Methadone is a proven first-line treatment in opioid dependence but few studies have addressed the efficacy of different isoforms of methadone or the transfer from one form to the other. This was a 4-week open study to examine the feasibility and safety of transfer from racemic methadone to (R)-methadone in primary care patients. A total of 1552 opioid-dependent patients formerly treated with racemic methadone were included and followed for 4 weeks after transfer to (R)-methadone. There were few drop-outs, and 1426 patients (91.9%) completed the 4-week transfer period. There were few adverse events or side effects and no deaths occurred during treatment. The number of drug-positive urine screens decreased from 61.2 to 39.8%. Withdrawal symptoms, craving and compliance improved significantly after transfer to (R)-methadone. We conclude that transfer from racemic to (R)-methadone is a safe and practical procedure.
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http://dx.doi.org/10.1080/15622970802416057 | DOI Listing |
J Am Chem Soc
January 2025
Faculty of Pharmaceutical Sciences, Shenzhen University of Advanced Technology, Shenzhen 518107, China.
The synthesis of chiral tetrahydroquinolines (THQs) has garnered significant interest from medicinal chemists due to their frequent presence as pharmacophores in bioactive compounds. While existing synthetic methods have primarily focused on THQs with single or multiple endocyclic chiral centers, the selective construction of THQs with both and cyclic chiral centers remains a significant challenge that requires further development. This study introduces a dynamic kinetic resolution (DKR)-based transfer hydrogenation of racemic 2-substituted quinolines, which yields structurally novel chiral THQs with consecutive and cyclic chiral centers in excellent yields and stereoselectivities (59 examples, with generally >20:1 dr and >90% ee, up to three consecutive stereocenters).
View Article and Find Full Text PDFJ Am Chem Soc
January 2025
School of Natural Sciences, Department Chemie, and Catalysis Research Center (CRC), Technische Universität München, Lichtenbergstrasse 4, 85747 Garching, Germany.
By coupling a photochemical and a thermal step, a single chiral catalyst can establish a photostationary state in which the enantiopure form of a chiral compound is favored over its racemate. Following this strategy, 3-substituted 4,7-diaza-1-isoindolones were successfully deracemized (74-98% yield, 86-99% ) employing 2.5 mol % of a photocatalyst.
View Article and Find Full Text PDFOrg Chem Front
December 2024
Department of Chemistry, University of Basel St Johanns-Ring 19 Basel 4056 Switzerland https://www.chemie1.unibas.ch/Bmayor/.
This work explores the use of a cross-shaped organic framework that is used as a template for the investigation of multi-functionalized chromophores. We report the design and synthesis of a universal cross-shaped building block bearing two bromines and two iodines on its peripheral positions. The template can be synthesized on a gram scale in a five-step reaction comprising an oxidative homo-coupling macro-cyclization.
View Article and Find Full Text PDFJ Am Chem Soc
January 2025
Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.
Photochemical deracemization has emerged as one of the most straightforward approaches to access highly enantioenriched compounds in recent years. While excited-state events such as energy transfer, single electron transfer, and ligand-to-metal charge transfer have been leveraged to promote stereoablation, approaches relying on hydrogen atom transfer, which circumvent the limitations imposed by the triplet energy and redox potential of racemic substrates, remain underexplored. Conceptually, the most attractive method for tertiary stereocenter deracemization might be hydrogen atom abstraction followed by hydrogen atom donation.
View Article and Find Full Text PDFJ Am Chem Soc
December 2024
Laboratory of Asymmetric Catalysis and Synthesis, Institute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne 1015, Switzerland.
Chiral cyclopentadienyl (Cp) metal complexes are frequently used in asymmetric catalysis by virtue of their high reactivity and selectivity. Planar-chiral-only rhodium and iridium cyclopentadienyl complexes are particularly promising due to unrestricted chemical space for Cp ligand design while retaining structural simplicity. However, they are currently still niche because of a lack of efficient synthetic strategies that avoid lengthy chiral auxiliary routes or chiral preparatory HPLC resolution of the complexes.
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