Search Results (47)

A synthesis of substituted 1,4-benzodiazepines has been developed via palladium-catalyzed cyclization of N-tosyl-disubstituted 2-aminobenzylamines with propargylic carbonates. The reaction proceeds through the formation of π-allylpalladium intermediates, which undergo intramolecular nucleophilic attack by the amide nitrogen to afford seven-membered benzodiazepine cores. In reactions involving unsymmetrical diaryl-substituted carbonates, regioselectivity was observed to favor nucleophilic attack at the alkyne terminus substituted with the more electron-rich aryl group, suggesting that electronic effects play a key role in determining product distribution. The versatility of this reaction was further demonstrated by constructing a benzodiazepine framework found in bioactive molecules, indicating its potential utility in medicinal chemistry. Mechanistic insights supported by stereochemical outcomes and X-ray crystallographic analysis of key intermediates reinforce the proposed reaction pathway. This palladium-catalyzed protocol thus offers an efficient and practical approach to access structurally diverse benzodiazepine derivatives. Full article

Polypyrrole (PPy) is cationic in its conducting form, requiring a charge-balancing counterion, or dopant. The release of bioactive dopants, driven by the reduction of PPy films, offers a route to controlled drug delivery. Thiol-terminated long chain poly (ethylene glycol) (PEG) reacts with a dodecylbenzene sulfonate (DBSA)-doped PPy, forming a dense overlayer and partially liberating DBSA via the chemical reduction of the film. The resulting PEG brush acts as a barrier to dopant diffusion from the film, but proteins have been shown to disrupt this layer, releasing the DBSA. The mechanism by which this disruption occurs has not been thoroughly investigated. In this study, dopant release from PEG-PPy composites was examined via systematic exposure to a variety of chemical stimuli, including macromolecules such as poly (ethylene imine), polyethylene glycol, and poloxamers, as well as small-molecular-weight alcohols, carboxylic acids, and amines. Dopant release was quantified by quartz crystal microbalance. Poly (ethylene imine) efficiently released DBSA, while anionic and uncharged macromolecules did not. All classes of small molecules triggered dopant release, with longer homologues magnifying the response. The mechanisms of dopant removal are dependent on the functional groups of the stimulating agent and include ion exchange and nucleophilic reduction of the polycationic backbone. Tosylate, salicylate, and penicillin dopants showed release behaviors similar to DBSA, demonstrating the generality of the PEG barrier. Full article

Gastrointestinal (GI) cancers, which mainly include malignancies of the esophagus, stomach, intestine, pancreas, liver, gallbladder, and bile duct, pose a significant global health burden. Unfortunately, the prognosis for most GI cancers remains poor, particularly in advanced stages. Current treatment options, including targeted and immunotherapies, are less effective compared to those for other cancer types, highlighting an urgent need for novel molecular targets. NEK (NIMA related kinase) kinases are a group of serine/threonine kinases (NEK1-NEK11) that play a role in regulating cell cycle, mitosis, and various physiological processes. Recent studies suggest that several NEK members are overexpressed in human cancers, including gastrointestinal (GI) cancers, which can contribute to tumor progression and drug resistance. Among these, NEK2 stands out for its consistent overexpression in all types of GI cancer. Targeting NEK2 with specific inhibitors has shown promising results in preclinical studies, particularly for gastric and pancreatic cancers. The development and clinical evaluation of NEK2 inhibitors in human cancers have emerged as a promising therapeutic strategy. Specifically, an NEK2 inhibitor, T-1101 tosylate, is currently undergoing clinical trials. This review will focus on the gene expression and functional roles of NEKs in GI cancers, as well as the progress in developing NEK inhibitors. Full article

Cellulose tosylate (MCC-Tos) is a key derivative for surface modification and a crucial precursor for cellulose compatibilization in click reactions, enabling its functionalization for advanced applications. Replacing tosyl groups with alkyne groups broadens cellulose’s potential in biocompatible reactions, such as thiol-yne click chemistry and protein/enzyme immobilization. To achieve this, we optimized the heterogeneous synthesis of MCC-Tos using a Doehlert matrix statistical design, evaluating the influence and interaction of the reaction conditions. The optimized conditions—144 h reaction time, 10:1 molar ratio, and 30 °C—yielded a degree of substitution for tosyl groups (DS_tos) of 1.80, determined via elemental analysis and FTIR-ATR spectroscopy. The reaction kinetics followed a first-order model. A subsequent reaction with propargylamine produced aminopropargyl cellulose (MCC-P_NH), reducing DS_tos by 65%, which was confirmed via FTIR, and improving thermal stability by a margin of 30 °C (TGA/DTG). ¹³C CP/MAS NMR confirmed the alkyne group attachment, further validated via coupling an azide-functionalized coumarin through copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC). Fluorescence microscopy and UV spectroscopy were used to estimate a substitution degree of 0.21. This study establishes a feasible route for synthesizing alkyne-functionalized cellulose, paving the way for eco-friendly materials, including protein/enzyme bioconjugates, composites, and advanced materials via thiol-yne and CuAAC reactions. Full article

