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.     

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.     

Targeted Synthesis of Anthranilic Diamides Insecticides Containing Trifluoroethoxyl Phenylpyrazole

Aseries of novel anthranilic diamides analogues(9a-9t) containing trifluoroethoxyl pyrazole moiety was designed and synthesized and their insecticidal bioactivities against Mythimna separata(Walker, M. separata) and Plutellaxylostella (P. xylostella) were evaluated. The structures of the title compounds were confirmed by ¹H NMR, ¹³C NMR and HRMS. Preliminary insecticidal activities showed that some of the title compounds possessed good to excellent bioactivities towards M. separata and P. xylostella. Compounds 9c and 9t exhibited 100% mortality rate against M. separate at 0.2 mg/L. For the P. xylostella, the synthesized compounds(9c-9e, 9i and 9o) showed 70%, 80%, 75%, 65% and 60% insecticidal activities at 1×10^-6 mg/L, respectively, higher than that of chlorantraniliprole(0). Based on excellent insecticidal activities, the mode of the action was tested by the calcium-imaging technique, the results of which demonstrated that the novel compounds shared the same target with chlorantraniliprole. The binding pose of the most active compound 9t in RyRs of P. xylostella was predicted by molecular docking, which showed that compound 9t interacted with the residues Glu140(A) and His147(A) via hydrogen bond.     

Synthesis and structure-insecticidal activity relationship of novel phenylpyrazole carboxylic acid derivatives containing fluorine moiety

A series of novel phenylpyrazole carboxylic acid derivatives containing fluorine moiety,i.e.,diamides 11,simple aryl-bearing amides 12 and acylthioureas 14 were successfully synthesized based on the key fluo ro-containing phe nylpyrazole acid intermediate.The new compounds were identified and confirmed by melting point,1H NMR,13C NMR and elemental analysis or HRMS.The bioassay results indicated that some of the compounds possessed excellent insecticidal activities towards oriental armyworm,diamondback moth and corn borer at low concentrations.For examples,compounds 11a,11e-g and 14b exhibited remarkable larvicidal activities with LC50 values of 0.13-0.39 mg/L and 0.0002-0.0014 mg/L against oriental armyworm and diamondback moth,respectively,were comparable with those of the control chlorantraniliprole.Particularly,lie were found superior to chlorantraniliprole in oriental armyworm tests(LC50:0.23 mg/L vs.0.26 mg/L);11a,lie,11f and 14c in diamondback moth tests with LC50 values of 0.0002 mg/L,0.0002 mg/L,0.0008 mg/L and 0.0005 mg/L,respectively,we re more effective than that of chlorantraniliprole.In addition,12 a also showed a promising insecticidal potential and development/optimization advantage.Compounds 11a,lle-g,12a,14b and 14c could be considered as possible new leading structures for further study.The SAR investigation indicated that the compounds with fluorine motif(e.g.,-F,-CF2H,-CF3)held apparently favorable insecticidal potentials,which provided useful guidance for further design/development of new phenylpyrazole-containing agrochemicals.     

Design,Synthesis, Biological Evaluation and SARs of Anthranilic Diamide Derivatives Containing Pyrrole Moieties

In order to find a new variety of ryanodine receptor(RyR) regulator with greater biological activity, a series of anthranilic diamide derivatives possessing pyrrole structure was designed and synthesized in this study. The pyrrole derivatives were evaluated for their insecticidal activity against Mythimna separata and Plutella xylostella. As indicated by the preliminary biological activities, compounds 12h-12j and 12l-12n exhibited a remarkable insecticidal activity against M. separata at 0.25 mg/L. Compared to control chlorantraniliprole, compound 12j exhibited more excellent insecticidal activity at 0.1 mg/L. Meanwhile, compounds 12c, 12h, 12i, 12j, 12l, and 12m were selected to test the insecticidal activity against P. xylostella, which led to the desirable insecticidal activity at 1×10^-3 mg/L. Notably, compound 12l demonstrated 47% insecticidal activity at 5×10^-6mg/L over the control. In addition, the biological mechanism of action of compound 12j was investigated by means of insect electrophysiology experiment.     

