Metal- and Light-Free Decarboxylative Giese Addition Reaction Facilitated by Hantzsch Ester.

We have developed a novel strategy for decarboxylative radical addition reactions that employs ground-state reduced nicotinamide adenine dinucleotide (NADH) analogues under ambient and open-air conditions, facilitating the efficient formation of Csp-Csp bonds in a variety of substrates. This protocol is distinguished by its operational simplicity, mild reaction conditions, high efficiency, and the use of cost-effective starting materials. Furthermore, experimental studies have provided valuable insights into the reaction mechanism, elucidating the light-independent pathways that promote these transformations.

NADH Analogues Enable Metal- and Light-Free Decarboxylative Functionalization.

Here we report a metal- and light-free decarboxylative functionalization approach enabled by reduced nicotinamide adenine dinucleotide (NADH) analogues. The efficient and operationally simple approach, conducted in 5 minutes from in situ preparation of aryliodine (III) dicarboxylates under open-air and ambient conditions, enables diverse bond formation and exhibits a broad substrate scope of over 70 examples. Late-stage functionalization of drug molecules and natural products further demonstrates the synthetic utility of this method.

Pillar[5]arene-based Polymer Network for Efficiently Removing Perfluorooctanoic Acid through Synergistic Binding Interactions.

Perfluorooctanoic acid (PFOA) is currently one of the most important chemicals posing environmental risks, and there is an urgent need to find methods to efficiently remove PFOA from environmental media. Here, two decaamino-pillar[5]arene-based fluorine-rich polymer networks, called FA2P-P and FA6P-P, were constructed using a convenient method. FA6P-P had an excellent ability to take up PFOA, and had a capacity of 1423 (mg PFOA) (g FA6P-P), which is the second highest adsorption capacity reported for any PFOA sorbent.

Chemoselectivity Switch between Enantioselective [2,3]-Wittig Rearrangement and Conia-Ene-Type Reactions of Propargyloxyoxindoles.

Despite the existence of three competing reactions for propargyloxyoxindoles, we report a chemoselectivity switch between enantioselective propargyl [2,3]-Wittig rearrangement and Conia-ene-type reactions, with suppression of the [1,2]-Wittig-type rearrangement. Using C-symmetric imidazolidine-pyrroloimidazolone pyridine as the ligand and Ni(acac) as the Lewis acid, diverse 3-hydroxy 3-substituted oxindoles containing allenyl groups were obtained in up to 98 % yield and 99 % ee via asymmetric propargyl [2,3]-Wittig rearrangement. In the presence of AgOTf-Duanphos, chiral spiro dihydrofuran oxindoles were given in up to 98 % yield and 91 % ee through a Conia-ene-type reaction.

Achiral Counteranion-Induced Reversal of Enantioselectivity in Ni(II)-Catalyzed Friedel-Crafts Alkylation/Annulation of 2-Naphthols.

An achiral counteranion-induced reversal of enantioselectivity in Ni(II)-catalyzed Friedel-Crafts alkylation/annulation of 2-naphthols with β,γ-unsaturated α-keto esters was achieved. Using imidazolidine pyrroloimidazolone pyridine as the ligand and Ni(acac) as the Lewis acid, diverse naphthopyran derivatives were obtained in good yields (up to 94% yield) and high enantioselectivities (up to 99% ee). In the presence of Ni(OTf) as the Lewis acid, a series of chiral naphthopyran derivatives were obtained in good yields and with a controlled switch in stereoselectivity.

Discovery, Synthesis, and Activity Evaluation of Novel Five-Membered Sulfur-Containing Heterocyclic Nucleosides as Potential Anticancer Agents In Vitro and In Vivo.

A series of novel five-membered sulfur-containing heterocyclic nucleoside derivatives were designed, synthesized, and evaluated for their anticancer activities in vitro and in vivo. The structure-activity relationship studies revealed that some of them showed obvious antitumor activities in several cancer cell lines. Among them, compound exhibited remarkable antiproliferative activity against HeLa cells and was more potent than cisplatin (IC = 2.

