RESUMO
α-succinimide-substituted allenoates were employed as phosphine acceptors in phosphine-catalyzed (4 + 2) annulation with 1,1-dicyanoalkenes. They served as C4 synthons in the annulation reaction under mild reaction conditions and produced hexahydroisoindole derivatives in moderate to high yields with good to excellent diastereoselectivities.
RESUMO
In this paper, we reported the palladium-catalyzed formal [5 + 4] cycloaddition reactions between 4-vinyl-4-butyrolactones (VBLs) and azadienes. Under mild reaction conditions, a wide range of benzofuran-fused 9-membered heterocyclic compounds had been provided in moderate to excellent yields with exclusive regioselectivities and excellent diastereoselectivities. The practical applicability of the synthesis was demonstrated through scale-up reaction and further transformation.
RESUMO
In this paper, palladium-catalyzed [3 + 2] cycloaddition of 4-vinyl-4-butyrolactones with ketenes generated from easily available acyl chlorides was achieved. With Pd2(dba)3·CHCl3/XantPhos as the catalyst, the reaction proceeded smoothly under mild reaction conditions, affording a series of 2,3-dihydrofurans in moderate to high yields. The scale-up reaction and further transformations of the products are demonstrated, and a plausible mechanism is proposed as well.
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A palladium-catalyzed enantioselective umpolung allylation reaction of amido-tethered allyl carbonates with N-2,2,2-trifluoroethylisatin ketimines has been realized herein. The reaction worked well under mild reaction conditions to give various chiral oxindole derivatives in moderate to excellent yields with high enantioselectivities. Notably, this work represents the first Pd-catalyzed asymmetric umpolung allylation reaction of N-2,2,2-trifluoroethylisatin ketimines.
RESUMO
In this paper, Pd-catalyzed [4+2] decarboxylative cycloaddition of 4-vinylbenzodioxinones with barbiturate-derived alkenes has been developed, leading to various spirobarbiturate-chromane derivatives in high yields with excellent diastereo- and enantioselectivities. The scale-up reaction and further derivation of the product were demonstrated. A plausible reaction mechanism was also proposed.
RESUMO
In this paper, benzo-fused cyclic carbonates were designed and synthesized as a new type of precursor of π-allylpalladium zwitterionic intermediates, and were applied in Pd-catalyzed diastereo- and enantioselective (4+3) cycloaddition with C,N-cyclic azomethine imines, leading to various biologically important 1,3,4-benzoxadiazepine derivatives in 43-99% yields with 6 : 1 to >20 : 1 dr and up to 95% ee.
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Divergent transformations of allenylethylene carbonates with diboron reagents catalyzed by copper are disclosed. By using CuCl/IPr·HCl as the catalyst, the allenylethylene carbonates react with B2hex2 to afford 2,4-dien-1-ols as the product in the presence of Cs2CO3 as the base, iPrOH as the additive, and 1,4-dioxane as the solvent. And they react with B2pin2 to form boronic half acids in the presence of NaOtBu as the base, water as the additive, and THF as the solvent. The reactions afford corresponding products in good stereoselectivities and yields, and further derivatizations of boronic half acids and study of the mechanism are also demonstrated.
RESUMO
Phosphine-catalyzed cascade isomerization/annulation has been developed to realize a diastereoselective synthesis of allenes installed on the hexahydropentalene skeleton, which contains five chiral centers (and one axial chirality). This reaction tolerated a broad range of allenoates and enynes. The allene products were transformed to various halogen-substituted fused-ring compounds.
RESUMO
A series of γ-substituted Morita-Baylis-Hillman (MBH) carbonates were synthesized and subjected to phosphine-catalyzed annulations with electrophilic exocyclic alkenes, giving various valuable spirocyclopentenes in moderate to excellent yields with moderate to excellent diastereoselectivities. A large scope of MBH carbonates bearing γ-hydrogen, alkenyl, and alkynyl substituents was well tolerated. The annulation unprecedentedly involves ß-, γ-, and δ-carbons of MBH carbonates.
RESUMO
A palladium-catalyzed [4 + 2] cycloaddition of 2-methylidenetrimethylene carbonate or methylene cyclic carbamate with sulfamate-derived cyclic imines has been successfully developed under mild reaction conditions, affording pharmacologically interesting oxazine or hydropyrimidine derivatives in high yields (up to 99% yield). Furthermore, the cycloaddition reactions could be efficiently scaled up and several synthetic transformations were accomplished for the construction of other useful 1,3-oxazine and hydropyrimidinone derivatives.
