酮-O-((3-(4-硝基苯基)-4,5-二氢异噁唑-5-基)甲基)肟(9e)在1 mg/L浓度下对根结线虫的抑制率达55.6%.     

新型N-取代苯基-2-吡唑基烟酰胺类化合物的合成及其生物活性

基于含吡啶基吡唑的邻甲酰氨基苯甲酰胺类农药分子结构,采用"酰基移位"的策略,以2-氯-3-氰基吡啶和4-溴吡唑或3,5-二甲基吡唑为起始原料,简便合成了14个结构新颖的N-取代苯基-2-吡唑基烟酰胺类目标化合物.通过1H NMR、13CNMR和HRMS对新化合物进行了结构表征.初步生物活性测试结果表明,目标化合物在200mg/L浓度下大多具有明显的杀虫活性,其中N-[4-氯-2-(乙氨基甲酰基)-6-甲基苯基]-2-(3,5-二甲基-1H-吡唑-1-基)烟酰胺(Il)对东方粘虫(MythimnaseparataWalker)具有70%的致死率;部分化合物在50mg/L浓度下对苹果轮纹病菌(Physalospora piricola)和番茄早疫病菌(AlternariasolaniSorauer)表现出较好的杀菌活性,其中2-(4-溴-1H-吡唑-1-基)-N-[2-(环丙氨基甲酰基)-4-碘-6-甲基苯基]烟酰胺(If)和2-(4-溴-1H-吡唑-1-基)-N-[4-氯-2-(乙氨基甲酰基)-6-甲基苯基]烟酰胺(Ih)对苹果轮纹病菌的抑制率分别达到62.9%和54.3%,2-(4-溴-1H-吡唑-1-基)-N-[4-氯-2-(正丙氨基甲酰基)苯基]烟酰胺(Id)对番茄早疫病菌具有54.5%的抑制率.研究结果为今后新型2-吡唑基烟酰胺类衍生物的深入研究提供了重要参考信息.     

新型含1,2,4-三唑环结构的吡唑肟醚化合物的合成及其生物活性

利用活性亚结构拼接原理,设计制备了18个未见文献报道的新型含1,2,4-三唑环结构单元的吡唑肟醚衍生物.通过~1H NMR、~(13)C NMR和元素分析等手段确认了其结构.初步的生物活性测试结果表明,部分目标化合物对粘虫、蚜虫和朱砂叶螨表现出良好的杀灭效果.在测试浓度为500μg/m L时,目标化合物对粘虫的致死率在90%～100%,与对照药阿维菌素的杀虫效果相近,其中有4个化合物对蚜虫的致死率均为100%,与对照药吡虫啉的防效相当;1-甲基-3-甲基-5-(3,5-二氟苯氧基)-1H-吡唑-4-甲醛-O-[4-(1H-1,2,4-三唑-1-基)苯甲基]肟(8p)对朱砂叶螨的致死率为100%,与对照药唑螨酯的防效相当.当测试浓度降为100μg/m L时, 5个化合物对粘虫的致死率在90%～100%, 3个化合物对蚜虫的致死率在80%～100%;化合物8p对朱砂叶螨的致死率为80%.当测试浓度降至20μg/m L时, 2个化合物对粘虫的致死率分别为75%和70%.另外,部分化合物对人肝癌(SMMC-7721)细胞显示出一定的抗肿瘤活性.     

采用通透性处理的安大略假丝酵母全细胞高效合成(R)-2-氯-1-(3-氯苯基)乙醇(英文)

考察了利用安大略假丝酵母(Candida ontarioensis)静息细胞不对称催化2-氯-1-(3-氯苯基)乙酮合成(R)-2-氯-1-(3-氯苯基)乙醇的转化反应条件.结果表明,当底物浓度为10g/L时,在最适转化条件下反应72h,产物的ee值和产率分别达到99.9%和99.0%.采用4g/L十六烷基三甲基溴化铵对Candida ontarioensis细胞于4℃通透性处理20min后,全细胞的酶活提高2倍以上.当底物浓度提高为30g/L,转化24h后,产物的ee和产率分别达到99.9%和97.5%.该研究为高效制备(R)-2-氯-1-(3-氯苯基)乙醇提供了可行途径,并为生物催化合成芳基手性醇类手性中间体提供了理论指导。     

新型含氯代噻唑基团和嘧啶环的吡唑肟醚类衍生物的合成及其生物活性研究

为解决抗性问题,寻找新的活性化合物,在前期工作基础上,运用生物等排原理,以吡唑肟醚为骨架,引入了第二代新烟碱类重要药效团氯代噻唑和另一重要基团嘧啶环,设计合成了系列新型吡唑肟醚类化合物.以1H NMR,IR,元素分析及MS进行结构确证,并进行了杀虫、杀螨及杀菌活性测定.部分具有氯代噻唑环的A系列化合物显示了良好的杀蚊虫活性(100%,5 mg·L-1)、杀豆蚜活性(100%,200 mg/L)和杀螨活性(100%,200 mg/L);具有嘧啶环的B系列化合物显示了一定的杀菌活性.     

