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An anodically oxidizing trifluoromethylation cascade of N-cyanamide alkene bearing two electronically differentiated olefin moieties was reported, in which various N-unsaturated acyl cyanamide alkenes and CF3SO2Na acting as readily available starting materials furnished nonaromatic fused azaheterobicyclic compounds in a highly efficient and sustainable manner. The broad substrate scope, facile scalability, and sustainability enabled this electrochemical process to be an appealing complement for trifluoromethylated cyclic amidines.
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Pd(II)-catalyzed addition of sp2 C-H to nitrile/aerobic oxidation sequences for the preparation of functionalized α-imino ketones is described in which readily available heteroarenes and O-acyl cyanohydrins were employed. Various functionalized targeted molecules can be prepared in good yields with high atom and step economy. Moreover, a broad substrate scope and the ready manipulation and availability of the reaction partners enable this protocol to be appealing to explore the chemical space of the construction of functionalized α-imino ketones with high efficiency.
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BACKGROUND: There is a paucity of research investigating the application of machine learning techniques for distinguishing between lipid-poor adrenal adenoma (LPA) and subclinical pheochromocytoma (sPHEO) based on radiomic features extracted from non-contrast and dynamic contrast-enhanced computed tomography (CT) scans of the abdomen. METHODS: We conducted a retrospective analysis of multiphase spiral CT scans, including non-contrast, arterial, venous, and delayed phases, as well as thin- and thick-thickness images from 134 patients with surgically and pathologically confirmed. A total of 52 patients with LPA and 44 patients with sPHEO were randomly assigned to training/testing sets in a 7:3 ratio. Additionally, a validation set was comprised of 22 LPA cases and 16 sPHEO cases from two other hospitals. We used 3D Slicer and PyRadiomics to segment tumors and extract radiomic features, respectively. We then applied T-test and least absolute shrinkage and selection operator (LASSO) to select features. Six binary classifiers, including K-nearest neighbor (KNN), logistic regression (LR), decision tree (DT), random forest (RF), support vector machine (SVM), and multi-layer perceptron (MLP), were employed to differentiate LPA from sPHEO. Receiver operating characteristic (ROC) curves and area under the curve (AUC) values were compared using DeLong's method. RESULTS: All six classifiers showed good diagnostic performance for each phase and slice thickness, as well as for the entire CT data, with AUC values ranging from 0.706 to 1. Non-contrast CT densities of LPA were significantly lower than those of sPHEO (P < 0.001). However, using the optimal threshold for non-contrast CT density, sensitivity was only 0.743, specificity 0.744, and AUC 0.828. Delayed phase CT density yielded a sensitivity of 0.971, specificity of 0.641, and AUC of 0.814. In radiomics, AUC values for the testing set using non-contrast CT images were: KNN 0.919, LR 0.979, DT 0.835, RF 0.967, SVM 0.979, and MLP 0.981. In the validation set, AUC values were: KNN 0.891, LR 0.974, DT 0.891, RF 0.964, SVM 0.949, and MLP 0.979. CONCLUSIONS: The machine learning model based on CT radiomics can accurately differentiate LPA from sPHEO, even using non-contrast CT data alone, making contrast-enhanced CT unnecessary for diagnosing LPA and sPHEO.
Assuntos
Adenoma , Neoplasias das Glândulas Suprarrenais , Feocromocitoma , Humanos , Adenoma/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Lipídeos , Aprendizado de Máquina , Feocromocitoma/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
A synthetic approach for the construction of functionalized diverse 1-pyrrolines incorporating ß-quaternary carbon centers under mild reaction conditions has been reported, in which α-allyl α-(alkylideneamino)nitriles generated from a Lewis base-catalyzed allylic alkylation reaction engaged in a Lewis base-mediated tandem intramolecular cyclization to deliver the targeted molecules in a catalytically atom-economic fashion.
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A novel protocol for the efficient preparation of α-hydroxy allylic thioesters via a Lewis base-catalyzed tandem isomerization/allylic alkylation process is reported. The resulting allylic thioesters can serve as valuable scaffolds to undergo a stereoselective intramolecular cyclization to deliver 2,7-dioxabicyclo[2.2.1]heptan-3-one derivatives in a catalytically atom-economic fashion.
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An unprecedented electrochemical trifluoromethylation/SO2 â insertion/cyclization process has been achieved in an undivided cell in an atom-economic fashion. The protocol relies on tandem cyclization of N-cyanamide alkenes by using Langlois' reagent as a source of both CF3 and SO2 under direct anodically oxidative conditions, in which two C-C bonds, two C-X bonds (N-S and S-C), and two rings were formed in a single operation. This transformation enabled efficient construction of various trifluoromethylated cyclic N-sulfonylimines from readily accessible materials.