Indole derivatives are key components of natural products and possess a wide range of biological and pharmaceutical applications. Here, we present the synthesis of a new indole derivative, namely 2-(1-ethyl-5-nitro-1H-indole-7-carbonyl)butyl 4-methylbenzenesulfonate. The structural elucidation of this compound was accomplished through comprehensive spectroscopic analysis, including Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), and high-resolution mass spectrometry (HRMS). Our molecular docking study revealed that this compound exhibits strong affinity towards tyrosinase, making it a promising candidate as an antioxidant agent. Full article

Pyridinium salts of 2-piperidinyl-6-triazolylpurine derivatives were obtained by the introduction of pyridinium moieties into the propane-1,3-diol fragment at the N(9) position of purine to enhance the solubility of 2-amino-6-triazolylpurine derivatives in water. Target structures were obtained using the tosylation of hydroxyl groups of 2-(6-(4-(4-methoxyphenyl)-1H-1,2,3-triazol-1-yl)-2-(piperidin-1-yl)-9H-purin-9-yl)propane-1,3-diol, the subsequent introduction of pyridine, and ion exchange. The compounds were characterized using ¹H- and ¹³C-NMR spectra, FTIR, UV–Vis, and HRMS data. Full article

Herein, a general and practical temperature-controlled approach for the divergent synthesis of pyrazoles and 1-tosyl-1H-pyrazoles via electrophilic cyclization in the absence of transition-metal catalysts and oxidants was developed. The desired products were obtained in moderate to excellent yields from common starting materials in both ionic liquids and ethanol by simply tuning the reaction temperature. This strategy employs easily synthesized substrates, mild reaction conditions, and excellent functional-group tolerance. Full article

Replacing petroleum-based polymers with biopolymers such as polysaccharides is essential for protecting our environment by saving fossil resources. A research field that can benefit from the application of more sustainable and renewable materials is photochemistry. Therefore, cellulose-based photoresists that could be photocrosslinked via UV irradiation (λ = 254 nm and λ = 365 nm) were developed. These biogenic polymers enable the manufacturing of sustainable coatings, even with imprinted microstructures, and cellulose-based bulk materials. Thus, herein, cellulose was functionalized with organic compounds containing carbon double bonds to introduce photocrosslinkable side groups directly onto the cellulose backbone. Therefore, unsaturated anhydrides such as methacrylic acid anhydride and unsaturated and polyunsaturated carboxylic acids such as linoleic acid were utilized. Additionally, these cellulose derivatives were modified with acetate or tosylate groups to generate cellulose-based polymers, which are soluble in organic solvents, making them suitable for multiple processing methods, such as casting, printing and coating. The photocurable resist was basically composed of the UV-crosslinkable biopolymer, an appropriate solvent and, if necessary, a photoinitiator. Moreover, these bio-based photoresists were UV-crosslinkable in the liquid and solid states after the removal of the solvent. Further, the manufactured cellulose-based architectures, even the bulk structures, could be entirely regenerated into pure cellulose devices via a sodium methoxide treatment. Full article

The use of polyelectrolytes is emerging as a fascinating strategy for the functionalization of biomedical membranes, due to their ability to enhance biological responses using the interaction effect of charged groups on multiple interface properties. Herein, two different polyelectrolytes were used to improve the antibacterial properties of polycaprolactone (PCL) nanofibers fabricated via electrospinning. First, a new cationic cellulose derivative, cellulose-bearing imidazolium tosylate (CIMD), was prepared via the nucleophilic substitution of the tosyl group using 1-methylimidazole, as confirmed by NMR analyses, and loaded into the PCL nanofibers. Secondly, sodium alginate (SA) was used to uniformly coat the fibers’ surface via self-assembly, as remarked through SEM-EDX analyses. Polyelectrolyte interactions between the CIMD and the SA, initially detected using a FTIR analysis, were confirmed via Z potential measurements: the formation of a CMID/SA complex promoted a substantial charge neutralization of the fibers’ surfaces with effects on the physical properties of the membrane in terms of water adsorption and in vitro degradation. Moreover, the presence of SA contributed to the in vitro response of human mesenchymal stem cells (hMSCs), as confirmed by a significant increase in the cells’ viability after 7 days in the case of the PCL/CMID/SA complex with respect to the PCL and PCL/CMID membranes. Contrariwise, SA did not nullify the antibacterial effect of CMID, as confirmed by the comparable resistance exhibited by S. mutans, S. aureus, and E. coli to the PCL/CIMD and PCL/CIMD/SA membranes. All the reported results corroborate the idea that the CIMD/SA functionalization of PCL nanofibers has a great potential for the fabrication of efficient antimicrobial membranes for wound healing. Full article

