A base-promoted regioselective formal [3 + 2] annulation of pyridinium ylides with bromoalkynes is reported, producing a series of substituent-diverse indolizines in generally good yields. A mild KCO-promoted three-component formal [3 + 2] cyclization of pyridinium ylides and bromoalkynes at a 2:1 molar ratio delivered C2-acylmethylated indolizines, whereas C2-brominated indolizines were generated starting from pyridinium ylides bearing strong electron-withdrawing groups at the pyridinium unit by using 2,2,6,6-tetramethyl-1-piperidinyloxy as a dehydrogenating reagent. The current synthetic methodology offers a controllable and modular approach to access indolizines with different substitution patterns, featuring a wide substrate scope, good functional group compatibility, and complete regioselectivity without the demand of any transition-metal catalysts.
View Article and Find Full Text PDF1-Isochromene scaffolds are ubiquitous in natural products and significant bioactive molecules. Although several methods for these molecular syntheses have been developed, reports on the efficient construction of iminated isochromenes are still rather limited. Herein, we report a new Cu(II)-catalyzed annulation and sulfonylimination cascade of α-carbonyl-γ-alkynyl sulfoxonium ylides with sulfamides, enabling direct C-C σ-bond elimination to furnish iminated ()-1-isochromenes in 51-97% yields.
View Article and Find Full Text PDFThe translocation of an aryl group from selenium into carbon enabled by the cleavage of the C-Se bond is reported by using nitrogen atom-linked 1,7-diynes and diaryl diselenides as starting materials, leading to various selenophene derivatives in a regioselective manner. This method enables the construction of two C-Se bonds and two C-C bonds through sequential radical bicyclization and 1,2-aryl migration under metal-free conditions. Control experiments and mechanistic studies suggest that this reaction proceeds through the cleavage of the inert C(Ph)-Se bond, facilitating the aryl translocation process.
View Article and Find Full Text PDFA gold self-relay catalysis driving a double annulation cascade starting from soft electron-biased 1,2-di(-aminoaryl)alkynes and aldehydes is reported, enabling regioselective access to produce a series of [5]azahelicenes depending on the substitution pattern in generally good yields under mild conditions. This protocol exploits and unifies the π- and σ-Lewis acid capability of gold catalysts, featuring high molecular convergence, broad substrate flexibility, and good functional group compatibility and regioselectivity.
View Article and Find Full Text PDFA highly enantioselective Pd/Bim-catalyzed dearomative Michael reaction applying polycyclic tropones as non-benzenoid aromatic Michael acceptors and arylboronic acids as aryl pronucleophiles has been developed. The bridged biaryls bearing central and axial chirality, including pentacyclic cyclohepta[]indoles and 6,7-dihydrodibenzo[,][7]annulen-5-ones, are generally generated in good to high yields and excellent enantioselectivities and can be readily transformed into useful derivatives.
View Article and Find Full Text PDFFerroptosis is an emerging target in rheumatoid arthritis (RA). We previously reported that transient receptor potential melastatin 7 (TRPM7) expression is correlated with RA cartilage destruction and demonstrated that TRPM7 mediates ferroptosis in chondrocytes. Here, we further determined the role and mechanism of (R)-N-(Benzimidazol-2-yl)-1,2,3,4-tetrahydro-1-naphthylamine (NS8593), a TRPM7 inhibitor, in chondrocyte ferroptosis of RA.
View Article and Find Full Text PDFA Pd(II)/,'-disulfonyl bisimidazoline-catalyzed asymmetric 1,4-conjugate addition reaction of low-cost arylboronic acids with readily available βsubstituted cyclic enones is described, providing a straightforward way of constructing cyclic all-carbon quaternary stereocenters with high enantioselectivity, in which ≥96% ee was obtained in most cases. The reaction proceeded without the protection of inert gas, making the operation process simple. Theoretical calculations have been applied to understand the origins of enantioselectivity.
View Article and Find Full Text PDFArticular cartilage damage and chondrocyte apoptosis are among the distinguishing features of osteoarthritis. (R)-N-(benzimidazol-2-yl)-1,2,3,4-tetrahydro-1-naphtylamine (NS8593) is a transient receptor potential cation channel subfamily M member 7 (TRPM7) channel inhibitor and was initially considered a potent inhibitor of small-conductance Ca-activated K channels(SK1-3 or KCa2.1-2.
