Stereospecific Synthesis of m-Hydroxymexiletine Enantiomers

Title:Stereospecific Synthesis of m-Hydroxymexiletine Enantiomers

Volume: 6 Issue: 3

Author(s): Alessia Catalano, Alessia Carocci, Giovanni Lentini, Ivana Defrenza, Claudio Bruno and Carlo Franchini

Affiliation:

Keywords: Sodium channel blockers, asymmetric synthesis, m-Hydroxymexiletine, anti-arrhythmics, chirality.

Abstract: m-Hydroxymexiletine (MHM) is a metabolite of mexiletine, a well known class IB anti-arrhythmic drug, which presents almost twice the activity of the parent compound on cardiac voltage-gated sodium channels. Given the different activity of mexiletine enantiomers on sodium currents (being the R-isomer the eutomer), it is conceivable that (R)- and (S)-MHM could differ in pharmacodynamic and pharmacokinetic properties, too. Herein we report the efficient synthesis of MHM enantiomers that could represent useful tools for further investigations on stereospecific requirements of the voltage-gated sodium channel binding site. MHM enantiomers and all the homochiral intermediates were fully characterized. The ee values for (R)- and (S)-MHM were >99%, as assessed by capillary electrophoresis using β-cyclodextrin sulfated sodium salt as a chiral selector.

Cite this article as:

Catalano Alessia, Carocci Alessia, Lentini Giovanni, Defrenza Ivana, Bruno Claudio and Franchini Carlo, Stereospecific Synthesis of m-Hydroxymexiletine Enantiomers, Drug Metabolism Letters 2012; 6 (3) . https://dx.doi.org/10.2174/1872312811206030005