含1,3,4-噁二唑的葡萄糖苷衍生物的合成及抑菌活性

糖苷类化合物广泛存在于生物体内,并担负着重要生物功能,天然药物及中草药中的许多活性成分是糖苷化合物[1].糖苷类化合物的良好抗菌、抗癌活性激发了广大研究者的浓厚兴趣[2-3],启发人们通过糖苷化反应作为改变或增加生物活性的重要结构修饰方法[4],以增加化合物的水溶性和导向性,改进药理学性质.     

Ultrasound-assisted,one-pot,three-component synthesis and antibacterial activities of novel indole derivatives containing 1,3,4-oxadiazole and 1,2,4-triazole moieties

Thirteen novel indole derivatives were efficiently synthesized through ultrasound irradiation by using 4-amino-5-(1H-indol-3-yl)-4H-[1,2,4]triazole-3-thiol (8) and 2-mercapto-5-substituted-1,3,4-oxadiazoles (5a–m). Compared with conventional and microwave methods, yields increased to 82–93%, and reaction times decreased to 15–35 min. The structures of these novel compounds were characterized by spectral data and elemental analysis. Two out of the synthesized compounds (10f and 10l) exhibited excellent activity against Staphylococcus aureus and Escherichia coli, and thus warrant further research.     

Design and synthesis of oxaprozin-1,3,4-oxadiazole hybrids as potential anticancer and antibacterial agents

In the present study, we report design, synthesis and screening of new novel 5-substituted-2-mercapto-1,3,4-oxadiazole analogues appended to oxaprozin for their in vitro anticancer and antibacterial activity. The synthesised compounds were characterized using various spectroscopic techniques. Furthermore, the structure of 5b (2-(2-[4,5-diphenyloxazol-2-yl]ethyl)-5-(ethylthio)-1,3,4-oxadiazole) was unequivocally confirmed by X-ray analysis. Among the series 5c (2-(2-[4,5-diphenyloxazol-2-yl]ethyl)-5-(propylthio)-1,3,4-oxadiazole) showed most promising anticancer activity against A549 cancer cell line and all the reported analogues manifested satisfactory safety profiles against human normal cell line HEK293T. The products exhibited good antibacterial activity and among the tested 5j (2-(2-[4,5-diphenyloxazol-2-yl]ethyl)-5-([4-fluorobenzyl]thio)-1,3,4-oxadiazole) exhibited most potent.     

新的双枝[1,3,4]-噁二唑衍生物的设计与微波合成

在微波辐射条件下,以三氯氧磷作环合剂,以双酰肼为中间体,快速有效地合成了一系列新的1,3-二[(5-芳基-1,3,4-噁二唑-2-基)甲氧基]苯类化合物.十二个目标化合物(5a-5l)和五个中间体(4c,4d,4e,4j,4k)均为未见文献报道的新化合物,其结构经核磁、红外、质谱和元素分析所确证.该方法的显著优点是简单...     

Design,synthesis, and fungicidal activity of novel 1,3,4-oxadiazole derivatives

Employing the intermediate derivatization method (IDM), a series of 1,3,4-oxadiazole derivatives containing arylpyrazoloxyl moiety were designed and synthesized. In vitro bioassays showed that these compounds have moderate to significant fungicidal activity against rice sheath blight and sorghum anthracnose. Furthermore, compound 20 is a promising fungicide for further development.     

ZnCl2 catalyzed efficient synthesis of 1,3,4-oxadiazole and 1,3,4-thiadiazole

New methods for the synthesis of 1,3,4-oxadiazole and 1,3,4-thiadiazole have been described. No cyclizations took place in the absence of ZnCl₂. 1,3,4-Thiadiazoles are formed in the presence of ZnCl₂ alone, whereas oxadiazoles are produced when a base such as Et₃N or KOH was used along with ZnCl₂. % Yields are optimized.     

Synthesis of novel 1,3,4-oxadiazole derivatives and their nucleoside analogs with antioxidant and antitumor activities

A series of new (1,3,4-oxadiazol-2-yl)-1H-benzo[h]quinolin-4-one derivatives were synthesized, including glucose and xylose hydrazones that were obtained by the reaction of hydrazides with monosaccharides. Cyclization of the sugar hydrazones with acetic anhydride afforded substituted oxadiazoline derivatives. The newly synthesized compounds were evaluated for their antioxidant properties and cytotoxicity, and showed moderate to high activities.     

