A convenient new synthesis of quaternary ammonium glucuronides of drug molecules

Abstract N -Glucuronides, of various structural types, are frequently encountered as drug metabolites. Efficient chemical synthesis of these compounds, both as analytical standards and for toxicological investigation, is therefore an important goal. Earlier syntheses of N + - glucuronides of aliphatic tertiary amine drugs involved direct reaction of the drug molecule with a bromosugar, but yields were generally low and of poor reproducibility, with many by-products. In addition the final products were often of low stability, hindering effective isolation and purification. We now report that a stable, readily prepared glucuronic acid hemiacetal is a reliable precursor for metabolites of this type and give three pharmaceutically relevant examples. We report further on the stability of the final metabolites and the conditions required for their isolation and purification.