Nickel-Catalyzed Reductive Coupling of Aryl Halides with Secondary Alkyl Bromides and Allylic Acetate

A room-temperature Ni-catalyzed reductive method for the coupling of aryl bromides with secondary alkyl bromides has been developed, providing C(sp²)–C(sp³) products in good to excellent yields. Slight modification of this protocol allows efficient coupling of activated aryl chlorides with cyclohexyl bromide and aryl bromides with allylic acetate

A-kinase Anchoring Protein 5 Anchors Protein Kinase A to Mediate PLN/SERCA to Reduce Cardiomyocyte Apoptosis Induced by Hypoxia and Reoxygenation

A-kinase anchoring protein (AKAP) 5 has a variety of biological activities. This study explored whether AKAP5 is involved in cardiomyocyte apoptosis induced by H/R and its possible mechanism. H9C2 cells were used to construct an H/R model in vitro, followed by overexpression of AKAP5 in the cells. Flow cytometry was used to detect the rate of cardiomyocyte apoptosis. The expression of phospholamban (PLN) phosphorylation, SERCA2a and apoptosis-related proteins were determined by western blot. Immunofluorescence staining and immunoprecipitation were used to detect the distribution of and interaction between AKAP5, PKA, and PLN. After H/R induction, H9C2 cells had significantly reduced expression of AKAP5 protein. Upregulation of AKAP5 promoted cell survival and significantly reduced LDH level and apoptosis rate of H9C2 cells. In addition, the overexpression of AKAP5 was accompanied by the activation of the PLN/SERCA2a signaling pathway and a reduction in apoptosis. Immunofluorescence staining and immunoprecipitation revealed that AKAP5 colocalized and interacted with PLN and PKA.Interestingly,St-Ht31 inhibited the effect of AKAP5 overexpression on H/R-induced apoptosis in H9C2 cardiomyocytes. AKAP5 overexpression alleviated H/R-induced cardiomyocyte apoptosis, possibly through anchoring to PKA to mediate the PLN/SERCA pathway, suggesting that AKAP5 is a potential therapeutic target for the prevention and treatment of ischemia-reperfusion injury.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Nickel-Catalyzed Reductive Coupling of Aryl Bromides with Tertiary Alkyl Halides

A mild Ni-catalyzed reductive arylation of tertiary alkyl halides with aryl bromides has been developed that delivers products bearing all-carbon quaternary centers in moderate to excellent yields with excellent functional group tolerance. Electron-deficient arenes are generally more effective in inhibiting alkyl isomerization. The reactions proceed successfully with pyridine or 4-(dimethylamino)­pyridine, while imidazolium salts slightly enhance the coupling efficiency

Ni-Catalyzed Reductive Coupling of Alkyl Acids with Unactivated <i>Tertiary</i> Alkyl and Glycosyl Halides

This work highlights Ni-catalyzed reductive coupling of alkyl acids with alkyl halides, particularly sterically hindered unactivated <i>tertiary</i> alkyl bromides for the production of all carbon quaternary ketones. The reductive strategy is applicable to α-selective synthesis of saturated, fully oxygenated <i>C</i>-acyl glycosides through easy manipulations of the readily available sugar bromides and alkyl acids, avoiding otherwise difficult multistep conversions. Initial mechanistic studies suggest that a radical chain mechanism (cycle B, Scheme 1) may be plausible, wherein MgCl₂ promotes the reduction of Ni^II complexes

Changes of I_Kr in heart failure (HF).

<p>(A) Recording of I_kr tail current in a representative left ventricle (LV) myocyte before (left) and 10 min after exposure to dofetilide (1 µM) (right). (B) Representative tail traces of I_Kr in LV myocytes isolated from control (CTL, left) and HF guinea pigs (right). (C) The average current-voltage relationship of I_Kr plotted for control (n = 24 cells, 8 hearts) and HF (n = 33 cells, 10 hearts) myocytes (***p<0.001, HF vs. CTL). Test pulses were applied at various voltages from −40 to +40 mV (step width 20 mV, step duration 200 ms) before returning to −40 mV for tail current recording.</p

β₂-AR mediates the inhibition of I_kr by fenoterol (Feno) in heart failure (HF) myocytes.

<p>(A and B) Superimposed tail current traces of I_kr recorded before and 10 min after application of 10 µM fenoterol in the presence of the selective β₂-AR antagonist ICI118551 (ICI, 10 µM) and β₁-AR antagonist CGP20712A (CGP, 10 µM) in a HF myocyte, respectively. (C) Summarized data for percent decrease in the amplitude of I_Kr tail current evoked by ICI plus fenoterol, CGP plus fenoterol, and fenoterol alone (n = 5 and 6 cells, 3 hearts, *P<0.05, Feno+ICI versus Feno). Current amplitudes were measured at the voltage of +40 mV.</p

Effects of fenoterol (Feno) on I_kr.

<p>(A and B) Superimposed tail current traces of I_kr recorded before and 10 min after application of 10 µM Feno in a control myocyte and a heart failure (HF) myocyte, respectively. (C) Time-dependence of current reduction by the β₂-AR agonist fenoterol in control (n = 6 cells, 3 hearts) and HF myocytes (n = 6 cells, 4 hearts, *p<0.05, Feno+HF vs. HF). Current amplitudes were measured at the voltage of +40 mV.</p