One-pot synthesis, antibacterial and antifungal activities of novel 2,5-disubstituted-1,3,4-oxadiazoles

A series of novel 2,5-disubstituted-1,3,4-oxadiazoles have been synthesized from long-chain alkanoic and alkenoic acids. The structures of these compounds have been elucidated by elemental and spectral （IR, ^1H NMR, ^13C NMR, MS） analysis. Furthermore, compounds were screened for in vitro antibacterial activity against the representative panel of two Gram-positive and two Gram- negative bacteria. All the synthesized compounds were also tested for their inhibitory action against five strains of fungus. The various compounds show potent inhibitory action against test organisms. 2007 Abdul Rauf. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.     

Updates on synthesis and biological activities of 1,3,4-oxadiazole: A review

The new era of heterocyclic moieties which are developed in the decades plays a very important role in the treatment of various diseases. Among them are 1,3,4-oxadiazoles, a heterocyclic five-membered ring which plays an vital role in the development of newer medicinal compounds for treating various biological activities, such as proliferation of cells, tuberculosis, allergy, viral diseases, etc. The present review will summarize the various synthetic approaches which will be correlated with the biological activities so that the information in future may be used by many researches to give a path breaking lead in the field of medicinal chemistry.     

Synthesis of novel 1,3,4-oxadiazole derivatives containing diamides as promising antibacterial and antiviral agents

In this paper, a variety of novel 1,3,4-oxadiazole derivatives possessing diamides were synthesized and tested for their antibacterial and antiviral activity. Preliminary antibacterial assays indicated that some intermediates and title compounds displayed excellent inhibition effects against plant pathogens Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas axonopodis pv. citri (Xac). Further studies revealed that compound H15 exhibited the strongest activities against Xoo and Xac with minimal EC₅₀ values of 0.7 and 5.9 μg/mL, respectively. Antiviral bioassays suggested that some of these structures displayed appreciable curative activities and moderate protective effects against tobacco mosaic virus (TMV) in vivo. Among them, compound H8 exerted the best chemotherapeutic effect against TMV with the curative rate of 60.0% at 500 µg/mL, which was comparable with those of commercial agricultural antiviral agent ningnanmycin (54.2%). Given their significant biological activities, this kind of compound could serve as new leading compounds in the study of antibacterial and antiviral chemotherapy.     

Eco-friendly synthesis of 1,8-naphthyridine 5-aryl-1,3,4-oxadiazole derivatives under solvent-free solid-state conditions and their antimicrobial activity

Research on Chemical Intermediates - A simple and highly efficient green synthetic procedure has been described for the construction of...     

A convenient synthesis of 1,3,4-thiadiazole and 1,3,4-oxadiazole based peptidomimetics employing diacylhydrazines derived from amino acids

Synthesis of novel orthogonally protected 1,3,4-thiadiazole and 1,3,4-oxadiazole tethered dipeptide mimetics is described. Both the heterocycles are prepared via a set of diacylhydrazines derived from amino acids. 1,3,4-Thiadiazoles are synthesized by dehydrosulfurization using Lawesson’s reagent while 1,3,4-oxadiazoles are obtained by EDC mediated cyclodehydration.     

Stereoselective synthesis of pseudoglycosides catalyzed by TeCl4 under mild conditions

Catalytic amounts of tellurium(IV) tetrachloride were used to promote the O-glycosylation of 3,4,6-tri-O-acetyl-d-glucal to give the corresponding 2,3-unsaturated-O-glycosides. With simple alcohols, the desired compounds were obtained in good yields and excellent anomeric selectivity in a short reaction time using only 2 mol % of the catalyst. The application of the method in the synthesis of a small set of glycopyranosides with rigid or flexible linkers gave the corresponding α anomers as products in good yields. Further applications of some of the synthesized compounds in allylation reaction of aldehydes gave the corresponding homoallylic alcohols in good yields.     

