Theoretical and Experimental Studies on Elementary Reactions in Living Radical Polymerization via Organic Amine Catalysis

The reaction mechanism of living radical polymerization using organic catalysts, a reversible complexation mediated polymerization (RCMP), was studied using both theoretical calculations and experiments. The studied catalysts are tetramethyl­guanidine (TMG), triethyl­amine (TEA), and thiophene. Methyl 2-iodoisobutyrate (MMA-I) was used as the low-molar-mass model of the dormant species (alkyl iodide) of poly­(methyl methacrylate) iodide (PMMA-I). For the reaction of MMA-I with TEA to generate MMA^• and ^•I-TEA radicals (activation process), the Gibbs activation free energy for the inner-sphere electron transfer mechanism was calculated to be 39.7 kcal mol^–1, while the observed one was 25.1 kcal mol^–1. This difference of the energies suggests that the present RCMP proceeds via the outer-sphere electron transfer mechanism, i.e., single-electron transfer (SET) reaction from TEA to MMA-I to generate MMA^• and ^•I-TEA radicals. The mechanism of the deactivation process of MMA^• to generate MMA-I was also theoretically studied. For the studied three catalysts, the theoretical results reasonably elucidated the experimentally observed polymerization behaviors

Two-Step Synthesis of Difluoromethyl-Substituted 2,3‑Dihydrobenzoheteroles

3-Difluoromethylated 2,3-dihydrobenzo­heteroles, 2,3-dihydro­benzo­furans, 2,3-dihydro­benzo­thio­phenes, and indolines were readily synthesized from <i>ortho</i>-heterosubstituted bromobenzenes, 2-bromophenols, 2-bromo­benzene­thiols, and 2-bromo­anilines, respectively, in two steps: (1) γ-selective allylic substitution of 3-bromo-3,3-difluoro­propene with heteronucleophiles and (2) intramolecular radical cyclization of the resulting 3,3-difluoroallylic compounds

Palladium-Catalyzed [4 + 2] Cycloaddition of Aldimines and 1,4-Dipolar Equivalents via Amphiphilic Allylation

The combination of Pd catalyst and diethylzinc with triethylborane promotes the amphiphilic allylation of aldimines with 2,3-bismethylenebutane-1,4-diol derivatives to serve as bis-allylic zwitterion species to form 3,4-bismethylenepiperidines via a formal [4 + 2] cycloaddition reaction. 3,4-Bismethylenepiperidine rings are applicable for the synthesis of isoquinoline derivatives via the Diels–Alder reaction followed by an oxidation reaction with DDQ

Platform for Ring-Fluorinated Benzoheterole Derivatives: Palladium-Catalyzed Regioselective 1,1-Difluoroallylation and Heck Cyclization

The synthesis of difluoromethylene-containing heterocycles was achieved via the palladium-catalyzed 1,1-difluoroallylation of heteronucleophiles followed by intramolecular Heck reaction. The allylic substitution of 3-bromo-3,3-difluoropropene was regioselectively accomplished by heteronucleophiles without rearrangement to give the corresponding 1,1-difluoroallylated compounds whose Heck cyclization proceeded in a 5-<i>exo</i> manner to afford ring-difluorinated indolines and dihydrobenzofurans. Their defluorinative allylic substitution further provided 2-fluoroindoles and 2-fluorobenzofurans

The effects of denosumab and alendronate on glucocorticoid-induced osteoporosis in patients with glomerular disease: A randomized, controlled trial

<div><p>Introduction</p><p>The clinical utility of denosumab for the treatment of glucocorticoid-induced osteoporosis (GIOP) has yet to be established. This study aimed to compare the effects of denosumab on bone mineral density (BMD) and bone turnover markers to those of alendronate in patients with GIOP.</p><p>Methods</p><p>A prospective, single-center study of 32 patients (18 men; median age, 66.0 years) with glomerular disease receiving prednisolone (PSL) who were diagnosed as having GIOP and had not received bisphosphonates before was conducted. Participants were randomized to either alendronate (35 mg orally once a week) or denosumab (60 mg subcutaneously once every 6 months), and all subjects received calcitriol. The primary endpoint was the percent change in lumbar spine (LS) BMD at 12 months of treatment.</p><p>Results</p><p>The demographic and clinical characteristics at baseline were not significantly different between the groups. Denosumab treatment markedly decreased serum levels of t-PINP, BAP, and TRACP-5b at 12 months compared to baseline (-57.4%, p<0.001; -30.9%, p<0.01; -57.7%, p<0.001, respectively). After 12 months of alendronate treatment, serum levels of t-PINP, BAP, and TRACP-5b were also significantly decreased compared to pretreatment (-38.9%, p<0.01; -16.3%, p<0.05; -43.5%, p<0.01, respectively). However, no significant differences in the changes of bone turnover markers were found between the two groups. As for the effects on BMD, denosumab treatment markedly increased LS BMD from 6 months compared to baseline, whereas no significant difference compared to pretreatment was found in the alendronate group during the study period. In the comparison of the two groups, a large increase of LS BMD was found in the denosumab treatment group compared to the alendronate treatment group at 12 months (p<0.05).</p><p>Conclusions</p><p>In patients with GIOP, denosumab treatment markedly suppressed bone turnover, which led to a significantly greater increase in LS BMD than with alendronate treatment. These results suggest that denosumab is a therapeutic option for the treatment of GIOP.</p></div

Effects of denosumab and alendronate on BMD.

<p>Percent changes (mean ± SEM) in bone mineral density from baseline to 12 months in the lumbar spine (A), femoral neck (B), and ultra-distal radius (C) in the denosumab and alendronate groups. *<i>P</i> compared with the alendronate group (by Wilcoxon’s rank sum test). ^#<i>P</i> compared with baseline (by Wilcoxon’s signed rank test).</p

Clinical characteristics at baseline.

<p>Clinical characteristics at baseline.</p

Laboratory data and bone mineral density (BMD) at baseline.

<p>Laboratory data and bone mineral density (BMD) at baseline.</p

Patient disposition.

<p>Abbreviations: FAS, full analysis set.</p