PREPARATIVE RESOLUTION OF SACLOFEN AND HYDROXYSACLOFEN WITH ANALYTICAL-SCALE HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY

The preparative enantiomeric resolution of two analogues of baclofen: saclofen and hydroxysaclofen, potent gamma-aminobutyric acid(B) (GABA( B)) antagonists, was obtained by HPLC with an analytical crown ether c olumn (CR+) using isocratic conditions and multiple repetitive injecti ons. The preparative separation was optimized by adjusting the sample size, by detecting the sample where its UV absorbance was low and from a scale-up of the analytical method. The analytical separation was mo dified to provide a convenient method for the isolation of the two ena ntiomers. The best analytical results obtained were alpha=3.68, R(s)=2 0.96 with H2O-CH3OH (90:10) at 0.5 ml/min and 20 degrees C for hydroxy saclofen. Suitable fractionation allowed the isolation of pure (>99%) enantiomers for pharmacological testing.