Search Results (43)

The synthesis of three novel, valuable bioconjugates obtained by coupling cholesterol bromoacetate with pyridine derivatives via an SN2 reaction was successfully carried out. Each of the products was fully characterized by magnetic nuclear resonance (¹H, ¹³C, APT, ¹H−¹H COSY, ¹H–¹³C HMBC, ¹H–¹³C HSQC), infrared spectroscopy (IR), and high-resolution mass spectrometry (HRMS). Full article

A new synthetic strategy for pyrazolo[1,5-d][1,2,4]triazin-7(6H)-ones 4 through intramolecular cyclization of alkyl 2-(4-nitro-1H-pyrazol-3-yl)methylene)hydrazine-1-carboxylates 3 is described, allowing us to selectively modify the N-substituent in 3-position. The reduction in nitro compounds 4 with tin(II) chloride leads to amines 5, and their acetylation leads to acetamides 6. Via alkylation of 4 with bromoacetic acid alkyl esters and 2-chloro-5-(chloromethyl)pyridine, and the subsequent reduction in alkylated nitro compounds 7, the corresponding amines 8 and amides 9 were accessible in very good yields. The molecular structure of ethyl 2-(2-morpholino-3-nitro-7-oxopyrazolo[1,5-d][1,2,4]triazin-6(7H)-yl)acetate (7b) was confirmed by single-crystal X-Ray diffraction analysis. Antibacterial and cytotoxic properties were evaluated for 61 synthesized compounds. Full article

The synthesis of 7-O-carboxymethyl-4′-fluoroisoflavone 4 and 7-O-carboxymethyl-4′-fluoro-2-trifluormethylisoflavone 7 involved the cyclization of 2,4-dihydroxy-4′-fluorodeoxybenzoin 1, followed by 7-O-alkylation with methyl bromoacetate and subsequent acid-catalyzed hydrolysis. The structures of the novel compounds were validated using a range of techniques, including XRD crystallography (¹H, ¹⁹F, ¹³C)-NMR, and IR. Only interhalogen contacts were detected in 5, while they were completely lacking in 2 and 4, owing to the presence of crystalline ethanol in the crystal structure. The %F…F in 5 was 12.2% based on Hirshfeld calculations. The aromatic π-π stacking interactions were important only in 2 and 4 but not observed in 5. Isoflavones 4, 5, and 7 displayed anticancer activity against MCF-7 cancer cells, with IC₅₀ values of 13.66, 15.43, and 11.73 µM, respectively. Full article

The de-halogenation of highly concentrated halo-organic compounds using Zero Valent Iron entrapped in silica matrices as a catalyst was investigated. This study aimed to evaluate the effectiveness of the Zero Valent Iron-entrapped organically modified silica matrices in transforming highly concentrated hazardous halogenated compounds into environmentally benign materials in the presence of BH₄⁻. The Zero Valent Iron-entrapped silica gel matrices were synthesized using the sol–gel method. The de-halogenation products were analyzed using high-performance liquid chromatography. The results suggest that the Zero Valent Iron-entrapped silica matrices are effective catalysts in the de-halogenation reaction of halo-organics by BH₄⁻ with 100% efficiency. The current work also highlights the complete de-bromination of harmful wastewater generated by the bromoacetic acid manufacturing industry using Zero Valent Iron-entrapped silica matrices. Therefore, Zero Valent Iron-entrapped silica matrices can be considered potential candidates for the catalytic removal of highly concentrated halo-organic compounds from contaminated water. This technology can play a crucial role in reducing the environmental impact of hazardous substances. Full article