Design,synthesis and insecticidal activities of novel anthranilic diamides containing polyfluoroalkyl pyrazole moiety

In order to discover new molecules with good insecticidal activities, a series of anthranilic diamides containing polyfluoroalkyl pyrazole were designed and synthesized, and their structures were characterized by ¹H NMR and HRMS. Bioassays demonstrated that some of the title compound exhibited excellent insecticidal activities. The larvicidal activities of compound 8a, 8c, 8g, 8k and 8l against Mythimna separata Walker were 100% at 0.8 mg/L. The insecticidal activities of compound 8a, 8c, 8e, 8g, 8k and 8l against Plutella xylostella Linnaeus were 100% at 0.4 mg/L. Surprisingly compounds 8a and 8c still showed 100% larvicidal activities against Plutella xylostella Linnaeus at 0.08 mg/L comparable to the commercialized Chlorantraniliprole. The LC₅₀ of compound 8a and 8c against M. separata is 0.048 and 0.043 mg/L respectively.     

螺环季酮酸衍生物的合成及生物活性研究

为了寻求新颖的螺环季酮酸先导化合物,以3 -(2,4-二氯苯基)-4-羟基-1-氧杂螺[4.5]癸-3-烯-2-酮为原料,合成了21个螺环季酮酸衍生物,其结构经1H NMR,ESI MS和元素分析确认,并测定了化合物6b的晶体结构.初步生物活性测定表明,此类化合物对朱砂叶螨、蚜虫和粘虫都具有很好的生物活性,尤其是化合物5g和5m对朱砂叶螨的LD50分别为35.12和22.39 mg/L,高于螺螨酯的LD50:45.20 mg/L;化合物5b对蚕豆蚜的LD50为21.90 mg/L,而螺螨酯对蚕豆蚜的LD50为174.13 mg/L.     

Design,Synthesis and Fungicidal Activity of Novel Strobilurin-1, 2, 4-Triazole Derivatives Containing Furan or Thiophene Rings

A series of strobilurin-1,2,4-triazole derivatives containing a furan or thiophen ring was designed and synthesized. The structures of the compounds were characterized by ¹H NMR, ¹³C NMR and HRMS spectra. The bi-oassays indicated that the fungicidal activities of compounds 10b(EC₅₀=14.82 mg/L) and 10c(EC₅₀=18.72 mg/L) against Cercospora arachidicola Hori in vitro were much higher than that of Azoxystrobin as control(EC₅₀=40.54 mg/L) and the fungicidal activities of compounds 10u(EC₅₀=8.66 mg/L) and 10n(EC₅₀=9.89 mg/L) against Rhizotonia cerealis in vitro were higher than that of the same control(EC₅₀=10.86 mg/L). Compounds 10b, 10c, 10n and 10k could be considered as the leading compounds for further investigation.     

Synthesis and biological activities of(E)-β-farnesene analogues containing 1,2,3-thiadiazole

In order to discover novel compounds with high-activity to control aphid,a series of novel(E)-β-farnesene analogues containing 1,2,3-thiadiazole were designed and synthesized,and their structures were confirmed by IR,~1H NMR,~(13)C NMR,and HRMS(ESI).The stability of representative compounds was studied by HPLC and ~1H NMR techniques.Repellent activity results indicated that compounds 8h and 8j displayed 60.3%and 62.0%repellent rates,respectively.The aphicidal bioassay results showed that most analogues exhibited considerable aphicidal activity against Myzus persicae.Especially,analogues 81,8s and 8t exhibited high activity with LC_(50) values of 33.4 μg/mL,50.2 μg/mL and 61.8 μg/mL,respectively,which were higher than the lead compound(E)-β-farnesene,but lower than commercial insecticide pymetrozine with a LC_(50) of 7.1 μg/mL     

5-吡唑甲酰胺类衍生物的设计、 合成与生物活性

以2种5-吡唑甲酸为原料, 分别与噻唑胺和苯并呋喃胺发生缩合反应, 制备了23个新的5-吡唑甲酰胺类化合物; 采用核磁共振波谱和质谱等对目标化合物结构进行了表征; 对化合物B1和B3进行了量子化学计算、 前沿分子轨道及分子范德华表面静电势分析. 生物活性实验结果表明, 在500 mg/L浓度下部分化合物对黏虫和蚜虫有良好的杀虫活性, 其中化合物A1和B1对黏虫的致死率均为100%, 化合物B3, B4和C9对蚜虫的致死率分别为100%, 100%和95.54%; 在25 mg/L浓度下化合物A3对烟草赤星病菌的抑制率、 化合物C7对小麦赤霉病菌的抑制率以及化合物A1和A4对油菜菌核病菌的抑制率均大于50%.     