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A controllable stereoselective synthesis of tetrahydropyrrolo[2,1-a]isoquinoline derivatives bearing a sulfur moiety was demonstrated with high diastereoselectivity through a catalytic intramolecular acylsulfenylation of activated alkenes. This approach involved a catalytic thia-Michael addition triggered intramolecular aldol-type tandem sequence. Both cis- and trans-products can be readily prepared in moderate to high yields with excellent diastereoselectivities in a catalytically atom-economic fashion under the optimized mild reaction conditions.
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A novel asymmetric catalytic approach for the construction of enantioenriched functionalized 1,2-dihydropyridines and pyridine derivatives incorporating adjacent quaternary and tertiary stereocenters has been reported. This process involved a metal-free catalytic asymmetric allylic alkylation and a stereospecifically nonoxidative aromatization approach for the desired chiral molecules.
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A novel asymmetric synthetic approach for the construction of enantioenriched functionalized dihydroquinones incorporating adjacent quaternary and tertiary stereocenters has been reported, in which enantioenriched 3-allylic phthalides engaged in an unprecedented sulfa-Michael addition-triggered stereoselective ring-expansion reaction, and furnished the desired sulfur-incoporated dihydronaphthoquinones with high stereoselectivity.
Assuntos
Compostos Alílicos/química , Benzofuranos/química , Naftoquinonas/síntese química , Estrutura Molecular , Naftoquinonas/química , EstereoisomerismoRESUMO
A novel Lewis base-promoted rearrangement of allylic cyanohydrins has been developed, in which the cyano group was rearranged, directly coupled with the generation of new functional groups. This protocol provides a unique and facile way to prepare highly functionalized nitriles bearing 1,3-diketone moieties under mild reaction conditions. Furthermore, the synthetic transformations of the functionalized products have also been demonstrated.
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Cetonas/química , Bases de Lewis/química , Nitrilas/química , Fenômenos Bioquímicos , Catálise , Estrutura Molecular , EstereoisomerismoRESUMO
Pyrrolidine rings are common moieties for pharmaceutical candidates and natural compounds, and the construction of these skeletons has received much attention. α-Amino nitriles are versatile intermediates in synthetic chemistry and have been widely used in the generation of multiple polyfunctional structures. Herein, a novel nucleophilic phosphine-catalyzed intramolecular Michael reaction of N-allylic substituted α-amino nitriles has been developed for the efficient construction of functionalized 2,4-disubstituted pyrrolidines (N-heterocyclic α-amino nitriles) via 5-endo-trig cyclization. Furthermore, the one-pot sequence of the synthesis of pyrrolidine and the subsequent transformations of the functionalized products have also been demonstrated.
Assuntos
Compostos Heterocíclicos/síntese química , Nitrilas/química , Fosfinas/química , Pirrolidinas/síntese química , Catálise , Ciclização , Compostos Heterocíclicos/química , Estrutura Molecular , EstereoisomerismoRESUMO
The first tertiary amine catalyzed asymmetric allylic amination/cycloaddition cascade sequence has been developed, which provided a novel protocol to construct enantioenriched azapolyheterocycles under mild reaction conditions efficiently (up to 95% ee, endo/exo >20:1).
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The first asymmetric organocatalytic allylic alkylation of 1,2-dihydro-Reissert compounds and Morita-Baylis-Hillman (MBH) carbonates has been developed, which provided a novel protocol to construct enantioenriched functionalized 1,2-dihydroisoquinolines bearing vicinal quaternary and tertiary chiral centers at C-1 position (up to 94% ee, dr > 20 : 1).
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Compostos Alílicos/química , Isoquinolinas/química , Alquilação , Carbonatos/química , Catálise , Cristalografia por Raios X , Estrutura Molecular , EstereoisomerismoRESUMO
OBJECTIVE: To evaluate the clinical efficacy of the ARAR0331 protocol for treatment of childhood nasopharyngeal carcinoma. METHODS: The clinical data of eight children with nasopharyngeal carcinoma between May 2004 and May 2012 were retrospectively studied. The eight patients included six boys and two girls, and the onset age was between 3 and 13 years. Six patients were in AJCC Stage â ¢, one was in Stageâ ¡A and one was in Stage â £A. One patient had been treated with combined radiotherapy and chemotherapy which mainly included EAP, BEP and EA. The other seven patients had been treated with the ARAR0331 protocol provided by the America Children's Oncology Group (COG). RESULTS: The patient who had been treated with combined radiotherapy and chemotherapy developed multiple bony metastasis during the chemotherapeutic period. Four out of seven patients who had been treated with ARAR0331 protocol achieved complete remission, and two achieved partial remission. The seven patients were followed-up from 8 to 75 months and the survival rate was 100%. The ARAR0331 protocol treatment-related complications included radiodermatitis, mucocitis and nausea. Late toxicity was not found. CONCLUSIONS: Based on the limited cases, ARAR0331 protocol appears to be effective and safe for childhood nasopharyngeal carcinoma.
