RESUMEN
The 5-fluoroalkyl-1,2,3-triazoles, serving as a pivotal element in medicinal chemistry, hold substantial research significance. In this work, we developed a furan dearomatization reaction for the synthesis of various 5-fluoroalkyl-1,2,3-triazoles, which contains -CF3, -CF2H, -CF2CF3, -CF2CF2CF3, -CF2CO2Et, and -C6F5. This methodology relies on the intermolecular [3 + 2] cycloaddition/furan ring-opening triggered by α-fluoroalkyl furfuryl cation with azides to stereoselectively synthesize a series of (E)-fluoroalkyl enone triazoles. The reaction proceeds without metal participation, exhibits excellent substrate tolerance, and has excellent synthetic utility.
RESUMEN
Furan ring opening reactions are essential in organic synthesis, enabling the incorporation of diverse functional groups and the construction of complex molecular structures. A highly efficient and practical method for synthesizing 2,5-dicarbonyl-3-ene-phosphates from readily available biomass furan and dialkyl phosphonates is reported. The reaction, catalyzed by FeCl3, demonstrated wide substrate scope and high synthetic efficiency. Gram-scale synthesis was achieved, and a one-pot reaction provided a quick access route to the desired compounds. Additionally, a successful Diels-Alder reaction highlighted the versatility of the methodology.
RESUMEN
A dearomative dimerization of furfuryl azides for the construction of furfuryl triazoles is developed. As a rare leaving group, azide is capable of initiating the generation of a furfuryl cation under the Lewis acid-catalyzed conditions, followed by reacting with the other azide to realize an intermolecular [3 + 2] cycloaddition/furan ring-opening cascade. By extending the reaction time, a fragmentation reaction of resulting furfuryl triazoles occurs to afford 1H-triazoles in high yield. Control studies demonstrated that key furfuryl cations also can be obtained from furfuryl triazoles. Furthermore, a chemoselective cross-cycloaddition can be achieved between furfuryl azides and a benzyl azide.
Asunto(s)
Alquinos , Azidas , Catálisis , Reacción de Cicloadición , Dimerización , TriazolesRESUMEN
Triazole phosphonates are valuable structural motifs in chemical biology and the subject of growing recent interest. A novel methodology to synthesize triazolyl phosphonates starting from furfuryl phosphonate alcohols and organo-azides was developed. This method involved an intermolecular copper-catalyzed dearomatized [3 + 2] cycloaddition/furan ring-opening cascade reaction. A strategy involving a three-component reaction was realized for quick access to triazole phosphonates.
Asunto(s)
Cobre , Organofosfonatos , Alquinos/química , Catálisis , Cobre/química , Reacción de Cicloadición , Furanos , Triazoles/químicaRESUMEN
Oxidation reactions have been extensively studied in the context of the transformations of biomass-derived furans. However, in contrast to the vast literature on utilizing the stoichiometric oxidants, such as m-CPBA and NBS, catalytic methods for the oxidative furan-recyclizations remain scarcely investigated. Given this, we report a means of manganese-catalyzed oxidations of furan with low loading, achieving the Achmatowicz rearrangement in the presence of hydrogen peroxide as an environmentally benign oxidant under mild conditions with wide functional group compatibility.
Asunto(s)
Peróxido de Hidrógeno , Oxidantes , Catálisis , Manganeso , Oxidación-ReducciónRESUMEN
A new multicomponent synthesis of functionalized enamidyl triazoles starting from simple and readily available starting materials is described. A simple treatment of a dichloromethane solution of an azide, amine, and 5-bromo-2-furylcarbinol with a Lewis acid provides the enamidyl triazole in good to high yield. A triple domino sequence, formal [3+2] cycloaddition/ring-opening/amidation, is involved in this new skeleton-generating reaction.
RESUMEN
Novel warm-white emitting phosphors CaIn2O4:Dy3+ co-doped with Gd3+, Zn2+, or Al3+ ions were prepared by solid state reaction. In this paper, a strategy of co-doping with different ions was used with the aim of affecting the luminescence properties of CaIn204:0.6%Dy3+ under NUV excitation. The luminescence intensities of CaIn2O4:0.6%Dy3+ were enhanced by 0.2% Gd3+ or 0.2% Zn2+ ions co-doping under 367 nm excitation, but lowered by co-doping with 0.2% Al3+ ions. Furthermore, the chromaticity coordinates of CaIn2O4:0.6%Dy3+ can be tuned from the cold-white region to warm-white region with Gd3+ or Zn2+ ions co-doping. These findings show that CaIn2O4:0.6%Dy3+,0.2% Gd3+, and CaIn2O4:0.6%Dy3+,0.2% Zn2+ have potential application value as new warm-white LED phosphors.
