SOX9 promotes hypoxic pulmonary hypertension through stabilization of DPP4 in pulmonary artery smooth muscle cells.

Pulmonary hypertension (PH) is a progressive cardiopulmonary disorder characterized by pulmonary vascular remodeling (PVR), primarily due to the excessive proliferation of pulmonary artery smooth muscle cells (PASMCs). This study aimed to investigate the role and molecular mechanism of SOX9 in hypoxic PH in rats. The findings revealed that SOX9 was upregulated in the pulmonary arteries and PASMCs of hypoxia-exposed rats.

Eu(OTf) -Catalyzed Formal Dipolar [4π+2σ] Cycloaddition of Bicyclo-[1.1.0]butanes with Nitrones: Access to Polysubstituted 2-Oxa-3-azabicyclo[3.1.1]heptanes.

Herein, we have synthesized multifunctionalized 2-oxa-3-azabicyclo[3.1.1]heptanes, which are considered potential bioisosteres for meta-substituted arenes, through Eu(OTf) -catalyzed formal dipolar [4π+2σ] cycloaddition of bicyclo[1.

S-C Linkage for Allylsulfonximines via BF-Mediated Allylation.

A SuFEx linkage reaction between sulfonimidoyl fluoride and allyltrimethylsilane was achieved for the construction of -modified allylsulfoximines in minutes with BF as a nonmetal difunctional activator enabling the activation of both S-F and C-Si bonds to forge the S-C (sp) bond swiftly. Mechanistic studies and DFT calculations indicated that the linkage was initiated with the activation of sulfonimidoyl fluoride and then followed with the transfer of the fluoride anion to the TMS group.

Advances in the construction of diverse SuFEx linkers.

Sulfur fluoride exchange (SuFEx), a new generation of click chemistry, was first presented by Sharpless, Dong and co-workers in 2014. Owing to the high stability and yet efficient reactivity of the S-F bond, SuFEx has found widespread applications in organic synthesis, materials science, chemical biology and drug discovery. A diverse collection of SuFEx linkers has emerged, involving gaseous SOF and SOF hubs; SOF-derived iminosulfur oxydifluorides; -, - and -attached sulfonyl fluorides and sulfonimidoyl fluorides; and novel sulfondiimidoyl fluorides.

Linkage Chemistry of S(VI) Fluorides.

Sulfur(VI)-fluoride exchange linkage as a next generation of click chemistry was introduced by Sharpless and coworkers in 2014. Distinguished from CuAAC, the SuFEx reaction proceeds under metal-free conditions, and the reactive linkers are variable, enabling access to a diverse class of linkage compounds. Therein, a series of SuFEx linkers emerged has been widely prevalent in diverse fields.

The Linkage of Sulfonimidoyl Fluorides and Unactivated Alkenes via Hydrosulfonimidoylation.

Sulfur(VI) fluoride cleavage and exchanging linkage, a new generation of linkage chemistry, exhibits enormous potential for combining a range of functional molecules in an increasing number of fields. Herein, we established a metal-free linkage of unactivated alkenes and sulfonimidoyl fluorides via hydrosulfonimidoylation to construct sulfoximines within minutes. An intermolecular hydride transfer process is the key step, and it occurs via overlap of the LUMO in the sulfonimidoyl cation and HOMO in the unactivated alkene, which was confirmed via control experiments with deuterated compounds.

Self-made wire loop snare successfully treats gastric persimmon stone under endoscopy.

Background: Large gastric persimmon stones are generally resistant to standard endoscopic treatments. We applied an alternative endoscopic method using a hand-made snare for the treatment of large gastric phytobezoars.

Aim: To explore the clinical efficacy of a self-made wire loop snare to treat giant gastric persimmon stones.

Diastereo- and Enantioselective Synthesis of Bisbenzannulated Spiroketals and Spiroaminals by Ir/Ag/Acid Ternary Catalysis.

We reported herein an iridium/silver/acid ternary catalytic system to access bisbenzannulated [6,6]-spiroketals in high efficiency with generally high diastereo- and enantioselectivities (up to >20 : 1 dr, >99 % ee). In this procedure, readily available o-alkynylacetophenones undergo cycloisomerization to generate isochromenes in situ that participate in stereoselective allylation/spiroketalization sequence with 2-(1-hydroxyallyl)phenols. Meanwhile, 2-(1-hydroxyallyl)anilines were also compatible in this cascade reaction, furnishing structurally novel bisbenzannulated [6,6]-spiroaminals with good diastereoselectivities (8 : 1-12 : 1 dr) and excellent enantioselectivities (98 %->99 % ee).

Enantioselective Synthesis of Spiroketals and Spiroaminals via Gold and Iridium Sequential Catalysis.

