Development of a Route to the Most Active Nafronyl Stereoisomer by Coupling Asymmetric Synthesis and Chiral Chromatography Separation

Abstract

AbstractNafronyl is a pharmaceutically active compound used as a drug ingredient. It occurs in form of four stereoisomers, with however different biological activities. A procedure for preparation of the most active stereoisomer of nafronyl was developed. The stereoselective synthesis was used to produce a pair of diastereoisomers, which included the target stereoisomer. The mixture obtained was then separated by chiral chromatography in a batch mode. The efficiency of the separation in a continuous mode in a classical simulated moving‐bed system was assessed. To improve the yield of the whole operation, the less active diastereoisomer was subjected to diastereoisomeric conversion, which delivered back the pair of diastereoisomers that could be recycled to the chromatographic separation.