Design,Synthesis, and Biological Activity of Novel Triazole Sulfonamide Derivatives Containing a Benzylamine Moiety

The triazole sulfonamide played a very important role in the field of research of new agrochemical compounds as a novel heterocyclic compound with lack of reported resistance. For the research on the innovative triazole sulfonamide fungicide effective against cucumber downy mildew (CDM), the present article designed an array of 1,2,4‐triazole‐1,3‐disulfonamide derivatives. The derivatives were synthesized via coupling multiple benzylamine with triazole sulfonamide groups. ¹H‐NMR, ¹³C‐NMR, and LC–MS spectrometry were used to characterize these synthesized compounds. Most of these derivatives exhibited better fungicidal activities than that of the commercial cyanosole using bioassays. In particular, compounds 6g and 6h showed the best fungicidal activity against CDM (EC₅₀ = 6.91 and 10.62 mg/L). Comparative experiments demonstrated that the fungicidal activity of 6g and 6h was better than the commercial pesticides amisulbrom and cyanosole. According to the study, the compound 6g had a giant application potential on fungicide against CDM.     

Synthesis and biological activity of waltherione F-derived diamide derivatives containing 4-quinolone group

The exploitation of new fungicides and the discovery of action targets are effective ways to solve the problem of resistance, and structural optimization of natural products has become an resultful method to discover lead compounds. In this work, in conjunction with the structures of the fungicidal lead compounds h-I-9, X-I-3, and X-II-5 found in our previous project, waltherione F-derived diamide compounds were synthesized and characterized by ¹H NMR, ¹³C NMR, and HRMS. The biological assays suggested that the target compounds exhibited weak to good fungicidal activity against the tested pathogens, while most of the target compounds displayed high cellular cytotoxicity against Hela cells. The investigation of accidentally discovered fluorescence characteristics revealed that the compound I-1 exhibited the most vigorous fluorescence intensity at 350 nm, which was significantly higher than that of I-3 at 225 nm and was further elucidated by density functional theory (DFT) calculations. Overall, the above results would provide theoretical guidance for the design of active target molecules and the development of fluorescent probes.     

Synthesis and Biological Activity of Novel Furan/Thiophene and Piperazine‐Containing (Bis)1,2,4‐triazole Mannich Bases

Series of novel furan/thiophene and piperazine‐containing 1,2,4‐triazole Mannich bases and bis(1,2,4‐triazole) Mannich bases have been conveniently synthesized via Mannich reaction with triazole Schiff bases, various piperazine derivatives, and formaldehyde as intermediates in good yields. Their structures were characterized by melting points, ¹H NMR, ¹³C NMR, IR and elemental analysis. The preliminary bioassay showed that most compounds exhibited significant in vitro and in vivo fungicidal activity against several test plant fungi. Among 32 new compounds, the trifluoromethyl‐containing compounds showed superior activity than the methyl‐containing ones. Several compounds, such as F8 , F9 , F10 , G5 , H7 , H8 , I3 and I4 , were comparable with some commercial fungicides against different fungi during the present study and could be further structurally optimized. Meanwhile, several compounds showed good herbicidal activity against Brassica campestris at 100 µg/mL and KARI inhibitory activity at 200 µg/mL. However, compounds exhibited poor insecticidal activity against oriental armyworm at 200 µg/mL in the preliminary studies. The research results will provide useful information for the design and discovery of new agrochemicals with novel heterocyclic structures.     

Synthesis and Fungicidal Activity of Strobilurin Analogues Containing 1,2,4‐Triazole Oxime Ether Moiety

Strobilurins are a class of important agricultural fungicides that are used widely in plant protection. To find new strobilurin analogues with high activity against resistant pathogens, a series of new strobilurin derivatives bearing 1,2,4‐triazole oxime ether side chain 3a , 3b , 3c , 3d , 3e , 3f , 3g , 3h were designed and synthesized. Their structures were confirmed by IR, ¹H NMR, EIMS, and elemental analyses. Bioassays indicated that some of the compounds showed good fungicidal activities in the concentration of 50 mg/L. For example, compound 3f possessed 100%, 100%, and 95.5% inhibition against Fusarium omysporum, Physalospora piricola Nose, and Gibberella saubinetii at the concentration of 50 mg/L, respectively.     

