Synthesis of γ-Carbolines through Annulative Cyclization between Indolyl Azines and Alkynes under Rhodium Catalysis.

Functionalized carbolines play a crucial role in the discovery of bioactive compounds and functional materials. In this study, we report a Rh(III)-catalyzed annulative synthesis of γ-carbolines from indolyl azines and internal alkynes. Remarkably, indolyl azines can undergo N-N bond cleavage under the influence of a Rh(III) catalyst, yielding 2-fold ketimines, which demonstrates the atom economy of indolyl azines in catalytic C-H functionalizations.

Synthesis of 2-Hydroxycarbazoles via Rh(III)-Catalyzed Cascade Cyclization of Indolyl Nitrones with Alkylidenecyclopropanes.

The synthesis of functionalized carbazoles is an important tool in the discovery of bioactive molecules. Herein, we present a method for synthesizing 2-hydroxycarbazoles from indolyl nitrones and alkylidenecyclopropanes under Rh(III) catalysis. A notable reaction pathway involves [3 + 2] cycloaddition between indolyl nitrones and diene intermediates, followed by aromatization and reductive N-O bond cleavage in a cascade manner.

Distinct Selectivity of 2-Aryl Thioquinazolinones in the Sulfur Directing Rh(III)-Catalyzed Amidation Reaction.

Sulfur-directed C-H functionalization of N-heterocycles has emerged as an alternative solution to weakly coordinating carbonyl directing groups. In this study, we describe a sulfur-promoted Rh(III)-catalyzed C5 amidation of 4-thioquinazolinones using dioxazolones, yielding 5-amido-4-thioquinazolinones. The synthetic utility was demonstrated through a gram-scale experiment and synthetic modifications of the title compounds.

Awareness, attitudes and cost among patients for dental implants in teeth replacement.

Dental implants are increasingly viewed as a preferred treatment option for tooth replacement, yet gaps remain in patient knowledge, attitudes, and cost perceptions. This cross-sectional, study surveyed 150 adults aged 20-60 to assess their awareness, attitudes, and perceived costs of dental implants. Results show that while 70% of patients are aware of implants, only 30% understand the procedure.

C3-Heteroarylation of Indoles via Cu(II)-Catalyzed Aminocupration and Subsequent Nucleophilic Addition of -Alkynylanilines.

Transition-metal-catalyzed aminometalation of -alkynylanilines is a promising pathway for the synthesis of C3-functionalized indoles. Herein, we describe the Cu(II)-catalyzed site-selective C3-heteroarylation of indoles from -alkynylanilines and quinoline -oxides. A plausible reaction mechanism involving the aminocupration of -alkynylanilines followed by the nucleophilic addition of Cu(II)-indolyl complexes to quinoline -oxides was proposed.

Discovery of 1,4-Disubstituted Cyclohexene Analogues as Selective GPR119 Agonists for the Treatment of Type 2 Diabetes.

GPR119 has emerged as a promising target for treating type 2 diabetes and associated obesity, as its stimulation induces the secretion of glucagon-like peptide-1 and glucose-dependent insulinotropic peptide in the intestinal tract as well as the glucose-dependent release of insulin in pancreatic β-cells. We describe the design and synthesis of novel GPR119 agonists containing a 1,4-disubstituted cyclohexene scaffold. Compound displayed nanomolar potency (EC = 3.

Diastereoselective Synthesis of Cyclobutanes via Rh-Catalyzed Unprecedented C-C Bond Cleavage of Alkylidenecyclopropanes.

The stereoselective synthesis of highly substituted cyclobutanes is essential for the development of lead candidates in drug discovery. Herein, we present a novel Rh(III)-catalyzed reaction pathway for synthesizing substituted cyclobutanes, which involves a concerted N-C bond formation and C-C bond cleavage between 2-aryl quinazolinones and alkylidenecyclopropanes. Notably, the combination of Rh(III) catalyst and HFIP solvent plays a critical role in facilitating the formation of cyclobutane rings.

Dietary and Nutritional Aspects of Metabolic Syndrome Management: An Overview.

Sedentary lifestyles and prolonged physical inactivity are often linked to poor mental and physical health as well as an increased risk of a number of chronic illnesses, including cancer, obesity, type 2 diabetes, and cardiovascular problems. Metabolic Syndrome (MetS), as the new disease, has emerged as the world's leading cause of illness. Despite having its roots in the West, this issue has now completely globalized due to the development of the Western way of life throughout the world.

Synthesis of Quinoline-Indole Hybrids through Cu(II)-Catalyzed Amination and Annulation between -Oxides and -Alkynylanilines.