RESUMO
The 5-allenyloxazolidine-2,4-diones had been synthesized as novel precursors of π-allyl palladium zwitterion and were applied in a palladium-catalyzed enantioselective (3 + 2) annulation by using barbiturate-derived alkenes as the reaction partner in the presence of an axially chiral phosphoramidite ligand. This reaction proceeded smoothly under mild reaction conditions, affording highly functionalized spirobarbiturate-γ-lactam derivatives in excellent yields along with high diastereo- and enantioselectivities. The scale-up reaction and further transformation of the product were also successful.
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Glyphosate, the most used herbicide in the world, has a residue problem that cannot be ignored. However, glyphosate itself does not have fluorescence emission and lacks the conditions for fluorescence detection. In this work, a rapid and selective fluorescence detection method of glyphosate was designed by an 'on-off-on' fluorescent switch based on a luminous covalent organic framework (L-COF). Only the fixed concentration of Fe3+ as an intermediate could trigger the fluorescent switch and no incubation step was required. The proposed method showed good accuracy with a correlation coefficient of 0.9978. The method's limits of detection and quantitation were 0.88 and 2.93 µmol/L, which were lower than the maximum allowable residue limits in some regulations. Environmental water samples and tomatoes were selected as actual samples to verify the application in a complex matrix. A satisfactory mean recovery from 87% to 106% was gained. Furthermore, Fe3+ could induce fluorescence quenching of L-COF through the photo-induced electron transfer (PET) effect, while the addition of glyphosate could block the PET effect to achieve detection. These results demonstrated the proposed method had abilities to detect glyphosate and broaden the application of L-COF.
Assuntos
Estruturas Metalorgânicas , Estruturas Metalorgânicas/química , Espectrometria de Fluorescência , Corantes , Glicina/química , GlifosatoRESUMO
The phosphine-catalyzed tandem annulation of allenylic alcohols with 1,1-dicyanoalkenes has been developed, giving various bicyclic tetrahydrocyclopentafuran derivatives in 40-89% yields with moderate to excellent diastereoselectivities. The fused ring was furnished through a sequential (3 + 2) annulation/nucleophilic addition reaction. The unusual nucleophilic addition of an alkoxide ion to a cyano group led to a formation of tetrahydrofuran ring having an imino substituent.
RESUMO
In recent years, tetracyclines (TCs) is a hot research topic. Herein, we report an interesting discovery using the complexation of oxytetracycline and metal ions. In this study, according to the properties of Fe3O4nanoparticles (Fe3O4NPs) as a nanoenzyme, it can be used to catalyze the oxidation of KI by H2O2to produceI3-,while at the same timeI3-binds to rhodamine 6G (Rh6G) to form a conjoined particle (Rh6G â¼ I3)n, leading to a decrease in the fluorescence intensity of Rh6G. However, in the presence of TCs, Fe3O4NPs have a synergistic effect with TCs, leading to enhanced catalytic activity, as well as better selectivity compared to the activity of other reducing enzymes. Consequently,the fluorescent signal based on a resonance scattering effect between Rh6G andI3-is dependent on the concentration of TCs, thus achieving highly facile and robust detection of TCs. The limits of detection (LOD) of the method were 20 nM, 10 nM and 40 nM for oxytetracycline(OTC), tetracycline(TC) and chlortetracycline(CTC), respectively. Most importantly, the method can be successfully applied to the detection of TCs in milk, eggs, and honey. The recoveries of spiked samples ranged from 83.11 to 118.95%. Thus, a stable, hands-on strategy for the detection of TCs is proposed, which has potential applications in the field of food safety and environmental protection.
Assuntos
Nanopartículas Magnéticas de Óxido de Ferro , Oxitetraciclina , Antibacterianos , Tetraciclina , Tetraciclinas , Fluorescência , Nanopartículas Magnéticas de Óxido de Ferro/químicaRESUMO
Inspired by a fungicide, we designed 5-vinyloxazolidine-2,4-diones as new precursors of π-allylpalladium zwitterionic intermediates and developed palladium-catalyzed asymmetric (5 + 3) cycloaddition with azomethine imines and (3 + 2) cycloaddition with 1,1-dicyanoalkenes. Both reactions proceeded smoothly under mild reaction conditions to produce various chiral heterocyclic compounds in high yields with excellent enantioselectivities. These results revealed that 5-vinyloxazolidine-2,4-diones were a type of suitable precursor for palladium catalysis and will find extensive applications in Pd-catalyzed reactions such as cycloaddition and allylic alkylation.
