Synthesis of (+)-Ambrisentan via Chiral Ketone-Catalyzed Asymmetric Epoxidation

The synthesis of optically pure (+)-ambrisentan has been achieved from 3,3-diphenylacrylate in four steps with 53% overall yield and >99% ee at the >100 g scale without column purification. The chiral epoxide intermediate was prepared via asymmetric epoxidation with a fructose-derived diacetate ketone as catalyst

Synthesis of (+)-Ambrisentan via Chiral Ketone-Catalyzed Asymmetric Epoxidation

The synthesis of optically pure (+)-ambrisentan has been achieved from 3,3-diphenylacrylate in four steps with 53% overall yield and >99% ee at the >100 g scale without column purification. The chiral epoxide intermediate was prepared via asymmetric epoxidation with a fructose-derived diacetate ketone as catalyst

A Platform for Decarboxylative Couplings via Photoredox Catalysis: Direct Access to Carbocations from Carboxylic Acids for Carbon–Oxygen Bond Formation

Within the past decade, photoredox catalysis has enabled numerous decarboxylative transformations to couple carboxylic acids with a variety of partners primarily through carbon-centered radical intermediates. Herein, we describe a method for the construction of carbon–oxygen bonds using a dual photoredox/iodine­(III) platform directly from simple carboxylic acids and alcohols. This activation platform enables the direct utilization of readily available acids and alcohols without the need for prefunctionalization and works broadly across primary, secondary, and tertiary carboxylic acid substrates. We propose that this transformation proceeds via a radical-polar crossover event to generate a discrete carbocation intermediate which is intercepted by a nucleophilic coupling partner, thereby overcoming the electronically mismatched nature inherent in previous radical-based decarboxylative couplings. The application of this mechanistic approach toward additional nucleophiles is also demonstrated using water, enabling a direct decarboxylative-hydroxylation reaction. Finally, we demonstrated that the decarboxylative etherification can be applied to a peptide substrate, selectively functionalizing serine over other nucleophilic residues, providing support for future potential bioconjugation applications

The Direct Decarboxylative <i>N</i>‑Alkylation of Azoles, Sulfonamides, Ureas, and Carbamates with Carboxylic Acids via Photoredox Catalysis

Herein, we describe a method for the direct decarboxylative C–N coupling of carboxylic acids with a range of nitrogen nucleophiles. This platform employs visible-light-mediated photoredox catalysis and an iodine­(III) reagent to generate carbocation intermediates directly from aliphatic carboxylic acids via a radical-polar crossover mechanism. A variety of C–N bond-containing products are constructed from a diverse array of nitrogen heterocycles, including pyrazoles, imidazoles, indazoles, and purine bases. Furthermore, sulfonamides, ureas, and carbamates can also be utilized as the nucleophile to generate a selection of N-alkylated products. Notably, a two-step approach to construct free amines directly from carboxylic acids is accomplished using Cbz-protected amine as the nucleophile

Table_1_Effects of Exercise Intervention on Peripheral Skeletal Muscle in Stable Patients With COPD: A Systematic Review and Meta-Analysis.docx

Objectives: Peripheral skeletal muscle dysfunction is an important extrapulmonary manifestation of chronic obstructive pulmonary disease (COPD) that can be counteracted by exercise training. This study aimed to review the effect of three major exercise training modalities, which are used in pulmonary rehabilitation to improve on skeletal muscle mass, function, and exercise capacity in COPD.Methods: PubMed, Embase, EBSCO, Web of Science, and the PEDro database were searched on April 25, 2020. Only randomized controlled studies published in English evaluating the effects of exercise interventions on peripheral skeletal muscle mass, strength, and exercise capacity in stable COPD patients were included. The quality of included studies was evaluated using the PEDro scale. The mean difference (MD) or the standardized mean difference (SMD) with 95% CI was calculated to summarize the results. Subgroup meta-analysis was used to investigate the effects of different exercise training modalities and different outcome measures. The Grading of Recommendations Assessment, Development, and Evaluation guidelines were used to rate evidence quality.Results: A total of 30 randomized controlled trials involving 1,317 participants were included. Data from trials investigating endurance exercise (EE), resistance exercise (RE), and combined aerobic and resistance exercise (CE) were pooled into a meta-analysis, and the differences compared with the non-exercising COPD control were improvement in the muscle strength and exercise capacity in stable COPD patients. Subgroup meta-analysis for different exercise training modalities showed that RE significantly improved muscle strength (SMD = 0.6, 95% CI 0.35–0.84, I2 = 61%), EE and CE significantly increased VO2peak (EE: MD = 3.5, 95% CI 1.1–5.91, I2 = 92%; CE: MD = 1.66, 95% CI 0.22–3.1, I2 = 1%). Subgroup meta-analysis for different outcome measures showed that only isotonic strength was improved after exercise interventions (SMD = 0.89, 95% CI 0.51–1.26, I2 = 71%).Conclusion: Moderate evidence supports that exercise training in stable COPD patients has meaningful and beneficial effects on peripheral skeletal muscle strength and exercise capacity. Peripheral skeletal muscle shows a higher response to RE, and the isotonic test is relatively sensitive in reflecting muscle strength changes. The proportion of aerobic and resistance exercise components in a combined exercise program still needs exploration.Systematic Review Registration: The review was registered with the PROSPERO: (The website is https://www.crd.york.ac.uk/PROSPERO/, and the ID is CRD42020164868).</p

