Stereospecific Synthesis of m-Hydroxymexiletine Enantiomers
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.
Keywords: Sodium channel blockers, asymmetric synthesis, m-Hydroxymexiletine, anti-arrhythmics, chirality.
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