3-[(5-取代硫基)-4H-1,2,4-三唑-3-基]苯并吡喃-2-酮的合成与抑菌活性

为寻找具有杀菌活性的三唑类先导化合物,采用活性亚结构拼接方法,将香豆素环和硫醚结构单元引入到三唑类化合物分子中,合成一系列未见文献报道的新型含香豆素环和硫醚结构的三唑类衍生物。经~1H NMR、~(13)C NMR、IR、MS和元素分析对所合成化合物的结构进行了表征。初步生物活性测试表明,部分目标化合物在试验浓度下具有一定的抑菌活性。     

Synthesis and bioactivity of novel pyrazole oxime derivatives containing oxazole ring

A series of novel pyrazole oxime derivatives containing oxazole ring were designed and synthesized. The title compounds were structurally confirmed by 1H NMR, 13C NMR spectra and elemental analyses. Preliminary bioassay results showed that some of the title compounds displayed promising fungicidal activity besides insecticidal and acaricidal activity. Particularly, compound 8c exhibited potent fungicidal activity against cucumber Pseudoperonospora cubensis beyond good insecticidal activity against Aphis craccivora and Nilaparvata lugens.     

3-芳基-1-二茂铁基-2-(1H-1,2,4-三唑-1-基)-2-丙烯酮类衍生物的选择性还原、产物结构表征及其生物活性研究

以烯效唑和苄氯三唑醇为目标先导化合物,通过在分子中引入二茂铁基团,设计合成了两类20个新颖的含二茂铁基取代的三唑醇类衍生物,并对α,β-不饱和二茂铁基酮的选择性还原条件进行了讨论.所合成化合物的结构经元素分析、1HNMR谱和X射线晶体衍射分析得以确证.生物活性测试表明,部分化合物具有一定的植物生长调节活性.     

Synthesis and Antifungal Activity of Novel 1,2,4‐Triazole Derivatives Containing 1,2,3‐Thiadiazole Moiety

Starting from carbonic acid diethyl ester, a series of 1,2,4‐triazole derivatives containing 1,2,3‐thiadiazole were synthesized. Reactions were performed by microwave irradiation or ultrasonic irradiation as well as by conventional heating. The structure of title compounds was characterized by ¹H‐NMR, MS, and elemental analyses. The fungicidal activities of these compounds were tested in vivo. Most of title compounds exhibited good antifungal activity against Pseudoperonospora cubensis. Some of title compounds displayed moderate antifungal activities against Fusarium oxysporum, Pseudoperonospora cubensis, Sphaerotheca fuligenea, Corynespora cassiicola, and Xanthomonas axonopodis.     

4,5-二氢-1,2,4-三唑-5-硫酮席夫碱的合成和生物活性

以4-氨基-4,5-二氢-3-苯氧甲基-1氢-1,2,4-三唑-5-硫酮与取代苯甲醛为原料反应制得了9个新的三唑硫酮席夫碱类化合物,经IR、1H NMR和元素分析确定了各化合物结构。初步室内毒力测试结果表明该类化合物其具有较好的杀菌活性。     

Synthesis and Fungicidal Activity of Some Novel Thiazole Schiff Bases Derived from Benzo[d][1,3]dioxole

A series of novel thiazole Schiff base derivatives containing benzo[d][1,3]dioxole moiety was designed, synthesized and screened for their fungicidal activities. The preliminary results demonstrated that compounds 6p, 6q and 6r possessed potent activities against Phytophthora infestans, Pyricularia oryzae and Septoria tritici in vitro. Compounds 6d and 6r exhibited remarkable activities against Botrytis cinerea(whole plant) and Phytophthora infestans(leaf disk) respectively in vivo, which were identified as the most promising candidates for further study and could be used as possible lead compounds for developing new fungicides.     