Pd-catalyzed 5- cyclization/etherification cascade of -propargyl arylamines for the synthesis of polysubstituted furans.

A method for the synthesis of furans bearing indoline skeletons was developed an intramolecular palladium-catalyzed 5- cyclization/etherification cascade of -propargyl arylamines containing a 1,3-dicarbonyl side chain. This method realized the first capture of vinyl carbopalladiums by ketones as -nucleophiles and showed a wide range of substrate tolerability affording trisubstituted furans in various yields. The enantioselective version for this domino process and diverse derivatizations of the reaction products were also studied.

Dearomative [2 + 1] Spiroannulation of Bromophenols with Electron-Deficient Alkenes.

A base-assisted dearomative [2 + 1] spiroannulation of /-bromophenols with activated olefins (methylenemalonates) to construct various cyclopropyl spirocyclohexadienone skeletons is reported. Furthermore, several other halophenols (X = Cl, I) were also tolerated in this process. Control experiments reveal a dearomative Michael addition of phenols at their halogenated positions to methylenemalonates, followed by intramolecular radical-based S1 dehalogenative cyclopropanation.

Enantioselective construction of stereogenic-at-sulfur(IV) centres via catalytic acyl transfer sulfinylation.

Chiral sulfur pharmacophores are crucial for drug discovery in bioscience and medicinal chemistry. While the catalytic asymmetric synthesis of sulfoxides and sulfinate esters with stereogenic-at-sulfur(IV) centres is well developed, the synthesis of chiral sulfinamides remains challenging, which has primarily been attributed to the high nucleophilicity and competing reactions of amines. In this study, we have developed an efficient methodology for the catalytic asymmetric synthesis of chiral sulfinamides and sulfinate esters by the sulfinylation of diverse nucleophiles, including aromatic amines and alcohols, using our bifunctional chiral 4-arylpyridine N-oxides as catalysts.

Construction of thioglycoside bonds an asymmetric organocatalyzed sulfa-Michael/aldol reaction: access to 4'-thionucleosides.

Thioglycoside bond formation an asymmetric sulfa-Michael/aldol reaction of ()-β-nucleobase acrylketones and 1,4-dithiane-2,5-diol has been achieved with a cinchona alkaloid-derived bifunctional squaramide chiral catalyst. Diverse purine, benzimidazole, and imidazole substrates are well tolerated and generate 4'-thionucleoside derivatives containing three contiguous stereogenic centers with excellent results (30 examples, up to 97% yield, >20 : 1 dr and up to 99% ee). Moreover, the novel strategy provides an efficient and convenient synthetic route to construct chiral 4'-thionucleosides.

Cough flows as a criterion for decannulation of autonomously breathing patients with tracheostomy tubes.

Background: Adequate cough or exsufflation flow can indicate an option for safe tracheostomy decannulation to noninvasive management. Cough peak flow via the upper airways with the tube capped is an outcome predictor for decannulation readiness in patients with neuromuscular impairment. However, this threshold value is typically measured with tracheotomy tube removed, which is not acceptable culturally in China.

Reconfigurable Micro/Nano-Optical Devices Based on Phase Transitions: From Materials, Mechanisms to Applications.

In recent years, numerous efforts have been devoted to exploring innovative micro/nano-optical devices (MNODs) with reconfigurable functionality, which is highly significant because of the progressively increasing requirements for next-generation photonic systems. Fortunately, phase change materials (PCMs) provide an extremely competitive pathway to achieve this goal. The phase transitions induce significant changes to materials in optical, electrical properties or shapes, triggering great research interests in applying PCMs to reconfigurable micro/nano-optical devices (RMNODs).

Cobalt(II)-Catalyzed Enantioselective Propargyl Claisen Rearrangement: Access to Allenyl-Substituted Quaternary β-Ketoesters.

