PREPARATION OF FOUR STEREOISOMERS OF LABETALOL USING S-(-)-ALPHA-METHYLBENZYL ISOCYANATE AS A CHIRAL DERIVATIZING REAGENT

Abstract

Stereoisomers of labetalol were derivatized with (S)-(-)-alpha- methylbenzyl isocyanate (S-(-)-MBIC) forming their diastereomers, R,S- labetalol-S-(-)-MBIC, S,R-labetalol-S-(-)-MBIC, R,R-labetalol-S-(- )-MBIC, and S,S-labetalol-S-(-)-MBIC. Diastereomeric mixture was then chromatographically resolved by semi-preparative HPLC (Inertsil ODS C18 column, 250 mm x 10 mm i.d. 5 m) eluted with methanol- water (56: 44, v/v) at a flow rate of 3 mL/min. Then, the diastereomers were hydrolyzed with 30 mM H2SO4 to produce their stereoisomers at 60oC for 56 hours, and the decomposed mixture was further purified by semi-preparative HPLC. The stereoisomeric purity and final yield of four stereoisomer of labetalol were at least 99.95% and 16%, respectively.