title: Stereospecific synthesis of m-Hydroxymexiletine enantiomers.
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.
authors.affiliation: Dipartimento di Farmacia- Scienze del Farmaco, Universita degli Studi di Bari "Aldo Moro", via Orabona 4, 70126 Bari, Italy. alessia.catalano@uniba.it.
authors.forename: Alessia
authors.initials: A
authors.lastname: Catalano
authors.forename: Alessia
authors.initials: A
authors.lastname: Carocci
authors.forename: Giovanni
authors.initials: G
authors.lastname: Lentini
authors.forename: Ivana
authors.initials: I
authors.lastname: Defrenza
authors.forename: Claudio
authors.initials: C
authors.lastname: Bruno
authors.forename: Carlo
authors.initials: C
authors.lastname: Franchini
mesh_terms: D019075:Electrophoresis, Capillary / Q000379:methods*; D008801:Mexiletine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D013237:Stereoisomerism; D013431:Sulfates / Q000737:chemistry; D061567:Voltage-Gated Sodium Channel Blockers / Q000138:chemical synthesis* / Q000737:chemistry; D047392:beta-Cyclodextrins / Q000737:chemistry
chemical_list: D013431:Sulfates; D061567:Voltage-Gated Sodium Channel Blockers; D047392:beta-Cyclodextrins; C069734:3-hydroxymexiletine; D008801:Mexiletine