The synthesis of (iso)quinoline-indole hybrids by reacting (iso)quinoline -oxides with -alkynylanilines in the presence of a combination of copper(II) catalyst and a bidentate 2,2'-bipyridine ligand is described. The utility of this method was demonstrated through site-selective functionalization of the synthesized products. A plausible reaction pathway for site-selective amination followed by annulative indole formation was elucidated by a series of mechanistic investigations.

Urazoles as Heterocyclic Directing Groups in Ru(II)-Catalyzed Annulation of N-H/C-H Bonds with Vinylene Carbonate.

The development of novel directing groups is a valuable strategy to secure the advancement of catalytic C-H functionalization. To illustrate the feasibility of urazoles as heterocyclic directing groups, we herein present the ruthenium(II)-catalyzed annulation of N-H/C-H bonds on -aryl urazoles with vinylene carbonate. This transformation provides the rapid construction of triazolocinnoline derivatives as hemiaminal and dehydrated forms.

Applications of Clauson-Kaas Reaction in Organic Synthesis.

Pyrrole-embedded organic molecules received a considerable importance due to their numerous biological and material applications. Hence, several synthetic strategies have been devised for the construction of diverse pyrrole analogues over the years. Among these, the Clauson-Kaas reaction is one of the most widely used protocols for the synthesis of various N-substituted pyrroles.

Thione-Directed C-H Amidation of Chromone Analogues with Dioxazolones under Rh(III) Catalysis.

Sulfur-containing organic molecules are recognized as promising candidates for catalytic C-H functionalization and medicinal chemistry owing to the exceptional ability of the sulfur atom to bind to transition metals and target enzymes. In this study, we report the Rh(III)-catalyzed thione-directed C-H amidation of various thiochromone analogues derived from flavones, isoflavones, and xanthones. Post-transformations of C5-amidated thiochromone products were investigated, and a series of mechanistic studies were performed.

Discovery of 2,6-Naphthyridine Analogues as Selective FGFR4 Inhibitors for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and is responsible for 90% of cases. Approximately 30% of patients diagnosed with HCC are identified as displaying an aberrant expression of fibroblast growth factor 19 (FGF19)-fibroblast growth factor receptor 4 (FGFR4) as an oncogenic-driver pathway. Therefore, the control of the FGF19-FGFR4 signaling pathway with selective FGFR4 inhibitors can be a promising therapy for the treatment of HCC.

Sulfur-Directed α-C(sp)-H Amidation of Pyrrolidines with Dioxazolones under Rhodium Catalysis.

Site-selective functionalization of saturated N-heterocycles such as pyrrolidines is a central topic in organic synthesis and drug discovery. We herein report the sulfur-assisted rhodium(III)-catalyzed sp C-H amidation of pyrrolidines with dioxazolones as amidating agents. The amenability of the thioamide directing group is elucidated by a series of control experiments.

Design and synthesis of 4th generation EGFR inhibitors against human triple (Del19/T790M/C797S) mutation.

Epidermal growth factor receptor (EGFR)-targeted therapy is used to treat EGFR mutation-induced non-small cell lung cancer (NSCLC). However, its efficacy does not last beyond a certain period due to the development of primary and secondary resistance. First and second-generation inhibitors (e.

Target protein degradation by protacs: A budding cancer treatment strategy.

Cancer is one of the most common causes of death. So, its lethal effect increases with time. Near about hundreds of cancers are known in humans.

Catalyst-Controlled C-H Allylation and Annulation of 2-Aryl Quinazolinones with 2-Methylidene Cyclic Carbonate.

The site-selective modification of quinazolinone as a privileged bicyclic N-heterocycle is an attractive topic in medicinal chemistry and material science. We herein report the ruthenium(II)-catalyzed C-H allylation of 2-aryl quinazolinones with 2-methylidene cyclic carbonate. In addition, tandem C-H allylation and annulation are achieved under rhodium(III) catalysis, resulting in the formation of tetracyclic quinazolinones including a tertiary carbon center.

Unravelling a trichloroacetic acid-catalyzed cascade access to benzo[]chromeno[2,3-]quinoxalinoporphyrins.

A facile one-pot four-component synthetic methodology is evolved to construct novel copper(II) benzo[]chromeno[2,3-]quinoxalinoporphyrins in good yields via a sequential reaction of copper(II) 2,3-diamino-5,10,15,20-tetraarylporphyrins, 2-hydroxynaphthalene-1,4-dione, aromatic aldehydes, and dimedone in the presence of a catalytic amount of trichloroacetic acid in chloroform at 65 °C. Further, the newly prepared copper(II) porphyrins were transformed to the corresponding free base and zinc(II) benzo[]chromeno[2,3-]quinoxalinoporphyrins under standard demetallation and zinc insertion conditions. The absorption and emission properties of the obtained porphyrins were investigated by using UV-visible and fluorescence spectroscopy.

