Atroposelective Synthesis of Biaryl N-Oxides via Cu-Catalyzed De Novo Heteroaromatic N-Oxide Ring Formation.

Heteroaromatic N-oxides, renowned for their highly polar N─O bond and robust structure, exhibit significant bioactivities and have played a pivotal role in various drug development projects since the discovery of Minoxidil. Moreover, heteroaromatic N-oxides, featuring axially chiral biaryl frameworks, are indispensable as Lewis base catalysts and ligands in organic synthesis. Despite their importance, synthesizing these chiral compounds is challenging, necessitating chiral starting materials or resolution processes.

Molecular Editing of Ketones through -Heterocyclic Carbene and Photo Dual Catalysis.

The molecular editing of ketones represents an appealing strategy due to its ability to maximize the structural diversity of ketone compounds in a straightforward manner. However, developing efficient methods for the arbitrary modification of ketonic molecules, particularly those integrated within complex skeletons, remains a significant challenge. Herein, we present a unique strategy for ketone recasting that involves radical acylation of -functionalized ketones facilitated by -heterocyclic carbene and photo dual catalysis.

-Heterocyclic carbene catalytic 1,2-boron migrative acylation accelerated by photocatalysis.

The transformation of organoboron compounds plays an important role in synthetic chemistry, and recent advancements in boron-migration reactions have garnered considerable attention. Here, we report an unprecedented 1,2-boron migrative acylation upon photocatalysis-facilitated -heterocyclic carbene catalysis. The design of a redox-active boronic ester substrate, serving as an excellent β-boron radical precursor, is the linchpin to the success of this chemistry.

A promising future of metal-N-heterocyclic carbene complexes in medicinal chemistry: The emerging bioorganometallic antitumor agents.

Metal complexes based on N-heterocyclic carbene (NHC) ligands have emerged as promising broad-spectrum antitumor agents in bioorganometallic medicinal chemistry. In recent decades, studies on cytotoxic metal-NHC complexes have yielded numerous compounds exhibiting superior cytotoxicity compared to cisplatin. Although the molecular mechanisms of these anticancer complexes are not fully understood, some potential targets and modes of action have been identified.

Palladium-catalyzed ()-selective allylation of phosphine oxides with vinylethylene carbonates to construct phosphorus allyl alcohols.

Allylphosphine oxide compounds are important building blocks with broad applications in organic synthesis and pharmaceutical science. Herein, we report an unprecedented palladium-catalyzed allylation of phosphine oxides with vinylethylene carbonates, producing various phosphorus allyl alcohols in excellent yields with high -selectivity. In addition, gram-scale synthesis and further functional group transformations demonstrate the practical utility of this synthetic method.

Local injection of platelet-rich plasma offers a new therapeutic option for the treatment of esophagotracheal fistula: a case report.

Esophagotracheal fistula (ETF), one of the most serious complications in the treatment of esophageal cancer, presents a complex management challenge. Early diagnosis and treatment are crucial to alleviate clinical symptoms and improve the quality of life of patients with ETF. The most commonly used method for treating ETF is esophageal stenting.

Direct Acylation of Unactivated Alkyl Halides with Aldehydes through N-Heterocyclic Carbene Organocatalysis.

Catalytic acylation of organohalides with aldehydes is an ideal strategy for the direct synthesis of ketones. However, the utilization of unactivated alkyl halides in such a transformation remains a formidable challenge. In this study, we developed a cross-coupling reaction of aldehydes with unactivated alkyl halides through N-heterocyclic carbene catalysis.

Gasdermin D-mediated pyroptosis: mechanisms, diseases, and inhibitors.

Gasdermin D (GSDMD)-mediated pyroptosis and downstream inflammation are important self-protection mechanisms against stimuli and infections. Hosts can defend against intracellular bacterial infections by inducing cell pyroptosis, which triggers the clearance of pathogens. However, pyroptosis is a double-edged sword.

