Organocatalytic Enantioselective Michael-Type Friedel-Crafts (Hetero)arylations of Aurone-Derived Azadienes with Indolizines.

Herein, we describe an enantioselective 1,4-addition of benzofuran-derived azadienes with indolizines under the catalysis of chiral phosphoric acid, which afforded new enantioenriched triarylmethane products in generally good yields (up to 90%) with high enantioselectivities (up to 98% ee). This method enabled the precise synthesis of enantioenriched triarylmethane products, which are notable for their intricate structures and the presence of two (hetero)aryls.

Enantioselective Synthesis of α-Aryl-α-fluoroketones by CPA-Catalyzed Desymmetrization of 1,3-Indanediones.

Herein, we report the use of electrophilic fluorine-containing building blocks─α-fluoro-α-aryl-1,3-indanediones─as substrates for investigating asymmetric catalytic desymmetrization via imine condensation reactions. This method exhibits remarkable compatibility with a broad range of substrates, thereby providing various enantiopure α-aryl-α-fluoro carbonyl compounds with high enantioselectivities and yields. Density functional theory (DFT) calculations indicate that F-H interactions between the F atom of the α-fluoro-α-aryl-1,3-indanediones and the NH group of 5-aminopyrazole, as well as π-π stacking interactions between the two coupling partners, likely play crucial roles in controlling the enantioselectivity of this transformation.

Organocatalytic Regio- and Enantioselective C1-Alkylation of Indolizines with δ-Aryl-δ-cyano-disubstituted -Quinone Methides.

Nitriles bearing all-carbon quaternary stereocenters are frequently observed in a wide range of biologically active molecules. Herein, we present asymmetric regio- and enantioselective C1-alkylation of indolizines with δ-aryl-δ-cyano-disubstituted -quinones enabled by the CPA catalyst system, leading to construction of all-carbon quaternary centers bearing CN groups. The approach efficiently afforded various chiral cyano-substituted triarylmethanes bearing all-carbon quaternary centers in up to 85% yield and 96% ee.

Enantioselective Construction of -Difluorinated Tetrahydroindolo[2,1-]quinazolines via CPA-Catalyzed Asymmetric [4 + 2]-Annulation.

Indoloquinazolinones are widely acknowledged as essential scaffolds for the development of diverse biologically active compounds, pharmaceutical agents, and natural products. Given the critical role of fluorine atoms in enhancing the properties of pharmaceuticals and agrochemicals, fluorinated indoloquinazolinones exhibit substantial promise in drug discovery and development. Herein, we developed the CPA-catalyzed asymmetric enantioselective [4 + 2]-annulation reactions between 2-aminophenyl enones and 3,3-difluoro-2-aryl-3-indoles.

Enantioselective Synthesis of Chiral 2,2-Difluoro-spiroindanone-dihydroquinazolinones by CPA-Catalyzed Cyclization Reactions.

The synthesis of chiral -difluorinated spiro-heterocyclic compounds continues to be a significant challenge in organic chemistry due to their widespread applications across various fields. Therefore, efficient asymmetric approaches for the synthesis of -difluorinated spiroindanone-dihydroquinazolinones are particularly valuable, especially in the industrial manufacturing of chiral fluorinated drugs. Herein, we developed the CPA-catalyzed asymmetric enantioselective cyclization reactions of -difluoroalkyl 1,3-indandiones with anthranilamides to achieve various chiral 2,2-difluoro-spiroindanone-dihydroquinazolinones in good to high yields with excellent enantioselectivities.

A Multicomponent [2+2+1] Cascade Cyclization to Synthesize Thiazol-2(3)-one.

A multicomponent [2+2+1] tandem cyclization of alkynones with amines and water using potassium thiocyanate as electrolyte and raw material to access thiazol-2(3)-ones has been developed. This transformation proceeded smoothly via electrocatalytic oxidative C-H bond thiolation, and nucleophilic cascade cyclization to build the (C-S/C-N) bonds to construct the C-O bond. The reaction avoided using transition metal catalysts or oxidation reagents, making it more sustainable and renewable.

Copper and electrocatalytic synergy for the construction of fused quinazolinones with 2-aminobenzaldehydes and cyclic amines.

A new copper and electrocatalytic synergy strategy for efficiently constructing fused quinazolinones has been developed. In the presence of cupric acetate and oxygen, aryl ketones and 1,2,3,4-tetrahydroisoquinoline can smoothly participate in this transformation, thus providing a variety of substituted quinazolones in an undivided cell. The reaction shows good functional group tolerance and provides universal quinazolinones at a good yield under mild conditions.

Asymmetric Synthesis of Axially Chiral N, N-1,2-Pentatomic Heterobiaryl Diamines by an Organocatalytic Arylation Reaction.

