Beilstein Journal of Organic Chemistry最新文献

Herein, we report a highly efficient, environmentally benign protocol for the domino synthesis of 2,4-disubstituted and 4-substituted quinoline molecules. The developed strategy involves an earth-abundant Fe-catalyzed C(sp²)-C(sp²) bond cleavage of styrene, followed by the hydroamination of the cleaved synthons with arylamines and subsequent C-H annulation to yield two valuable quinoline derivatives. Key features of this protocol include the use of O₂ as an ideal, green oxidant, operational simplicity and scalability, high atom- and step-economy, and cost-effectiveness, collectively enabling the single-step synthesis of two medicinally relevant N-heterocycles in excellent combined yields.

Both chiral bisoxazolines and bisimidazolines are efficient chiral ligands in metal-catalyzed asymmetric organic transformations. Chiral cyclohexane-linked bisimidazolines were prepared from optically active cyclohexane-1,2-dicarboxylic acid and 1,2-diphenylethane-1,2-diamines via the monosulfonylation of 1,2-diphenylethane-1,2-diamines, condensation of N-sulfonylated 1,2-diphenylethane-1,2-diamines and cyclohexane-1,2-dicarboxylic acid, and the final cyclization with the in situ generated Hendrickson reagent.

Intelligent controlled-release drug delivery systems that are responsive to various external stimuli have garnered significant interest from researchers and have broad applications in the biomedical field. Aromatic macrocycles, including calixarenes and pillararenes, are considered ideal candidates for the construction of supramolecular drug delivery systems because of their simple synthesis, ease of modification, electron-rich and hydrophobic cavities, and highly selective molecular recognition. In recent years, numerous supramolecular drug delivery systems utilizing aromatic macrocycles have been developed. This review article provides an overview of the advancements of controlled drug release systems based on host-guest selective recognition, self-assembly, and nano-valves by the use of of calixarenes and pillararenes from five perspectives: pH, light, enzyme, hypoxia, and multi-stimuli combination responses. Furthermore, the article projects the future clinical application prospects of controlled-release technologies, with the aim of offering a reference for the utilization of aromatic macrocycles in drug-controlled release applications.

In single crystals of C-N atropisomeric N-(2-halophenyl)quinolin-2-one and the thione analogue, a unique association based on a halogen-π interaction was detected. In racemic and optically pure N-(2-bromo- or 2-chlorophenyl)quinolin-2-ones, homochiral layered polymers, which consist of (P)- or (M)-atropisomers, were formed through intermolecular halogen-π association. The halogen-π association in the racemates is due to a halogen bond (C-X···π) between a σ-hole on the halogen atom and a π-electron on the quinolinone benzene ring, while that in optically pure forms is caused by an n-π* interaction between a lone electron pair on the halogen atom and a π* orbital of the quinolinone. In contrast to the formation of the homochiral layered polymer in quinolinones, in racemic N-(2-bromophenyl)quinoline-2-thione, heterochiral layered polymers, in which (P)- and (M)-atropisomers were alternately connected, were formed through an n-π* interaction between a lone electron pair on the bromine atom and a π* orbital of the quinoline-2-thione.

N-Alloc-protected furfuryl amino alcohols derived from furfural and ʟ- or ᴅ-valinol were subjected to Torii-type ester electrosynthesis to obtain the corresponding unsaturated esters. These served as key intermediates to prepare (S)- and (R)-enantioenriched unsaturated amides by N-Alloc deprotection which induced concomitant methoxymethyl group cleavage, O-to-N rearrangement, and isomerization of the double bond. An oxazoline ring formation in the resulting unsaturated amides provided the corresponding enantioenriched vinyloxazoline. The reactivity of the electron-deficient double bond in the vinyloxazoline was explored in several reactions. Out of these, the aza-Diels-Alder reaction with TsNCO was successful, leading to a highly diastereoselective formation of an oxazolo[3,2-c]pyrimidine derivative.

Cyclopropane is a significant alicyclic motif, widely utilized in medicinal chemistry, while fluorination serves as a powerful tool to modulate properties that enhance the performance of pharmaceuticals and materials. This quantum-chemical study explores the energetic implications of fluorinating cyclopropane, providing insights into molecular characteristics arising from the polar C-F bond. Isodesmic reactions revealed that the conversion of cyclopropane and methyl fluoride into mono-, di-, tri-, tetra-, penta-, and hexafluorinated cyclopropanes is exothermic, except for the all-cis-1,2,3-trifluorocyclopropane (1.2.3-c.c.). Compounds featuring geminal fluorines are particularly stabilized due to anomeric-like n _F → σ*_CF interactions. Generally, cis-C-F bonds are less favored than their trans counterparts, not primarily because of steric repulsion, but due to reduced stabilizing electron-delocalization interactions. Among the series, 1.2.3-c.c. stands out as the most polar compound, enabling unique stacking interactions between its electrostatically complementary negative and positive faces. These interactions are mediated through electrostatic hydrogen bonds. This "Janus-like" polarity also facilitates interactions with ions, particularly sodium and chloride. These findings contribute valuable insights for the rational design of drugs and advanced materials, particularly those whose properties rely on the polarity and spatial arrangement of C-F bonds within a cyclopropane framework.