Highly Stereoselective Synthesis of Bis--ferrocenyl Glycosides via Palladium-Catalyzed Directed C-H Glycosylation.

Conjugation of carbohydrates to ferrocene scaffolds is of great value in drug design, given the nontoxic and lipophilic nature of ferrocene. However, the efficient and stereoselective synthesis of -ferrocenyl glycosides remains a challenge. Herein, we developed a Pd-catalyzed stereoselective C-H glycosylation to provide rapid access to sole bis--ferrocenyl glycosides in good to high yields (up to 98% yield) with exclusive stereoselectivity.

A straightforward access to trifluoromethylated natural products through late-stage functionalization.

Covering: 2011 to 2021Trifluoromethyl (CF)-modified natural products have attracted increasing interest due to their magical effect in binding affinity and/or drug metabolism and pharmacokinetic properties. However, the chemo and regioselective construction of natural products (NPs) bearing a CF group still remains a long-standing challenge due to the complex chemical scaffolds and diverse reactive sites of NPs. In recent years, the development of late-stage functionalization strategies, including metal catalysis, organocatalysis, light-driven reactions, and electrochemical synthesis, has paved the way for direct trifluoromethylation process.

Sulphur ylide-mediated cyclopropanation and subsequent spirocyclopropane rearrangement reactions.

The efficient construction of cyclopropyl spiroindoline skeletons and the exploration of related follow-up synthetic transformations have elicited considerable interest amongst members of the chemistry community. Here, we describe a formal (2 + 1) annulation and three-component (1 + 1 + 1) cascade cyclisation sulphur ylide cyclopropanation under mild conditions. The spiro-cyclopropyl iminoindoline moiety can be readily transformed into another medicinally interesting pyrrolo[3,4-]quinoline framework through a novel rearrangement process.

Suzuki-type cross-coupling of alkyl trifluoroborates with acid fluoride enabled by NHC/photoredox dual catalysis.

The Suzuki-Miyaura cross-coupling of C(sp)-hybridised boronic compounds still remains a challenging task, thereby hindering the broad application of alkyl boron substrates in carbon-carbon bond-forming reactions. Herein, we developed an NHC/photoredox dual catalytic cross-coupling of alkyl trifluoroborates with acid fluorides, providing an alternative solution to the classical acylative Suzuki coupling chemistry. With this protocol, various ketones could be rapidly synthesised from readily available materials under mild conditions.

Radical Acylalkylation of 1,3-Enynes To Access Allenic Ketones via -Heterocyclic Carbene Organocatalysis.

An -heterocyclic carbene organocatalytic 1,4-difunctionalization of 1,3-enynes was developed. This organocatalytic strategy was suitable for a broad spectrum of substrates to efficiently synthesize allenic ketones bearing diverse substituents. Preliminary mechanistic studies suggest a radical reaction pathway for this organocatalytic acylalkylation process.

Remote C(sp )-H Acylation of Amides and Cascade Cyclization via N-Heterocyclic Carbene Organocatalysis.

The direct functionalization of inert C(sp )-H bonds under environmentally benign catalytic conditions remains a challenging task in synthetic chemistry. Here, we report an organocatalytic remote C(sp )-H acylation of amides and cascade cyclization through a radical-mediated 1,5-hydrogen atom transfer mechanism using N-heterocyclic carbene as the catalyst. Notably, a diversity of nitrogen-containing substrates, including simple linear aliphatic carbamates and ortho-alkyl benzamides, can be successfully applied to this organocatalytic system.

Diastereoselective [3 + 1] Cyclization Reaction of Oxindolyl Azaoxyallyl Cations with Sulfur Ylides: Assembly of 3,3'-Spiro[β-lactam]-oxindoles.