The utilization of axially chiral biaryl diamines has been widely acknowledged as highly advantageous structures for the advancement of chiral catalysts and ligands. This highlights their extensive range of applications in asymmetric catalysis and synthesis. Herein, we devised a direct arylation reactions of 5-aminopyrazoles with azonaphthalenes, utilizing chiral phosphoric acid as the catalyst.

Electrochemical Dimerization of -Aminophenols and Hydrogen Borrowing-like Cascade to Synthesize N-Monoalkylated Aminophenoxazinones via Paired Electrolysis.

A novel electrocatalytic dimerization of -aminphenols and a hydrogen borrowing-like cascade for synthesizing N-monoalkylated aminophenoxazinones have been developed. This electrocatalytic reaction uses a constant current mode in an undivided cell and is free of metal catalysis, open to the air, and eco-friendly. In particular, this protocol exhibits a wide substrate range and provides versatile N-monoalkylated aminophenoxazinones in medium to good yields.

Tetramerization of PKM2 Alleviates Traumatic Brain Injury by Ameliorating Mitochondrial Damage in Microglia.

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Microglial activation and neuroinflammation are key cellular events that determine the outcome of TBI, especially neuronal and cognitive function. Studies have suggested that the metabolic characteristics of microglia dictate their inflammatory response.

Semaphorin 7A impairs barrier function in cultured human corneal epithelial cells in a manner dependent on nuclear factor-kappa B.

Aim: To evaluate the role of semaphorin 7A (Sema7A) and its associated regulatory mechanisms in modulating the barrier function of cultured human corneal epithelial cells (HCEs).

Methods: Barrier models of HCEs were treated with recombinant human Sema7A at concentrations of 0, 125, 250, or 500 ng/mL for 24, 48, or 72h . Transepithelial electrical resistance (TEER) as well as Dextran-fluorescein isothiocyanate (FITC) permeability assays were conducted to assess barrier function.

Electrochemical-induced solvent-tuned selective C(sp)-H bond activation towards the synthesis of C3-functionalized chromone derivatives.

An unprecedented solvent-tuned electrochemical method for selective C(sp)-H bond activation towards the synthesis of C3 functionalized chromone derivatives has been developed. This electrosynthesis protocol provides an efficient and green way to access various C3-functionalized chromones by avoiding traditionally employed transition metals and high temperatures. The swappable chemoselectivity was controlled mainly by altering the solvent and the current.

B(CF)/CPA-Catalyzed Aza-Diels-Alder Reaction of 3,3-Difluoro-2-Aryl-3H-indoles and Unactivated Dienes.

Here we report B(CF)CPA-catalyzed enantioselective aza-Diels-Alder reaction of 3,3-difluoro-2-Aryl-3H-indoles with unactivated dienes to access chiral 10,10-difluoro-tetrahydropyrido[1,2-a]indoles. This protocol allows the formation of pyrazole-based C2-quaternary indolin-3-ones with high enantioselectivities and regioselectivities. Moreover, gram-scale synthesis of the 10,10-difluoro-tetrahydropyrido[1,2-a]indole skeleton was successfully achieved without any reduction in both yield and enantioselectivity.

Electrochemical multicomponent [2+2+1] cascade cyclization of enaminones and primary amines towards the synthesis of 4-acylimidazoles.

An electrochemical multicomponent [2+2+1] cascade cyclization of enaminones and primary amines towards the synthesis of 4-acylimidazoles has been developed. In an undivided cell, enaminones and primary amines can smoothly participate in this reaction to provide a series of 1,2-disubstituted 4-acylimidazoles at room temperature. The reaction avoids the use of both transition-metal catalysts and oxidation reagents, which makes it more sustainable and renewable.

Electrochemical-Induced C-N Bond Formation: A New Method to Synthesis ()-Quinazolinone Oximes Using Primary Amines and Quinazolin-4(3)-one.

A novel and highly selective electrochemical method for the synthesis of diverse quinazolinone oximes via direct electrooxidation of primary amines/C(sp)-H functionalization of oximes has been developed. The reaction is conducted in an undivided cell under constant current conditions and is oxidant-free, open-air, and eco-friendly. Notably, the protocol shows good functional group tolerance, providing versatile quinazolinone oximes in good yields.

Asymmetric Organocatalyzed Cyclization Cascade Reactions of 3,3-Difluoro-2-aryl-3-indoles and Enamides.

The direct functionalization of β-C(sp)-H bonds in enamides has garnered increasing attention within the realm of organic synthesis. However, these remarkable advancements are predominantly dependent on transition metals; limited success has been achieved via organocatalytic catalysis. Herein, we report a CPA-catalyzed β-C(sp)-H functionalization of enamides cascade intramolecular cyclization to synthesize the chiral dihydropyrimido[1,6-]indoles bearing -difluoromethylene.

