Copper(II)-catalyzed enantioselective hydrosilylation of halo-substituted alkyl aryl and heteroaryl ketones: asymmetric synthesis of (R)-fluoxetine and (S)-duloxetine.

A set of reaction conditions has been established to facilitate the non-precious copper-catalyzed enantioselective hydrosilylation of a number of structurally diverse ß-, γ- or ε-halo-substituted alkyl aryl ketones and α-, ß- or γ-halo-substituted alkyl heteroaryl ketones under air to afford a broad spectrum of halo alcohols in high yields and good to excellent enantioselectivities (up to 99% ee). The developed procedure has been successfully applied to the asymmetric synthesis of antidepressant drugs (R)-fluoxetine and (S)-duloxetine, which highlighted its synthetic utility.

Copper-dipyridylphosphine-catalyzed hydrosilylation: enantioselective synthesis of aryl- and heteroaryl cycloalkyl alcohols.

The non-precious metal copper-catalyzed enantioselective hydrosilylation of a vast array of aryl cycloalkyl ketones with different ring sizes was studied systematically for the first time (up to 99% enantiomeric excess). The results demonstrated that the steric size of cycloalkyl groups has a significant influence on the reaction outcomes. The first stereoselective formation of a selection of cyclohexyl heteroaryl alcohols of up to 97% enantiopurity was realized as well. Dramatic temperature effects on both the enantiopurity and the absolute configuration of the alcohol products were observed in the reduction of some cyclohexyl pyridyl ketones.

Cu(II)-catalyzed asymmetric hydrosilylation of diaryl- and aryl heteroaryl ketones: application in the enantioselective synthesis of orphenadrine and neobenodine.

With certain amounts of sodium tert-butoxide and tert-butanol as additives, catalytic amounts of an inexpensive and easy-to-handle copper source Cu(OAc)(2)⋅H(2)O, a commercially available and air-stable non-racemic dipyridylphosphine ligand, as well as the stoichiometric desirable hydride donor polymethylhydrosiloxane (PMHS), formed a versatile in situ catalyst system for the enantioselective reduction of a broad spectrum of prochiral diaryl and aryl heteroarylketones in air, in high yields and with good to excellent enantioselectivities (up to 96 %). In particular, the practical viability of this process was evinced by its successful applications in the asymmetric synthesis of optically enriched potent antihistaminic drugs orphenadrine and neobenodine.

[Value of QT hysteresis during treadmill exercise test for diagnosing coronary heart disease].

OBJECTIVE: To investigate the value of QT hysteresis index during treadmill exercise test (TET) in diagnosing coronary heart disease (CHD). METHODS: One hundred consecutive patients suspected for CHD were referred for TET and selective coronary angiography (CAG). Patients were divided into positive [n = 55, age (56.0 ± 7.9) years] and negative [n = 45, age (53.2 ± 6.7) years] group based on their CAG results. For each TET recording, 50 points were selected for the RR, QTp, and QTe interval measurements. QTp and QTe interval was plotted against corresponding RR interval. QT/RR curve was constructed by connect all point, QT hysteresis index was calculated for each patient. RESULTS: The QTp [(22.4 ± 10.3) ms vs. (6.7 ± 4.6) ms, P < 0.001] and QTe [(27.1 ± 11.1) ms vs. (7.6 ± 4.6) ms, P < 0.001] hysteresis index of patients in positive group were significantly higher than those in negative group. The sensitivity of QTp and QTe hysteresis index for diagnosing CHD was 89.1% (49/55) and 94.5% (52/55), respectively, and the specificity was 82.2% (37/45) and 80.0% (36/45), respectively. If the patient fulfilled both the classical TET and QT hysteresis criteria, the sensitivity for diagnosing CHD increased to 94.3% (33/35, QTp) and 94.6% (35/37, QTe), and the specificity were both 100% (26/26, 26/26). Moreover, QTp (r = -0.399, P < 0.001) and QTe (r = -0.547, P < 0.001) hysteresis index highly correlated to Duke treadmill score. CONCLUSION: QT hysteresis index is useful parameter for CHD diagnosis and which could improve the diagnostic value of TET for CHD in combination with the classical TET criteria for diagnosis of CHD.

