A Telescoped Continuous Flow Enantioselective Process for Accessing Intermediates of 1-Aryl-1,3-diols as Chiral Building Blocks.

A telescoped continuous flow process is reported for the enantioselective synthesis of chiral precursors of 1-aryl-1,3-diols, intermediates in the synthesis of ezetimibe, dapoxetine, duloxetine, and atomoxetine. The two-step sequence consists of an asymmetric allylboration of readily available aldehydes using a polymer-supported chiral phosphoric acid catalyst to introduce asymmetry, followed by selective epoxidation of the resulting alkene. The process is highly stable for at least 7 h and represents a transition-metal free enantioselective approach to valuable 1-aryl-1,3-diols.

Harnessing a Continuous-Flow Persulfuric Acid Generator for Direct Oxidative Aldehyde Esterifications.

Persulfuric acid is a well-known oxidant in various industrial-scale purification procedures. However, due to its tendency toward explosive decomposition, its usefulness in organic synthesis remained largely underexplored. Herein, a continuous in situ persulfuric acid generator was developed and applied for oxidative esterification of aldehydes under flow conditions. Sulfuric acid served as a readily available and benign precursor to form persulfuric acid in situ. By taking advantage of the continuous-flow generator concept, safety hazards were significantly reduced, whilst a robust and effective approach was ensured for direct transformations of aldehydes to valuable esters. The process proved useful for the transformation of diverse aliphatic as well as aromatic aldehydes, while its preparative capability was verified by the multigram-scale synthesis of a pharmaceutically relevant key intermediate. The present flow protocol demonstrates the safe, sustainable, and scalable application of persulfuric acid in a manner that would not be amenable to conventional batch processing.

Effect of retinol in the vitrification medium on viability of vitrified ovine preantral follicles and expression of key developmental and apoptosis related genes.

BACKGROUND: Vitrification increases the production of reactive oxygen species (ROS) and the antioxidants in the vitrification solution may be beneficial by reducing excessive ROS production. OBJECTIVE: To evaluate the effect of retinol supplementation in vitrification solution on viability, apoptosis and development-related gene expression in vitrified sheep preantral follicles. MATERIALS AND METHODS: Preantral follicles were isolated and randomly assigned into one of five groups: Group1, control fresh preantral follicles; Group 2, vitrification treatment; Group 3, vitrification + 2 µM retinol; Group 4, vitrification + 5 µM retinol; Group 5, vitrification + 10 µM retinol. Preantral follicles were placed in vitrification solutions and then plunged into liquid nitrogen (-196°C). After a week, the follicles were thawed and analyzed for follicular viability by trypan blue exclusion method and for gene expression. RESULTS: Vitrification with 5 µM retinol positively affected viability in comparison with vitrification without retinol (P < 0.05). There was no significant difference in viability among the Group 1, Group 2, Group 3 and Group 5. Expression of apoptotic genes BAX and Casp 3 were higher in the vitrified group, and vitrification with 5 µM retinol (Group 4) is comparable to the control fresh. Expressions of other apoptosis-related genes (i.e., BCL2L1, BAD and BAK) showed significant difference between the control fresh group and the vitrification group with 5 µM retinol. Expression of Annexin5 was also significantly different among various groups. The expression of development competence genes GDF-9 and BMP-15 were higher (P < 0.05) in the Group vitrified with 5 µM retinol. CONCLUSION: The supplementation of 5 µM retinol in vitrification solution was beneficial for the vitrification of ovine preantral follicles.

Enantioselective Flow Synthesis of Rolipram Enabled by a Telescoped Asymmetric Conjugate Addition-Oxidative Aldehyde Esterification Sequence Using in Situ-Generated Persulfuric Acid as Oxidant.

A novel approach is reported for the enantioselective flow synthesis of rolipram comprising a telescoped asymmetric conjugate addition-oxidative aldehyde esterification sequence followed by trichlorosilane-mediated nitro group reduction and concomitant lactamization. The telescoped process takes advantage of a polystyrene-supported chiral organocatalyst along with in situ-generated persulfuric acid as a robust and scalable oxidant for direct aldehyde esterification. This approach demonstrates significantly improved productivity compared with earlier methodologies while ensuring environmentally benign metal-free conditions.

Is the outcome in acute aortic dissection type A influenced by of femoral versus central cannulation?

BACKGROUND: The purpose of this study was to evaluate the single-center experience in initial femoral versus central cannulation of the extracorporeal circulation for acute aortic dissection type A (AADA). METHODS: Between January 2003 and December 2015, 235 patients underwent repair of AADA. All patients were evaluated for the type of arterial cannulation (femoral vs. central) for initial bypass. Demographic data and outcome parameters were accessed. RESULTS: One hundred and twenty seven (54.0%) were initially cannulated in the central aortic vessels (ascending aorta or subclavian/axillary artery) and 108 (46.0%) in the femoral artery. Patients were comparable between age (62.4±14.4 vs. 62.9±14.4 years, P=0.805), gender (male, 62.2 vs. 69.4%, P=0.152) and previous sternotomy (15.7 vs. 16.7%, P=0.861) between both cannulation groups; while EuroSCORE I (11.5±4.0 vs. 12.7±4.2, P=0.031) and ASA Score (3.5±0.81 vs. 3.8±0.57, P=0.011) were significantly higher in the femoral artery cannulation group. Bypass (249±102 vs. 240±81 min, P=0.474), X-clamp (166±85 vs. 157±67 min, P=0.418) and circulatory arrest time (51.6±28.7 vs. 48.3±21.7 min, P=0.365) were similar between the groups as were lowest temperature (18.1±2.0 vs. 18.1±2.2, P=0.775). Postoperative neurologic deficit and 30-day mortality were comparable between both cannulation groups (11.7 vs. 7.2%, P=0.449 and 20.2 vs. 16.9%, P=0.699, central vs. peripheral cannulation). Multivariate analysis revealed only EuroScore I above 13 as single preoperative predictor for mortality. CONCLUSIONS: AADA can be operated with both femoral and central cannulation with similar results. Risk for early mortality was driven by the preoperative clinical and hemodynamic status before operation rather than the cannulation technique.

Stereopsis testing in a preschool vision screening program.

We conducted a preschool vision screening study using stereopsis testing with the Random Dot E and Lang stereotests as a complement to visual acuity measurement. Over 6000 children were screened. Stereopsis testing at a threshold of 600 seconds of arc was cognitively easier for the children than visual acuity measurement. At this threshold there was no effect on reducing the rate of visual acuity overreferrals, but ten children with abnormal binocular vision were detected who were not referred by visual acuity criteria. Though a large number of children passed only one of the two stereotests, there was no significant difference in their degree of difficulty. Stereopsis testing with these two stereotests may be a useful adjunct to preschool vision screening programs though further studies are required.