Discovery of Cysteine and Its Derivatives as Novel Antiviral and Antifungal Agents

Based on the structure of the natural product cysteine, a series of thiazolidine-4-carboxylic acids were designed and synthesized. All target compounds bearing thiazolidine-4-carboxylic acid were characterized by ¹H-NMR, ¹³C-NMR, and HRMS techniques. The antiviral and antifungal activities of cysteine and its derivatives were evaluated in vitro and in vivo. The results of anti-TMV activity revealed that all compounds exhibited moderate to excellent activities against tobacco mosaic virus (TMV) at the concentration of 500 μg/mL. The compounds cysteine (1), 3–4, 7, 10, 13, 20, 23, and 24 displayed higher anti-TMV activities than the commercial plant virucide ribavirin (inhibitory rate: 40, 40, and 38% at 500 μg/mL for inactivation, curative, and protection activity in vivo, respectively), especially compound 3 (inhibitory rate: 51%, 47%, and 49% at 500 μg/mL for inactivation, curative, and protection activity in vivo, respectively) with excellent antiviral activity emerged as a new antiviral candidate. Antiviral mechanism research by TEM exhibited that compound 3 could inhibit virus assembly by aggregated the 20S protein disk. Molecular docking results revealed that compound 3 with higher antiviral activities than that of compound 24 did show stronger interaction with TMV CP. Further fungicidal activity tests against 14 kinds of phytopathogenic fungi revealed that these cysteine derivatives displayed broad-spectrum fungicidal activities. Compound 16 exhibited higher antifungal activities against Cercospora arachidicola Hori and Alternaria solani than commercial fungicides carbendazim and chlorothalonil, which emerged as a new candidate for fungicidal research.     

Synthesis,Crystal Structure,Antifungal Activity,and Docking Study of Difluoromethyl Pyrazole Derivatives

Nine novel difluoromethylpyrazole acyl urea derivatives were synthesized via seven steps conveniently. All the structures were determined by ¹H‐NMR, ¹³C‐NMR, HRMS, and X‐ray diffraction. The in vivo fungicidal activities were determined against Corynespora mazei, Botrytis cinerea, Fusarium oxysporum, and Pseudomonas syringae, respectively. The bioassay results indicated that some of them displayed good control effective (around 50 and 80%) against P. syringae and B. cinerea at 50 mg/L, respectively, which is better than control. It is possible that difluoromethylpyrazole acyl urea derivatives can be a leading compound for the development of new fungicides against the two fungi with further structure optimization. Furthermore, docking model was studied to establish structure–activity relationship of difluoromethylpyrazole acyl urea derivatives.     

Synthesis and Biological Activities of Novel 6‐Alkylamino‐11,12‐dihydro‐11‐arylbenzo[c]phenanthridine Derivatives

A series of novel benzo[c]phenanthridine derivatives 2a , 2b , 2c , 2d , 2e , 2f , 2g , 2h , 2i , 2j , 2k , 2l , 2m and 3a , 3b , 3c , 3d , 3e , 3f bearing an alkylamino side chain at their 6‐position were synthesized. All of the target compounds were confirmed by ¹H NMR, ¹³C NMR, and HRMS, and some of them were also characterized by IR and ¹⁹F NMR. The preliminary bioassays showed that the target compounds displayed fungicidal activities; for example, compound 2l showed 60.0% and 70.0% inhibitive activity against Alternaria solani and Cercospora arachidicola at 50 mg/L, respectively, and some compounds also displayed plant growth‐regulating activities.     

Design,Synthesis and Biological Evaluation of Isothiazole Based 1,2,4‐Trizaole Derivatives

A series of novel 3,4‐dichloroisothiazole based 1,2,4‐triazole derivatives were rationally designed and synthesized. Their structures were confirmed by ¹H NMR, ¹³C NMR, HRMS or elemental analysis; the typical crystal structure was determined by X‐ray diffraction for validation. All target compounds were evaluated for their in vitro fungicidal and in vivo anti‐TMV activities. The bioassay results indicated that compound 6b , namely 1‐(3,4‐dichloroisothiazol‐5‐yl)‐1‐(4‐fluorophenyl)‐2‐(1H‐1,2,4‐triazol‐1‐yl)ethanol, exhibited excellent growth inhibition against B. cinerea, C. arachidicola and P. piricola with median effective concentrations (EC₅₀) of 6.98, 2.73 and 3.07 μg/mL, respectively, and good in vivo anti‐TMV activity of over 60% of inactivation and induction activity at 100 μg/mL. These data demonstrate that compound 6b is both a fungicide and an anti‐TMV lead, deserving further studies.     

