Carbofunctionalization of Terminal Alkynes via Rhodium Catalysis Enabling Formations of Four Different Bonds.

Described here is the oxygenative carbofunctionalization of terminal alkynes mediated by combined rhodium catalysis that enables regioselective quadruple formation of C-C, C-H, C-O, and C-heteroatom bonds. Mechanistic studies suggest that a disubstituted rhodium vinylidene complex is generated upon C-C bond formation at the terminal alkyne with tethered electrophiles such as alkyl halides, aldehydes, imines, and Michael acceptors. Subsequent intermolecular transfer oxygenation of the rhodium vinylidene with pyridine N-oxide generates a rhodium-complexed ketene intermediate that reacts with a variety of heteroatom nucleophiles to give rise to cyclic carboxylic acid derivatives.

Silyloxymethanesulfinate as a sulfoxylate equivalent for the modular synthesis of sulfones and sulfonyl derivatives.

An efficient protocol for the modular synthesis of sulfones and sulfonyl derivatives has been developed utilizing sodium tert-butyldimethylsilyloxymethanesulfinate (TBSOMS-Na) as a sulfoxylate (SO2 2-) equivalent. TBSOMS-Na, easily prepared from the commercial reagents Rongalite™ and TBSCl, serves as a potent nucleophile in S-alkylation and Cu-catalyzed S-arylation reactions with alkyl and aryl electrophiles. The sulfone products thus obtained can undergo the second bond formation at the sulfur center with various electrophiles without a separate unmasking step to afford sulfones and sulfonyl derivatives such as sulfonamides and sulfonyl fluorides.

Effect of sex and age on the association between suicidal behaviour and obesity in Korean adults: a cross-sectional nationwide study.

OBJECTIVES: To examine the hypothesis that the relationship between obesity and the risk of suicidal behaviour would differ according to sex and age. SETTING: Data from the 2007-2012 Korean National Health and Nutrition Examination Survey (KNHANES) were used. PARTICIPANTS: 36 211 adults with body mass index (BMI) data were included and the mean age was 49.6 years. INDEPENDENT VARIABLE: BMI. PRIMARY AND SECONDARY OUTCOME MEASURES: Suicide ideation and attempts. DESIGN AND ANALYSIS: A cross-sectional study was performed. Multiple logistic regressions after controlling for socioeconomic variables and concomitant diseases were applied to see the relationship between obesity level and suicidal ideation or attempt. RESULTS: Women with severe obesity had the highest prevalence of suicide attempts and ideation, whereas among males, underweight men had the highest prevalence. After adjustment, obese men had a lower OR for suicide ideation (OR=0.87, 95% CI 0.76 to 1.00). Among women, the ORs of severely obese and underweight women were 1.27 (95% CI 1.06 to 1.52) and 1.24 (95% CI 1.06 to 1.45), respectively. When grouped by age category, the ORs for suicide ideation in severely obese women aged 18 to <30 years or attempts in severely obese women aged 30 to <50 years were 2.30 (95% CI 1.36 to 3.89) and 3.07 (95% CI 1.50 to 6.31), respectively. However, overweight and obese women aged more than 50 years exhibited significantly less ORs of suicide ideation, when compared with counterparts of normal weight. CONCLUSIONS: The association between obesity and suicidal behaviour exhibited a different pattern by sex and age in South Korea. In particular, severely obese young women had a substantial risk of suicidal behaviour. Our study results highlighted the importance of obesity management in the prevention of suicide among young women, and may be helpful for the drafting of the health agenda in Asian countries with an obesity prevalence and culture similar to those in Korea.

Involvement of serotonin receptors 5-HT1 and 5-HT2 in 12(S)-HPETE-induced scratching in mice.

The mechanisms of 12(S)-hydroperoxyeicosa-5Z,8Z,10E,14Z-tetraenoic acid (12(S)-HPETE)-induced scratching were studied in ICR mice. In a recent paper, we demonstrated that the 12(S)-HPETE-induced scratching was reduced not by U75302 (BLT(1) receptor antagonist), but by LY255283 (BLT(2) receptor antagonist). In the present study, we tested various compounds to elucidate the mechanism of 12(S)-HPETE-induced scratching relating to transient receptor potential vanilloid type-1 (TRPV1), histamine receptor (H(1)) and several serotonin receptors (5-HT(1), 5-HT(2), and 5-HT(3)). As a result, 12(S)-HPETE-induced scratching was suppressed by capsaicin (TRPV1 receptor agonist), but not by capsazepine (TRPV1 receptor antagonist). Additionally, chlopheniramine (H(1) receptor antagonist) did not suppress 12(S)-HPETE-induced scratching, but cyproheptadine (H(1) receptor and serotonin 5-HT(2) receptor antagonist) potently suppressed the same response. Therefore, we tested several serotonin receptor antagonists to explain the detailed mechanisms relating to serotonin receptors. The scratching was reduced by WAY100635 (5-HT(1) receptor antagonist), or ketanserin (5-HT(2) receptor antagonist), but not by ondansetron (5-HT(3) receptor antagonist), after intradermal injection of 12(S)-HPETE. These results suggest that serotonin 5-HT(1/2) receptors are implicated in 12(S)-HPETE-induced scratching in ICR mice and that the TRPV1 receptor might not be directly related to 12(S)-HPETE-induced scratching.

12(S)-HPETE induces itch-associated scratchings in mice.

The itch-associated responses evoked by intradermal injection of 12(S)-HPETE and leukotriene B4 were compared in ICR-mice. 12(S)-HPETE and leukotriene B4 (0.01-0.2 nmol/site) induced scratching of the injected site, respectively; the dose-responses were a peak at 0.05 nmol/site (12(S)-HPETE) or 0.03 nmol/site (leukotriene B4). The scratching response by 12(S)-HPETE (0.05 nmol/site) started within 1 min, peaked in the first 10 min period, had almost subsided by 25 min whereas the effect of leukotriene B4 peaked in the second 10 min. The effect of leukotriene B4 is slightly stronger than that of 12(S)-HPETE in 40 min of count. The scratching induced by 12(S)-HPETE was inhibited by capsaicin, naltrexon, and LY255283. These results suggest the possibility that 12-lipoxygenase product can be added to a new member of an endogenous itch mediator in the skin.

PEP8-TAT2, a membrane-permeable peptide, inhibits cyclin-Cdk2 activity in HeLa cells.

Here we show that the PEP8-TAT2 peptide is effectively transduced into HeLa cells and that it inhibits cellular cyclin-Cdk2 activity. Like the PEP8 peptide, the PEP8-TAT2 peptide inhibits Cdk2 activity in vitro with an IC50 value of 5 nM, as determined by an immuno-complex kinase assay. It also inhibits DNA synthesis in and proliferation of cultured HeLa cells by arresting cell cycle at the G1/S transition. Further, the PEP8-TAT2 peptide inhibits cell death-associated Cdk2 activity and thereby prevents apoptotic progression in paclitaxel-treated cells. We propose that this inhibitor peptide is an effective agent to suppress the proliferation of human cancer cells, as well as apoptotic progression, by blocking cellular cyclin-dependent Cdk kinase activity.