View Article and Find Full Text PDFA visible-light-driven photocatalytic protocol is established for the diastereoselective synthesis of pyrrolo[3,2,1-]carbazoles via a radical-triggered multicomponent bicyclization reaction starting from readily available indole-tethered 1,6-enynes and α-benzyl-α-bromomalonates under mild conditions. This photocatalytic approach exhibits a wide substrate compatibility and excellent tolerability toward various functional groups and boasts the benefit of efficient ring formation and chemical bond creation.
View Article and Find Full Text PDFTransient receptor potential melastatin 7 (TRPM7) is a cation channel that plays a role in the progression of rheumatoid arthritis (RA), yet its involvement in synovial hyperplasia and inflammation has not been determined. We previously reported that TRPM7 affects the destruction of articular cartilage in RA. Herein, we further confirmed the involvement of TRPM7 in fibroblast-like synoviocyte (FLS) proliferation, metastasis and inflammation.
View Article and Find Full Text PDFBackground: Finding a drug for early intervention in the hepatic fibrosis process has important clinical significance. Previous studies have suggested SUMOylation as a potential target for intervention in hepatic fibrosis. However, the role of SAE1, a marker of SUMOylation, in hepatic fibrosis is unknown.
View Article and Find Full Text PDFChem Commun (Camb)
February 2024
A base-promoted olefin skeletal rearrangement strategy from -quinone methides (-QMs) and -fluoroarenesulfonamides is reported, enabling direct nitrogen insertion of olefins to produce a series of multiarylated ()--sulfonyl amidines with complete stereoselectivity and generally good yields. Using -QMs without -hydroxy substituents gave triarylated -sulfonyl amidines, whereas tetraarylated ,'-disulfonyl amidines were synthesized with the existence of -hydroxy groups.
View Article and Find Full Text PDFA copper(II)/DBU relay catalyzed annulation of α-carbonyl-γ-alkynyl sulfoxonium ylides as a new class of sulfoxonium ylide reagents with sulfonyl hydrazides is reported, enabling intramolecular oxygen migration to produce a series of -sulfonamido 2-isoindoles with good yields. The present annulation proceeded readily by combining the Cu(II)-catalyzed 6- oxo-cyclization with the DBU-catalyzed isochromene skeletal rearrangement, resulting in the formation of multiple new chemical bonds.
View Article and Find Full Text PDFA metal-free protocol for the direct construction of C(sp)-N and C-O bonds a PhI(OAc)-mediated dehydrogenative aminoacyloxylation of β,γ-unsaturated hydrazones with Togni reagent II is reported. Initiated by the carboxyl-containing species generated from Togni reagent II, this method offers a new solution for regioselective functionalization at a remote site on β,γ-unsaturated hydrazones, thus providing a straightforward method for the synthesis of acyloxyl-substituted pyridazines. This reaction features a broad substrate scope and mild conditions.
View Article and Find Full Text PDFA palladium-catalyzed asymmetric annulative dearomatization of phenols with butene dicarbonate is reported, enabling twofold decarboxylative allylation to regioselectively produce a range of spirocyclohexadienones with 29-95% yields and 74-99% ee. A catalytic dearomative formal [4 + 2] cyclization of 1,1'-biphenyl-2,4'-diols delivered spiro[chromane-4,1'-cyclohexane]-2',5'-dien-4'-ones with high enantioselectivity, whereas enantioenriched spiro[cyclohexane-1,4'-quinoline]-2,5-dien-4-ones were generated starting from 2'-amino-[1,1'-biphenyl]-4-ols as 1,4-dinucleophiles.
View Article and Find Full Text PDFA direct arylsulfonylation of β,γ-unsaturated hydrazones method, in which sulfonated pyrazolines are accessed by a three-component reaction of β,γ-unsaturated hydrazones, DABSO, and aryldiazonium tetrafluoroborates, has been developed without external oxidants or catalysts. This transformation is triggered by the formation of arylsulfonyl radicals in situ from the reaction of aryldiazonium tetrafluoroborates and DABSO, and is enabled by controllable generation of C center radical, in which DABSO was utilized as the sulfone source and an oxidant in this radical-mediated cascaded reaction. A wide range of substrates can be applied in this process to afford pyrazolines in good yield, and it is amenable for gram-scale synthesis.