Synthesis, Crystal Structure and Biological Activities of O, O-Dialkyl α-[1-（2-Chlorothiazol-5-ylmethyl）-5-methyl- 1 H-1,2,3-triazol-4-ylcarbonyloxy]alkylphosphonates

In order to search for novel agrochemicals with high activity and low toxicity, a series of phosphonate derivatives containing 1,2,3-triazole and thiazole rings were designed and synthesized using 2-chloro-5-（chloromethyl）- thiazole as the starting material. Their structures were confirmed by IR, ^1H NMR, ^31p NMR, EI-MS or ESI-MS and elemental analyses. The crystal structure of 7a was determined by single crystal X-ray diffraction. Preliminary bioassays indicated that most of the target compounds did not display insecticidal activities, but a fraction of them possessed herbicidal and fungicidal activities to some extent.     

Synthesis of 3-perfluoroalkyl-substituted 1,2,4-triazinones through copper(I)-catalyzed interrupted click reaction

A Cu-catalyzed interrupted click reaction for the synthesis of 3-perfluoroalkyl-substituted 1,2,4-triazinones is developed. The reaction between the terminal alkynes with azides and pentafluoropropionic or heptafluorobutyric anhydride proceeds smoothly to afford the corresponding pentafluoroethylated or heptafluoropropyled products in good yields. This protocol is applicable to various types of substrates including arylacetylenes and aliphatic azides having electron-rich and electron-deficient groups. The broad substrate scope and functional group tolerance of the reaction makes this approach a practical method for the synthesis of valuable 3-perfluoroalkyl-substituted 1,2,4-triazinones. Some of the title compounds showed fungicidal activity against cucumber downy mildew (CDM).     

Design,Synthesis and Biological Evaluation of Novel Thienylpyridyl- and Thioether-Containing Acetamides and Their Derivatives as Pesticidal Agents

Referring to the structural information of the “hit” compound A from the reported pharmacophore-based virtual screening, a series of novel thienylpyridyl- and thioether/sulfoxide/sulfone-containing acetamide derivatives have been designed and synthesized. The structures of new compounds were confirmed by ¹H NMR, ¹³C NMR and HRMS. The single-crystal structure of A was firstly reported. All the new synthesized compounds were evaluated for insecticidal activities on Mythimna separata Walker and Plutella xylostella L. Through a step-by-step structural optimization, the high insecticidal agents, especially towards Plutella xylostella L., have been found, and thienylpyridyl- and sulfone/thioether-containing acetamides Iq, Io, Ib and A, which are comparable with the control insecticides cartap, triflumuron and chlorantraniliprole in the present study, can be used as novel lead structures for new insecticides innovation research. In addition, some of the compounds, e.g., A, Ih, Id, Io and Iq, also exhibited favourable fungicidal activities against Physalospora piricola, Rhizoctonia cerealis and Sclerotinia sclerotiorum and would provide useful guidance for the design and development of new fungicides.     

Synthesis and Characterization of Nitrogen Heterocyclic Derivatives Containing Sulfur–Ether and Schiff Base

Abstract

A series of new nitrogen heterocyclic compounds containing sulfur–ether (8a–8f) and Schiff-base (9a–9q) functionalities were synthesized by the reaction of the pharmaceutical lead compound containing both benzimidazole and 1,2,4-triazole rings. The compounds were characterized by ¹H NMR, ¹³C NMR, FT-IR, HR-MS, and ESI-MS.     

含1,2,4-三唑杂环的新型Strobilurins衍生物的合成及杀菌活性

为了寻找新的高活性先导化合物, 设计合成了14个未见文献报道的Strobilurins类衍生物, 结构经MS, ¹H NMR, 元素分析确认. 并用X-ray单晶衍射测定了(E)-3-甲氧基-2-[(5-甲基-4-邻溴代苯亚甲基亚胺基-1,2,4-三唑)-3-硫亚甲基]-苯基丙烯酸甲酯(5i)的晶体结构, 证实了分子中的两个C＝C均为E-式构型. 初步生物活性测试结果表明, 在实验浓度下部分化合物具有一定的杀菌活性.     

Synthesis of Polysubstituted‐1,2,4‐Triazoles

A new series of substituted 1,2,4‐triazole derivatives have been synthesized using substituted imido derivatives and isonicotinyl hydrazine (or 4‐nitrobenzoylhydrazine) as the key intermediates. These compounds include different donor or acceptor substituents on the 1,2,4‐triazole derivatives. The structures of these compounds were confirmed by FTIR, ¹H‐NMR, ¹³C‐NMR, and elemental analysis.