INCREMENTAL DEVELOPMENT OF CHIRAL SELECTORS FOR UNDERIVATIZED PROFENS

Using a previously advanced mechanistic hypothesis, a conformationally rigid, [2.2.2]-bicyclooctane-based, selector intended to differentiat e between the enantiomers of underivatized profens, an important group of non-steroidal antiinflammatory drugs, was designed, synthesized, r esolved, and immobilized on silica. The resulting chiral stationary ph ase effectively discriminates between the enantiomers of the various p rofens. The discriminating ability of this selector is ascribed to a ' preorganized' cleft which provides an active site in which but one ena ntiomer of a profen can undergo simultaneous hydrogen bonding, pi-pi f ace-to-face stacking, and pi-pi face-to-edge interaction while in a re latively low energy conformation. The multi-step synthesis of the race mic selector is relatively efficient and employs inexpensive starting materials. The racemic selector is easily resolved on a preparative ch iral column derived from the diallyl amide of (S)-naproxen.