Stereoselective, Ag-Catalyzed Cyclizations To Access Polysubstituted Pyran Ring Systems: Synthesis of C₁–C₁₂ Subunit of Madeirolide A

The exploration into the scope of a silver-catalyzed cyclization (AgCC) of propargyl benzoates for accessing pyran ring systems has been reported. The impact of the degree of substitution, nature of the substitution on the carbon backbone/benzoate moiety, and stereochemistry has been evaluated. The application of this methodology to the synthesis of the C₁–C₁₂ southern fragment of madeirolide A is disclosed

Chemo-Enzymatic Synthesis, Structural and Stereochemical Characterization, and Intrinsic Degradation Kinetics of Diastereomers of 1‑β‑<i>O</i>‑Acyl Glucuronides Derived from Racemic 2‑{4-[(2-Methylprop-2-en-1-yl)amino]phenyl}propanoic Acid

Alminoprofen, (<i>RS</i>)-2-{4-[(2-methylprop-2-en-1-yl)­amino]­phenyl}­propanoic acid (ALP) <b>1</b>, is a racemic drug categorized as a 2-arylpropanoic acid-class nonsteroidal anti-inflammatory drug. Pharmacokinetic studies of <b>1</b> in patients have revealed that the corresponding acyl glucuronide <b>5</b> is a major urinary metabolite, but little is known about the structure and stereochemistry of <b>5</b>. The present work describes the synthesis of a diastereomeric mixture of 1-β-<i>O</i>-acyl glucuronides (2<i>RS</i>)-<b>5</b> from <b>1</b> and methyl 2,3,4-tri-<i>O</i>-acetyl-1-bromo-1-deoxy-α-d-glucopyranuronate <b>2</b> using our chemo-enzymatic method that has complete specificity for the β-configuration. The structure of (2<i>RS</i>)-<b>5</b> was characterized by ¹H and ¹³C NMR spectroscopy and high-resolution mass spectrometry as well as by complete hydrolysis by β-glucuronidase. The absolute stereochemistry of (2<i>RS</i>)-<b>5</b> was determined by comparison with (2<i>R</i>)-<b>5</b> synthesized alternatively from (2<i>R</i>)-<b>1</b> and <b>2</b>. Compound (2<i>R</i>)-<b>1</b> was prepared in two steps starting from chiral (<i>R</i>)-2-(4-nitrophenyl)­propanoic acid (2<i>R</i>)-<b>6</b>. Chiral resolution of (2<i>RS</i>)-<b>1</b> was achieved using a chiral high-performance liquid chromatography column, and its stereochemistry was determined by comparison with (2<i>R</i>)-<b>1</b>. The intrinsic degradation rate constant of (2<i>R</i>)-<b>5</b> was 0.405 ± 0.002 h^–1, which is approximately twice that of (2<i>S</i>)-<b>5</b> (the <i>k</i> value was 0.226 ± 0.002 h^–1) under physiological conditions (pH 7.40, 37 °C)

Stereoselective, Ag-Catalyzed Cyclizations To Access Polysubstituted Pyran Ring Systems: Synthesis of C₁–C₁₂ Subunit of Madeirolide A

The exploration into the scope of a silver-catalyzed cyclization (AgCC) of propargyl benzoates for accessing pyran ring systems has been reported. The impact of the degree of substitution, nature of the substitution on the carbon backbone/benzoate moiety, and stereochemistry has been evaluated. The application of this methodology to the synthesis of the C₁–C₁₂ southern fragment of madeirolide A is disclosed

Correlations between the distance-corrected near visual acuity (DCNVA) and amplitude of accommodation (AA), the distance-corrected near functional visual acuity (DCNFVA), and AA in each group.

<p>The vertical axis shows the VA and the horizontal axis shows the AA. Significant linear correlations are seen in both of the presbyopia group’s combinations, and the slope of the linear regression between the DCNFVA and AA is steeper than between the DCNVA and AA. D, diopters.</p

A representative printout of typical functional visual acuity (VA) testing.

<p>The blue line denotes the Landolt corrected VA. The red line shows the time-wise changes in the VA during testing. The green line denotes the mean logarithm of the minimum angle of resolution (logMAR) over 60 seconds, defined as the functional VA. The yellow dots show the number of correct responses; the blue triangles indicate spontaneous blinks.</p

Additional file 1 of The association between team job crafting and work engagement among nurses: a prospective cohort study

Additional file 1. STROBE Statement—checklist of items that should be included in reports of observational studies

The Functional Visual Acuity Measurement Device, the Kowa AS-28.

<p>The Functional Visual Acuity Measurement Device, the Kowa AS-28.</p

Enantioselective Total Synthesis of Mandelalide A and Isomandelalide A: Discovery of a Cytotoxic Ring-Expanded Isomer

The total synthesis of mandelalide A and its ring-expanded macrolide isomer isomandelalide A has been achieved. Unexpected high levels of cytotoxicity were observed with the ring-expanded isomandelalide A with a rank order of potency: mandelalide A > isomandelalide A > mandelalide B. Key aspects of the synthesis include Ag-catalyzed cyclizations (AgCC’s) to construct both the THF and THP rings present in the macrocycle, diastereoselective Sharpless dihydroylation of a <i>cis</i>-enyne, and lithium acetylide coupling with a chiral epoxide

Baseline characteristics and outcomes of GIB compared between direct oral anticoagulant (DOAC) and warfarin users (n = 157).

<p>Baseline characteristics and outcomes of GIB compared between direct oral anticoagulant (DOAC) and warfarin users (n = 157).</p

Baseline characteristics and outcomes of anticoagulant users compared between upper and lower GI bleeding (n = 157).

<p>Baseline characteristics and outcomes of anticoagulant users compared between upper and lower GI bleeding (n = 157).</p