The enantioselective cascade reaction between racemic 2-(1-hydroxyallyl)phenols and alkynols/alkynamides was realized by using a gold and iridium sequential catalytic system. In this procedure, the in situ generated exocyclic vinyl ethers or enamides undergo the asymmetric allylation/spiroketalization with π-ally-Ir amphiphilic species, which provides an efficient and straightforward access to spiroketals and spiroaminals with excellent enantioselectivities. Moreover, racemic 2-(1-hydroxyallyl)anilines were also suitable in this reaction along with a kinetic resolution process, affording enantioenriched spiroaminals and 2-(1-hydroxyallyl)anilines in good yields.

Photoredox-Catalyzed α-Sulfonylation of Ketones from Sulfur Dioxide and Thianthrenium Salts.

A photoredox-catalyzed sulfonylation of silyl enol ethers with DABCO·(SO) and thianthrenium salts is achieved, providing diverse β-keto sulfones in moderate to good yields. This protocol features easily accessible starting materials and good functional group compatibility, enabling the introduction of various functionalized sulfonyl groups into ketones. Furthermore, as one of the important industrial raw materials, methanol can be employed as the methyl source to prepare α-methylsulfonated ketones through a methyl thianthrenium intermediate for the first time.

Regio- and Enantioselective γ-Allylic Alkylation of In Situ-Generated Free Dienolates via Scandium/Iridium Dual Catalysis.

An unprecedented asymmetric γ-allylic alkylation of free dienolates via Sc/Ir dual catalysis is reported, which affords a range of synthetically versatile γ-allylic crotonaldehydes in high efficiency with excellent chemo-, regio-, and enantioselectivities. The dienolates bearing no essential auxiliary groups were generated in situ by scandium triflate-mediated Meinwald rearrangement of vinyloxiranes atom-economically. With the assistance of computational density functional theory calculations, a Sc/Ir bimetallic catalytic cycle was proposed to illustrate the reaction mechanism.

Recent advances in the treatment of systemic lupus erythematosus with belimumab in children.

Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organs, and lupus nephritis (LN) is the most common renal complication of SLE. Belimumab is a fully humanized monoclonal antibody that can reduce the number of B cells, thereby reducing the formation of autoantibodies. Belimumab can improve SLE response index and SLE disease activity score and delay the progression of LN in both adults and children and thus plays an important role in the treatment of SLE and LN.

Copper-Catalyzed Regioselective 1,4-Selenosulfonylation of 1,3-Enynes to Access Cyanoalkylsulfonylated Allenes.

By employing CuOAc as the catalyst, we realize a four-component reaction of 1,3-enynes, diselenides, DABCO·(SO), and cycloketone oxime esters, providing facile access to diverse cyanoalkylsulfonylated allenyl selenides in moderate to good yields. This reaction features high functional group tolerance and a broad substrate scope, enabling the regioselective, sequential formation of C-SO and C-Se bonds under mild reaction conditions. Moreover, the utility of this methodology is further illustrated through the late-stage functionalization of drug-based molecules.

Iridium-Catalyzed Asymmetric Cascade Allylation/Pictet-Spengler Cyclization Reaction for the Enantioselective Synthesis of 1,3,4-Trisubstituted Tetrahydroisoquinolines.

An iridium-catalyzed trifluoroacetic acid-promoted asymmetric cascade allylation/Pictet-Spengler cyclization reaction of azomethine ylides with aromatic allylic alcohols is reported. This protocol provides a facile and scalable method for the construction of 1,3,4-trisubstituted tetrahydroisoquinolines containing two stereogenic centers in good yields (up to 96%) with generally excellent diastereo- and enantioselectivities (up to >20:1 dr and >99% ee). Furthermore, a series of aromatic heterocycle-fused piperidines were also obtained with excellent enantiocontrol by this methodology.

Case Report: Neuronal Intranuclear Inclusion Disease With Oromandibular Dystonia Onset.

Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disease. Because of variable clinical manifestations, NIID was often misdiagnosed. According to published case reports, the common clinical manifestations of NIID include dementia, muscle weakness, autonomic impairment, sensory disturbance, rigidity, ataxia convulsions, etc.

Sulfone as a Transient Activating Group in the Palladium-Catalyzed Asymmetric [4 + 3] Cycloaddition of Trimethylenemethane Enabling the Enantioselective Synthesis of Fused Azepines.

The palladium-catalyzed asymmetric [4 + 3] cycloaddition of a sulfonyl-trimethylenemethane (TMM) donor with azadienes furnished various sulfonyl-fused azepines with exclusive regioselectivities and excellent stereoselectivities (up to >20:1 dr, >99% ee) in high yields (up to 93%). Moreover, sulfone, serving as a transient activating group of the TMM species, can be easily removed from the cycloadducts to provide the structurally simple fused azepines with excellent enantioselectivities. This strategy demonstrates sulfonyl-TMM as an effective surrogate of naked TMM with high reactivity, exclusive regioselectivity, and excellent stereoselectivity.

Iridium-Catalyzed Diastereo- and Enantioselective [4 + 3] Cycloaddition of 4-Indolyl Allylic Alcohols with Azomethine Ylides.

