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

The photolabile analogue of the broad-spectrum opioid antagonist naloxone, 3-<i>O</i>-(4,5-dimethoxy-2-nitrophenyl)­carboxymethyl naloxone (also referred to as “caged naloxone”, 3-<i>O</i>-(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 α<i>R</i>,5<i>R</i>,9<i>R</i>,13<i>S</i>,14<i>S</i> and α<i>S</i>,5<i>R</i>,9<i>R</i>,13<i>S</i>,14<i>S</i> 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