Isolation, Identification and Structural Verification of a Methylene-Bridged Naloxone Dimer Formed by Formaldehyde

Schmidt, Philipp; Kolb, Christine; Reiser, Andreas; Philipp, Markus; Mueller, Hans-Christian und Karaghiosoff, Konstantin (2022): Isolation, Identification and Structural Verification of a Methylene-Bridged Naloxone Dimer Formed by Formaldehyde. In: Journal of Pharmaceutical Sciences, Bd. 111, Nr. 6: S. 1682-1689

Abstract

We report the isolation and characterization of a methylene bridged dimer of the opioid antagonist Naloxone, previously detected in experimental Buprenorphine-Naloxone oral films. This compound was found to form via an aldol addition followed by a condensation reaction under acidic conditions between two units of Naloxone and one unit of formaldehyde. HPLC-UV-HRMS analysis revealed the formation of three individual stereoisomers during this reaction, which were separately isolated using solid-phase extraction. These isomers were shown to freely react into one another in solvent, forming an equilibrium. The structure of the unknown compound was determined via HRMS spectrometry and 1D and 2D NMR spectroscopy. (C) 2021 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Chemie und Pharmazie > Department Chemie
• Themengebiete: 500 Naturwissenschaften und Mathematik > 540 Chemie
• ISSN: 0022-3549
• Sprache: Englisch