Microwave-Assisted Palladium-Catalyzed Crossover-Annulation: Access to Fused Polycyclic Benzofuran Scaffolds.

This study demonstrates quick access to heteroatom-embodied complex fused polycyclic frameworks through a palladium-catalyzed domino process facilitated by microwave-assisted crossover annulation of -alkynylarylhalides and dihydrobenzofurans derivatives. The overall success of this process lies in the careful design of dihydrobenzofuran precursors that direct the initial palladium-mediated annulation step to proceed in a highly regioselective manner to furnish a single regioisomeric product. Notably, this one-pot method has witnessed good substrate scope and has furnished products with excellent yields.

A rapid pathway to molecular complexity: a palladium-catalyzed six-fold domino process to access polycyclic frameworks.

Herein, we present a hitherto unexplored efficient strategy for rapidly constructing structurally constrained and intriguing polycyclic frameworks with two adjacent quaternary centers. Remarkably, this becomes possible through palladium-catalyzed six-fold domino crossover annulations of simple 1,2-bis(2-bromoaryl)ethynes and 1,2-diarylethynes. Notably, this approach demonstrates the synthesis of both C-symmetric and unsymmetric polycyclic products.

Computational and binding studies of the redesigned pentoxifylline analogue against phosphodiesterases function in sperm.

Pentoxifylline (PTX) is a widely used pharmacological agent for the selection of motile sperm in both normozoospermic and asthenozoospermic ejaculates prior to their use in assisted reproductive technologies (ARTs), e.g. intracytoplasmic sperm injection (ICSI).

Aliphatic Nitrile Template Enabled -C-H Olefination of Indene Enoate Esters under Microwave Accelerating Conditions.

Site-selective activation of a particular remote C-H bond in molecules with multiple C-H bonds remains challenging in organic synthesis. In addition, evolving such transformations via the utilization of unconventional techniques is highly desirable. We demonstrated hitherto unexplored double bond geometry-guided and end-on nitrile-template-assisted -C-H functionalization of indene enoate esters under microwave-accelerated conditions.

Allergic potential & molecular mechanism of skin sensitization of cinnamaldehyde under environmental UVB exposure.

Fragrance, a key ingredient in cosmetics, often triggers skin allergy causes rashes, itching, dryness, and cracked or scaly skin. Cinnamaldehyde (CA), derived from the bark of the cinnamon tree, used as a fragrance and is a moderate skin sensitizer. CA exhibits strong UVB absorption, its allergic potential and the molecular mechanisms underlying skin sensitization under UVB exposure remain largely unexplored.

Electrochemical stereoselective borylation of Morita-Baylis-Hillman adducts to functionalized allylic boronates.

Herein, we disclose a highly efficient and facile electrochemical borylation of Morita-Baylis-Hillman adducts without using any metal catalyst. This methodology demonstrates excellent regio- and stereo-selectivity, leading to a wide range of functionalized -allylic boronates, including derivatives of ibuprofen and menthol. Under mild and straightforward conditions, this redox-neutral reaction, combined with the scalability and synthetic applications of the allylic boronate esters, underscores its potential for a wide range of applications in organic synthesis.

Electrochemically driven regioselective construction of 4-sulfenyl-isochromenones from -alkynylbenzoates and diaryl disulfides.

Herein, we report a convenient and environmentally friendly electrochemical technique that enables the regioselective construction of 4-sulfenyl-1-isochromen-1-ones using readily available precursors such as -alkynyl benzoates and diaryl disulfides. This electrochemical process has been accomplished through constant current electrolysis in an undivided cell under external acid, catalyst, oxidant, or metal-free conditions. Owing to this protocol's mild reaction conditions, the products are obtained in good to very good yields, demonstrating a broad substrate scope and functional group tolerance.

Acid-Mediated Domino Cyclization of -Formyl Cinnamate Esters: Synthesis of Substituted Indene/Indane Esters and Indeno[]indenones.

A Bro̷nsted acid-driven protocol to access substituted monoarylindene esters, biarylindane esters, and indeno[]indenones from simple -formylcinnamate esters and external arenes has been revealed. Remarkably, this single-pot process enabled the construction of two, three, and four new C-C bonds in building monoarylindene esters, biarylindane esters, and indeno[]indenones, respectively, under metal-free and mild reaction parameters triggering the inactive cinnamate ester moiety. In addition, the present strategy is investigated with widespread substrate scope.

Acid-Promoted Domino Access to Substituted Benzo[]carbazoles.