An unprecedented iridium-catalyzed asymmetric [4 + 3] cycloaddition of racemic 4-indolyl allylic alcohols with azomethine ylides is reported. The ability of acid promoter zinc triflate to perform multiple roles is the key factor for the success of this strategy. This method provides scalable and efficient access to biologically important azepino[3,4,5-] indoles in good yields with generally excellent diastereo- and enantioselectivities (up to >20:1 dr and >99% ee).

Catalytic Asymmetric [3 + 2] Annulation via Indolyl Copper-Allenylidene Intermediates: Diastereo- and Enantioselective Assembly of Pyrrolo[1,2-]indoles.

A catalytic asymmetric decarboxylative [3 + 2] annulation via indolyl copper-allenylidene amphiphilic intermediates has been developed. This protocol offers a straightforward method for the synthesis of biologically important pyrrolo[1,2-]indoles bearing contiguous quaternary and tertiary stereogenic centers with excellent diastereo- and enantioselectivities (up to >20:1 dr and >99% ee). In addition, the diversity-oriented synthesis of pyrrolo[1,2-]indoles was achieved via versatile transformations of the alkyne-containing cycloadducts.

Organocatalytic Regiodivergent Ring Expansion of Cyclobutanones for the Enantioselective Synthesis of Azepino[1,2-]indoles and Cyclohepta[]indoles.

A regiodivergent organocatalytic enantioselective Michael addition/three-atom ring expansion sequence of electron-withdrawing group activated cyclobutanones with 2-nitrovinylindoles was developed. A series of azepino[1,2-]indoles were obtained with exclusive regioselectivities and high diastereo- and enantioselectivities (up to >20:1 dr, 96% ee) with the application of the N1 nucleophilic site of the indole nucleus. Meanwhile, various cyclohepta[]indoles could be accessed with high enantiopurity (up to 96% ee) through the Michael addition/boron-trifluoride-etherate-promoted indole C3-attack ring expansion process.

Palladium-Catalyzed Asymmetric [4+3] Cyclization of Trimethylenemethane: Regio-, Diastereo-, and Enantioselective Construction of Benzofuro[3,2-b]azepine Skeletons.

The palladium-catalyzed asymmetric [4+3] cyclization of trimethylenemethane donors with benzofuran-derived azadienes furnishes chiral benzofuro[3,2-b]azepine frameworks in high yields (up to 98 %) with exclusive regioselectivities and excellent stereoselectivities (up to >20:1 d.r., >99 % ee).

Enantioselective Rhodium-Catalyzed Addition of Arylboroxines to N-Unprotected Ketimines: Efficient Synthesis of Cipargamin.

Highly enantioselective rhodium-catalyzed addition of arylboroxines to N-unprotected ketimines is realized for the first time by employing chiral BIBOP-type ligands with a Rh loading as low as 1 mol %. A range of chiral α-trifluoromethyl-α,α-diaryl α-tertiary amines or 3-amino-3-aryloxindoles were formed with excellent ee values and yields by employing either WingPhos or PFBO-BIBOP as the ligand. The method has enabled an efficient enantioselective synthesis of cipargamin.

Synergistic Catalysis for Asymmetric [3 + 2] Cycloadditions of 2-Indolylmethanols with -Unsaturated Aldehydes.

A catalytic asymmetric [3 + 2] cycloaddition of 2-indolylmethanols with -unsaturated aldehydes was developed for the first time. This transformation was achieved by a synergistic catalytic system consisting of a palladium complex, a Brønsted acid, and a chiral secondary amine to synthesize biologically active cyclopenta[]indole derivatives with excellent diastereo- and enantioselectivities (up to >20:1 dr, up to 99% ee).

Enantioselective Construction of Dihydropyrido[1,2-]indoles via Organocatalytic Arylmethylation of 2-Enals with Inert Aryl Methane Nucleophiles.

An organocatalytic asymmetric arylmethylation/-hemiacetalization of 2-indolyl methane derivatives and 2-enals was developed. Notably, the 2-methyl of indole was readily deprotonated to produce highly reactive nucleophilic species by introducing the nitro group at the C3 position of the indole ring. A spectrum of valuable chiral dihydropyrido[1,2-]indoles were efficiently constructed with excellent enantioselectivity (up to >99% ee).

Ligand-controlled switch in diastereoselectivities: catalytic asymmetric construction of spirocyclic pyrrolidine-azetidine/oxe(thie)tane derivatives.

An efficient catalytic asymmetric 1,3-dipolar cycloaddition of azomethine ylides with four-membered ring-containing exocyclic alkenes has been developed, and either the exo or endo spirocyclic pyrrolidine-azetidine/oxe(thie)tane derivatives were diastereodivergently generated by employing Cu(i)/tBu-Phosferrox and a Cu(i)/N,O-ligand complex, respectively. Notably, various heteroatom-containing (N, O, S) exocyclic alkenes were found to be well-tolerated in this transformation.