RESUMO
An unexpected deprotonative process of thiirenium ions is presented, which provides a new synthesis of aryl thioalkynes directly from terminal alkynes via the electrophilic activation of the carbon-carbon triple bonds. The conditions are well compatible with various functional-group-substituted aryl alkynes. The direct elimination from the thiirenium ion intermediate, or its tautomer, benzyl vinyl carbocation, is supported by control experiments and labeling reaction.
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Oxidative cross-coupling of two thiols is the most direct tool for the synthesis of unsymmetrical disulfides and highly desirable across academia and industry. However, the inevitable formation of significant amounts of the corresponding symmetrical by-products is a major issue. We herein present a method toward the synthesis of unsymmetrical disulfides in which the homo-coupling of the thiols is effectively inhibited by adding the two thiols sequentially, taking advantage of rapid oxidation of the thiol by bromodimethylsulfonium bromide.
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A new metal-free synthesis of pyrrole from allyl ketone and amine has been established. The reaction proceeds via an thiolative activation of the C-C double bond with dimethyl(methylthio)sulfonium trifluoromethanesulfonate, followed by a nucleophilic ring-opening addition of primary amine to the generated episulfonium intermediate, and then an internal condensation and aromatization. This mild procedure provides a novel strategy to the construction of substituted pyrroles through a formal [4 + 1] cycloaddition reaction.
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Methylthioether is involved in the methylthiotransfer process in organisms, and therefore its functionality is of paramount importance to living organisms. Several methods for the installation of the methylthio group in small molecules have been reported previously; however, procedures starting from unactivated alkenes are rare. Herein, we report a formal hydro/deuteromethylthiolation of alkenes by using dimethyl(methylthio)sulfonium trifluoromethanesulfonate as the stimulator and sodium borohydride/deuteride as the hydrogen/deuterium source. The process represents a mild, transition metal-free and methanethiol-free route towards the synthesis of methylthioethers from unactivated alkenes.
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The synthesis of pyridines through direct intermolecular cycloaddition of alkynes and nitriles is a contemporary challenge in organic synthesis. A Brønsted acid mediated formal [2+2+2] cycloaddition of heteroalkynes and nitriles was developed that proceeds under mild conditions. This constitutes a modular approach to highly substituted pyridine cores.
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A Brønsted acid catalyzed redox arylation of ynamides that employs aryl sulfoxides as the arylating agents is reported. This metal-free transformation proceeds at room temperature and efficiently affords α-arylated oxazolidinones in a redox-neutral, atom-economic fashion.
RESUMO
Sulfur-containing amino acids and peptides play critical roles in organisms. Thiol-ene reactions between the thiol residues of L-cysteine and the alkenyl fragments in the designed coupling partners serve as primary tools for constructing CâS bonds in the synthesis of unnatural sulfur-containing amino acid derivatives. These reactions are favored due to the preference for hydrogen transfer from thiol to ß-sulfanyl carbon radical intermediates. In this paper, the study proposes utilizing carbon-centered radicals stabilized by the capto-dative effect, generated under photocatalytic conditions from N-aryl glycine derivatives. The aim is to compete with the thiol hydrogen, enabling radical CâC bond formation with ß-sulfanyl carbon radicals. This protocol is robust in the presence of air and water, offers significant potential as a modular and efficient platform for synthesizing sulfur-containing amino acids and modifying peptides, particularly with abundant disulfides and styrenes.
Assuntos
Carbono , Glicina , Peptídeos , Estirenos , Enxofre , Peptídeos/química , Peptídeos/síntese química , Glicina/química , Glicina/análogos & derivados , Enxofre/química , Carbono/química , Estirenos/química , Radicais Livres/química , CatáliseRESUMO
Carboxylic functionalities are among the pivotal groups in bioactive molecules and in the synthesis of new lead compounds because of their unique character in the formation of hydrogen bonds and the possibility of constructing molecular complexes via amide couplings. We adopt the reductive radical-polar crossover strategy to introduce carboxyalkyl groups into arenes with styrenes and CO2 via thianthrenium salts. This protocol exhibits excellent potential as a straightforward and modular platform for site-selective carboxylative derivation of bioactive molecules.
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Micro-nano-plastic (MNP) particles (p) in the environment can enter the human body and pose a potential threat to human health. However, it is unknown whether these substances are present in polypropylene (PP) plastic-bottled injections, which are used as high-frequency intravenous infusions to treat diseases. Therefore, the objective of this study was to identify and quantify insoluble MNP particles in 16 batches of injectable formulations within the validity period. Primarily, ethylene-propylene copolymer or P(E-P) micro-plastic (MP) particles (2-10 µm, 216 p/mL) were identified by micro-Raman spectroscopy, and nano-particles (<50 nm, 2.1 × 104 p/mL) similar to PP containing only carbon were detected by scanning electron microscopy-energy-dispersive X-ray spectroscopy (photoelectron). Furthermore, P(E-P) MP particles (1 × 103 to 1 × 105 ng/L) from the injections were enriched on the GF-B filter, and PP or P(E-P) nano-plastic (NP) particles (1 × 103 to 4 × 104 ng/L) enriched on the alumina film were detected by pyrolysis-gas chromatography/mass spectrometry. Finally, the total insoluble particles in injections were 6 × 104 to 1 × 107 p/mL (0.02-100 µm). Our findings are the first to identify and quantify MNPs in PP-bottled injections. Considering that they can enter the blood circulation, so whether cause disease remains to be investigated.
