Synthesis of Sulfone Methylene-Substituted Indolines by Radical Cascade Cyclization of 2-Alkynylaniline Derivatives.

A radical cascade cyclization of 2-alkynylaniline derivatives with sulfonyl chlorides was developed to construct C3-sulfone methylene-substituted indolines in yields of 21 to 85% with a broad substrate scope under metal- and base-free conditions. This protocol could simultaneously build three new chemical bonds and employ a solvent-radical relay strategy, providing a rapid and concise approach toward an indoline framework. Scale-up reactions of this method and further transformations to afford useful indolines were also demonstrated.

Enantioselective de novo construction of 3­oxindoles via organocatalyzed formal [3 + 2] annulation from simple arylamines.

The de novo construction of enantioenriched 3-hydroxyindolenines and 3-oxindoles from easily available starting materials has been highly desired. Herein, an enantioselectively intermolecular direct [3 + 2] annulation of aryl amine with 2,3-diketoesters to construct 3-hydroxyindolenines with a chiral tertiary alcohol has been disclosed. The results of control experiments and DFT calculation revealed that π - π interaction plays a pivotal role in the enantioselectivity-determining process of [3 + 2] annulation. The following unusual concerted [1,2]-ester migration provides a family of chiral 3-oxindoles in good to excellent yields with excellent enantioselectivity.

Insight on photocatalytic synchronous oxidation and reduction for pollutant removal: Chemical energy conversion between macromolecular organic pollutants and heavy metal.

Collaborative treatment of pollutants is a promising approach for wastewater treatment. In this work, a covalent organic framework material (COFs) with an imine structure was synthesised by the Schiff base reaction, and photochemical tests showed good photochemical effects. It was used to explore the photocatalytic treatment of co-existing pollutants (heavy metal ions and antibiotics) and the performance of treating co-existing wastewater was investigated. The degradation performance of levofloxacin (LVX) and Cr(VI) was improved in the coexisting pollutants system, with the LVX degradation being 4.2 times more effective than that of the LVX solitary system. Moreover, this phenomenon was also observed in LVX/Ag(I), LVX/Fe(III), sulfadiazine/Cr(VI), norfloxacin/Cr(VI) and tetracycline/Cr(VI) systems. The analysis of active species suggesting that the synergistic promotion of photocatalytic oxidation-reduction systems was not only promoting from the improvement of simple charge separation, but it was also found that high-valent metal species can act directly in the oxidative decomposition of antibiotics. The interaction of pollutants and intermediates were rationally exploited and confirmed by control experiments and theoretical calculation. This conclusion helps us to re-examine the underlying mechanisms of photocatalytic synchronous oxidation and reduction reactions, simultaneously beneficial for the development of mixed pollutant control processes.

Copper-Catalyzed Bifunctionalization/Annulation of Unactivated Alkene with Alkyl Bromides.

ß-Lactam is a ubiquitous scaffold in bioactive compounds and pharmaceuticals. Herein, we disclose a streamlined method for the construction of ß-lactams starting from unactivated alkenes and alkyl bromides via a Cu-catalyzed inter-/intramolecular carboamidation. This reaction proceeded smoothly under mild reaction conditions and exhibited a broad substrate scope and various functional groups. This protocol is not only compatible with 1, 2, and 3° alkyl bromides but also suitable for α-bromo nitrile as well as various benzyl bromides. The mechanism exploration indicated that sequential radical addition/reductive elimination was involved.

Thiol-promoted intermolecular cyclization to synthesize 1,2,4-oxadiazoles including tioxazafen under transition metal-free conditions.

A simple and efficient one-pot intermolecular annulation reaction for the synthesis of 1,2,4-oxadiazoles from amidoximes and benzyl thiols has been developed, in which benzyl thiols act as not only reactants but also organo-catalysts. The control experiments proved that thiol substrates could facilitate the dehydroaromatization step. High yield, functional group diversity and transition metal-free, extra oxidant-free, and mild conditions are the important practical features. Moreover, this protocol provides an effective alternative method for the synthesis of a commercially available broad-spectrum nematicide, tioxazafen.

Transition Metal-Controlled Divergent Annulations of Azomethine Imines with Iodonium Ylides via C-Centered [1,2]-Rearrangement.

