A formal total synthesis of the potent renin inhibitor aliskiren is disclosed exploiting an alternative coupling strategy recently developed by this laboratory for the preparation of the hydroxyethylene isostere-based class of protease inhibitors. The thioester derivative of the amino acid representing the C5-C9 fragment of the aliskiren carbon skeleton underwent a carbon chain extension via a SmI2-promoted radical addition to n-butyl acrylate. Introduction of the C3-isopropyl group with the correct relative configuration was accomplished via stereoselective reduction of the obtained ketone with concomitant lactonization, followed by an aldol reaction with acetone. Further functional group and protecting group manipulation culminated in a formal total synthesis of aliskiren in 10 steps from the corresponding fully protected non-natural amino acid.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/jo060296c | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Romosozumab adverse event profile: a pharmacovigilance analysis based on the FDA Adverse Event Reporting System (FAERS) from 2019 to 2023.
Aging Clin Exp Res
January 2025
Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, 710054, Shaanxi, China.
Objective: This study aims to analyze adverse drug events (ADE) related to romosozumab from the second quarter of 2019 to the third quarter of 2023 from FAERS database.
Methods: The ADE data related to romosozumab from 2019 Q2 to 2023 Q3 were collected. After data normalization, four signal strength quantification algorithms were used: ROR (Reporting Odds Ratios), PRR (Proportional Reporting Ratios), BCPNN (Bayesian Confidence Propagation Neural Network), and EBGM (Empirical Bayesian Geometric Mean).
Background: Polysomnography (PSG) is resource-intensive but remains the gold standard for diagnosing Obstructive Sleep Apnea (OSA). We aimed to develop a screening tool to better allocate resources by identifying individuals at higher risk for OSA, overcoming limitations of current tools that may under-diagnose based on self-reported symptoms.
Methods: A total of 884 patients (490 diagnosed with OSA) were included, which was divided into the training, validation, and test sets.
Experiences of African women who migrate to a developed country and encounter intimate partner violence: a systematic review of qualitative evidence.
JBI Evid Synth
January 2025
School of Nursing and Midwifery, University of Newcastle, Newcastle, New South Wales, Australia.
Objective: The objective of this review was to synthesize the available evidence on the experiences of African women who migrated to a developed country and encountered intimate partner violence (IPV).
Introduction: IPV is a significant public health issue, and migrant women living in developed countries are particularly vulnerable to IPV, experiencing disproportionately higher rates of IPV. Understanding the experiences of these women can inform health policy and decision-making in clinical practice to minimize IPV.
Small mammals and associated infections in China: a systematic review and spatial modelling analysis.
Lancet Reg Health West Pac
January 2025
State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Science, Beijing, PR China.
Background: As natural reservoirs of diverse pathogens, small mammals are considered a key interface for guarding public health due to their wide geographic distribution, high density and frequent interaction with humans.
Methods: All formally recorded natural occurrences of small mammals (Order: Rodentia, Eulipotyphla, Lagomorpha, and Scandentia) and their associated microbial infections in China were searched in the English and Chinese literature spanning from 1950 to 2021 and geolocated. Machine learning models were applied to determine ecological drivers for the distributions of 45 major small mammal species and two common rodent-borne diseases (RBDs), and model-predicted potential risk locations were mapped.
Global Perspectives on Returning Genetic Research Results in Parkinson Disease.
Neurol Genet
December 2024
From the Division of Neurology (A.H.T., S.-Y.L.), Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; Programa de Pós-Graduação em Ciências Médicas da Universidade Federal do Rio Grande do Sul (P.S.-A.), Clínica Santa María, Santiago, Chile; Departamento de Farmacologia (A.F.S.S.), Universidade Federal do Rio Grande do Sul; Serviço de Neurologia (A.F.S.S.), Hospital de Clínicas de Porto Alegre, Brazil; Institute of Neurogenetics (H.M., M.L.D., C.K.), University of Lübeck, Germany; Department of Biomedical Science (A.A.-A.), Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; The Michael J. Fox Foundation for Parkinson's Research (J.S., B.F.), New York; Department of Medical and Molecular Genetics (C.E.W.), Indiana University, Indianapolis; Department of Neuroscience and Brain Health (M.L.D.), Metropolitan Medical Center, Manila, Philippines; Centre for Preventive Neurology (S.D., M.T.P., A.J.N.), Wolfson Institute of Population Health, Queen Mary University of London, United Kingdom; Unidad de Trastornos del Movimiento (M.T.P.), Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Spain; Laboratory of Neurogenetics (M.B.M.), National Institute on Aging, National Institutes of Health, Bethesda, MD; Department of Clinical and Movement Neurosciences (M.B.M., H.R.M.), UCL Queen Square Institute of Neurology, University College London, United Kingdom; Department of Neurology (R.N.A.), Columbia University Irving Medical Center, New York; Movement Disorders Division (R.N.A.), Neurological Institute, Tel Aviv Sourasky Medical Center and Tel Aviv School of Medicine, Tel Aviv University, Israel; Molecular Medicine Laboratory and Neurology Department (K.R.K.), Concord Clinical School, Concord Repatriation General Hospital, The University of Sydney; Translational Neurogenomics Group (K.R.K.), Genomic and Inherited Disease Program, Garvan Institute of Medical Research; and St Vincent's Healthcare Campus (K.R.K.), Faculty of Medicine, UNSW Sydney, Darlinghurst, New South Wales, Australia.
Background And Objectives: In the era of precision medicine, genetic test results have become increasingly relevant in the care of patients with Parkinson disease (PD). While large research consortia are performing widespread research genetic testing to accelerate discoveries, debate continues about whether, and to what extent, the results should be returned to patients. Ethically, it is imperative to keep participants informed, especially when findings are potentially actionable.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!