Data_Sheet_1_Effects of Exercise Intervention on Peripheral Skeletal Muscle in Stable Patients With COPD: A Systematic Review and Meta-Analysis.pdf

Objectives: Peripheral skeletal muscle dysfunction is an important extrapulmonary manifestation of chronic obstructive pulmonary disease (COPD) that can be counteracted by exercise training. This study aimed to review the effect of three major exercise training modalities, which are used in pulmonary rehabilitation to improve on skeletal muscle mass, function, and exercise capacity in COPD.Methods: PubMed, Embase, EBSCO, Web of Science, and the PEDro database were searched on April 25, 2020. Only randomized controlled studies published in English evaluating the effects of exercise interventions on peripheral skeletal muscle mass, strength, and exercise capacity in stable COPD patients were included. The quality of included studies was evaluated using the PEDro scale. The mean difference (MD) or the standardized mean difference (SMD) with 95% CI was calculated to summarize the results. Subgroup meta-analysis was used to investigate the effects of different exercise training modalities and different outcome measures. The Grading of Recommendations Assessment, Development, and Evaluation guidelines were used to rate evidence quality.Results: A total of 30 randomized controlled trials involving 1,317 participants were included. Data from trials investigating endurance exercise (EE), resistance exercise (RE), and combined aerobic and resistance exercise (CE) were pooled into a meta-analysis, and the differences compared with the non-exercising COPD control were improvement in the muscle strength and exercise capacity in stable COPD patients. Subgroup meta-analysis for different exercise training modalities showed that RE significantly improved muscle strength (SMD = 0.6, 95% CI 0.35–0.84, I2 = 61%), EE and CE significantly increased VO2peak (EE: MD = 3.5, 95% CI 1.1–5.91, I2 = 92%; CE: MD = 1.66, 95% CI 0.22–3.1, I2 = 1%). Subgroup meta-analysis for different outcome measures showed that only isotonic strength was improved after exercise interventions (SMD = 0.89, 95% CI 0.51–1.26, I2 = 71%).Conclusion: Moderate evidence supports that exercise training in stable COPD patients has meaningful and beneficial effects on peripheral skeletal muscle strength and exercise capacity. Peripheral skeletal muscle shows a higher response to RE, and the isotonic test is relatively sensitive in reflecting muscle strength changes. The proportion of aerobic and resistance exercise components in a combined exercise program still needs exploration.Systematic Review Registration: The review was registered with the PROSPERO: (The website is https://www.crd.york.ac.uk/PROSPERO/, and the ID is CRD42020164868).</p

sj-docx-5-tar-10.1177_17534666231218086 – Supplemental material for Effects of external diaphragm pacing combined with conventional rehabilitation therapies in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis

Supplemental material, sj-docx-5-tar-10.1177_17534666231218086 for Effects of external diaphragm pacing combined with conventional rehabilitation therapies in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis by Linhong Jiang, Pingping Sun, Peijun Li, Weibing Wu, Zhenwei Wang and Xiaodan Liu in Therapeutic Advances in Respiratory Disease</p

sj-docx-3-tar-10.1177_17534666231218086 – Supplemental material for Effects of external diaphragm pacing combined with conventional rehabilitation therapies in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis

Supplemental material, sj-docx-3-tar-10.1177_17534666231218086 for Effects of external diaphragm pacing combined with conventional rehabilitation therapies in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis by Linhong Jiang, Pingping Sun, Peijun Li, Weibing Wu, Zhenwei Wang and Xiaodan Liu in Therapeutic Advances in Respiratory Disease</p

sj-docx-1-tar-10.1177_17534666231218086 – Supplemental material for Effects of external diaphragm pacing combined with conventional rehabilitation therapies in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis

Supplemental material, sj-docx-1-tar-10.1177_17534666231218086 for Effects of external diaphragm pacing combined with conventional rehabilitation therapies in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis by Linhong Jiang, Pingping Sun, Peijun Li, Weibing Wu, Zhenwei Wang and Xiaodan Liu in Therapeutic Advances in Respiratory Disease</p

sj-docx-4-tar-10.1177_17534666231218086 – Supplemental material for Effects of external diaphragm pacing combined with conventional rehabilitation therapies in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis

Supplemental material, sj-docx-4-tar-10.1177_17534666231218086 for Effects of external diaphragm pacing combined with conventional rehabilitation therapies in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis by Linhong Jiang, Pingping Sun, Peijun Li, Weibing Wu, Zhenwei Wang and Xiaodan Liu in Therapeutic Advances in Respiratory Disease</p