Transition metal-controlled divergent annulation reactions of azomethine imines with iodonium ylides via C-centered [1,2]-rearrangement have been developed. The azomethine imino group, as a switchable and transient directing group (DG), underwent intramolecular nucleophilic addition and in situ generated bicyclic diaziridine, which facilitated the C-centered [1,2]-rearrangement and subsequent divergent annulations in the presence of different metal complexes as the catalysts. The benzo[c]chromen-1-one and pyrano[de]isochromene scaffolds could be independently constructed with Rh(III) and Ru(II), respectively. It was worth noting that the azomethine imino group was employed first as the switchable DG through rearrangement progress.

Copper-Catalyzed Hydroxyperfluoroalkylation of Unactivated Alkenes: Access to ß-Perfluoroalkyl Alcohols.

An expeditious copper-catalyzed three-component hydroxyperfluoroalkylation of unactivated alkenes starting from commercially available perfluoroalkyl iodides and an O2 molecule from air as the oxygen source was developed. The Cu/B2pin2 catalytic system offered a novel pattern for the generation of perfluoroalkyl radicals and overcame the previous limitations in the hydroxyperfluoroalkylation of unactivated alkenes. This catalytic protocol features high regioselectivity and broad substrate scope to access valuable ß-perfluoroalkyl alcohols expediently. 18O-labeling experiments demonstrated that the oxygen atom of the OH group stems from O2 in air.

2-Butyne Biscarbonate as a "Bridge" in Rhodium(III)-Catalyzed [4 + 2] Cyclization and Diels-Alder Reaction.

Described herein is the development of an unprecedented approach to construct multiple heterocycles with high selectivity through Rh(III)-catalyzed two- or three-component cyclization reaction from simple and readily available starting materials: N-methoxybenzamides, 2-butyne biscarbonate, and maleimides. This methodology provides an efficient strategy for the synthesis of diverse and complicated heterocycles in a one-pot manner and displays excellent features of extremely mild reaction conditions, easy operation, excellent regioselectivity, and good functional group compatibility.

Synthesis of Difluoroarymethyl-Substituted Benzimidazo[2,1-a]isoquinolin-6(5H)-ones under Mild Conditions.

A highly efficient method for synthesis of difluoroarymethyl-substituted benzimidazo[2,1-a]isoquinolin-6(5H)-ones using 2-arylbenzoimidazoles with α,α-difluorophenylacetic acid as reaction substrates has been developed through radical cascade cyclization. The advantage of this strategy lies in excellent functional group tolerance to generate the corresponding products in good yields under base- and metal-free conditions.

TBAI-Catalysed Formal [4+4]-Cycloaddition: Easy Access to Oxa-Bridged Eight-Membered Heterocycles.

TBAI-catalysed [4+4]-cyclization reaction of anthranils with hydrazones to deliver oxa-bridged eight-membered heterocycles in accepted yields was developed. Preliminary mechanistic studies indicated that the reaction involved the in situ generation of vinyldiazenes from readily available hydrazones followed by an aza-Michael addition of the anthranil substrates onto the vinyldiazenes and subsequent annulation. This transformation involved the formation of two new C-N bonds and C-O bond in one pot, overcoming the synthetic limitations of anthranils in organic chemistry. This strategy benefits from high efficiency and atomic economy with mild reaction conditions.

MiR-302c-5p affects the stemness and cisplatin resistance of nasopharyngeal carcinoma cells by regulating HSP90AA1.

Nasopharyngeal carcinoma (NPC) is one of the most frequent malignant tumors diagnosed in China. Cisplatin is one of the most commonly used anticancer drugs containing platinum in combined chemotherapy. The molecular mechanism of NPC is still largely unknown, and we aim to spare no effort to elucidate it. Normal human nasopharyngeal epithelial cells and NPC cell lines were cultured. The expression levels of miR-302c-5p and HSP90AA1 were detected with quantitative real-time PCR. Western blotting was used to analyze levels of the HSP90AA1, protein kinase B (AKT), p-AKT, CD44 and SOX2 proteins. The interaction between miR-302c-5p and HSP90AA1 was detected using a luciferase reporter assay. The bicinchoninic acid assay was used to observe cisplatin resistance in NPC cells. Our records confirmed that the expression of miR-302c-5p was substantially reduced and HSP90AA1 was increased in NPC cells. Additionally, miR-302c-5p inhibited cisplatin resistance and the traits of stem cells in NPC. A luciferase assay confirmed that miR-302c-5p is bound to HSP90AA1. Overexpression of HSP90AA1 may reverse the effects of overexpressed miR-302c-5p and inhibit cisplatin resistance and stem cell traits of NPC. This study investigated whether miR-302c-5p inhibited the AKT pathway by regulating HSP90AA1 expression and altered the resistance of NPC cells to cisplatin and the traits of tumor stem cells, which has not yet been reported.