Design and Synthesis of Novel 3,4-Dihydro-2H-1,2,4-benzothiadiazine 1,1-Dioxides-based Strobilurins as Potent Fungicide Candidates

To discover novel strobilurins analogues with good and broad spectrum activity, a series of novel 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides-based strobilurins was designed, synthesized, and tested against various phytopathogenic fungi. Compounds 7b, 7c, and 7k exhibited substantial and broad spectrum antifungal activities against the tested phytopathogenic fungi, especially compound 7b, which showed 100%, 80%, 90%, and 90% antifungal activity(in virto) against Erysiphe graminis(E. graminis), Puccinia sorghi Schw.(P. sorghi Schw.), Colletotrichum lagenarium(C. lagenarium), and Pseudoperonospora cubensis(P. cubensis) at 300 μg/mL, respectively, better or comparable to the positive control azoxystrobin. Moreover, compound 7b exhibited 85% greenhouse inhibition activity(in vivo) against E. graminis even at 0.2 μg/mL, equal to azoxystrobin(90%) and trifloxystrobin(90%). Meanwhile, compound 7b against P. cubensis displayed 70% and 55% greenhouse inhibition activity(in vivo) at 1.56 and 0.2 μg/mL, respectively, much better than those of azoxystrobin and trifloxystrobin(both 0% at 1.56 and 0.2 μg/mL). Therefore, compound 7b could be considered as the most promising fungicidal candidate for further study. Furthermore, based on the effective concentration(EC₅₀) against C. arachidicola, the built CoMSIA model provided the useful reference for the further structural optimization design.     

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.     

新型含苯基取代嘧啶基磺酰脲衍生物的设计、 合成及生物活性

将苯基引入到嘧啶环的4位, 设计、 合成了2个系列共24个结构新颖的磺酰脲类衍生物, 并对其生物活性进行了研究. 抑菌实验结果表明, 目标化合物对苹果轮纹病菌和小麦纹枯病菌表现出优异的抑制率, 其中化合物9f对5种病菌的抑制率均超过65%. 进一步研究发现, 化合物9f对苹果轮纹病菌的EC₅₀值为8.63 mg/L, 略高于对照药百菌清(7.33 mg/L); 化合物8k和9k对小麦纹枯病菌的EC₅₀值分别为5.48和6.09 mg/L, 与百菌清(4.26 mg/L)接近. 同时, 盆栽法除草测试结果表明, 在75 g/ha剂量下, 化合物8d和9d对油菜具有较好的芽前除草活性, 分别为86%和73%; 化合物9h对反枝苋的土壤处理抑制活性为100%, 优于对照药氯磺隆(96%).     

Facile three-component synthesis and insecticidal evaluation of hexahydroimidazo[1,2-a]pyridine derivatives

A series of new hexahydroimidazo[1,2-α]pyridine derivatives were synthesized via convenient and practical three-component reactions.Preliminary bioassays showed that majority of the target compounds exhibited moderate to excellent insecticidal activity against cowpea aphids(Aphis craccivora).Among them,compound 91 demonstrated significant activity with LC_(50) value of0.00918 mmol/L which was about 3.8-fold higher than that of imidacloprid(IMI).Furthermore,the study of stereostructure-activity relationship of four isomers of 9k indicated that configuration played a key role in insecticidal activity of these compounds.     

Design,Synthesis and Insecticidal Activity of Novel Anthranilic Diamides Containing Oxime Ester and Diacylhydrazine Moieties

Two series of novel anthranilic diamides containing oxime ester and diacylhydrazine moieties were designed and synthesized.Their structures were characterized by melting points,1H NMR,13C NMR and high resolution mass spectrometry（HRMS）.The single crystal structure of compound 7e was determined by X-ray diffraction and their evaluated insecticidal activity against oriental armyworm（Mythimna separata） indicates that some of the compounds exhibited moderate insecticidal activities.Among the 20 compounds,6a and 6b show 100％ larvicidal activity against Mythimna separate Walker at the test concentration of 100 mg/L.     

白杨素甘氨酸类化合物的合成及抗癌活性

以白杨素为起始原料, 通过卤代和水解反应制得中间产物7-O-羧烷基化的白杨素衍生物(6~9); 然后以1-乙基-3-(3-二甲氨基丙基)碳二亚胺(EDCI)、 1-羟基苯并三氮唑(HOBt)和4-二甲氨基吡啶(DMAP)为催化体系, 4个中间产物分别与甘氨酸甲酯盐酸盐进行酰胺缩合反应, 制得白杨素甘氨酸甲酯类化合物12~15; 化合物12~15在pH=10~11和室温下水解得到相应的白杨素甘氨酸类化合物(16~19). 所有目标化合物的结构均经 ¹H NMR, ¹³C NMR, IR以及MS确认. 以顺铂为阳性对照药物, 采用噻唑蓝比色(MTT)法检测了目标化合物对人肝癌细胞HepG2和人胃癌细胞MGC-803的体外增殖抑制作用. 结果表明, 目标化合物14~16, 18和19的体外抗肿瘤活性明显强于白杨素, 且化合物18(IC₅₀=4.36 μmol/L)对MGC-803细胞的增殖抑制作用强于阳性药物顺铂(IC₅₀=4.40 μmol/L).     