The reaction of indigo with two equivalents of the electrophile ethyl bromoacetate with caesium carbonate as a base result in the formation of structurally complex polyheterocyclics, including a fused spiroimidazole and a spiro[1,3]oxazino derivative, together with a biindigoid-type derivative, through a convenient one-pot reaction. Further assessment of the reaction using five equivalents of the electrophile gave rise to other molecules incorporating the 2-(7,13,14-trioxo-6,7,13,14-tetrahydropyrazino[1,2-a:4,3-a′]diindol-6-yl) scaffold. The reaction of ethyl bromoacetate with the less reactive indirubin resulted in the synthesis of three derivatives of a new class of polyheterocyclic system via a cascade process, although yields were low. These compounds were derived from the parent indolo[1,2-b]pyrrolo[4,3,2-de]isoquinoline skeleton. Despite the modest yields of the reactions, they represent quick cascade routes to a variety of heterocycles from cheap starting materials, with these structures otherwise being difficult to synthesise in a traditional stepwise manner. These outcomes also contribute significantly to the detailed understanding of the indigo/indirubin cascade reaction pathways initiated by base-catalysed N-alkylation. Full article

The urgency of water remediation and the conversion of toxic pollutants into non-toxic compounds is increasingly crucial in our industrialized world. Heterogeneous catalysts based on metal nanoparticles, which are cost-effective, non-toxic, and readily available, have garnered significant attention in the market due to their unique catalytic properties. This study presents sol–gel-based hybrid silica matrices that encapsulate nickel, designed for the efficient reductive de-halogenation of tri-bromoacetic acid (TBAA), di-bromoacetic acid (DBAA), mono-bromoacetic acid (MBAA), tri-chloroacetic acid (TCAA), mono-chloroacetic acid (MCAA), and Chloroacetanilide (CAA). A detailed study of the product distribution from each halo-acetic acid (HAA) is presented. The study points out that other products are formed from Ni-catalyzed reduction reactions of HAAs, breaking the conventional rules of stepwise reduction mechanisms. The plausible mechanisms of the catalytic processes are discussed. Full article

Derivatives combining acridine, pyrrole, and thiazolidine rings have emerged as promising candidates in the field of antitumor drug discovery. This paper aims to highlight the importance of these three structural motifs in developing potent and selective anticancer agents. The integration of these rings within a single molecule offers the potential for synergistic effects, targeting multiple pathways involved in tumor growth and progression. Spiro derivatives were efficiently synthesized in a two-step process starting from isothiocyanates and 2-cyanoacetohydrazide. The thiourea side chain in spiro derivatives was utilized as a key component for the construction of the thiazolidine-4-one ring through regioselective reactions with bifunctional reagents, namely methyl-bromoacetate, dietyl-acetylenedicarboxylate, ethyl-2-bromopropionate, and ethyl-2-bromovalerate. These reactions resulted in the formation of a single regioisomeric product for each derivative. Advanced spectroscopic techniques, including 1D and 2D NMR, FT-IR, HRMS, and single-crystal analysis, were employed to meticulously characterize the chemical structures of the synthesized derivatives. Furthermore, the influence of these derivatives on the metabolic activity of various cancer cell lines was assessed, with IC₅₀ values determined via MTT assays. Notably, derivatives containing ester functional groups exhibited exceptional activity against all tested cancer cell lines, boasting IC₅₀ values below 10 μM. Particularly striking were the spiro derivatives with methoxy groups at position 3 and nitro groups at position 4 of the phenyl ring. These compounds displayed remarkable selectivity and exhibited heightened activity against HCT-116 and Jurkat cell lines. Additionally, 4-oxo-1,3-thiazolidin-2-ylidene derivatives demonstrated a significant activity against MCF-7 and HCT-116 cancer cell lines. Full article

