Enantioselective Synthesis of Tetrahydro-1-1,3-methanocarbazoles by Formal (3 + 3)-Cycloaddition Using Bicyclo[1.1.0]butanes.

Asymmetric synthesis presents many challenges, with the selective formation of chiral bridged polyheterocycles being a notable example. Cycloadditions using bicyclo[1.1.

Ligand interaction landscape of transcription factors and essential enzymes in E. coli.

Knowledge of protein-metabolite interactions can enhance mechanistic understanding and chemical probing of biochemical processes, but the discovery of endogenous ligands remains challenging. Here, we combined rapid affinity purification with precision mass spectrometry and high-resolution molecular docking to precisely map the physical associations of 296 chemically diverse small-molecule metabolite ligands with 69 distinct essential enzymes and 45 transcription factors in the gram-negative bacterium Escherichia coli. We then conducted systematic metabolic pathway integration, pan-microbial evolutionary projections, and independent in-depth biophysical characterization experiments to define the functional significance of ligand interfaces.

A Precise Route to Tetrasubstituted Allyl Amines via Regioselective Dicarbofunctionalization of Masked Propargyl Amines.

Allyl amines are vital components in various biologically important molecules and play a significant role in their function. Presently, most methods are geared toward the preparation of di- and trisubstituted allyl amines, leaving a gap for the development of more versatile approaches. We herein describe an approach to yield tetrasubstituted allyl amines through palladium (Pd)-catalyzed regioselective dicarbofunctionalization of masked N-phthalimide-protected propargyl amines.

Formal [2σ + 2σ]-Cycloaddition of Aziridines with Bicyclo[1.1.0]butanes: Access to Enantiopure 2-Azabicyclo[3.1.1]heptane Derivatives.

Saturated nitrogen heterocycles are among the most significant structural components in small-molecule pharmaceuticals. Herein, a protocol for the construction of enantiopure 2-azabicyclo[3.1.

Regioselective Twofold Annulation of Propargyl Acetates.

The regioselective annulation of unsymmetrical alkynes has always been a focused research topic. A Pd-catalyzed double annulation of unsymmetrical alkynes (i.e.

A comprehensive review on the risks assessment and treatment options for Sarcopenia in people with diabetes.

Objectives: This comprehensive review aims to examine the reciprocal interplay between Type 2 diabetes mellitus (T2DM) and sarcopenia, identify prevailing research gaps, and discuss therapeutic approaches and measures to enhance healthcare practices within hospital settings.

Methods: A thorough literature review was conducted to gather relevant studies and articles on the relationship between T2DM and sarcopenia. Various databases were searched, including Google Scholar, PubMed, Scopus, and Science Direct databases.

Two-component symmetrical diarylation of ynamides.

The present study describes a method for the dicarbofunctionalization of ynamide a palladium-catalyzed two-component diarylation with aryl boronic acids. The reaction involves a consecutive transmetalation of the aryl boronic acids with a Pd(II)-complex making the transformation stereoselective. Importantly, the reaction proceeds under mild conditions and tolerates a broad range of functional groups.

Regioselective Difunctionalization and Annulation of Ynamide.

The use of ynamides in organic synthesis has gained significant attention due to their ability to provide access to complex molecular structures through transformations such as 1,2-difunctionalization and annulation reactions. These reactions enable the formation of highly functionalized N-bearing olefins and unusual N-bearing heterocycles. In this minireview, we present a systematic overview of the regioselective difunctionalization and annulation reactions of ynamides.

Three Component syn-1,2-Arylmethylation of Internal Alkynes.

A Pd-catalyzed three-component syn-1,2-arylmethylation of internal alkynes (ynamides/yne-acetates/alkynes) is described. The readily available and bench stable coupling partners iodo-arenes, and methyl boronic acid are successfully used in this coupling strategy to access the methyl-containing tetra-substituted olefins; the scope is broad showing excellent functional-group tolerance. Notably, the transformation is regio- as well as stereoselective.

A 6--dig Thiolative Cyclization of Yne-Ynamides: Access to Thiodihydropyridin-2-ones.

A straightforward regioselective intramolecular 6--dig cyclization of yne-tethered ynamide is herein developed. The reaction involves an intramolecular enolate attack of ketene--acetals, generated in situ from yne-ynamide and methanesulfonic acid, to the alkyne moiety activated by a sulfonium cation. The transformation enables access to structurally diverse 5-(arylthio)-3,6-dihydropyridin-2(3)-ones with broad functional group compatibility.

Influence of SGLT2 Inhibitors in Remodeling, Substrate and Ion Metabolism of Myocardium to Prevent Cardiovascular Risks: Recent Work and Advancement.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of drugs that lower blood glucose levels while decreasing blood pressure, volume loss, and weight loss. SGLT2 inhibitors were studied to determine their effectiveness in treating cardiovascular disease and their side effects. Study outcomes related to cardiovascular and metabolic outcomes were examined in patients on SGLT2 inhibitors by searching PubMed, Embase, Cochrane, and SCOPUS.

Emerging Trends in Immunotherapy for Cancer.

Recent advances in cancer immunology have enabled the discovery of promising immunotherapies for various malignancies that have shifted the cancer treatment paradigm. The innovative research and clinical advancements of immunotherapy approaches have prolonged the survival of patients with relapsed or refractory metastatic cancers. Since the U.

Pathogenesis of Viral Infections and Male Reproductive Health: An Evidence-Based Study.