Copper(II)-catalyzed hydrosilylation of ketones using chiral dipyridylphosphane ligands: highly enantioselective synthesis of valuable alcohols.

In the presence of PhSiH(3) as the reductant, the combination of enantiomeric dipyridylphosphane ligands and Cu(OAc)(2)·H(2)O, which is an easy-to-handle and inexpensive copper salt, led to a remarkably practical and versatile chiral catalyst system. The stereoselective formation of a selection of synthetically interesting ß-, γ- or δ-halo alcohols bearing high degrees of enantiopurity (up to 99.9% enantiomeric excess (ee)) was realized with a substrate-to-ligand molar ratio (S/L) of up to 10,000. The present protocol also allowed the hydrosilylation of a diverse spectrum of alkyl aryl ketones with excellent enantioselectivities (up to 98% ee) and exceedingly high turn-over rates (up to 50,000 S/L molar ratio in 50 min reaction time) in air, under very mild conditions, which offers great opportunities for the preparation of various physiologically active targets. The synthetic utility of the chiral products obtained was highlighted by the efficient conversion of optically enriched ß-halo alcohols into the corresponding styrene oxide, ß-amino alcohol, and ß-azido alcohol, respectively.

Cobalt(II)-catalyzed asymmetric hydrosilylation of simple ketones using dipyridylphosphine ligands in air.

In the presence of PhSiH(3) as the hydride donor, catalytic amounts of non-racemic dipyridylphosphine and an easy-to-handle cobalt salt Co(OAc)(2)·4H(2)O formed in situ an effective catalyst system for the asymmetric reduction of a diverse range of aryl alkyl ketones with moderate-to-excellent enantioselectivities (up to 96% ee). This approach tolerated the handling of both catalyst and reactants under air without special precautions.

Screening and validating the immune-related gene expression signatures in peripheral blood mononuclear cells of nonischaemic cardiomyopathy.

Background: Mountainous evidence has revealed that an activated immune response in the heart can provoke left ventricular dysfunction and result in adverse cardiac remodelling. This study was designed to explore the potential mechanisms and identify core biomarkers in peripheral blood mononuclear cells (PBMCs) of nonischaemic cardiomyopathy (NICM). Methods: GSE9128, particularly, the samples of PBMCs from 3 control individuals and 4 NICM patients, was downloaded from the GEO database to identify differentially expressed genes (DEGs). DAVID was employed to perform gene ontology (GO) and Kyoto PBMC of Genes and Genomes (KEGG) analyses. Meanwhile, a protein-protein interaction (PPI) network was constructed to display the interactions among these DEGs. The expression of the top 5 upregulated and downregulated DEGs was validated in a NICM mice model induced by isoproterenol via real-time PCR. Results: In this study, a total of 371 DEGs (fold change > 2), consisting of 288 upregulated DEGs and 83 downregulated DEGs, were captured in the PBMCs. GO and KEGG analysis demonstrated that these DEGs were particularly enriched in inflammatory response, immune response, extracellular exosome and cell differentiation. Additionally, the hub genes with the 15 highest connectivity degrees were also identified, namely, JUN, MYC, HSP90AA1, PCNA, CREB1, IL1B, IL8, SMARCA2, TLR4, RB1, RANBP2, EGR1, PTGS2, ENO1 and XPO1. Finally, our in vitro experiment not only validated the mRNA expression levels of the top 5 upregulated and downregulated DEGs in mice but also further clarified their expression in subtypes of PBMCs. Conclusion: Our study unveiled potential biomarkers and molecular mechanisms in NICM, which could provide a non-invasive strategy for the diagnosis and treatment of NICM.

Nickel(II)-dipyridylphosphine-catalyzed enantioselective hydrosilylation of ketones in air.

Out of thin air: Catalytic amounts of nickel(II) salt and non-racemic dipyridylphosphine ligand, as well as the stoichiometric hydride source PhSiH(3), formed an effective catalyst system for the Ni(II)-catalyzed asymmetric hydrosilylation of a diverse range of electron-deficient aryl alkyl ketones with enantioselectivities up to 90% ee. The practical potential of the protocol was evinced by its good air-stability.