ENANTIODIVERGENT SYNTHESIS OF (R)-ROLIPRAM AND (S)-ROLIPRAM

Both enantiomers of rolipram (1) have been prepared in large quantity from a common intermediate rac-3-(3'-cyclopentyloxy-4'-methoxy)phenyl- 4-nitro butyric acid (6), which was resolved by way of the two readily separable diastereoisomeric amides obtained with (S)-(-)-phenylethyla mine. Reduction of the nitro group and intramolecular transamidation g ave (R)-(-)-1 and (S)-(+)-1, respectively. CD spectra of both enantiom ers of rolipram are reported and discussed. Both enantiomers of rolipr am presented the same potency of inhibitory activity against recombina nt cyclic-AMP-selective phosphodiesterase (PDE4) subtypes.