Enantioseparation of aminoglutethimide and thalidomide by high performanceliquid chromatography or supercritical fluid chromatography on mono-2 and mono-6-O-pentenyl-beta-cyclodextrin-based chiral stationary phases

Mono-2 and mono-6-O-pentenyl-beta -cyclodextrin (mono-2-pent-P-CD and mono- 6-pent-beta -CD), covalently linked to mercaptopropylsilica gel (thiol-Si) through thioether or sulfone linkage, reveal differentiated enantioselectiv ities in the separation of piperidine-2,6-dione-related drugs. namely amino glutethimide and thalidomide, in supercritical fluid conditions. Supercriti cal fluid chromatographic resolution on completely defined mono-cyclodextri n derivative-based chiral stationary phases (CSP) is a method of choice for the separation of aminoglutethimide but not effective for thalidomide. For both high performance liquid chromatography (HPLC) and supercritical fluid chromatography (SFC) conditions, the impact of the position, imposed to be 2 or 6 in our synthetic pathway, of the pentenyl moiety on one of the gluc opyranosidics of the CD cage is of crucial importance in the chiral discrim ination phenomenon. Additionally, the nature of the heteroatom present in t he spacer arm between the CD and the silica gel, in this case thioether or sulfone functionality, is also essential for the chiral recognition mechani sm(s) for the solute enantiomer. Copyright (C) 2001 John Wiley & Sons, Ltd.