View Article and Find Full Text PDFIn vivo articular cartilage degeneration is an essential hallmark of osteoarthritis (OA), involving chondrocyte senescence, extracellular matrix degradation, chondrocyte death, cartilage loss, and bone erosion. Among them, chondrocyte death is one of the major factors leading to cartilage degeneration. Many studies have reported that various cell death modes, including apoptosis, ferroptosis, and autophagy, play a key role in OA chondrocyte death.
View Article and Find Full Text PDFA novel gold(I)/Brønsted acid relay catalysis enabling azofuran activation to induce annulative rearrangement from 3-yne-1,2-diols and aryldiazonium tetrafluoroborates is reported, producing a series of furan-2-yl-substituted pyrrol-2-ones bearing a quaternary carbon center with good yields. Exchanging aryldiazonium tetrafluoroborate for azofuran led to skeletally identical but substituent-diverse furan-2-yl-containing pyrrol-2-ones with good yields, supporting the key azofuran activation and annulative rearrangement by gold/Brønsted acid relay catalysis.
View Article and Find Full Text PDFA new gold(I) self-relay catalysis reaction enabling the annulative oxygenation of propargylic alcohols with various O-nucleophiles, such as carboxylic acids, alcohols and TBHP, is reported, producing a series of functionalized benzofurans in moderate to good yields under mild conditions. This protocol benefits from the π- and σ-Lewis acid capability of gold complexes, demonstrating high molecular convergence, broad substrate flexibility, high functional group compatibility and mild conditions.
View Article and Find Full Text PDFA catalytic site-selective ring deconstruction of cyclobuteno[]naphthalene-4-ones with alcohols is reported, enabling the direct production of a wide range of unsymmetric 1,1-diarylated olefins with good yields and complete regioselectivity. The late-stage application of these resulting terminal olefins demonstrates great possibilities to apply this strategy to complex molecules. The protocol features good functional group compatibility, broad substrate scope, and controllable site selectivity.
View Article and Find Full Text PDFThe Schmidt rearrangement, a reaction that enables C-C or C-H σ bond cleavage and nitrogen insertion across an aldehyde or ketone substrate, is one of the most important and widely used synthetic tools for the installation of amides and nitriles. However, such a reaction frequently requires volatile, potentially explosive, and highly toxic azide reagents as the nitrogen donor, thus limiting its application to some extent. Here, we show a Schmidt-type reaction where aryldiazonium salts act as the nitrogen precursor and in-situ-generated cyclopenta-1,4-dien-1-yl acetates serve as pronucleophiles from gold-catalyzed Nazarov cyclization of 1,3-enyne acetates.
View Article and Find Full Text PDFA palladium-catalyzed asymmetric annulative allylic alkylation reaction of 2-[(1-indol-2-yl)methyl]malonates with ()-but-2-ene-1,4-diyl dicarbonates is described, leading to the regio- and enantioselective synthesis of dihydropyrido[1,2-]indoles with a chiral cyclic allyl stereocenter adjacent to the ring-junction nitrogen atom in moderate to good yields. The salient features of this protocol include mild conditions, a broad substrate scope, and good compatibility with substituents as well as high regio- and stereoselectivities, providing a catalytic asymmetric entry for fabricating chiral pyridoindole scaffolds.
View Article and Find Full Text PDFRheumatoid arthritis (RA) is a common autoimmune disease characterized by chronic inflammation. Immune dysfunction is an essential mechanism in the pathogenesis of RA and directly linked to synovial inflammation and cartilage/bone destruction. Intermediate conductance Ca-activated K channel (KCa3.
View Article and Find Full Text PDFA new electrochemical selective annulative amino-ketalization and amino-oxygenation of 1,6-enynes with disulfonimides and alcohols is reported, producing a series of functionalized benzofurans under catalyst- and oxidant-free conditions. The annulative aminoketalization proceeds with simple short-chain alcohols such as methanol, ethanol and -propanol as -nucleophilic reagents, while the reaction occurs in the annulative aminooxygenation direction in the presence of water and large steric -butyl alcohol (SBA).
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