Rh(III)-Catalyzed C8-Spiroannulation of 1-Aminonaphthalenes with Maleimides.

The rhodium(III)-catalyzed C8-spiroannulation of 1-aminonaphthalenes with maleimides is described herein. Initially formed C8-alkenylated 1-aminonaphthalenes can intercept nucleophilic 1-amino groups through the intramolecular aza-Michael reaction, resulting in the formation of spirofused tetracyclic frameworks. This protocol displayed a wide substrate scope and a broad functional group compatibility.

Cascade Amination and Aza-6π-Annulation-Aromatization Strategy for the Synthesis of β-Pyrimidine-Fused Porphyrins.

Novel nickel(II) and copper(II) complexes of 2-(,-dimethylformamidine)-3-formyl-5,10,15,20-tetraarylporphyrins have been synthesized for the first time from 2-aminoporphyrins under Vilsmeier-Haack conditions. These porphyrins are utilized as new building blocks to construct diverse β-pyrimidine-fused 5,10,15,20-tetraarylporphyrins in good yields a cascade ammonia-mediated condensation and intramolecular aza-6π-annulation/aromatization in 1,2-dichloroethane at 80 °C. Furthermore, copper(II) β-pyrimidine-fused porphyrins underwent demetallation in the presence of conc.

Bifunctionalized nanobioprobe based rapid color-shift assay for typhoid targeting Vi capsular polysaccharide.

Typhoid fever is an acute illness caused by Salmonella Typhi and the current diagnostic gap leads to inaccurate, over-diagnosis of typhoid leading to excessive use of antibiotics. Herein, to address the challenges we describe a new rapid color-shift assay based on a novel bifunctional nanobioprobe (Vi-AgNP probe) that is functionalized with specific biomarker Vi polysaccharide and also has the co-presence of Ag as urease inhibitor. The immunoreactions between the Vi with specific antibodies (Abs) present in typhoid patient sample forms a shielding barrier over Vi-AgNP probe rendering the urease to be active, generating colored output.

Rhodium(III)-Catalyzed Conjugate Addition of β-CF-Enones with Quinoline -Oxides.

The site-selective incorporation of a trifluoromethyl group into biologically active molecules and pharmaceuticals has emerged as a central topic in medicinal chemistry and drug discovery. Herein, we demonstrate the rhodium(III)-catalyzed conjugate addition of β-trifluoromethylated enones with quinoline -oxides, which result in the generation of β-trifluoromethyl-β'-quinolinated ketones. The reaction proceeds under mild conditions with complete functional group tolerance.

Tandem C-S Coupling and Debrominative Cyclization Enables an Easy Access to β-Thiazole-Fused Porphyrins.

A catalyst-free synthetic approach to β-thiazole-fused 5,10,15,20-tetraarylporphyrins via a cascade reaction of nickel(II) or copper(II) 2-amido-3-bromo-5,10,15,20-tetraarylporphyrins and Lawesson's reagent is described. During the course of the reaction, 3-bromo-2-thioamido-5,10,15,20-tetraarylporphyrins formed undergo debrominative cyclization in refluxing toluene to provide novel β-thiazole-fused porphyrin macrocycles in good yields. Furthermore, free-base and zinc(II) β-thiazole-fused porphyrins have also been constructed in excellent yields by using standard demetalation and zinc metal insertion procedures.

Targeting dendritic cells with TLR-2 ligand-coated nanoparticles loaded with Mycobacterium tuberculosis epitope induce antituberculosis immunity.

Novel vaccination strategies are crucial to efficiently control tuberculosis, as proposed by the World Health Organization under its flagship program "End TB Strategy." However, the emergence of drug-resistant strains of Mycobacterium tuberculosis (Mtb), particularly in those coinfected with HIV-AIDS, constitutes a major impediment to achieving this goal. We report here a novel vaccination strategy that involves synthesizing a formulation of an immunodominant peptide derived from the Acr1 protein of Mtb.

Gene Expression and Proteomics Studies Suggest an Involvement of Multiple Pathways Under Day and Day-Night Combined Heat Stresses During Grain Filling in Wheat.

Recent weather fluctuations imposing heat stress at the time of wheat grain filling cause frequent losses in grain yield and quality. Field-based studies for understanding the effect of terminal heat stress on wheat are complicated by the effect of multiple confounding variables. In the present study, the effect of day and day-night combined heat stresses during the grain-filling stage was studied using gene expression and proteomics approaches.