Cathinones - Routine NMR methodology for enantiomer discrimination and their absolute stereochemistry assignment, using R-BINOL

Abstract

The demand for narcotics is still rising in societies worldwide and designer drugs, new psychoactive substances, (NPS) such as chiral cathinones, play an increasing role in a market. Since the psychoactive properties of their enantiomers may differ substantially in biological activity, there is an urgent need for simple unambiguous method of assessment of their enantiomer composition, which is not yet published. Here we propose a simple NMR methodology of chiral discrimination for several cathinones using R-BINOL as CSA (chiral solvating agent). The distinct differences are observed in 1H, 13C and NOESY spectra of solvation complexes of both enantiomers of mephedrone with R-BINOL. Due to these large differences in chemical shifts, if unequal population of the enantiomers are found, the limit of detection can be on the level of 13C satellite lines (0.55% of a major enantiomer) and their relative intensity can be validated by the integral comparison of a minor form with that of a satellite line of a major form. The methodology of the absolute stereochemistry of enantiomers is also proposed basing on observed differences in kinetics of solvation shifts and NOESY effects in both diastereromers. The computed structures of both solvation complexes are discussed. It helps validation of the assessment of the absolute configuration of both enantiomers.