Caged Naloxone: Synthesis, Characterization, and Stability of 3‑O‑(4,5-Dimethoxy-2-nitrophenyl)carboxymethyl Naloxone (CNV-NLX)

• Published in: ACS chemical neuroscience 2018-03, Vol.9 (3), p.563-567
• Main Authors: Lewin, Anita H, Fix, Scott E, Zhong, Desong, Mayer, Louise D, Burgess, Jason P, Mascarella, S. Wayne, Reddy, P. Anantha, Seltzman, Herbert H, Carroll, F. Ivy
• Format: Article
• Language: English
• ISSN: 1948-7193; 1948-7193
• DOI: 10.1021/acschemneuro.7b00378

The photolabile analogue of the broad-spectrum opioid antagonist naloxone, 3-O-(4,5-dimethoxy-2-nitrophenyl)­carboxymethyl naloxone (also referred to as “caged naloxone”, 3-O-(α-carboxy-6-nitroveratryl)­naloxone, CNV-NLX), has been found to be a valuable biochemical probe. While the synthesis of CNV-NLX is simple, its characterization is complicated by the fact that it is produced as a mixture of αR,5R,9R,13S,14S and αS,5R,9R,13S,14S diastereomers. Using long-range and heteronuclear NMR correlations, the 1H NMR and 13C NMR resonances of both diastereomers have been fully assigned, confirming the structures. Monitoring of solutions of CNV-NLX in saline buffer, in methanol, and in DMSO has shown CNV-NLX to be stable for over a week under fluorescent laboratory lights at room temperature. Exposure of such solutions to λ 365 nm from a hand-held UV lamp led to the formation of naloxone and CNV-related breakdown products.