KIF2C: An important factor involved in signaling pathways, immune infiltration, and DNA damage repair in tumorigenesis.

Backgrounds: Poorly regulated mitosis and chromosomal instability are common characteristics in malignant tumor cells. Kinesin family member 2 C (KIF2C), also known as mitotic centromere-associated kinesin (MCAK) is an essential component during mitotic regulation. In recent years, KIF2C was shown to be dysregulated in several tumors and was involved in many aspects of tumor self-regulation.

Highly Enantioselective Synthesis of 3-Fluorofuro[3,2-]indolines via Organocatalytic Aza-Friedel-Crafts Reaction/Selective C-F Bond Activation.

Fluoroalkylated compounds are of high interest in drug discovery and have inspired the evolution of diverse C-F bond activation methodologies. However, the selective activation of polyfluorinated compounds remains challenging. Herein, we describe an unprecedented strategy for synthesizing enantioenriched fluorofuro[3,2-]indolines through the organocatalytic aza-Friedel-Crafts reaction coupled with selective C-F bond activation.

Enantioselective Alkynylation of 2-Aryl-3H-indol-3-ones via Cooperative Catalysis of Copper/Chiral Phosphoric Acid.

A facile enantioselective alkynylation of cyclic ketimines attached to a neutral functional group utilizing the dual Cu(I)-CPA catalysis is described. The strategy of the alkynylation of 2-aryl-3H-indol-3-one directly to chiral propargylic amines containing indolin-3-one moiety in good yields and enantioselectivities. Moreover, gram-scale synthesis of chiral propargylamines based C2-quaternary indolin-3-ones was performed.

Asymmetric Intramolecular Hydroalkylation of Internal Olefin with Cycloalkanone to Directly Access Polycyclic Systems.

An asymmetric intramolecular hydroalkylation of unactivated internal olefins with tethered cyclic ketones was realized by the cooperative catalysis of a newly designed chiral amine (SPD-NH ) and Pd complex, providing straightforward access to either bridged or fused bicyclic systems containing three stereogenic centers with excellent enantioselectivity (up to 99 % ee) and diastereoselectivity (up to >20 : 1 dr). Notably, the bicyclic products could be conveniently transformed into a diverse range of key structures frequently found in bioactive terpenes, such as Δ -protoilludene, cracroson D, and vulgarisins. The steric hindrance between the Ar group of the SPD-NH catalyst and the branched chain of the substrate, hydrogen-bonding interactions between the N-H of the enamine motif and the C=O of the directing group MQ, and the counterion of the Pd complex were identified as key factors for excellent stereoinduction in this dual catalytic process by density functional theory calculations.

Changes in blood pressure, oxygen saturation, hemoglobin concentration, and heart rate among low-altitude migrants living at high altitude (5380 m) for 360 days.

Background: This article aimed to study the adjustment and adaptation of resting systolic blood pressure (SBP), diastolic blood pressure (DPB), oxygen saturation (SpO ), hemoglobin concentration ([Hb]), and heart rate (HR) in low-altitude migrants during a 1-year stay at high altitude.

Materials And Methods: Our study enrolled 35 young migrants who were exposed to a hypoxia environment at 5380 m altitude on the Qinghai Tibetan Plateau between June 21, 2017, and June 16, 2018. We set 14-time points (the 1st-10th, 20th, 30th, 180th, and 360th day after arriving at 5380 m) for obtaining the measurements of resting SBP, DBP, HR, SpO and [Hb] and compared them with the control values recorded prior to migration.

B(CF)-catalyzed β-C(sp)-H alkylation of tertiary amines with 2-aryl-3-indol-3-ones.

The β-C-H functionalization of amines is one of the most powerful tools for the synthesis of saturated nitrogen-containing heterocycles in organic synthesis. However, the β-C-H functionalization of amines redox-neutral addition with cyclic-ketimines is still unprecedented. Herein, the β-C-H functionalization of tertiary amines is described, providing the corresponding 1,3-diamines containing the indolin-3-one moiety in high yields the B(CF)-catalyzed borrowing hydrogen strategy.

Organocatalyzed Enantioselective Aza-Morita-Baylis-Hillman Reaction of Cyclic Ketimine with α,β-Unsaturated γ-Butyrolactam.

The enantioselective aza-MBH reaction is an efficient strategy for constructing novel carbon-carbon bonds, providing access to multitudinous chiral densely functionalized MBH products. However, the enantioselective aza-MBH reaction of cyclic-ketimines that would generate a versatile synthon is still missing and challenging. Herein, we developed a challenging direct organocatalytic asymmetric aza-MBH reaction involving cyclic ketimines attached to a neutral functional group.