Much effort has been devoted to the development of efficient heterogeneous catalysts for the conversion of carbon dioxide (CO₂) into high-value chemicals. Generally, the cycloaddition of CO₂ to epoxides is considered a green and atom-economic reaction for the production of cyclic carbonates. Based on this, three kinds of silicon-based catalysts modified using zinc(Ⅱ) 2-bromoacetic (Si-ZnBA-n, n = 1, 2, 3) were facilely synthesized and employed for the chemical fixation of CO₂ to epoxides with the use of potassium iodide (KI). A series of characterization techniques were used to characterize the textual structures and physicochemical properties of Si-ZnBA-n. The synergistic effects of Zn, –NH_2, –OH and the nucleophilic group guaranteed the catalytic activity of Si-ZnBA-n. Si-ZnBA-1 exhibited the best catalytic activity among Si-ZnBA-n because Si-ZnBA-1 possessed the highest Zn content. Additionally, the effects of the reaction conditions (temperature, pressure, time and catalyst loadings) were also discussed. The propylene carbonate (PC) yield could reach 97% under 130 °C, 2 MPa, for 5 h without the employment of organic solvent, and its selectivity was 99%. In addition, the recycling property of Si-ZnBA-1/KI was also investigated, and the catalytic system exhibited good cycle performance. Meanwhile, the catalyst showed outstanding versatility for CO₂ application to various epoxides, and a possibly synergistic reaction mechanism was proposed. Finally, a dynamic model was developed to discuss the activation energy of the CO₂ cycloaddition reaction over the Si-ZnBA-1 catalyst. Full article

This work deals with the study of the synthesis of new bis-indole analogues with a phenyl linker derived from indole phytoalexins. Synthesis of target bis-indole thiourea linked by a phenyl linker was achieved by the reaction of [1-(tert-butoxycarbonyl)indol-3-yl]methyl isothiocyanate with p-phenylenediamine. By replacing the sulfur of the thiocarbonyl group in bis-indole thiourea with oxygen using mesityl nitrile oxide, a bis-indole homodimer with a urea group was obtained. A cyclization protocol utilizing bis-indole thiourea and methyl bromoacetate was applied to synthesize a bis-indole homodimer with a thiazolidin-4-one moiety. Bis-indole homodimers derived from 1-methoxyspirobrassinol methyl ether were prepared by bromospirocyclization methodology. Among the synthesized analogues, compound 49 was selected for further study. To evaluate the mode of the mechanism of action, we used flow cytometry, Western blot, and spectroscopic analyses. Compound 49 significantly inhibited the proliferation of lung cancer cell line A549 with minimal effects on the non-cancer cells. We also demonstrated that compound 49 induced autophagy through the upregulation of Beclin-1, LC3A/B, Atg7 and AMPK and ULK1. Furthermore, chloroquine (CQ; an autophagy inhibitor) in combination with compound 49 decreased cell proliferation and induced G1 cell cycle arrest and apoptosis. Compound 49 also caused GSH depletion and significantly potentiated the antiproliferative effect of cis-platin. Full article

Synthesis of thiazolidinone based on quinolone moiety was established starting from 4-hydroxyquinol-2-ones. The strategy started with the reaction of ethyl bromoacetate with 4-hydroxyquinoline to give the corresponding ethyl oxoquinolinyl acetates, which reacted with hydrazine hydrate to afford the hydrazide derivatives. Subsequently, hydrazides reacted with isothiocyanate derivatives to give the corresponding N,N-disubstituted thioureas. Finally, on subjecting the N,N-disubstituted thioureas with dialkyl acetylenedicarboxylates, cyclization occurred, and thiazolidinone derivatives were obtained in good yields. The two series based on quinolone moiety, one containing N,N-disubstituted thioureas and the other containing thiazolidinone functionalities, were screened for their in vitro urease inhibition properties using thiourea and acetohydroxamic acid as standard inhibitors. The inhibition values of the synthesized thioureas and thiazolidinones exhibited moderate to good inhibitory effects. The structure−activity relationship revealed that N-methyl quinolonyl moiety exhibited a superior effect, since it was proved to be the most potent inhibitor in the present series achieving (IC₅₀ = 1.83 ± 0.79 µM). The previous compound exhibited relatively much greater activity, being approximately 12-fold more potent than thiourea and acetohydroxamic acid as references. Molecular docking analysis showed a good protein−ligand interaction profile against the urease target (PDBID: 4UBP), emphasizing the electronic and geometric effect of N,N-disubstituted thiourea. Full article

