Electrochemical method uses heavy water to install programmable deuterium labels at chosen sites in over 70 amine drugs
- Electrochemistry with heavy water as the sole deuterium source avoids costly prefunctionalised deuterated reagents.
- Toxic polyhalides are reduced in situ to reactive deuterated building blocks that deliver the label directly.
- Over 70 drugs were labelled, with mono-, di- or trideuteration selectable at N-benzyl, N-methyl, O-benzyl and S-benzyl sites, across many functional groups.
💡 Points Based on the abstract
A quick way to test a metabolic soft-spot hypothesis: if N-demethylation or O-debenzylation drives clearance, the d3 or d2 analogue can come straight from the lead without a new route. Still needed are isotopic purity, any scrambling at neighbouring positions, and microsomal data showing a real isotope effect, since metabolic switching to other sites can erase the gain.
📄 Paper · Journal of the American Chemical Society ↗ Site-Selective and Deuterium-Programmable Electrochemical Synthesis of Deuterated Pharmaceuticals