Oxindoles and β-lactams are attractive structural motifs because of their unique biological importance. However, the fusion of the two moieties featuring 3,3'-spirocyclic scaffolds is a challenging task in organic synthesis. Herein we designed a novel type of oxindole-based azaoxyallyl cation synthons, which could readily participate in the [3 + 1] cyclization with sulfur ylides.

Asymmetric organocatalysis: an enabling technology for medicinal chemistry.

The efficacy and synthetic versatility of asymmetric organocatalysis have contributed enormously to the field of organic synthesis since the early 2000s. As asymmetric organocatalytic methods mature, they have extended beyond the academia and undergone scale-up for the production of chiral drugs, natural products, and enantiomerically enriched bioactive molecules. This review provides a comprehensive overview of the applications of asymmetric organocatalysis in medicinal chemistry.

Highly Chemoselective [2+1] Annulation of α-Alkylidene Pyrazolones with α-Bromonitroalkenes: Synthesis of Pyrazolone-Based Vinylcyclopropanes and Computational Studies.

A highly chemoselective [2+1] annulation of α-alkylidene pyrazolones with α-bromonitroalkenes has been achieved under mild conditions. α-Alkylidene pyrazolones were unprecedentedly used as a C1 synthon to participate in annulation reactions, providing access to diverse vinylcyclopropane-based pyrazolone products. In addition, a spectrum of pharmaceutically interesting pyrazole-fused pyranone oximes could be rapidly obtained through a [2+1] annulation/rearrangement sequential process.

Single-Electron Transfer Reactions Enabled by N-Heterocyclic Carbene Organocatalysis.

Over the past decades, N-heterocyclic carbene (NHC) organocatalysis has undergone a flourish of development on the basis of closed-shell reaction paths. By contrast, the emerging area of single-electron transfer (SET) reactions enabled by NHC catalysis still remain underdeveloped, but offer plenty of opportunities to develop new catalytic modes and useful synthetic methods. A number of interesting transformations were triggered by the SET process from the electron-rich Breslow intermediates to various single-electron acceptors.

Palladium-catalysed cyclisation of vinylethylene carbonates and anhydrides: a new approach to diverse medium-sized bislactones.

Efficient construction of medium-sized lactones has attracted considerable interest over several decades, but remains a formidable challenge in synthetic chemistry. Here, we describe an unprecedented palladium-catalysed regioselective [5 + n] cyclisation (n = 5, 6, and 7) between vinylethylene carbonates and various anhydrides. Catalytic transformation occurs under mild, room-temperature conditions and offers an exceptional substrate scope.

Bifunctional Brønsted Base Catalyzed [3 + 3] Annulations of Indolin-2-imines and α,β-Unsaturated Imides: An Enantioselective Approach to α-Carbolinones.

Asymmetric construction of α-carbolinones with easily available starting materials has recently attracted considerable attention from the synthesis community, and the development of effective catalysis for this target is in great demand. Here, a bifunctional Brønsted base catalyzed asymmetric [3 + 3] cyclization of indolin-2-imines and α,β-unsaturated -acylated succinimides was developed by using the strategy of noncovalent bonding catalysis. With this organocatalytic protocol, a variety of tetrahydro-α-carbolinones bearing different substituents were synthesized with up to 99% yield and up to 96:4 er.

Erxian decoction, a famous Chinese medicine formula, antagonizes corticosterone-induced injury in PC12 cells, and improves depression-like behaviours in mice.

In folk medicine, erxian decoction (EXD) is used to treat perimenopausal syndrome in women. It is also used clinically to treat depression, but the mechanism remains unknown. To investigate the neuroprotective effect of EXD, and its antidepressant potential.

Palladium-catalysed decarboxylative annulations of vinylethylene carbonates leading to diverse functionalised heterocycles.

Heterocycles are the fundamental structural motifs found in natural products and biologically active compounds. The construction of these structures is therefore an important task in organic chemistry. Vinylethylene carbonates (VECs) are versatile building blocks that can undergo transition metal catalysed decarboxylation to enable various kinds of interesting transformations.