Highly enantioselective propargyl Claisen rearrangement of -propargyl β-ketoesters was achieved under 2.5 mol % of the chiral cobalt complex as the catalyst under mild reaction conditions. With Co(OTf) as the Lewis acid and -symmetric imidazoline-pyrroloimidazolone pyridine as the ligand, diverse chiral allenyl-substituted all-carbon quaternary β-ketoesters were obtained in good yields (up to 97% yield) and high enantioselectivities (up to 98% ee).

Reversal of Enantioselectivity for the Desymmetrization of -1,2-Diols Catalyzed by Pyridine--oxides.

The desymmetrization of --diols with a reversal of enantioselectivity catalyzed by chiral pyridine--oxides with l-proline as a single source of chirality is reported. With chiral 3-substituted ArPNO and 2-substituted 4-(dimethylamino)pyridine--oxide as catalysts, a wide range of monoesters were obtained with satisfactory results with a complete and controlled switch in stereoselectivity (up to 97:3 and 1:99 er). Chiral six-membered carbocyclic uracil nucleosides were generated with excellent enantioselectivities after derivatization.

Ruthenium(II)-Catalyzed [4 + 2] Electro-Oxidative Annulation of -Arylpurines/Purine Nucleosides.

A sustainable pathway for the synthesis of tetracyclic purinium salts via ruthenium-catalyzed electro-oxidative annulation of -arylpurine nucleosides with alkynes without a stoichiometric metal oxidant has been developed. The protocol described herein exhibits high regioselectivity, broad scope, and wide functional group tolerance, allowing efficient coupling of various biologically important molecules including acyclic, ribosyl, arabinosyl, and deoxyribosyl purine nucleoside derivatives. A novel purinoisoquinolinium-coordinated ruthenium(0) sandwich intermediate has been isolated, crystallographically characterized, and electrochemically analyzed, offering direct mechanistic insight.

ArPNO-Catalyzed Acylative Dynamic Kinetic Resolution of 3-Hydroxyphthalides: Access to Enantioenriched Phthalidyl Esters.

A chiral 4-aryl-pyridine--oxide nucleophilic organocatalyst was used to synthesize chiral phthalidyl ester prodrugs by the acylative dynamic kinetic resolution process. By using the 3,5-dimethylphenyl-derived ArPNO catalyst, the phthalidyl esters were obtained in up to 97% yield with 97% ee at room temperature. Two phthalidyl esters of prodrugs, talosalate and talmetacin, were generated.

Dearomative [4 + 2] Annulation of Electron-Poor N-Heteroarenes with Azoalkenes for Access to Polycyclic Tetrahydro-1,2,4-triazines.

A direct dearomative [4 + 2] annulation of electron-poor N-heteroarenes with azoalkenes generated in situ from α-halogeno hydrazones was developed under mild conditions. Accordingly, a series of fused polycyclic tetrahydro-1,2,4-triazines with potential biological activity were obtained in up to 96% yield. Various α-halogeno hydrazones and N-heteroarenes, such as pyridines, quinolines, isoquinolines, phenanthridine, and benzothiazole, were tolerated by this reaction.

Design of C-symmetric tridentate ligands for enantioselective dearomative [3 + 2] annulation of indoles with aminocyclopropanes.

Chiral polycyclic indolines are widely present in natural products and have become the focus of extensive synthetic efforts. Here, we show the catalytic asymmetric dearomative [3 + 2] annulation of indoles with donor-acceptor aminocyclopropanes to construct tricyclic indolines. Key to the success of the reaction is the rational design of C-symmetric bifunctional tridentate imidazoline-pyrroloimidazolone pyridine ligand.

Cu-Catalyzed -Arylation of Prolinamides: Access to Enantioenriched DMAP Analogues and Its Application in Black Rearrangement.

