Diastereomeric selectivity of carbon-coated zirconia reversed-phase liquid chromatographic media

The determination of enantiomeric excess, that is, the relative amount of any pair of optical antipodes, constitutes a integral part of the work of analytical and synthetic chemists involved in natural products research or pharmaceutical development. Mosher's reagent [alpha-methoxy-alpha-(trifluoromethyl)phenylacetyl chloride] has evolved into a major tool for the determination of absolute configuration by NMR. We report here on the separation of diastereomers formed by derivatizing enantiomers with Mosher's reagent. We have shown that reversed-phase liquid-solid adsorption chromatography on carbon surfaces frequently gives considerably superior resolution of diastereomeric pairs than does RPLC on conventional bonded phases. The improved resolution results from the very high sensitivity of solid carbon surfaces to the geometric organization of the solute rather than from differences in column efficiency. We compare the separation of pharmaceutically and biologically important stereoisomeric mixtures, including (+/-)-warfarin and (+/-)-amino acid esters, on both conventional bonded phases and carbon surfaces prepared by chemical vapor deposition of organic compounds on porous zirconia microparticles.