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A practical method that enables the fluorosulfenylation of unactivated alkenes processed directly with thiols and fluoride salts is presented. Good to excellent efficiencies and functional group tolerance are observed for both alkene substrates and thiols. The procedure also allows the use of gaseous ethylene as a two-carbon building block for ß-fluoro thioether products.
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C-Glycosyl peptides possess excellent metabolic stability and therapeutic properties and thus play critical roles in biological studies as well as drug discoveries. However, the limited accessibility of C-glycosyl amino acids has significantly hindered the broader research of their structural features and mode of action. Herein, for the first time we disclose a novel visible-light-driven radical conjugate addition of 1,4-dihydropyridine (DHP)-derived glycosyl esters with dehydroalanine derivatives, generating C-glycosyl amino acids and C-glycosyl peptides in good yields with excellent stereoselectivities. Redox-active glycosyl esters, as readily accessible and bench-stable radical precursors, could be easily converted to glycosyl radicals via anomeric C(sp3)-O bond homolysis under mild conditions. Importantly, the generality and practicality of this transformation were fully demonstrated in >40 examples including 2-dexosugars, oligosaccharides, oligopeptides, and complex drug molecules. Given its mild reaction conditions, robust sugar scope, and high anomeric control and diastereoselectivity, the method presented herein could find widespread utility in the preparation of C(sp3)-linked sugar-based peptidomimetics.
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Tetraphenylethylene (TPE)-based ligands are appealing for constructing metal-organic frameworks (MOFs) with new functions and responsiveness. Here, we report a non-interpenetrated TPE-based scu Zr-MOF with anisotropic flexibility, that is, Zr-TCPE (H4TCPE = 1,1,2,2-tetra(4-carboxylphenyl)ethylene), remaining two anisotropic pockets. The framework flexibility is further anisotropically rigidified by installing linkers individually at specific pockets. By individually installing dicarboxylic acid L1 or L2 at pocket A or B, the framework flexibility along the b-axis or c-axis is rigidified, and the intermolecular or intramolecular motions of organic ligands are restricted, respectively. Synergistically, with dual linker installation, the flexibility is completely rigidified with the restriction of ligand motion, resulting in MOFs with enhanced stability and improved separation ability. Furthermore, in situ observation of the flipping of the phenyl ring and its rigidification process is made by 2H solid-state NMR. The anisotropic rigidification of flexibility in scu Zr-MOFs guides the directional control of ligand motion for designing stimuli-responsive emitting or efficient separation materials.
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Lack of MHC-II is emerging as a causal factor in cancer immune evasion, and the development of small-molecule MHC-II inducers is an unmet clinical need. Here, we identified three MHC-II inducers, including pristane and its two superior derivatives, that potently induce MHC-II expression in breast cancer cells and effectively inhibit the development of breast cancer. Our data suggest that MHC-II is central in promoting the immune detection of cancer to increase the tumor infiltration of T cells and enhance anti-cancer immunity. By discovering the malonyl/acetyltransferase (MAT) domain in fatty acid synthase (FASN) as the direct binding target of MHC-II inducers, we demonstrate that evasion of immune detection and cancer metabolic reprogramming are directly linked by fatty acid-mediated MHC-II silencing. Collectively, we identified three MHC-II inducers and illustrated that lack of MHC-II caused by hyper-activated fatty acid synthesis to limit immune detection is a potentially widespread mechanism underlying the development of cancer.
Assuntos
Neoplasias da Mama , Antígenos de Histocompatibilidade Classe II , Humanos , Feminino , Antígenos de Histocompatibilidade Classe II/metabolismo , Linfócitos T , Ácidos GraxosRESUMO
Vinyl triflates are commonly employed as electrophilic vinyl sources in complex synthesis. The triflation of enolates is commonly required for the preparation of vinyl triflates, generally under strongly basic conditions. Herein, the reaction between alkynes and dimethyl(methylthio)sulfonium trifluoromethanesulfonate is presented, which leads to the development of a facile synthesis of ß-methylthio vinyl triflates in a chemo-, regio-, and stereoselective manner under neutral and extremely simple conditions.
