Catalytic Enantioselective Construction of Decalin Derivatives by Dynamic Kinetic Desymmetrization of C2-Symmetric Derivatives through Aldol–Aldol Annulation

We have developed and investigated a catalytic desymmetrization reaction strategy that affords functionalized decalin derivatives with high enantioselectivities from C2-symmetric derivatives through aldol–aldol annulation. We identified the structural moieties of the catalyst necessary for the formation of the decalin derivative with high enantioselectivity. We elucidated the mechanisms of the catalyzed reactions: the first aldol reaction step was reversible, and the second aldol step was rate-limiting and stereochemistry-determining and was enantioselective. Using theoretical calculations guided by the experimental results, we identified the interactions between the catalyst and the transition state that led to the major enantiomer. The information obtained in this study will be useful for the development of catalysts and chemical transformations

Bilateral Well Leg Compartment Syndrome Localized in the Anterior and Lateral Compartments following Urologic Surgery in Lithotomy Position

Well leg compartment syndrome (WLCS) is a rare but severe complication after the surgery in lithotomy position. We present a case of bilateral WLCS that occurred after the prolonged urologic surgery in lithotomy position. A 50-year-old man complained of severe bilateral lower leg pain and swelling sixteen hours after the surgery. Physical examination, elevated serum creatine kinase value, contrasting computed tomography, and elevated compartment pressure strongly suggested the development of bilateral WLCS localized in the anterior and lateral compartments. Emergent single-incision fasciotomy was performed four hours after diagnosis. The patient was treated successfully without any neuromuscular dysfunction. An early and accurate diagnosis is important to avoid the delay of treatment and development of neuromuscular dysfunction

The vitamin D analogue ED71 but Not 1,25(OH)2D3 targets HIF1α protein in osteoclasts.

Although both an active form of the vitamin D metabolite, 1,25(OH)2D3, and the vitamin D analogue, ED71 have been used to treat osteoporosis, anti-bone resorbing activity is reportedly seen only in ED71- but not in 1,25(OH)2D3 -treated patients. In addition, how ED71 inhibits osteoclast activity in patients has not been fully characterized. Recently, HIF1α expression in osteoclasts was demonstrated to be required for development of post-menopausal osteoporosis. Here we show that ED71 but not 1,25(OH)2D3, suppress HIF1α protein expression in osteoclasts in vitro. We found that 1,25(OH)2D3 or ED71 function in osteoclasts requires the vitamin D receptor (VDR). ED71 was significantly less effective in inhibiting M-CSF and RANKL-stimulated osteoclastogenesis than was 1,25(OH)2D3 in vitro. Downregulation of c-Fos protein and induction of Ifnβ mRNA in osteoclasts, both of which reportedly block osteoclastogenesis induced by 1,25(OH)2D3 in vitro, were both significantly higher following treatment with 1,25(OH)2D3 than with ED71. Thus, suppression of HIF1α protein activity in osteoclasts in vitro, which is more efficiently achieved by ED71 rather than by 1,25(OH)2D3, could be a reliable read-out in either developing or screening reagents targeting osteoporosis

ED71 or 1,25(OH)₂D₃ activity requires the VDR.

<p>(<b>A, B</b> and <b>C</b>) M-CSF-dependent osteoclast progenitor cells were isolated from wild-type (WT) or VDR-deficient (VDR KO) mice and cultured in the presence of M-CSF alone (50 ng/ml) or M-CSF + RANKL (25 ng/ml) with or without indicated concentrations of ED71 or 1,25(OH)₂D₃ for 5 days. Cells were then stained with TRAP (<b>A</b>), and multi-nuclear TRAP-positive cells were counted (<b>B</b>). Expression of <i>Ctsk</i>, <i>NFATc1</i> and <i>DC-STAMP</i> was assessed by realtime PCR (<b>C</b>). Data represent mean <i>Ctsk</i>, <i>NFATc1</i> or <i>DC-STAMP</i> expression relative to that of <i>Actb</i> ± SD (<i>n</i> = 5).</p