RESUMO
The common aldehyde dehydrogenase 2 (ALDH2) alcohol flushing variant known as ALDH2*2 affects â¼8% of the world's population. Even in heterozygous carriers, this missense variant leads to a severe loss of ALDH2 enzymatic activity and has been linked to an increased risk of coronary artery disease (CAD). Endothelial cell (EC) dysfunction plays a determining role in all stages of CAD pathogenesis, including early-onset CAD. However, the contribution of ALDH2*2 to EC dysfunction and its relation to CAD are not fully understood. In a large genome-wide association study (GWAS) from Biobank Japan, ALDH2*2 was found to be one of the strongest single-nucleotide polymorphisms associated with CAD. Clinical assessment of endothelial function showed that human participants carrying ALDH2*2 exhibited impaired vasodilation after light alcohol drinking. Using human induced pluripotent stem cell-derived ECs (iPSC-ECs) and CRISPR-Cas9-corrected ALDH2*2 iPSC-ECs, we modeled ALDH2*2-induced EC dysfunction in vitro, demonstrating an increase in oxidative stress and inflammatory markers and a decrease in nitric oxide (NO) production and tube formation capacity, which was further exacerbated by ethanol exposure. We subsequently found that sodium-glucose cotransporter 2 inhibitors (SGLT2i) such as empagliflozin mitigated ALDH2*2-associated EC dysfunction. Studies in ALDH2*2 knock-in mice further demonstrated that empagliflozin attenuated ALDH2*2-mediated vascular dysfunction in vivo. Mechanistically, empagliflozin inhibited Na+/H+-exchanger 1 (NHE-1) and activated AKT kinase and endothelial NO synthase (eNOS) pathways to ameliorate ALDH2*2-induced EC dysfunction. Together, our results suggest that ALDH2*2 induces EC dysfunction and that SGLT2i may potentially be used as a preventative measure against CAD for ALDH2*2 carriers.
Assuntos
Doença da Artéria Coronariana , Células-Tronco Pluripotentes Induzidas , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Camundongos , Animais , Aldeído-Desidrogenase Mitocondrial/genética , Estudo de Associação Genômica Ampla , Células-Tronco Pluripotentes Induzidas/metabolismo , Aldeído DesidrogenaseRESUMO
We herein designed and synthesized allenyl benzoxazinones of a novel type, which were then involved in a Pd-catalyzed asymmetric cascade intramolecular cyclization/intermolecular Michael addition reaction with 1-azadienes. A broad range of chiral C2-functionalized quinoline derivatives were afforded in moderate to good yields (up to 93%) with high enantioselectivities (up to 93% ee) in this reaction.
RESUMO
Despite a strong genetic component, only a few genes have been identified in congenital heart diseases (CHDs). We introduced systems analyses to uncover the hidden organization on biological networks of mutations in CHDs and leveraged network analysis to integrate the protein interactome, patient exomes, and single-cell transcriptomes of the developing heart. We identified a CHD network regulating heart development and observed that a sub-network also regulates fetal brain development, thereby providing mechanistic insights into the clinical comorbidities between CHDs and neurodevelopmental conditions. At a small scale, we experimentally verified uncharacterized cardiac functions of several proteins. At a global scale, our study revealed developmental dynamics of the network and observed its association with the hypoplastic left heart syndrome (HLHS), which was further supported by the dysregulation of the network in HLHS endothelial cells. Overall, our work identified previously uncharacterized CHD factors and provided a generalizable framework applicable to studying many other complex diseases. A record of this paper's Transparent Peer Review process is included in the supplemental information.
Assuntos
Cardiopatias Congênitas , Síndrome do Coração Esquerdo Hipoplásico , Humanos , Síndrome do Coração Esquerdo Hipoplásico/genética , Síndrome do Coração Esquerdo Hipoplásico/metabolismo , Células Endoteliais/metabolismo , Cardiopatias Congênitas/genética , Mutação/genética , Análise de SistemasRESUMO
A phosphine-catalyzed (4 + 2) annulation of tetrahydrobenzofuranone-derived allenoates and benzofuran-derived azadienes (BDAs) has been achieved to construct the decahydro-2H-naphtho[1,8-bc]furan derivatives, which were subsequently treated with 4-methylbenzenethiol and trimethylamine to produce thio-Michael addition products in high to excellent yields with good diastereoselectivities.
Assuntos
Benzofuranos , Fosfinas , Catálise , EstereoisomerismoRESUMO
In this paper, a palladium-catalyzed [4 + 2] cycloaddition of 5-methylene-1,3-oxazinan-2-ones with 4-arylidene-2,4-dihydro-3H-pyrazol-3-ones has been developed to produce spiropyrazolones in high yields with excellent diastereoselectivities in nearly all cases. The cycloaddition reaction was scaled-up without significant loss of yield, and its synthetic utility has been demonstrated by further transformations of the products. The reaction type of N-Ts cyclic carbamates under palladium catalysis was extended to include [4 + 2] cycloaddition for the first time.