Chiral macrocycles hold significant importance in various scientific fields due to their unique structural and chemical properties. By controlling their size, shape, and substituents, chiral macrocycles offer a platform for designing and synthesizing highly efficient catalysts, chemosensors, and functional materials. We have recently made strides in developing macrocyclic organocatalysts; however, their synthesis remains challenging. In this work, we aimed to discover a straightforward method for producing a diverse range of chiral macrocycles, thereby enabling further exploration in the field of interlocked and macrocyclic organocatalysts. We successfully established optimized synthetic routes for the synthesis of chiral macrocycles containing one or two stereogenic units, featuring varying ring sizes and substituents (21 examples in total).

Lipophilic yeasts of the genus Malassezia are commensal fungi that constitute the normal skin microbiota but may become pathogenic. These fungi, especially M. furfur, convert tryptophan into various alkaloid indoles such as malassezione, which may serve as virulence factors. To facilitate testing of malassezione as an aryl hydrocarbon receptor agonist and potential glucokinase activator, we developed a convenient synthetic route from commercially available indole-3-acetic acid. Treatment of the N-Boc-protected indole-3-acetic acid with N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide (EDC) in the presence of DMAP generates the N,N'-Boc-protected malassezione, which upon deprotection yields malassezione in an overall yield of ca. 20%. This is an improvement over the preparation of the isonitrile followed by an Fe hydride initiated isonitrile-olefin intramolecular coupling reaction, which generated malassezione with an overall yield of ca. 5%. Furthermore, the present method may also be used to prepare related compounds.

Nonreducing disaccharides are prevalent in non-mammalian glycans and glycolipids, serving as pivotal structural components in mycobacterial glycans, microbial oligosaccharide and nucleoside antibiotics, as well as biologically active mimetics of bacterial pathogen-associated molecular patterns (PAMPs). As integral components of PAMPs, 1,1'-linked disaccharide-containing biomolecules play important roles in host-pathogen interactions, cellular signaling, and pathogenesis. Accessing complex biomolecules containing nonreducing disaccharides is often hindered by difficulties in isolating them from natural sources, which can result in impure or degraded products, particularly when sensitive functional groups are involved. Consequently, approaches to 1,1'-glycosylation for the synthesis of nonreducing disaccharides with defined anomeric configurations are essential for the development of 1,1'-disaccharide-containing biomolecules used in vaccine research, as well as for therapeutic and diagnostic applications. The assembly of nonreducing 1,1'-linked disaccharides presents greater challenges than conventional chemical glycosylation due to the need for simultaneous control of stereochemistry at two anomeric centers. The structural complexity of natural biomolecules entailing 1,1'-disaccharides, which feature asymmetrically distributed functional groups across their two pyranose rings, emphasizes the importance of robust, stereoselective synthetic strategies capable of producing fully orthogonally protected 1,1'-linked sugars suitable for selective chemical modification. This review highlights recent advances in 1,1'-glycosylation and provides an overview of selected glycosylation strategies, including those aimed at forming α,β-, β,β-, and α,α-1,1'-glycosidic linkages. Particular emphasis is placed on the challenges of achieving stereoselectivity with lactol glycosyl acceptors, which commonly exist as mixtures of anomers and are therefore problematic to use in chemical glycosylation reactions.

Flow chemistry technology has demonstrated significant potential in advancing the green transformation of the chemical industry while enhancing inherent process safety. Safety, cost-effectiveness, and operational efficiency serve as pivotal drivers for advancing flow chemistry in nitration processes. This review provides a comprehensive analysis of the continuous-flow nitration technology - a process historically recognized as one of the most hazardous industrial operations - focusing on its technological advancements in process design, reaction kinetics characterization, and practical implementation over the past decade. Detailed discussions encompass system configuration strategies, critical process parameters and operating ranges, performance evaluation metrics, universal methodologies for kinetics analysis, safety assessment protocols, and scale-up approaches. The presented content aims to offer actionable guidance for researchers and engineers engaged in the development of continuous-flow nitration systems.