新型瑞香酮类似物的合成及杀菌活性

以瑞香狼毒中分离的天然产物(E)-1,5-二苯基-2-烯-1-戊酮(A)为先导, 引入色酮片段设计合成了15个新型的瑞香酮类似物, 其结构均经IR, ¹H NMR, ¹³C NMR及元素分析或HRMS确证. 杀菌活性测试结果表明, 在100 mg/mL浓度下, 部分化合物的杀菌活性优于先导化合物A, 其中化合物6d对水稻纹枯病菌和黄瓜灰霉病菌的抑制率分别为87%和86%, 与对照药剂苯醚甲环唑相当, 值得进一步优化研究.     

Design,Synthesis and Insecticidal Activities of Novel 5-Alkoxyfuran-2(5H)-one Derivatives

A series of novel 5?alkoxyfuran-2(5H)-one derivatives was synthesized, and characterized by 1H NMR, 13C NMR and HRMS. Biological activities of all the title compounds were evaluated systematically. Preliminary bioassays indicated that most of the compounds exhibited moderate insecticidal activities against Aphis craccivora and Nilaparvata lugens at 100 mg/L. Compounds 4h and 4w exhibited 100% mortality rate against Aphis craccivora at 100 mg/L, and compound 4h exhibited good mortality rate against Aphis craccivora and Nilaparvata lugens (60% and 75%, respectively) even at 4 mg/L. The results demonstrated the impact of various chemical groups on insecticidal activities and provided a potential clue for further exploring novel high-effective broad-spectrum insecticides.     

新型3,5-二芳基吡唑衍生物的合成与抑菌活性

以2-氯苯甲醛与2,4-二氯苯乙酮缩合形成α,β不饱和酮,然后和水合肼关环形成3-(2,4-二氯苯基)-5-(2-氯苯基)吡唑结构骨架,合成了8个未见文献报道的3-(2,4-二氯苯基)-5-(2-氯苯基)-4,5二氢-N-酰基吡唑类衍生物。经过元素分析、红外光谱、核磁共振氢谱测试技术对其结构进行了表征。对新合成的化合物进行了初步生物活性测试结果表明,在化合物的质量浓度为50 mg/L时,化合物3f对水稻纹枯菌和稻瘟病菌的抑菌率分别为55.2%和57.1%。化合物3g对水稻纹枯菌、稻瘟病菌和油菜菌核菌的抑菌率分别为52.3%、60.0%和50.4%。     

Synthesis, Crystal Structure and Fungicidal Activity of （Z）-3,3-Dimethyl-1-（1H-1,2,4-triazol-1-yl）butan-2-one O-2-Chlorobenzyl Oxime Nitrate

The title compound has been synthesized by the reaction of 3,3-dimethyl-1-(1H-1,2,4-triazol-1-yl)butan-2-one oxime with 2-chlorobenzyl chloride, and then treated with 65～68% HNO3. Its crystal structure was determined by single-crystal X-ray diffraction. The crystal belongs to the monoclinic system, space group P21/c with a = 14.5481(8), b = 9.3351(5), c = 13.1911(7) , β = 98.9450(10)°, Z = 4, V = 1769.67(17) 3, Mr = 369.81, Dc = 1.388 g/cm3, S = 1.06, μ = 0.247 mm-1, F(000) = 776, the final R = 0.0352 and wR = 0.0960 for 3069 observed reflections (I > 2σ(I)). X-ray crystal structure presents the intramolecular N–H…O hydrogen bond. The packing is nearly parallel without π-π stacking interactions between two adjacent phenyl rings and stabilized by Van der Waals force. The preliminary bioassay shows that the title compound possesses fungicidal activity against Gibberella zeae at the dosage of 25 mg/L.     