RESUMO
Photocatalytic CO2 reduction reaction has been developed as an effective strategy to convert CO2 into reusable chemicals. However, the reduction products of this reaction are often of low utilization value. Herein, we effectively connect photocatalytic CO2 reduction and amino carbonylation reactions in series to reconvert inexpensive photoreduction product CO into value-added and easily isolated fine chemicals. In this tandem transformation system, we synthesize an efficient photocatalyst, NNU-55-Ni, which is transformed into nanosheets (NNU-55-Ni-NS) in situ to improve the photocatalytic CO2-to-CO activity significantly. After that, CO serving as reactant is further reconverted into organic molecules through the coupled carbonylation reactions. Especially in the carbonylation reaction of diethyltoluamide synthesis, CO conversion reaches up to 85%. Meanwhile, this tandem transformation also provides a simple and low-cost method for the 13C isotopically labeled organic molecules. This work represents an important and feasible pathway for the subsequent separation and application of CO2 photoreduction product.
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BACKGROUND: Several recent findings have revealed that targeting of cell cycle reentry and (or) progression may provide an opportunity for the therapeutic intervention of Alzheimer's disease (AD). FOXG1 has been shown to play important roles in pattern formation, cell proliferation, and cell specification. Thus far, the roles of FoxG1 and its involvement in AD are largely unknown. OBJECTIVE: Our study aimed to explore the intervention effect of FOXG1 on AD pathology and its potential mechanism with a particular focus on cell cycle regulation. METHODS: We investigated the association of Foxg1 gene variants with AD-like behavioral deficits, p21 expression, neuronal apoptosis, and amyloid-ß (Aß) aggregate formation; we further determined whether targeting FOXG1-regulated cell cycle has therapeutic potential in AD. RESULTS: Paralleling AD-like behavioral abnormalities, neuronal apoptosis, and Aß deposits, a significant reduction in the expression of FOXG1 was observed in APP/PS1 mice at 6 months of age. Using the APP/PS1;Foxg1fl/fl-CreAAV mouse line, we found that FOXG1 potentially antagonized cell cycle reentry by negatively regulating the levels of p21-activated kinase (PAK3). By reducing p21cip1-mediated arrest at the G2 stage and regulating cyclin A1- and cyclin B-dependent progression patterns of the cell cycle, FOXG1 blocked neuronal apoptosis and Aß deposition. CONCLUSION: These results indicate that FOXG1 contributes to the regulation of the neuronal cell cycle, thereby affecting brain abnormalities in AD. An elevation of the FOXG1 level, either pharmacologically or through other means, could present a therapeutic strategy for AD.
Assuntos
Doença de Alzheimer , Fatores de Transcrição Forkhead , Proteínas do Tecido Nervoso , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Doença de Alzheimer/terapia , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Ciclo Celular , Modelos Animais de Doenças , Fatores de Transcrição Forkhead/metabolismo , Humanos , Camundongos , Camundongos Transgênicos , Proteínas do Tecido Nervoso/metabolismo , Presenilina-1/metabolismo , Quinases Ativadas por p21/metabolismoRESUMO
The electrophilic alkylthiolation of alkenes, initiated by dimethyl(methylthio)sulfonium salts and the subsequent addition of various heteronucleophilies has been well-established. Regarding the use of carbon nucleophiles, however, only carefully designed sp-type carbon sources have been successfully applied. We herein present our findings on the methylthiolation of alkenes with dimethyl(methylthio)sulfonium trifluoromethanesulfonate, followed by carbon-carbon bond formation in the presence of organozinc reagents, thus achieving a catalyst-free protocol toward to the carbosulfenylation of alkenes.
RESUMO
A novel reference film was characterized to improve the oxygen gas transmission measurement accuracy of plastic materials for pharmaceutical packaging. The material processing, homogeneity, stability, jointly determined value and uncertainty evaluation were discussed. The film is the first reference film characterized by multiple laboratories using both manometric and coulometric methods. The oxygen transmission rate of the reference film was 20.53 with the expanded uncertainty of 1.36. The newly characterized reference film can be used in the calibration and self-calibration of oxygen transmission measurement equipment and analytical method verification to improve the measurement accuracy and achieve traceable data.
RESUMO
The catalytic reductive transformation of carboxylic esters into α-branched ethers is described. The procedure pivots on the chemoselective iridium-catalyzed hydrosilylation of ester and lactone functionality to afford a silyl acetal intermediate. Upon treatment with a Lewis acid, these hemilabile intermediates dissociate to form reactive oxocarbenium ions, which can be intercepted by allyltributyltin nucleophiles, resulting in the formation of valuable α-branched alkyl-alkyl ether derivatives. This reductive allylation procedure was found to be amenable to a range of carboxylic ester starting materials, and good chemoselectivity for ethyl over tert-butyl esters was demonstrated. Furthermore, downstream synthetic manipulation of α-amino acid-derived products led to the efficient formation of pyrrolidine, piperidine, and azepane frameworks.