RESUMEN
Herein, we describe an original synthetic method for a series of fluorescent thieno[3,2-b]pyridine-5(4H)-one derivatives prepared via the gold(I)-catalyzed 6-endo-dig intramolecular hydrothiophenylation process involving N-thiophen-3-yl alkynylamides. The brightness was improved; emission could be tuned, and larger Stokes shifts were recorded. We also designed and synthesized the phalloidin-based fluorescent chemical probes KF-P1 and KF-P2 to realize fluorescent F-actin imaging.
Asunto(s)
Colorantes Fluorescentes , Tiofenos , Actinas , Catálisis , Colorantes Fluorescentes/química , Oro , Piridinas/químicaRESUMEN
We describe a synthetic approach for a set of fluorescent thieno[3,2- b]pyridine-5(4 H)-one derivatives and their photophysical properties. These fluorophores are prepared by a series of reactions employing the Suzuki-Miyaura cross-coupling reaction and a regioselective aza-[3 + 3] cycloaddition of 3-aminothiophenes with α,ß-unsaturated carboxylic acids. Our findings revealed that the photophysical properties are chemically tunable by an appropriate choice of functional group on the thieno[3,2- b]pyridine-5(4 H)-one scaffold.
RESUMEN
The level of human serum albumin (HSA) in biological fluids is a key health indicator and its quantitative determination has great clinical importance. In this study, we developed a selective and sensitive fluorescent HSA probe by fluorescence-based high-throughput screening of a set of fluorescent thieno[3,2-b]pyridine-5(4H)-one derivatives against major plasma proteins: HSA, bovine serum albumin (BSA), globulin, fibrinogen, and transferrin. The fluorophore chosen finally (4) showed noticeable fluorescence enhancement in the presence of HSA (160-fold increase), and it exhibited rapid response, high sensitivity (detection limit 8 nM), and the ability to clearly distinguish HSA from BSA in pH 9 buffer condition. Moreover, the probe could be applicable to detect trace amounts of HSA in an artificial urine sample; further, it might be applied to the determination of the HSA concentration in complex biological samples for pre-clinical diagnosis.
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Colorantes Fluorescentes/química , Albúmina Sérica Bovina/química , Albúmina Sérica Humana/química , Animales , Bovinos , Fibrinógeno/química , Globulinas/química , Humanos , Transferrina/químicaRESUMEN
A new and mild synthetic approach for the N-arylation of 2-pyridones with diaryliodonium salts has been developed. Most reactions proceed readily at room temperature in the presence of 10 mol % of copper chloride. As a result, a wide range of N-arylpyridine-2-ones were synthesized in yields of 23% to 99%. With this method, an antifibrotic drug, Pirfenidone, was successfully synthesized in 99% yield within 30 min at room temperature.
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Cobre/química , Compuestos Onio/química , Piridonas/química , Catálisis , Estructura Molecular , Sales (Química)/química , Análisis Espectral/métodos , Estereoisomerismo , TemperaturaRESUMEN
A mild and efficient synthesis of N-arylcarbamates was achieved by reacting azidoformates with boronic acids in the presence of 10 mol % of copper chloride catalyst. The reaction proceeds readily in an open flask at room temperature without additional base, ligand, or additive. Rapid access to urea analogues via a two-step one-pot procedure is enabled by reacting N-arylcarbamates with aluminum-amine complexes. In addition, among several boronic acid derivatives prepared, dimethylphenyl boronate was found to react rapidly in its reaction with benzyl azidoformate, invoking in situ generation of this species in the catalytic cycle.
Asunto(s)
Azidas/química , Ácidos Borónicos/química , Carbamatos/síntesis química , Cobre/química , Carbamatos/química , Catálisis , Ligandos , Estructura Molecular , TemperaturaRESUMEN
Herein, we report the first- and second-generation syntheses of (+)-ieodomycins A and B and their stereoisomers via the late-stage elaboration of their conjugated E-diene side chains. Key steps for successful synthesis included Keck asymmetric allylation to introduce a hydroxyl group at the C5 position, consecutive Wipf's carboalumination modification, iodination, Sharpless asymmetric dihydroxylation, one-carbon homologation via cyanation, Mukaiyama lactonization, and Stille cross-coupling to form the conjugated E-diene moiety. Further, the preliminary in vitro bioactivity profile against various disease-related molecular targets and cell lines was investigated. Results indicated that compounds 30b and 30c, diastereoisomers of (+)-ieodomycin B (2), serve as α-glucosidase inhibitors, while compounds 30b and 30d inhibit the angiotensin-converting enzyme.
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Fluorescent probes are attractive tools for biology, drug discovery, disease diagnosis, and environmental analysis. In bioimaging, these easy-to-operate and inexpensive probes can be used to detect biological substances, obtain detailed cell images, track in vivo biochemical reactions, and monitor disease biomarkers without damaging biological samples. Over the last few decades, natural products have attracted extensive research interest owing to their great potential as recognition units for state-of-the-art fluorescent probes. This review describes representative natural-product-based fluorescent probes and recent discoveries, with a particular focus on fluorescent bioimaging and biochemical studies.
RESUMEN
Herein, we describe a gold(I)-catalyzed intermolecular formal [2 + 2 + 2] cycloaddition of a carbonyl compound and a propiolate. A series of highly substituted 2H-pyrans are accessed regioselectively from acyclic and cyclic ketones and aldehydes with various substituted propiolates using Ph3PAuCl (0.1-1 mol %) with two distinct metal triflate additives [0.75-7.5 mol %; In(OTf)3/Cu(OTf)2 for ketones, Bi(OTf)3/Hf(OTf)4 for aldehydes]. This method should provide an opportunity for further development of synthetic access to other heterocyclic compounds.
RESUMEN
A fluorescent probe (4-(2-(4-(diethylamino)phenyl)-4-methyl-5-oxo-4,5-dihydrothieno[3,2-b]pyridin-7-yl)phenyl 2,4-dinitrobenzenesulfonate, KF-DNBS) for facile detection of H2S in serum was developed based on the combination of an environment-sensitive fluorophore (2-(4-(diethylamino)phenyl)-7-(4-hydroxyphenyl)-4-methylthieno[3,2-b]pyridin-5(4H)-one, KF) with albumin and the 2,4-dinitrobenzene sulfonyl (DNBS) group as a recognition unit for H2S. KF-DNBS showed remarkable fluorescence enhancement due to H2S-triggered thiolysis followed by the formation of a fluorescent fluorophore (KF)-albumin complex. The H2S detection limit of KF-DNBS was estimated to be 3.2 µM, and KF-DNBS achieves a high selectivity to H2S over biothiols by employing 2-formyl benzene boronic acid (2-FBBA) as an effective masking reagent. Furthermore, under optimized sensing conditions, KF-DNBS could be applied to accurately determine spiked H2S in human serum without the need for any further procedure for the removal of serum proteins.