Russian Journal of Organic Chemistry最新文献

Alzheimerʼs disease is a progressive neurological illness marked by the formation of amyloid plaques and tangled neurofibrillary chains in the brain, which impairs cognitive function and leads to neuronal death. The benzothiazoles and benzoxazoles rings have shown promising results as scaffolds for the design and development of neuronal protective agents which prevents oxidative stress, inhibit acetylcholinesterase (AChE), and blocks amyloid Aβ(1–42) aggregation. In this study, we successfully synthesized a series of benzothiazole or benzoxazole heteroarenes by the condensation of 2-sulfanylphenol or 2-aminophenol with heteroaromatic aldehydes under oxidative conditions, followed by Vilsmeier–Haack formylation, and gave the corresponding formyl derivatives, which served as key intermediate for the synthesis of new arylidene derivatives. Additionally, a series of arylbenzothiazole bromides was synthesized in high yields. The anti-Alzheimer inhibitory potential of the synthesized compounds was evaluated by in silico analysis. Promising results indicate that several compounds exhibit higher activity against Aβ(1–42) and AChE than galantamine and curcumin, respectively. Furthermore, the ADMET profiling of the selected compounds was performed using chemoinformatic tools to assess their druglikeness, efficacy, and safety for clinical use.

The Ritter reaction of 2-(2-methoxyphenyl)-1-methylcyclohexan-1-ols with various nitriles was investigated. Depending on the nature of the nitrile and the substituents on the 2-methoxyphenyl fragment of the alcohols, the reaction can lead to both N-2-(2-methoxyphenyl)-1-methylcyclohexyl)amides and derivatives of partially hydrogenated spiroindolenines in a diastereoselective manner.

In the present study, the biphenyl ether group of triclosan was modified with an isoquinoline ring, resulting in the synthesis of a series of novel, biologically active [(benzoyloxy)phenyl]isoquinolinamines. The synthesized compounds were characterized by ¹H NMR, ¹³C NMR, and ESI–HRMS, and their antibacterial activities were evaluated in comparison with the parent molecule against some Gram-positive and Gram-negative bacterial strains. Among the tested compounds, N¹-{6-[3-(benzyloxy)phenyl]isoquinolin-1-yl}ethane-1,2-diamine exhibited the highest potency with MIC 2 μg/mL against S. aureus and 8 μg/mL against E. coli. A molecular docking study of the novel [(benzoyloxy)phenyl]isoquinolinamine derivatives, conducted to gain atomic-level insight into their binding mechanism, revealed binding energies higher than that of triclosan—a result consistent with experimental observations.

New sulfur-containing Mannich bases derived from 1-(octylsulfanyl)hexan-2-ol, secondary amines (diethylamine, dibutylamine, piperidine, morpholine, hexamethyleneimine), and formaldehyde have been synthesized by three-component Mannich reaction and screened for antibacterial activity. The composition and structure of the synthesized compounds were confirmed by elemental analysis, IR and ¹H NMR spectroscopy, and mass spectrometry. The antimicrobial screening was performed using the disk diffusion assay. The synthesized Mannich bases showed high antimicrobial activity against Gram-positive and Gram-negative bacteria (S. aureus, E. coli, P. aeruginosa, and K. pneumoniae), as well as yeast-like fungi of the genus Candida in comparison with the reference antibacterial agents (rivanol, furacilin, carbolic acid, and chloramine). The resulting data allow the synthesized compounds to be recommended as candidate antimicrobial drugs.

A diastereoselective synthesis of 1,2,3,4,4a,14a-hexahydro-8aH-xantheno[9,8a-b]indole and 3,4b,5,6,7,8,8a,15b-octahydro-4H-benzo[d]naphtho[1,8-ab]carbazole-4-one derivatives has been developed based on a domino sequence that involves electrophilic ortho-spirodearomatization via the Ritter reaction and intramolecular nucleophilic trapping of spiro-σ-intermediates.

In organic synthesis, environmentally friendly reactions have special and critical features. With more eco-friendly and green methods for different organic transformations, considerable development has been achieved recently. In the context of green synthesis, MNPs as a green catalyst attract major attention. Different heterocycles have been synthesized using MNPs as green catalysts. Among heterocycles, isoxazole is a privileged scaffold and it provided multiple lead structures for the development of therapeutic candidates. The utilisation of MNPs as catalyst significantly enhances the demand for isoxazole synthesis. Consequently, there is a pressing and future necessity to generate an increasing number of isoxazole derivatives by using green synthetic methods. This article presents an updated report on the role of MNPs green catalysts in the development of a diverse array of isoxazoles.

The structure of 3-morpholinomethoxymethylbicyclo[2.2.1]hept-2-ene, an aminomethoxy derivative of bicyclo[2.2.1]hept-5-ene-2-methanol (norbornenylmethanol), was confirmed the independent synthesis by the three-component Mannich reaction using allyl alcohol, formaldehyde and morpholine. Along with the target compounds, the reaction gave a previously unknown Mannich base—3-(morpholinomethoxymethyl)propyl-1-ene. The compositions and structures of the synthesized compounds were confirmed by elemental analysis, IR and ¹H and ¹³C NMR spectroscopy, as well as mass spectrometry.

A series of N-hydroxy-2-[4-(2-R¹,3-R²,6-R³-quinolin-4-yl)phenyl]acetamides 4a–4n (R¹–R³ = Me, Et, Cl, Ph) was synthesized, screened for HDAC8 inhibition and antiproliferative activity, and analyzed via in silico molecular docking. The synthesis of the hydroxamic acid-functionalized quinoline scaffolds involved the Friedlander reaction followed by Friedel–Craft alkylation and ester hydrolysis. The in vitro HDAC8 inhibition potential and antiproliferative activity of the synthesized compounds were assessed by the MTT assays. Molecular docking was performed of the products to the HDAC8 target protein (PDB ID: 5FCW) was performed to determine the binding energies and sites, as well as nature of interactions In the in vitro HDAC8 inhibition activity, 4g showed a slightly higher (IC₅₀ = 9.53 µM), while 4a exhibited a slightly lower activity (IC₅₀ = 21.24 µM) than the other compounds. Scaffold 4g exhibited good in vitro anticancer activity (IC₅₀ = 3.69 µM) against the COLO 205 cell line, and scaffold 4h was found to be active against two cancer cell lines: HCT 116 (IC₅₀ = 6.91 µM) and COLO320 DM (IC₅₀ = 8.91 µM). Molecular docking predicted high binding affinities of compounds 4g and 4n (–8.1 and –7.9 kcal/mol) to the HDAC8 target protein. The results highlight the HDAC8 inhibitory and anticancer potential of the new hydroxamic acid–appended quinoline derivatives, identifying compound 4g as a particularly promising candidate for further development.

A method for the synthesis of 4-amino-5-bromo-1,3-diarylimidazolium salts is developed. The approach involves the selective bromination of 4-amino-1,3-diarylimidazolium salts using bromomalononitrile as a mild brominating agent. The subsequent functionalization of these products is demonstrated via reaction of the amino group with electrophilic reagents.

The regio- and stereoselective synthesis of new (Z)-selenocyanatoacrylamides containing N-alkylamide groups and cyclic amide substituents (yields 76–93%) by the reaction of potassium selenocyanate with 3-trimethylsilyl-2-propynamides was developed. The reaction proceeded in aqueous acetonitrile in the presence of ammonium chloride and was accompanied by a desilylation process.