R. Aav et al., Preparation of highly enantiopure stereoisomers of 1-(2,6-dimethylphenoxy)-2-aminopropane (mexiletine), TETRAHEDR-A, 10(15), 1999, pp. 3033-3038
Mexiletine [1-(2,6-dimethylphenoxy)-2-aminopropane], an orally effective an
tiarrhythmic agent, exhibits enantioselective pharmacokinetics and pharmaco
dynamics during mexiletine therapy. The purpose of this paper is to emphasi
ze the advantage of tetrahydropyranyl-protected mandelic acid (THPMA) in th
e resolution of mexiletine enantiomers. Both enantiomers of mexiletine were
obtained in 99% enantiomeric excess. Judging by the differential shielding
effects in the H-1 and C-13 NMR analyses, we have observed the opposite pr
edominant conformation for the mexiletine mandelates in comparison with the
O-methylmandelates. (C) 1999 Elsevier Science Ltd. All rights reserved.