Ruthenium-Catalyzed ortho-C-H Hydroxyfluoroalkylation of Arenes with Fluorinated Alcohols.

A facile and mild Ru(II)-catalyzed ortho-C-H hydroxyfluoroalkylation of arenes with cheap and easily accessible fluorinated alcohols has been developed in the presence of 2,2,6,6-tetramethyl-1-piperidinyloxyl (TEMPO). The readily available fluorinated alcohols were used as hydroxyfluoroalkylation reagents to form various α-aryl-α-trifluoromethyl alcohols. The present work provides a new method for the introduction of hydroxyfluoroalkyl groups into arenes.

Lewis Acid-Catalyzed [3 + 2]-Cyclization of Iodonium Ylides with Azadienes: Access to Spiro[benzofuran-2,2'-furan]-3-ones.

A highly regioselective synthesis of spiro[benzofuran-2,2'-furan]-3-ones has been explored via Lewis acid-catalyzed [3 + 2] cyclization of iodonium ylides with azadienes. The acidity of the Lewis acid was significantly strengthened with strong hydrogen bond donors, thereby promoting the enolization isomerization of iodonium ylides for the subsequent cycloaddition. This reaction was compatible with a broad range of substrates under the mild reaction conditions, and efficiently delivered spiro-heterocycles with excellent stereoselectivity.

[4 + 2] cycloaddition reactions of ß-naphtha-1-thioquinones generated from 2-naphthols and DAST.

An original and facile method for the generation of ß-naphtha-1-thioquinones using DAST and 2-naphthols has been developed. A series of dehydro-2-naphthol-1-sulphides or naphtha-oxathiane derivatives were synthesized by in situ Diels-Alder cycloaddition reactions of ß-naphtha-1-thioquinone with itself or various alkenes.

A simple approach to C3-ethoxycarbonylmethylation of thiophenes/furans with diethyl bromomalonate.

A mild and efficient visible-light-induced radical method was developed to produce C3-malonated five-membered heterocycles using 2-substituted thiophenes/furans and diethyl bromomalonate as the starting materials. Various 2-substituted (benzo)thiophenes/furans were suitable for the C3-ethoxycarbonylmethylation. The free radical mechanism was proposed based on the results of control experiments, cyclic voltammetry experiments and luminescence quenching experiments. We suggested that the heteroleptic halogen-bridged iridium(III) dimers might play an important role in this system.

Copper-assisted trifluoromethylthiolation/radical cascade cyclization of alkynes to construct SCF3-containing dioxodibenzothiazepines.

A mild and efficient Cu-assisted trifluoromethylthiolation/radical cascade cyclization of alkynes with readily available and stable AgSCF3 as the trifluoromethylthiolating reagent has been disclosed. This transformation provides an opportunity to construct a series of potential medicinally valuable trifluoromethylthio-substituted dioxodibenzothiazepines with wide functional group compatibility. This protocol opens up a new avenue for the construction of useful trifluoromethylthiolated seven-membered N-heterocycles.

EIF4A3-induced circFIP1L1 represses miR-1253 and promotes radiosensitivity of nasopharyngeal carcinoma.