Design,synthesis and in silico study of pyridine based 1,3,4-oxadiazole embedded hydrazinecarbothioamide derivatives as potent anti-tubercular agent

Development of novel, safe and effective drug candidates combating the emerging drug resistance has remained a major focus in the mainstream of anti-tuberculosis research. Here, we inspired to design and synthesize series of new pyridin-4-yl-1,3,4-oxadiazol-2-yl-thio-ethylidene-hydrazinecarbothioamide derivatives as potential anti-tubercular agents. The anti-tubercular bioactive assay demonstrated that the synthesized compounds exhibit potent anti-tubercular activity (MIC = 3.9–7.81 μg/mL) in comparison with reference drugs Rifampicin and Isoniazid.We employed pharmacophore probing approach for the identification of CYP51 as a possible drug target for the synthesized compounds. To understand the preferable binding mode, the synthesized molecules were docked onto the active site of Sterol 14 α-demethylases (CYP51) target. From the binding free energy of the docking results it was revealed that the compounds were effective CYP51 inhibitors and acts as antitubercular agent.     

Synthesis and antibacterial activities of novel imidazo[2,1-b]-1,3,4-thiadiazoles

2-Amino-5-(2-aryl-2H-1,2,3-triazol-4-yl)-1,3,4-thiadiazoles 2-4 have been synthesized by the reaction of 2-aryl-2H-1,2,3-triazole-4-carboxylic acids 1 with thiosemicarbazide. Their reaction with phenacyl (p-substituted phenacyl) bromides led to formation of the respective 6-aryl-2-(2-aryl-2H-1,2,3-triazol-4-yl)imidazo[2,1-b]-1,3,4-thiadiazoles 5. Reactivity of the latter fused ring towards reaction with different electrophilic reagents afforded the corresponding 5-substituted derivatives 6-8. The structure of the above compounds was confirmed from their spectral characteristics. Some of these compounds were found to possess slight to moderate activity against the microorganisms Staphylococcus aureus, Candida albicans, Pseudomonas aeruginosa, and Escherichia coli.     

Synthesis,in vitro antibacterial and antifungal evaluation of novel 1,3,4-oxadiazole thioether derivatives bearing the 6-fluoroquinazolinylpiperidinyl moiety

A series of structurally novel 1,3,4-oxadiazole thioether derivatives(6a-6z) containing a 6-fluoroquinazolinylpiperidinyl moiety were designed and synthesized using pharmacophore hybrid approach,and their structures were fully characterized by ^1H NMR,¹³C NMR and HRMS spectra.Among them,the structure of compound 6 d was further corroborated via single-crystal X-ray diffraction analysis.In vitro antibacterial bioassays showed that compounds 6 a,6 g,6 u and 6 v possessed EC₅₀ values of 30.4,30.6,27.5 and 26.0 μg/mL against phytopathogenic bacterium Xanthomonas oryzae pv.oryzae,respectively,which were significantly superior to that of commercially-available bactericide Bismerthiazol(85.1 μg/mL).Moreover,in vitro antifungal bioassays indicated that seven compounds demonstrated broad-spectrum fungicidal acitivties against six types of phytopathogenic fungi at 50 μg/mL.The present work showed the potential of 1,3,4-oxadiazole thioether derivatives carrying a 6-fluoroquinazolinylpiperidinyl moiety as effective antimicrobial agents for crop protection,deserving further investigations in the future.     

A convenient synthesis of pyrroles catalyzed by acidic resin under solvent-free condition

<正>A convenient and effective Paal-Knorr condensations of 2,5-hexanedione with most amines have been carried out at room temperature under solvent-free condition.Macroporous strongly acidic styrol resin(D001) as a novel,efficient,cost-effective,and reusable solid acid catalyst for the synthesis of pyrroles under the same conditions.The pyrroles were obtained in high yields in short reaction times.     

Utility of thiophene-2-carbonyl isothiocyanate as a precursor for the synthesis of 1,2,4-triazole, 1,3,4-oxadiazole and 1,3,4-thiadiazole derivatives with evaluation of their antitumor and antimicrobial activities

Abstract

The reaction of thiophene-2-carbonyl isothiocyanate with phenylhydrazine gave 1-phenyl-5-(thien-2-yl)-1,2,4-triazole-3-thiol which was transformed by follow-up reactions into derivatives substituted in the 3-position by 1,2,4-oxadiazole and 1,2,4-thiadiazole moieties via thioethers linkages. The antitumor activity of the products against two human tumor cell lines, namely hepatocellular carcinoma HePG-2 and mammary gland breast cancer MCF-7 as well as the antimicrobial activity of some of these compounds was evaluated.