Tetrahedron最新文献

A commercially available nickel was utilized as an effective catalyst for the exclusive hydrogenation of nitroarenes to primary anilines in gram-scale without additional column chromatographic purification. This novel synthetic hydrogenation strategy features wide substrate scope, mild conditions and operational simplicity in aqueous media at room temperature. Further transformations resulted in the delivery of important amine-containing drugs and pharmaceutical intermediates.

The diastereoselective Michael addition of ketones to maleimides using bifunctional organocatalysts presents a significat challenge. We developed a protocol in which the addition of 5 equivalents of water boosted the diastereoselectivity of six-membered ring ketones. However, the results were influenced by steric effects and varied outcomes were observed with different ring sizes of ketones and acyclic carbonyl compounds. The improvement in the asymmetric synthesis of succinimides due to water appears to be more related to hydrogen bonds at the interface rather than a water molecule embedded in the transition state. Additionally, we explored 3-substituted maleimides and found that only those with phenyl and phenylethynyl groups underwent the reaction. Finally, the desymmetrization of N-(2-tert-butylphenyl)maleimide generated the atropoisomer with good selectivity.

BINAM (1,1′-binaphthyl-2,2′-diamine)-derived bis-urea-catalyzed nucleophilic ring-opening of optically active and diastereomerically pure 2-EWG (electron-withdrawing group)-substituted N-(1-(1-naphthyl)ethyl)azetidinium salts with cesium fluoride in dichloromethane at room temperature proceeds at the less sterically hindered 4-position over the electronically deficient 2-position. Selective ring-opening at the 4-position is achieved by the combination of chiral stereocenters, as in N-(1-(1-naphthyl)ethyl)azetidinium salt, and steric bulk of the chiral bis-urea catalysts. The reaction affords the corresponding γ-fluoro-α-aminobutyric acid derivatives in diastereomerically pure. This protocol is applicable to the synthesis of enantiomerically enriched (98 % ee) γ-fluoro-α-amino acid derivatives starting from the commercially available chiral 1-(1-naphthyl)ethylamine.

3-Selenyl quinolines are an important class of compounds that have found significant applications in pharmaceuticals and synthetic chemistry. Herein, we describe an electrochemical oxidative selenocyclization under undivided electrolytic conditions, thereby providing an efficient rout to access 3-selenyl quinolines. The merit of this method has been well demonstrated by its green and environmental-friendly conditions, being external oxidant-free, short reaction time, broad substrate scope and ease of scale-up to gram scale.

This article describes the employment of commercially available, cheap pentafluoropyridine (PFPy) for a simple and straightforward one-pot synthesis of 2, 3-Dihydroquinazolin-4(1H)-ones. The reported protocol involves PFPy-mediated multicomponent condensation reaction of aldehyde, amine and isatoic anhydride at elevated temperature. This research work exploited the electron-withdrawing nature of fluorine atoms in PFPy for the nucleophilic substitution at para to the N-atom to produce fluoride ions that assisted the synthesis of the 2,3-Dihydroquinazolin-4(1H)-ones in excellent yield. The broad substrate scope, easy purification, short reaction times, high yields and ease of operation enhance the versatility of the protocol.

Phosphodiesterase-4 (PDE4) is a protease belonging to the phosphodiesterase family, with a specific function of hydrolyzing intracellular cyclic adenosine monophosphate (cAMP). PDE4 is widely distributed across various human tissues and cells, where it plays a pivotal role in modulating intracellular cAMP levels, particularly in immune and inflammatory cells. Consequently, PDE4 inhibitors have been proven to effectively dampen inflammatory responses in these cells, leading to a reduction in the release of pro-inflammatory factors such as lipid mediators, reactive oxygen species (ROS) hydrolases, cytokines, and chemokines. Despite the considerable interest from both academia and pharmaceutical industries in exploiting this target for drug development, only a handful of PDE4 inhibitors are available in the market. The aim of this study was to identify novel PDE4B inhibitors through a combined approach of computer-aided drug design, synthesis, and activity evaluation. The study implemented three phases of structure optimization from the hit compound MR9, which was previously obtained by virtual screening, with reference to structure-based drug design (SBDD) and ligand-based drug design (LBDD) approaches. The optimized compound MR9-302 (PDE4B IC₅₀ = 2.02 ± 0.2888 μM) exhibited enhanced inhibitory activity compared to MR9.

In the present scenario, environment-friendly reactions in organic synthesis have a unique and irreplaceable place. In the past, there are significant progress in the development of more nature-friendly and sustainable methods for various organic transformations. The nature-friendly and sustainable methods make a tool named green synthesis which utilizes for the synthesis of various drug candidates. Within perspectives of green synthesis, the magnetic nanoparticles attract considerable attention due to its many characteristics and utilization in the green synthesis. In organic synthesis, magnetic nanoparticles have been used as a green catalyst for the formation of various heterocycles. In the realm of organic compounds, imidazole is considered a preferred and highly valuable motif among aza-heterocycles. It presents a favourable opportunity for discovering lead structures in the quest for new synthetic molecules with potential therapeutic properties and other significant prospects. The synthesis of imidazole due to its exciting profile is very much demanding by using magnetic nanoparticles as a green catalyst. Accordingly, the pure and functionalized magnetic nanoparticles display significant potential in the synthesis of a diverse range of imidazole derivatives. Therefore, this manuscript compiles the current research (from 2004 to present) on the role of environmentally safe pure and functionalized magnetic nanoparticles for generating a wide variety of valuable imidazoles.