Herein, a straightforward Bro̷nsted acids-promoted domino pathway to build substituted benzo[]carbazoles has been described from easily accessible -formyl (or -acyl) cinnamate esters and indoles. Noticeably, the protocol was amenable to protecting group-free indoles. Notably, this methodology is based on a single-pot regioselective construction of two new C-C bonds and aromatization sequences under mild and metal-free reaction conditions.

Electrochemical selenofunctionalization of unactivated alkenes: access to β-hydroxy-selenides.

This work demonstrates the electrochemical construction of 2-methyl-1-aryloxy-3-(arylselanyl)propan-2-ol/2-hydroxy-2-methyl-3-(arylselanyl)propyl 2-(2-hydroxy-2-methyl-3-(arylselanyl)propoxy)benzoate starting from aryl allyl ethers/allyl benzoates and diaryl diselenides under additive-free electrochemical conditions. This environmentally friendly method was achieved through constant current electrolysis in an undivided cell setup under acid, oxidant, or catalyst-free conditions. Additionally, this technique enabled the synthesis of a variety of β-hydroxy selenides including late-stage functionalization of drug derivatives in good to exceptional yields across various substrates under mild reaction conditions.

Distal-C-H Functionalization of Biphenyl Scaffolds Assisted by Easily Removable/Recyclable Aliphatic Nitrile Templates.

We present here the distal-C-H activation/functionalization of biphenyl scaffolds using aliphatic nitrile templates. The approach has demonstrated good to exclusive selectivities over a wide range of olefination and acetoxylation substrates. In addition, bis-olefination has been accomplished in a one-pot, sequential manner.

Palladium-Catalyzed [3 + 2] Annulation of Substituted Iodoarenes with Maleimides via a Consecutive Double Heck-type Strategy.

Herein, we report an efficient [3 + 2] annulation of -substituted iodoarenes with maleimides a palladium-catalyzed consecutive double Heck-type strategy, leading to fused tricyclic frameworks of pharmaceutical relevance. The protocol ensued through consecutive inter- and intramolecular Heck couplings effectively. This approach was compatible with a large variety of substrates and functional groups, and it was remarkably tolerated with unprotected maleimide.

Transition metal-free and temperature dependent one-pot access to phenanthrene-fused heterocycles a 1,3-dipolar cycloaddition pathway.

A versatile, operationally simple, temperature-dependent, and transition metal-free one-pot protocol has been devised for the preparation of novel phenanthrene-fused pyrazoles. Notably, the overall process involved an intermolecular condensation, an intramolecular 1,3-dipolar cycloaddition, and an aromatization sequence starting from biaryl-2,2'-aldehydes bearing enoate esters with various hydrazine hydrochlorides. Notably, the sequential one-pot three-component operation has also been achieved.

Acid-Mediated Cascade Cyclization Pathway to Indeno[2,1-]chromen-6(7)-ones.

Developing mild and effective synthetic strategies for producing significant molecules starting from readily available starting materials is indispensable in organic synthesis. Herein, we present a triflic acid-driven dual cyclization pathway to produce functionalized indeno[2,1-]chromen-6(7)-ones from simple 2-formyl (or 2-acyl) cinnamate esters and phenols. Notably, this protocol enabled the construction of two C-C bonds and one C-O bond under metal-free reaction conditions the activation of the unreactive ester moiety in a single pot.

A two-step access to fused-/spiro-polycyclic frameworks double Heck cascade and acid-driven processes.

This report illustrates the rapid construction of two divergent classes of polycyclic frameworks, benzo[]fluorenones and spiro-chromenone indenes, a double Heck cascade and an acid-driven cyclization from easily accessible precursors, alkyl 2-bromocinnamate esters and diphenylacetylenes. The present strategy has surveyed a broad substrate scope and delivered an array of products with interesting structural features. Besides, fluorescence studies were performed for the synthesized benzo[]fluorenones.

Access to distal -C-H functionalization of arylmethanesulfonic acid derivatives.

Herein, we report the -C-H olefination of arylmethanesulfonates aided by a potentially versatile aliphatic nitrile-directing group under microwave irradiation conditions with fair to very good yields and good to outstanding regioselectivities. Significantly, the protocol showed broad substrate scope including olefin-derived drugs and cyclic olefins. Remarkably, a dual -C-H bond was amenable to generating the bis-olefination products.

A TBADT photocatalyst-enabled radical-induced cyclization pathway to access functionalized dihydrobenzofurans.

