Beilstein Journal of Organic Chemistry最新文献

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.

Pyruvate ketal is a biologically essential moiety due to its key role as an intermediate in metabolic pathways, serving as a key precursor for the synthesis of various essential biomolecules in organisms. However, the R/S stereochemistry of pyruvate ketal is difficult to control through chemical methods. In this study, the acid-labile pyruvate ketal linked to the 4- and 6-positions of galactose was cautiously constructed, and the X-ray analysis of the R-configured product was successfully obtained. Subsequently, the compound was used for the synthesis of zwitterionic polysaccharide A1 (PS A1) precursor, and a clear structural elucidation was applied by using nuclear magnetic resonance and X-ray.

Reducing agents with phosphorus-hydrogen bond, such as sodium hypophosphite, phosphite, and hypophosphorous acid are commercially available in bulk amounts, however, their usage is understudied in organic processes. While NaH₂PO₂ has proved to be an efficient four-electron reductant in the catalyst-free reductive amination, the influence of cation in hypophosphite salt has not been studied yet. This issue is a fundamentally important factor. In the present work, the reactivity of the hypophosphites of alkali metals (Li, K, Rb, and Cs) in reductive amination was explored for the first time. A set of secondary and tertiary amines was synthesized from various types of carbonyl compounds and amines. The remedy for Parkinson's disease, piribedil, was obtained in high yield. The plausible mechanism of the elaborated process was proposed and supported by DFT calculations.

Beyond the conventional carbon-centered chirality, catalytic asymmetric transformations of isocyanides have recently emerged as a powerful strategy for the efficient synthesis of structurally diverse scaffolds featuring axial, planar, helical, and inherent chirality. Herein, we summarize the exciting achievements in this rapidly evolving field. These elegant examples have been organized and presented based on the reaction type as well as the resulting chirality form. Additionally, we provide a perspective on the current limitations and future opportunities, aiming to inspire further advances in this area.

A formal synthesis of product VI with tetrahydroflurenone structure as selective estrogen receptor modulator has been realized. The Rh-catalyzed [3 + 2 + 1] reaction of yne-vinylcyclopropanes and CO (20 mmol scale, in 87% yield) for building the 6/5/5 skeleton, and a Heck coupling reaction constructing the [3.2.1] framework, are the two key reactions in this 11-step synthesis.