Asunto(s)
Compuestos de Calcio/síntesis química , Mediciones Luminiscentes/métodos , Nanopartículas del Metal/química , Nanopartículas del Metal/ultraestructura , Cristalización/métodos , Luz , Luminiscencia , Ensayo de Materiales , Tamaño de la PartículaRESUMEN
The transcriptional activator ß-catenin is the primary mediator of the canonical Wnt/ß-catenin signaling pathway. The aberrant formation of the ß-catenin/T-cell factor (Tcf) complex leads to many cancers and organ fibroses. Selective inhibition of ß-catenin/Tcf protein-protein interactions represents an appealing therapeutic strategy. In this study, two new robust, homogeneous high-throughput assays, AlphaScreen and fluorescence polarization, were established to study ß-catenin/Tcf interactions. These two new assays reproduce native ß-catenin/Tcf interactions, quantify inhibitory potency, and are complementary with each other. The establishment of these two high-throughput screenings enables quick identification of inhibitors of ß-catenin/Tcf protein-protein interactions.
Asunto(s)
Ensayos Analíticos de Alto Rendimiento/métodos , Factores de Transcripción TCF/metabolismo , beta Catenina/metabolismo , Secuencia de Aminoácidos , Unión Competitiva , Biotinilación , Polarización de Fluorescencia , Humanos , Cinética , Datos de Secuencia Molecular , Péptidos/química , Péptidos/metabolismo , Unión Proteica , Coloración y Etiquetado , Factores de TiempoRESUMEN
A platinum-catalyzed tandem reaction involving enynyl ester isomerization and subsequent intramolecular [3 + 2] cyclization has been developed. This strategy provides an efficient approach to five-, six-, or seven-membered cyclic polyfunctional compounds.
RESUMEN
The highly stereoselective syntheses of four diastereomers of natural 3,9,12-trihydroxycalamenene are described. The syntheses highlight the utility of an unusual framework of benzobicyclo[3.3.1] lactones, which were accomplished via an intramolecular Friedel-Crafts-type Michael addition of alpha,beta-unsaturated lactones.
Asunto(s)
Compuestos Bicíclicos con Puentes/química , Terpenos/síntesis química , Lactonas/química , Estructura Molecular , Sesquiterpenos Policíclicos , Estereoisomerismo , Terpenos/químicaRESUMEN
The 1,2,3-triazole-containing polycyclic architecture widely exists in a broad spectrum of synthetic bioactive molecules, and the development of expeditious methods to synthesize these skeletons remains a challenging task. In this work, the catalytic cyclization of biomass-derived 2-furylcarbinols with an azide to form fused triazoles is described. This approach takes advantage of a single catalyst Yb(OTf)3 and operates via a furfuryl-cation-induced intramolecular [3 + 2] cycloaddition/furan ring-opening cascade.
RESUMEN
An Fe(III)-catalyzed intramolecular N-N coupling of aliphatic azidoamines that forms diverse five- and six-membered semisaturated diazoheterocycles using air as an oxidant is reported, providing an alternative to hydrazine-based methods. Mechanistic studies suggest that a N-radical induced intramolecular homolytic substitution (SH2) is involved in ring closure. The power of this N-N bond-forming method is also demonstrated by using it as the final step in a total synthesis of (-)-newbouldine.
RESUMEN
A novel stereospecific synthesis of ( Z)- and ( E)-ß-triazole-acrylates by the combined use of a multicomponent reaction and photocatalyst-free photoisomerization is presented. The former can be regarded as a furfuryl cation induced formal [3 + 2]-cycloaddition/ring-opening/esterification domino sequence, which provides fast access to a variety of structurally diverse ( Z)-ß-triazole-acrylates. The products were further photoisomerized to ( E)-configuration by UV irradiation. This efficient strategy was utilized in the concise synthesis of histone deacetylase inhibtor NSC746457 in high yield.
