Synthesis of succinimidyl-(S)-naproxen ester and its application for indirect enantioresolution of penicillamine by reversed-phase high-performance liquid chromatography

Abstract

Synthesis of N-succinimidyl-(S)-2-(6-methoxynaphth-2-yl) propionate was carried out by the reaction of (S)-naproxen with N-hydroxysuccinimide in the presence of dicyclohexyl carbodiimide. It was characterized and was used as a chiral derivatizing reagent, under mild conditions, to form diastereomers of dl-penicillamine which were resolved by reversed-phase high-performance liquid chromatography using triethyl ammonium phosphate buffer (pH 4.0, 5mM)-acetonitrile (linear gradient (30min) of acetonitrile from 30 to 70%). Excellent separation was achieved with gradient mobile phase. The detection limit was at pmol level.