We report an efficient method to prepare polysubstituted 3-hydroxypyridines from amino acids, propargyl alcohols, and arylboronic acids. The process involves Pd(0)-catalyzed anti-selective arylative cyclizations of N-propargyl-N-tosyl-aminoaldehydes with arylboronic acids (“anti-Wacker”-type cyclization), oxidation of the resulting 5-substituted-3-hydroxy-1,2,3,6-tetrahydropyridines to 3-oxo derivatives, and elimination of p-toluenesulfinic acid. This method provides diverse polysubstituted 3-hydroxypyridines, whose hydroxy group can be further substituted by a cross-coupling reaction via a triflate. Full article

In biomedical applications, bacterial cellulose (BC) is widely used because of its cytocompatibility, high mechanical properties, and ultrafine nanofibrillar structure. However, biomedical use of neat BC is often limited due to its lack of antimicrobial properties. In the current article, we proposed a novel technique for preparing cationic BC hydrogel through in situ incorporation of cationic water-soluble cellulose derivative, cellulose bearing imidazolium tosylate function group (Cell-IMD), in the media used for BC preparation. Different concentrations of cationic cellulose derivative (2, 4, and 6%) were embedded into a highly inter-twined BC nanofibrillar network through the in situ biosynthesis until forming cationic cellulose gels. Cationic functionalization was deeply examined by the Fourier transform infrared (FT–IR), NMR spectroscopy, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and X-ray diffraction (XRD) methods. In vitro studies with L929 cells confirmed a good cytocompatibility of BC/cationic cellulose derivatives, and a significant increase in cell proliferation after 7 days, in the case of BC/Cell-IMD3 groups. Finally, antimicrobial assessment against Staphylococcus aureus, Streptococcus mutans, and Candida albicans was assessed, recording a good sensitivity in the case of the higher concentration of the cationic cellulose derivative. All the results suggest a promising use of cationic hybrid materials for biomedical and bio-sustainable applications (i.e., food packaging). Full article

An efficient method for the synthesis of pyrazolo [4,3-b]pyridines has been developed on the basis of readily available 2-chloro-3-nitropyridines via a sequence of SNAr and modified Japp–Klingemann reactions. The method offers a number of advantages including utilization of stable arenediazonium tosylates, operational simplicity as well as combining the azo-coupling, deacylation and pyrazole ring annulation steps in a one-pot manner. An unusual rearrangement (C-N-migration of the acetyl group) was observed and a plausible mechanism was proposed based on the isolated intermediates and NMR experiments. In addition, the developed protocol was successfully applied to the synthesis of 1-arylindazoles combining the Japp–Klingemann reaction and cyclization of the resulting hydrazone as a one-pot procedure. Full article

3,4-dihydropyridin-2-ones are of considerable importance due to the large number of these core structures exhibiting a diverse array of biological and pharmacological activities. The Michael-type addition of 1,3-dithiane-2-carbothioates to α,β-unsaturated N-tosyl imines, followed by intramolecular annulation driven by a sulfur leaving group, provides a practical reaction cascade for the synthesis of a variety of substituted 3,4-dihydropyridin-2-ones. In this work, the reaction was carried out under solid–liquid phase transfer catalysis (SL-PTC) conditions at room temperature, in short reaction times in the presence of cheap Bu₄N⁺HSO₄^– and solid KOH. The new PTC method exhibited adequate functional group tolerance, proving to be a green and reliable method and easy to scale up to furnish rapid access to 3,4-dihydropyridin-2-ones after desulfurization from simple, readily available starting materials. Full article

A practical and efficient Suzuki coupling of phenols has been developed by using trans-NiCl(o-Tol)(PCy₃)₂/2PCy₃ as a catalyst in the presence of tosyl fluoride as an activator. The key for the direct use of phenols lies in the compatibility of the nickel catalyst with tosyl fluoride (TsF) and its sulfur(VI) fluoride exchange (SuFEx) with C_Ar-OH. Water has been found to improve the one-pot process remarkably. The steric and electronic effects and the functional group compatibility of the one-pot Suzuki coupling of phenols appear to be comparable to the conventional one of pre-prepared aryl tosylates. A series of electronically and sterically various biaryls could be obtained in good to excellent yields by using 3–10 mol% loading of the nickel catalyst. The applications of this one-pot procedure in chemoselective derivatization of complex molecules have been demonstrated in 3-phenylation of estradiol and estrone. Full article

Halogenation of 2-trifluoromethylindole afforded 3-chloro-, 3-bromo- and 3-iodo derivatives in up to 98% yield. Methyl-, benzyl- and tosyl-groups can be installed at the nitrogen atom of prepared indoles in high yields by base catalyzed reaction with the corresponding alkylating (sulfonylating) reagents. A high synthetic utility of the prepared haloindoles in the reaction with various nucleophilies was shown. The reaction with 4-methylthiophenol and copper cyanide afforded the corresponding sulfides and nitriles in high yield. Palladium catalyzed cross-coupling with phenyl boronic acid and phenylacetylene gave the corresponding 3-phenyl-2-CF₃-indoles and acetylenic derivatives in 72–98% yield. Full article