RESUMEN
A TiCl4-promoted cascade formal [3 + 2] cycloaddition/double ring-opening/chlorination of 2-furylcyclobutanols with alkyl or aryl azides is described. This highly efficient transformation involves the formation/cleavage of several C-N, C-Cl, C-C, and C-O bonds in a single operation. It enables the quick construction of trisubstituted 1,2,3-triazoles with an ( E)-enone moiety and a 3-chloropropyl unit. The chlorinated products are readily transformed into other structurally diverse analogues.
RESUMEN
A Lewis acid promoted cascade cycloaddition/ring-opening of 2-furylcarbinols with alkyl or aryl azides is described. The reaction features an initial formal [3 + 2] cycloaddition to form a trisubstitued triazole motif, followed by a ring opening of furan to generate the (E)-configuration of the enone. A wide range of highly functionalized triazoles is expediently and efficiently synthesized in a highly step-economical manner.
Asunto(s)
Azidas/química , Furanos/química , Triazoles/síntesis química , Catálisis , Técnicas Químicas Combinatorias , Reacción de Cicloadición , Ácidos de Lewis/química , Estructura Molecular , Estereoisomerismo , Triazoles/químicaRESUMEN
A new hot spot-based design strategy using bioisostere replacement is reported to rationally design nonpeptidic small-molecule inhibitors for protein-protein interactions. This method is applied to design new potent inhibitors for ß-catenin/T-cell factor (Tcf) interactions. Three hot spot regions of Tcf for binding to ß-catenin were quantitatively evaluated; the key binding elements around K435 and K508 of ß-catenin were derived; a bioisostere library was used to generate new fragments that can match the proposed critical binding elements. The most potent inhibitor, with a molecular weight of 230, has a Kd of 0.531 µM for binding to ß-catenin and a Ki of 3.14 µM to completely disrupt ß-catenin/Tcf interactions. The binding mode of the designed inhibitors was validated by the site-directed mutagenesis and structure-activity relationship (SAR) studies. This study provides a new approach to design new small-molecule inhibitors that bind to ß-catenin and effectively disrupt ß-catenin/Tcf interactions specific for canonical Wnt signaling.
Asunto(s)
Diseño de Fármacos , Bibliotecas de Moléculas Pequeñas/farmacología , Factores de Transcripción TCF/antagonistas & inhibidores , beta Catenina/antagonistas & inhibidores , Polarización de Fluorescencia , Modelos Moleculares , Estructura Molecular , Peso Molecular , Unión Proteica/efectos de los fármacos , Bibliotecas de Moléculas Pequeñas/síntesis química , Bibliotecas de Moléculas Pequeñas/química , Relación Estructura-ActividadRESUMEN
The angularly fused 6,3,5-tricyclic system is readily generated via a cascade cyclization under acid promotion. The reaction proceeds at room temperature with high stereochemical fidelity from the electrophilic center of the epoxide to the cyclopropane product. This methodology provides a potentially useful approach for the synthesis of mycorrhizin A and its analogues.
Asunto(s)
Antibacterianos/síntesis química , Productos Biológicos/síntesis química , Cumarinas/síntesis química , Antibacterianos/química , Productos Biológicos/química , Técnicas Químicas Combinatorias , Cumarinas/química , Ciclización , Estructura MolecularRESUMEN
A step-economic method to construct the tetrahydropyran ring, involving sequential benzylic/allylic C-H bond activation via DDQ oxidation and nucleophilic attack of an unactivated olefin, is described. The equatorial-trisubstituted Prins products are obtained from benzyl and allyl homoallylic ethers with high yield and stereochemical fidelity.
Asunto(s)
Éteres/química , Piranos/síntesis química , Ciclización , Cicloparafinas/química , Cloruro de Metileno/química , Oxidación-Reducción , Piranos/químicaRESUMEN
Concise and efficient total syntheses of 11-alpha-methoxycurvularin and 11-beta-methoxycurvularin were accomplished for the first time. The three-component linchpin coupling and intramolecular acylation reactions were key steps, in which we found the spectral data of 11-alpha-methoxycurvularin and 11-beta-methoxycurvularin, reported in the literature, were reversed with each other.