Expedient Synthesis of 1,5-Diketones by Rhodium-Catalyzed Hydroacylation Enabled by C–C Bond Cleavage

A rhodium-catalyzed inter­molecular hydro­acylation reaction of vinyl cyclobutanols with non-chelating aldehydes has been developed. This reaction offers a new and atom-economical approach for the selective preparation of 1,5-diketones in high yields. Experimental data suggest a sequential ring-opening, transfer hydrogenation, and hydro­acylation mechanism. We propose that aldehyde decarbonylation is avoided by the formation of a novel rhodium enolate species that also accounts for the compatibility of a broad range of aldehydes and its <i>anti</i>-Markovnikov selectivity

Mitochondrial function following ethanol exposure: Cardiomyocyte mitochondrial membrane potential (MMP) in FVB and ADH mice with or without acute ethanol exposure.

<p>JC-1 fluorochrome was shown as the ratio of red to green fluorescence. CCCP was used a positive control. Mean ± SEM, n = 9–14 cells per group, * p<0.05 <i>vs.</i> FVB, # p<0.05 <i>vs.</i> FVB-EtOH group.</p

Mitochondrial O₂^•− generation following ethanol exposure: Mitochondrial O₂^•− generation using the MitoSOX Red probe in cardiomyocytes from FVB and ADH mice with or without acute ethanol exposure.

<p>Cohorts of non-ethanol-treated FVB cardiomyocytes were incubated with the ADH enzymatic metabolite of ethanol, acetaldehyde (ACA, 100 µM), for 4 hrs at 37°C prior to MitoSOX Red measurement. A–E: Representative fluorescence images (40x) from FVB, FVB-EtOH, ADH, ADH-EtOH and FVB-ACA groups. F: Pooled data. Mean ± SEM, n = 15–20 fields per group, * p<0.05 <i>vs.</i> FVB, # p<0.05 <i>vs.</i> FVB-EtOH group.</p

Effect of ethanol exposure on cardiac function: Effect of acute ethanol exposure on cardiac contractile function using a Langendorff perfusion system in FVB and ADH mice.

<p>A: Left ventricular developing pressure (LVDP); B and C: Maximal velocity of pressure development (+dP/dt) and decline (−dP/dt). Mean ± SEM, n = 5–10 hearts per group, * p<0.05 <i>vs.</i> FVB, # p<0.05 <i>vs.</i> FVB-EtOH group.</p

Mitochondrial death pathway in myocardium following ethanol exposure: Expression of pro-caspase-9 (B), cytosolic pro-caspase-9 (C), cytosolic cytochrome C (D), cytosolic pro-caspase-8 (E) and cytosolic AIF (F) in myocardium from FVB and ADH mice with or without acute ethanol exposure.

<p>Panel A depicts representative gels using specific antibodies. Mean ± SEM, n = 4–8 samples per group, all samples were in duplicates with the average being used, * p<0.05 <i>vs.</i> FVB group.</p

Histological analyses following ethanol exposure: Histological analyses hearts from FVB and ADH mice with or without ethanol exposure.

<p>A - D: H&E staining micrographs of transverse sections of left ventricular myocardium (x 400) from FVB, FVB-EtOH, ADH and ADH-EtOH groups; E: Quantitative analysis of cardiomyocyte cross-sectional (transverse) area using measurements of ∼150 cardiomyocytes from 3–5 mice per group. Mean ± SEM, * p<0.05 <i>vs.</i> FVB, # p<0.05 <i>vs.</i> FVB-EtOH group.</p

Expression of pan and phosphorylated LKB1 in myocardium from FVB and ADH mice with or without acute ethanol challenge (3 g/kg, i.p. for 3 days).

<p>A: Representative gel blots depicting expression of LKB1, phosphorylated LKB1 (pLKB) and GAPDH (loading control); B: pan LKB1; C: pLKB1; and D: pLKB1/LKB1 ratio. Mean ± SEM, n = 6–8 samples per group, * p<0.05 <i>vs.</i> FVB group, # p<0.05 <i>vs</i>. FVB-EtOH group.</p

Change in cardiomyocyte contraction in response to increasing stimulus frequency (0.1–5.0 Hz) in adult FVB and ADH mice with or without acute ethanol (EtOH) challenge (3 g/kg, i.p. for 3 days).

<p>Peak shortening (PS) amplitude was normalized to the PS value obtained at 0.1 Hz from the same cell. Mean ± SEM, n = 24–26 cells from 3–4 mice per group, * p<0.05 <i>vs.</i>FVB group, # p<0.05 <i>vs.</i> FVB-EtOH group.</p

Expression of protein phosphatases in myocardium from FVB and ADH mice with or without acute ethanol challenge (3 g/kg, i.p. for 3 days).

<p>A: Representative gel blots depicting expression of PP2AA, PP2AB, PP2Cα and GAPDH (loading control); B: PP2AA; C: PP2AB; and D: PP2Cα. Mean ± SEM, n = 6–8 samples per group, * p<0.05 <i>vs.</i> FVB group, # p<0.05 <i>vs</i>. FVB-EtOH group.</p

Expression of insulin receptor β (IR-β), PPAR-γ, PGC1α and Glut4 in myocardium from FVB and ADH mice with or without acute ethanol challenge (3 g/kg, i.p. for 3 days).

<p>A: IR-β; B: PPAR-γ; C: PGC1α and D: Glut4. Insets: Representative gel blots depicting expression of IR-β, PPAR-γ, PGC1α, Glut4 and GAPDH (loading control). Mean ± SEM, n = 6–8 samples per group, * p<0.05 <i>vs.</i> FVB group, # p<0.05 <i>vs</i>. FVB-EtOH group.</p