Effects of mobile phase composition and temperature on the supercritical fluid chromatography enantioseparation of chiral fluoro-oxoindole-type compounds with chlorinated polysaccharide stationary phases

The indole ring is present in many pharmaceutically active compounds, as in MaxiPost™ (or BMS-204352), an active pharmaceutical ingredient for post-stroke neuroprotection. Two different fluoro-oxindole-type chiral solutes derived from MaxiPost were prepared. The structural modification was placed on the NH indole function, which is probably taking part in the bioactivity, but also probably in the chromatographic enantiomer separation. Baseline resolution of the enantiomers of MaxiPost and the two derivatives was achieved on two commercial chlorinated polysaccharide stationary phases: cellulose tris-(3-chloro-4-methylphenylcarbamate) and amylose tris-(5-chloro-2-methylphenylcarbamate) (Lux Cellulose-2 and Lux-Amylose-2 from Phenomenex) in supercritical fluid chromatography (SFC). The effects of molecular structure on SFC retention and enantioresolution are studied. The effect of temperature, modifier nature (methanol or ethanol) and proportion were investigated in order to select the best conditions for preparative purposes. A temperature study led to Van’t Hoff plots that were strongly dependent on the mobile phase composition. From linear portions of the plots for separation, thermodynamic parameters of the separation could be calculated. Incidentally, particular adsorption–desorption effects were observed. Semi-preparative resolution was then achieved, allowing retrieving about 10 mg purified enantiomers for bioactivity testing.