BACKGROUND: Radiation is currently used to be a mainstay of salvage therapy for nasopharyngeal carcinoma (NPC), however, development of radioresistance largely limits the radiation efficacy. Circular RNAs (circRNAs) have been shown to affect NPC progression, but its role in radioresistance remain unclear. METHODS: The circular structure of circFIP1L1(circ_0069740) was verified by RNA-sequencing, RT-PCR based on gDNA or cDNA, RNase R treatment, and actinomycin D treatment. Cellular localization of circFIP1L1 and miR-1253 was detected by nucleoplasmic separation and/or fluorescence in situ hybridization. Expression of non-coding RNAs and mRNAs was detected by qRT-PCR, protein expression was detected by Western blot. Functionally, EdU, CCK-8, and colony formation experiments were employed to assess cell proliferation, flow cytometry was adopted to estimate cell cycle and apoptosis. Xenograft tumor growth was performed to detect the role of circFIP1L1 in vivo. Mechanistically, we examined the interplay between miR-1253 and circFIP1L1 or EIF4A3 through dual-luciferase reporter assay. The potential regulatory impacts of EIF4A3 on circFIP1L1 or PTEN was examined by RNA immunoprecipitation and RNA pull-down assays. RESULTS: CircFIP1L1 overexpression and miR-1253 knockdown repressed NPC cell proliferation, facilitated NPC cell apoptosis, and enhanced NPC radiosensitivity. Mechanistically, circFIP1L1 was revealed to repress miR-1253 by binding to it, and EIF4A3 is a target gene of miR-1253. CircFIP1L1 regulated NPC proliferation, apoptosis, and radiosensitivity through miR-1253/EIF4A3. Moreover, we found that EIF4A3 bound to FIP1L1 mRNA transcript and induced circFIP1L1 formation, and thus stabilizing PTEN mRNA. CONCLUSION: Our findings suggested that EIF4A3-induced circFIP1L1 repressed NPC cell proliferation, facilitated NPC cell apoptosis, and enhanced NPC radiosensitivity by miR-1253.

Cobalt(II)-Catalyzed C-H and N-H Functionalization of 1-Arylpyrazolidinones with Dioxazolones as Bifunctional Synthons.

Dioxazolone has been attractive as an important synthon for a direct C-H amidation through a nitrene intermediate or Curtius rearrangement to form the isocyanate. However, the combination of two reaction models of dioxazolone has not been reported. Herein, a cobalt-catalyzed C-H and N-H functionalization of 1-arylpyrazolidinones with dioxazolones was developed. The dioxazolones acted as an amidated and carboxamidated reagent. Three C-N bonds were formed in a "one-pot" manner, which promoted the requirement of synthetic diversity.

Pd-Pd/PdO as active sites on intercalated graphene oxide modified by diaminobenzene: fabrication, catalysis properties, synergistic effects, and catalytic mechanism.

Pd-Pd/PdO nanoclusters well dispersed on intercalated graphene oxide (GO) (denoted as GO@PPD-Pd) were prepared and characterized. GO@PPD-Pd exhibited high catalytic activity (a TOF value of 60 705 h-1) during the Suzuki coupling reaction, and it could be reused at least 6 times. The real active centre was Pd(200)-Pd(200)/PdO(110, 102). A change in the Pd facets on the surface of PdO was a key factor leading to deactivation, and the aggregation and loss of active centres was also another important reason. The catalytic mechanism involved heterogeneous catalysis, showing that the catalytic processes occurred at the interface, including substrate adsorption, intermediate formation, and product desorption. The real active centres showed enhanced negative charge due to the transfer of electrons from the carrier and ligands, which could effectively promote the oxidative addition reaction, and Pd(200) and the heteroconjugated Pd/PdO interface generated in situ also participated in the coupling process, synergistically boosting activity. Developed GO@PPD-Pd was a viable heterogeneous catalyst that may have practical applications owing to its easy synthesis and stability, and this synergistic approach can be utilized to develop other transition-metal catalysts.

Rh(III)-Catalyzed Synthesis of Indazolo[2,3-a]quinolines: Vinylene Carbonate as C1 and C2 Building Blocks.

A rhodium-catalyzed cyclization of azobenzenes and vinylene carbonate via C-H bond activation to construct indazolo[2,3-a]quinolines has been developed. This protocol offers an efficient method for synthesis of the titled products in good yields with broad functional group tolerance. In this reaction, three C-C bonds and C-N bond are formed in one pot, and vinylene carbonate (VC) acts as C1 and C2 synthons as well as "vinylene transfer" agent and acylation reagent in the construction of target-fused heterocycles. Moreover, the products exhibit favorable fluorescence properties, which indicate their potential application as fluorescent materials and biosensors.