哌啶并[2,3-b]哌嗪类衍生物的设计、合成及其抗血小板聚集活性研究

以2,3-二氨基吡啶和2,3-丁二酮为起始原料,经环化、催化氢化和亲核取代反应合成了10个新型哌啶并[2,3-b]哌嗪类衍生物(3a~3j),其结构经¹H NMR、¹³C NMR和HR-MS确证。体外抗血小板聚集活性研究表明,化合物3d、3e、3g、3h和3j具有一定的抗血小板聚集作用,其中化合物3h(IC₅₀=1.24mmol/L)的活性显著优于母体化合物川芎嗪(IC₅₀=3.96mmol/L)和阳性药物阿司匹林(IC₅₀=2.41mmol/L)。     

Synthesis and Bioactivity Evaluation of Novel N-Pyridylpyrazolemethanamine Derivatives

To further explore the structure-activity relationship(SAR) of amide bridge moeity of anthranilic diamides derivatives, a series of N-pyridylpyrazole derivatives was designed, synthesized and their biological activities were evaluated. The chemical structures of novel target compounds were confirmed by ¹H nuclear magnetic resonance (NMR), ¹³C NMR and elemental analyses(EA). Bioassay results of insecticidal activity demonstrated that the target compound 6h displayed 70% lethality rate against oriental armyworms at 200 mg/L. Moreover, most compounds displayed moderate to excellent antifungicidal activities against Fusarium oxysporum f. sp. cucumerinum, Cercospora arachidicola Hori, Botryosphaeria dothidea, Alternaria solani, Gibberella zeae and Phytophthora capsici at 50 mg/L. In particular, compound 6e showed 61.5% and 92.3% inhibition rate against Cercospora arachidicola Hori and Botryosphaeria dothidea, which was superior to the commercial positive control Chlorothalonil. These results will provide a potential clue for exploring novel high-effective agrochemicals.     

Microwave-assisted Catalyzed Synthesis and In vitro Bioactivity Evaluation of Benzimidazoles Bearing Phenolic Hydroxyl

An efficient and facile method was introduced for the synthesis of benzimidazoles in this paper. The optimum reaction conditions were determined. A series of benzimidazoles bearing phenolic hydroxyl(2a-2t) were synthesized in moderate to excellent yields starting from differently substituted hydroxyl benzaldehyde and 4-position substituted o-phenylenediamine via nucleophilic addition in the presence of catalyst Na₂S₂O₅ under microwave irradiation condition. Herein, effects of the catalyst, molar ratio of reactants, reaction temperature and solvent were investigated. The optimal reaction condition was determined. The effect of DMF and EtOH solvent on the reaction was compared. The synthesized compounds were characterized by FTIR, HRMS, ¹H NMR and ¹³C NMR spectroscopy. Further, the bacteriostatic activities of the synthesized compounds were evaluated with ciprofloxacin and itraconazole as a positive control, respectively. Compounds 2b, 2n, 2q and 2r exhi-bited some antibacterial activity. The lowest MIC of antibacterial activity of compound 2b was 32 μg/mL. Meanwhile, the luminescence property of compound 2b was studied. The antibacterial activity of compound 2b, along with their good fluorescence performance highlighted the potential of these compounds as lead structures and owned fluorescence trace for further study towards the development of novel drugs and functional mechanisms in living organisms.     

Synthesis and insecticidal activities of 1,8-naphthyridine derivatives

1,8-Naphthyridines (NAP) are biological important scaffolds in bioactive molecules design. By hybrid of NAP with neonicotinoid core structure, nine novel NAP derivatives were synthesized and subjected to insecticidal activities evaluation. Some of the compounds showed excellent insecticidal activity against cowpea aphids (Aphis craccivora) with LC₅₀ values ranging from 0.011 mmol/L to 0.067 mmol/L. The results indicated that 1,8- naphthyridine can be used as insecticidal structure for further modification.