(Z)-3,3-二甲基-1-(1H-1,2,4-三唑-1-基)-2-丁酮肟(5-芳基-1,3,4-噁二唑-2-基)甲基醚的合成和抑菌活性

以3,3-二甲基-1-（1H-1,2,4-三唑基）-2-丁酮肟为原料,经醚化、肼解及腙化3步反应得到（E）-N'-（取代苯亚甲基）-2-[（Z）-3,3-二甲基-1-（1H-1,2,4-三唑-1-基）丁基-2-亚甲氨氧基]乙酰肼（3a~3u）,化合物3与二乙酸碘苯（IBD）反应,合成了21个（Z）-3,3-二甲基-1-（1H-1,2,4-三唑-1-基）-2-丁酮肟-（5-芳基-1,3,4-噁二唑-2-基）甲基醚（4a~4u）,化合物4的化学结构经核磁共振谱、高分辨质谱和元素分析确证.采用单晶X射线衍射仪测定了化合物4c的晶体结构.抑菌活性测试结果表明,在500 mg/L浓度下,化合物4k,4f,4j和4n对纹枯病菌的防效率分别为70.9%,60.2%,60.0%和60.6%;在25 mg/L浓度下,化合物4b,4c,4d和4e对菌核病菌的抑制率为71.8%~76.9%.     

Synthesis and insecticidal bioactivities of 2,3-dihydroimidazo[1,2-a]pyridin-5(1H)-one derivatives

A novel synthesis of 2,3-dihydroimidazo[1,2-a]pyridin-5(1H)-one, and insecticidal derivatives were described.     

Cytotoxic and insecticidal activities of derivatives of harmine, a natural insecticidal component isolated from Peganum harmala

In a continuing effort to develop novel β-carbolines endowed with better insecticidal activity, a simple high-yielding method for the synthesis of harmine compounds starting from L-tryptophan has been developed and a series of 1,3-substituted β-carboline derivatives have been synthesized and evaluated for their cytotoxicity against insect cultured Sf9 cell line in vitro and insecticidal activities against 4th instar larvae of mosquitos, Culex pipiens quinquefasciatus and mustard aphid, Lipaphis erysimi. The results demonstrated that 1-phenyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (compound 2) and methyl 1-phenyl-β-carboline-3-carboxylate (compound 13) represented the best potential compounds, with Sf9 cells inhibition rates of 71.55% and 60.21% after 24 h treatment at concentrations of 50-200 mg/L, respectively. Both compounds 2 and 13 also showed strong insecticidal activity towards 4th instar larvae of mosquitos with LC(50) values of 20.82 mg/L and 23.98 mg/L, and their LC(90) values were 88.29 mg/L and 295.13 mg/L, respectively. Furthermore, the LC(50) values of compounds 2 and 13 against mustard aphids were 53.16 mg/L and 68.05 mg/L, and their LC(90) values were 240.10 mg/L and 418.63 mg/L after 48 h treatment. The in vitro cytotoxicity of these compounds was consistent with the insecticidal activity in vivo. The results indicated that the 1- and 3-positions of the β-carboline ring deserve further investigation to develop biorational insecticides based on the natural compound harmine as a lead compound.     

Synthesis and insecticidal evaluation of tetrahydroimidazo[1,2-a]pyridin-5(1H)-one derivatives

A series of novel tetrahydroimidazo[1,2-a]pyridine-5(1H)-one derivatives containing a electronegative pharmacophore(=CNO₂) were synthesized via practical aza-ene reaction and characterized by ¹H NMR, ¹³C NMR, ¹⁹F NMR and HRMS. Preliminary bioassays showed that some of the target compounds exhibited good insecticidal activity against brown planthopper(Nilaparvata lugens) and cowpea aphids(Aphis craccivora) at 500 mg L^-1. Among them, compound 11h was active against brown planthopper at 100 mg L^-1. The insecticidal activities varied significantly depending on the types and patterns of the substituents, which provided guidance for further investigation on structure modifications.     

Synthesis and Biological Evaluation of Novel Anthranilic Diamides Containing N-H/CH3-1H-Pyrazole

In order to systematically study the structure-activity relationship of anthranilic diamides and develop insecticides with simple structure and high efficiency, a series of novel anthranilic diamides containing N-H/CH₃-1H-pyrazole was designed and synthesized. Their chemical structures were characterized by ¹H NMR spectra, high resolution mass spectrometry(HRMS) or ¹³C NMR spectra. The preliminary bioassay results indicated that all title compounds displayed moderate insecticidal activity against oriental armyworm(Mythimna separata) at 200 mg/L and fungicidal activities against six kinds of fungi at 50 mg/L, especially compound 5i showed 50% insecticidal activity at 25 mg/L. In addition, some compounds exhibited certain antitumor activities. It was demonstrated that the introduction of CH₃ group into pyrazole ring was superior to H for the insecticidal activity.