DESIGN, SYNTHESIS, AND EVALUATION OF AN IMPROVED ENANTIOSELECTIVE NAPROXEN SELECTOR

The design, synthesis, and evaluation of an improved selector for the enantiomers of the nonsteroidal anti-inflammatory drug, naproxen, are described. So as to utilize the principle of reciprocity, two chiral stationary phases (CSPs) derived from (S)-naproxen were produced and HPLC techniques were used to screen candidate naproxen selectors. By determining how the structural features of the candidates influence enantioselective recognition by naproxen, a hypothetical chiral recognition mechanism for enantioselective recognition of naproxen was developed and used to design a selector which was incorporated into a new CSP. This comparatively simple CSP shows significant improvement in the separation of underivatized naproxen enantiomers relative to previous methods. Related compounds such as ibuprofen, ketoprofen, cicloprofen, fenoprofen, etc. are also resolved into their component enantiomers by this CSP.