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Neoplasias Nasofaríngeas/terapia , Adolescente , Carcinoma , Quimiorradioterapia/efeitos adversos , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/patologia , Estadiamento de Neoplasias , Estudos RetrospectivosRESUMO
A straightforward diastereo- and enantioselective Claisen rearrangement/oxa-Michael addition tandem sequence with a cinchona squaramide catalyst was described, which afforded a practical and atom-economical approach to access a range of valuable dihydropyrans in good to excellent yields with excellent stereoselectivities. The organo-bifunctional catalyst played a key role in enhancing stereoselectivity in this asymmetric tandem sequence. Moreover, the asymmetric catalytic sequential processes of the hydroalkoxylation/Claisen rearrangement/cyclization sequence and Claisen rearrangement/aza-Michael addition tandem sequence have also been afforded good yields and moderate stereoselectivities.
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The first tertiary amine-catalyzed multicomponent tandem Strecker-allylic-alkylation (SAA) reaction has been developed, which provides a facile access to functionalized α-amino nitriles, which could be readily converted into α-methylene-γ-butyrolactams.
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Lactamas/química , Nitrilas/química , Alquilação , Aminação , Catálise , Ciclização , Estrutura MolecularRESUMO
A straightforward three-component transformation for the preparation of functionalized benzosultams under TM-free and mild reaction conditions was described, in which easy-to-handle Na2S2O5, available bromodifluoroalkyl reagent, and N-(2-haloaryl) cyanamide were employed. Na2S2O5 was essential to the generation of difluoroalkyl radical, SO2 fixation, and cyclization, which enabled efficient construction of target products in a sustainable manner. A broad substrate scope and modular feature made this protocol attractive for exploring the chemical space of the construction of cyclic sulfonamides.
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A copper-catalyzed alkene-trifluoromethylation-triggered nitrile insertion/remote functionalization relay process has been achieved, in which "interrupted" remote 1,n-difunctionalizations of alkenes with nitrile insertion can deliver iminyl radical intermediates instead of C-based radicals, followed by subsequent 1,n-HAT to furnish corresponding remote functionalization. This relay protocol enables a straightforward approach to streamline the assembly of structurally diverse trifluoromethylated azaheterocycles.
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BACKGROUND: Drug reference apps promote self-management and improve the efficiency and quality of work for physicians, nurses, pharmacists, and patients. This study aimed to describe a systematic and stepwise process to identify drug reference apps in Taiwan, assess the quality of these apps, and analyze the influential factors for user ratings. METHODS: A two-step algorithm (KESS) consisting of keyword growing and systematic search was proposed. Seven independent reviewers were trained to evaluate these apps using Mobile App Rating Scale (MARS). A logistic regression model was fitted and average marginal effects (AME) were calculated to identify the effects of factors for higher user ratings. RESULTS: A total of 23 drug reference apps in Taiwan were identified and analyzed. Generally, these drug reference apps were evaluated as acceptable quality with an average MARS score of 3.23. Higher user engagement, more functionality, better aesthetics, and more information associated with higher user ratings. Navigation is the most influential factor on higher user ratings (AME: 13.15%) followed by performance (AME: 11.03%), visual appeal (AME: 10.87%), credibility (AME: 10.67%), and quantity of information (AME: 10.42%). CONCLUSIONS: User experience and information clearly affect user ratings of drug reference apps. Five key factors should be considered when designing drug reference apps.
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A copper-catalyzed difluoroalkylation of an alkene/nitrile insertion/cyclization tandem sequence of N-cyanamide alkene was described, which provided a convenient synthetic approach for accessing difluorinated bicyclic amidines bearing imine moieties in a sustainable fashion. This protocol is characterized by high yields, a broad substrate scope, and good functional group compatibility. In addition, the desired product can be readily converted into other valuable functionalized fluorinated aza-heterocycles.