用GITC手性试剂衍生化高效液相色谱法拆分β-氨基醇类药物对映体

RESOLUTION OF THE ENANTIOMERS OF SOME β-AMINO ALCOHOLS USING CHIRAL DERIVATIZATION AND REVERSED-PHASE LIQUID CHROMATOGRAPHY

近十年来,用手性高效液相色谱拆分对映体化合物的技术已得到飞速发展。新型的手性固定相和手性流动相不断出现,种类繁多。但作为最早发展起来的柱前手性衍生化方法,由于采用普通的色谱系统进行拆分,有简便、易行的特殊优点,而仍被广泛应用。

A convenient and rapid procedure for enantiomeric resolution of β-amino alcohol drugs, such as oxprenolol, propafenone, timolol and phenylephrine, is described. The method is based on derivatization with the chiral reagent 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl isothiocyanate (GITC), and resolution of the resulting diastereomeric thioureas by reversed-phase HPLC using methanol-aqueous monobasic ammonium phosphate mixture as the mobile phase. The salt forms of these drugs can be directly derivatized with GITC reagent instead of being converted into their free bases and without protection of the phenolic hydroxyl group of phenylephrine.