A CuI-catalyzed C-N coupling reaction of 3-bromo-DMAP with l-prolinamides was conducted at 80 °C in 12-16 h, where the prolinamide's structure had an accelerating effect on the Ullmann-type reaction. This reaction was used to construct chiral 3-amino DMAP catalysts. Furthermore, enantioenriched DMAP analogue was applied in an asymmetric Black rearrangement of 2-benzofuranylcarbonates, affording 3,3-disubstituted benzofuran-2-ones in up to 96% yield and 97% ee.

Efficacy and Safety of Remimazolam Besylate Combined with Alfentanil in Painless Gastroscopy: A Randomized, Single-Blind, Parallel Controlled Study.

Background: The efficacy and adverse reactions of remimazolam besylate (RB) in combination with alfentanil in patients with painless gastroscopy remain unclear.

Objective: The aim of the study is to observe the efficacy and adverse reactions of RB in combination with alfentanil in patients with painless gastroscopy RB.

Methods: All patients were randomly divided into two groups: RB combined with the alfentanil group (research group) and propofol combined with the alfentanil group (control group).

Substrate-Dependent Regioselectivity: Pd/PTC Cooperatively Catalyzed Domino Heck/Allylation of Allenamides with α-Carbon of Carbonyl Compounds.

A Pd/phase-transfer catalyst cooperatively catalyzed domino Heck/allylation reaction is first reported, which represents interesting substrate-dependent regioselectivity. Under the same conditions, Ts-protected -(2-iodophenyl)allenamides produced only linear allylation products, while Cbz, Ac, or Boc-protected -(2-iodophenyl)allenamides and -(2-iodobenzoyl)allenamides with various compounds generated branch allylation products with an exocylic C═C bond and two vicinal stereocenters. Up-scale syntheses and diverse fused cyclization transformations of products were then carried out.

Highly Chemoselective Synthesis of Purino[3,2-]oxazoles via the Asymmetric Dearomative [3+2] Cycloaddition of Purines with Donor-Acceptor Oxiranes.

A Ni(II)/bisoxazoline-catalyzed asymmetric dearomative [3+2] cycloaddition of substituted purines with donor-acceptor oxiranes was developed. This reaction, which proceeds via highly chemoselective C-C bond cleavage of the oxiranes, accesses chiral purino[3,2-]oxazole compounds (≤99% ee after enrichment via crystallization). The electronic effects of the purine ring determine the reactivity of the substrate.

The role of botulinum toxin type A related axon transport in neuropathic pain induced by chronic constriction injury.

Background: The mechanism of peripheral axon transport in neuropathic pain is still unclear. Chemokine ligand 13 (CXCL13) and its receptor (C-X-C chemokine receptor type 5, CXCR5) as well as GABA transporter 1 (GAT-1) play an important role in the development of pain. The aim of this study was to explore the axonal transport of CXCL13/CXCR5 and GAT-1 with the aid of the analgesic effect of botulinum toxin type A (BTX-A) in rats.

ArPNO-catalyzed acylative kinetic resolution of tertiary alcohols: access to 3-hydroxy-3-substituted oxindoles.

Bifunctional chiral 4-aryl-pyridine--oxides (ArPNO) were reported for the acylative kinetic resolution of 3-hydroxy-3-substituted oxindoles, where the oxygen acts as the nucleophilic site. Using less sterically hindered acetic anhydride, both the recovered tertiary heterocyclic alcohols and the ester products exhibited good to excellent results with -factors up to 167. Control experiments supported the dual activation manner, where the -oxide group and N-H proton in ArPNO were crucial for high selectivity and enhanced catalytic reactivity.

Tracheostomy decannulation protocol in patients with prolonged tracheostomy referred to a rehabilitation hospital: a prospective cohort study.

Background: The aim of the study was to assess the feasibility of a standardized tracheostomy decannulation protocol in patients with prolonged tracheostomy referred to a rehabilitation hospital.

Methods: This prospective cohort study recruited conscious patients with prolonged tracheostomy who were referred to the pulmonary rehabilitation department of a tertiary rehabilitation hospital between January 2019 and December 2021. A pulmonary rehabilitation team used a standardized tracheostomy decannulation protocol developed by the authors.