Viruses, being intracellular obligate parasites, can cause several congenital and sexually transmitted diseases. Depending on the site of infection, viruses can adopt various pathogenic mechanisms for their survival and to escape the host immune response. The male reproductive system is one of the attainable targets of many viruses including immunodeficiency virus (HIV), Zika virus (ZIKV), adenovirus, cytomegalovirus (CMV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and infection with such viruses may cause serious health issues.

Cationic-palladium catalyzed regio- and stereoselective syn-1,2-dicarbofunctionalization of unsymmetrical internal alkynes.

π-Extended tetrasubstituted olefins are widely found motifs in natural products, leading drugs, and agrochemicals. Thus, development of modular strategies for the synthesis of complex all-carbon-substituted olefins always draws attention. The difunctionalization of unsymmetrical alkynes is an attractive approach but it has remained faced with regioselectivity issues.

Palladium-Catalyzed Regioselective Arylalkenylation of Ynamides.

A cationic palladium-catalyzed arylalkenylation of ynamides is presented. The putative keteniminium arylpalladium intermediate likely dictates the regioselective carbopalladation of the ynamide to form a vinylpalladium species. The capture of this complex by the olefin yields linear conjugated β-alkenyl aminodienes (especially with selectivity).

Gold-Catalyzed Transformation of Ynamides.

Ynamide, a unique species with inherited polarization of nitrogen lone pair electron to triple bond, has been largely used for the developement of novel synthetic methods and the construction of unusual N-bearing heterocycles. The reaction versatility of ynamide on umpolung reactivity, radical reactions and asymmetric synthesis have been recently reviewed. This review provides an overall scenic view into the gold catalyzed transformation of ynamides.

Yb(iii)-catalysed syn-thioallylation of ynamides.

Reported herein is a syn-thioallylation of ynamides incorporating a sulfide moiety at the α-position and an allyl group at the β-position of the ynamide. The transformation is successful under ytterbium(iii)-catalysis, providing access to highly substituted thioamino-skipped-dienes with broad substrate scope. Thus, tetrasubstituted olefins (with four different functional groups: amide, phenyl, thioaryl/alkyl, and allyl on the carbon centers) are made in a single step from readily accessible ynamides, preserving complete atom economy.

Keteniminium-Driven Umpolung Difunctionalization of Ynamides.

A three-component Pd-catalyzed coupling of ynamides, aryl diazonium salts, and aryl boronic acids for the synthesis of novel triaryl-substituted enamides is described. This transformation represents the first example of an umpolung regioselective unsymmetrical syn-1,2-diarylation/aryl-olefination of ynamides. The aryl moieties of the diazonium salt (electrophile) and boronic acid (nucleophile) are explicitly incorporated in the electrophilic α- and nucleophilic β-position, respectively, of the ynamide, resulting in a single isomer of the N-bearing tetrasubstituted olefin.

Ring Expansion and 1,2-Migration Cascade of Benzisoxazoles with Ynamides: Experimental and Theoretical Studies.

Demonstrated herein is an Au -catalyzed annulation of sulfonyl-protected ynamides with substituted 1,2-benzisoxazoles for the synthesis of E-benzo[e][1,3]oxazine derivatives. The transformation involves the addition of benzisoxazole to the gold-activated ynamide, ring expansion of the benzisoxazole fragment to provide an α-imino vinylic gold intermediate, and 1,2-migration of the sulfonamide motif to the masked carbene center to deliver the respective ring-expanded benzo[e][1,3]oxazine of predominant E configuration. A trapping experiment justifies the participation of the α-imino masked gold carbene.

Thioarylative Radical Cyclization of Yne-Dienone.

We herein demonstrated a -hydroxyphthalimide (NHPI)-mediated chemo- and regioselective radical cyclization of yne-dienone with thiols to construct 3-thioaryl bearing [6,6]-fused dihydrochromenone derivatives. This transformation tolerates common functional groups and has broad scope. The reaction proceeds via the attack of a thioaryl radical to alkyne over the activated Michael acceptor.

Alkyne Versus Ynamide Reactivity: Regioselective Radical Cyclization of Yne-Ynamides.

Ynamides are typically more reactive than simple alkynes and olefins. However, a serendipitous observation revealed a rare case where the reactivity of simple alkynes exceeds that of ynamides. This led to the development of a unique sulfur-radical-triggered cyclization of yne-tethered ynamides, which involves attack of the alkyne by a thiyl radical followed by cyclization with the ynamide.

Gold-Catalyzed syn-1,2-Difunctionalization of Ynamides via Nitrile Activation.

Developed is an unprecedented Au(I)-catalyzed syn-1,2-difunctionalization of ynamides with 2-aminobenzonitriles via nitrile activation. The coupling between ynamides and 2-aminobenzonitriles is explicitly regioselective, providing a straightforward access to 2,4-diamino-substituted quinolines. Density functional theory (DFT) study provides insightful information and rationalizes the reaction pathway.

TRIP6 inhibits Hippo signaling in response to tension at adherens junctions.

The transcriptional co-activator YAP controls cell proliferation, survival, and tissue regeneration in response to changes in the mechanical environment. It is not known how mechanical stimuli such as tension are sensed and how the signal is transduced to control YAP activity. Here, we show that the LIM domain protein TRIP6 acts as part of a mechanotransduction pathway at adherens junctions to promote YAP activity by inhibiting the LATS1/2 kinases.