Herein, we report a facile synthesis of ethyl-2-(4-aminophenoxy)acetate 4 as a building synthon for novel dual hypoglycemic agents. This building template was synthesized by alkylation of 4-nitrophenol with ethyl bromo-acetate followed by selective reduction of the nitro group. This reduction methoddoes not require nascent hydrogen or any reaction complexity; it goes easily via consecutive reaction in NH₄Cl/Fe to yield our target synthon as very pure crystals. This product was characterized by ¹HNMR, ¹³CNMR, COSY, NOESY NMR spectroscopy, and elemental analysis. Additionally, its structure was studied and approved by X-ray single crystal structure determination. The unit cell parameters are a = 8.2104(6)Å, b = 10.3625(9)Å, c = 11.9562(9)Å, α = 101.787(7), β = 91.849(6), and γ = 102.755(7)°, indicating that 4 was crystallized in the triclinic crystal system. The cooperative non-covalent interactions are also discussed with the aid of Hirshfeld surface analysis. The H…H, H…C, and O…H interactions have a major contribution in the molecular packing of 4. Moreover, different quantum chemical parameters were computed and discussed based on DFT calculations. The experimental UV/Vis spectra showed two bands at 299 and 234 nm, which were calculated using the TD-DFT method at 286 (f = 0.068) and 226 nm (f = 0.294), respectively. These bands were assigned to HOMO→LUMO (95%) and HOMO→LUMO+2 (86%) transitions, respectively. Full article

In the last few decades, there has been an increasing trend for the usage of natural products and their derivatives as green and renewable oil-filed chemicals. Use of these compounds or their derivatives contributes to reducing the use of traditional chemicals, and enhances green chemistry principles. Curcumin (CRC) is one of the most popular natural products and is widely available. The green character, antioxidant action, and low cost of CRC prompt its use in several applications. In the present study, Curcumin was used to synthesize two new amphiphilic ionic liquids (AILs) by reacting with 1,3-propanesultone or bromoacetic acid to produce corresponding sulfonic and carboxylic acids, CRC-PS and CRC-BA, respectively. Following this, the formed CRC-PS and CRC-BA were allowed to react with 12-(2-hydroxyethyl)-15-(4-nonylphenoxy)-3,6,9-trioxa-12-azapentadecane-1,14-diol (HNTA) to form corresponding AILs, GCP-IL and GRB-IL, respectively. The chemical structures, surface tension, interfacial tension, and relative solubility number (RSN) of the synthesized AILs were investigated. The efficiency of GCP-IL and GRB-IL to demulsify water in heavy crude oil (W/O) emulsions was also investigated, where we observed that both GCP-IL and GRB-IL served as high-efficiency demulsifiers and the efficiency increased with a decreased ratio of water in W/O emulsion. Moreover, the data showed an increased efficiency of these AILs with an increased concentration. Among the two AILs, under testing conditions, GCP-IL exhibited a higher efficiency, shorter demulsification time, and cleaner demulsified water. Full article

A novel approach for synthesizing the key dolutegravir intermediate is described via MgBr₂-promoted intramolecular cyclization. Condensation of commercially available methyl oxalyl chloride and ethyl 3-(N,N-dimethylamino)acrylate afforded the vinylogous amide in an excellent yield. Subsequent substitution by aminoacetaldehyde dimethyl acetal and methyl bromoacetate gave rise to the expected precursor for cyclization, which was promoted by MgBr₂ to highly selectively convert into pyridinone diester. The key dolutegravir intermediate was finally prepared by the selective hydrolysis of the corresponding diester via LiOH. Full article

A new synthetic route for the quorum sensing signal Autoinducer-2 (AI-2) is described and used for the preparation of [4-¹³C]-AI-2 starting from [1-¹³C]-bromoacetic acid. The key step in this process was the enantioselective reduction of an intermediate ketone. This synthesis provides, selectively, both enantiomers of the labelled or unlabelled parent compound, (R) or (S)-4,5-dihydroxypentane-2,3-dione (DPD) and was used for an improved synthesis of [1-¹³C]-AI-2. Full article