Herein, this work describes a photoinduced visible light-mediated radical cyclization for constructing dihydrobenzofuran (DHB) scaffolds. Notably, this cascade photochemical process is tolerable with various aromatic aldehydes and diverse alkynyl aryl ethers and proceeds an intramolecular 1,5-hydrogen atom transfer (HAT) pathway. Significantly, acyl C-H activation under mild conditions has been achieved without the use of additives or reagents.

Early Detection and Staging of Lung Fibrosis Enabled by Collagen-Targeted MRI Protein Contrast Agent.

Chronic lung diseases, such as idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD), are major leading causes of death worldwide and are generally associated with poor prognoses. The heterogeneous distribution of collagen, mainly type I collagen associated with excessive collagen deposition, plays a pivotal role in the progressive remodeling of the lung parenchyma to chronic exertional dyspnea for both IPF and COPD. To address the pressing need for noninvasive early diagnosis and drug treatment monitoring of pulmonary fibrosis, we report the development of human collagen-targeted protein MRI contrast agent (hProCA32.

An electrochemical cascade process: synthesis of 3-selenylindoles from 2-alkynylanilines with diselenides.

Substituted organoselenium compounds are crucial structural motifs in pharmaceutical molecules. Herein, we report a metal, oxidant, and base-free electrochemical approach to access 3-selenylindoles through an oxidative cyclization of 2-alkynylanilines with diselenides. This environmentally friendly approach demonstrates a wide range of substrate scope under mild reaction conditions in an electrochemical undivided cell setup.

Functionalization of arylacetic acids directing-group-assisted remote -C-H activation.

Herein, we report the first microwave-assisted remote-C-H functionalization aided by a simple nitrile directing template. Notably, the present protocol showed a broad substrate scope enabling -C-H arylation, acetoxylation, and cyanation. Significantly, the microwave-accelerated -C-H functionalization was effective with short reaction times without compromising yields and site selectivity.

IKKβ Inhibition Attenuates Epithelial Mesenchymal Transition of Human Stem Cell-Derived Retinal Pigment Epithelium.

Epithelial-mesenchymal transition (EMT), which is well known for its role in embryonic development, malignant transformation, and tumor progression, has also been implicated in a variety of retinal diseases, including proliferative vitreoretinopathy (PVR), age-related macular degeneration (AMD), and diabetic retinopathy. EMT of the retinal pigment epithelium (RPE), although important in the pathogenesis of these retinal conditions, is not well understood at the molecular level. We and others have shown that a variety of molecules, including the co-treatment of human stem cell-derived RPE monolayer cultures with transforming growth factor beta (TGF-β) and the inflammatory cytokine tumor necrosis factor alpha (TNF-α), can induce RPE-EMT; however, small molecule inhibitors of RPE-EMT have been less well studied.

Development and implementation of "handshake rounds": An antibiotic stewardship intervention for hospitalized adult patients with hematologic malignancies.

Objective: To design and implement "handshake rounds" as an antibiotic stewardship intervention to reduce inpatient intravenous (IV) antibiotic use in patients with hematologic malignancies.

Design: Quasi-experimental analysis of antibiotic use (AU) and secondary outcomes before and and after handshake rounds were implemented.

Setting: Quaternary-care, academic medical center.

Electrochemical Oxidative Annulation of Inactivated Alkynes for the Synthesis of Sulfonated 2-Chromene Derivatives.

A unique, facile, and straightforward electrochemical oxidative annulation of inactivated propargyl aryl ethers with sulfonyl hydrazides leading to 3-sulfonated 2-chromenes has been achieved. Significantly, this protocol involves a green approach that works under mild reaction conditions using a constant current in an undivided cell and is devoid of oxidants and catalysts. Notably, the process exhibited a broad scope and functional group tolerance to deliver 2-chromenes and would represent an alternative and sustainable strategy versus conventional chromene synthesis.

Electrochemical synthesis of 2-alkyl-4-phenylalkan-2-ols cathodic reductive coupling of alkynes with unactivated aliphatic ketones.

Herein, we present an efficient electrochemical method for synthesizing 2-alkyl-4-phenylalkan-2-ols through an electrochemically driven cathodic reductive coupling of the terminal and internal acetylenes with unactivated aliphatic ketones under mild conditions. The process proceeds through a ketyl radical, which then activates the aryl acetylene and causes complete reduction of the triple bond of the acetylene moiety. This strategy is environmentally benign and exhibits a broad substrate scope with ubiquitously available starting materials.