THE CRYSTAL-STRUCTURE, ABSOLUTE-CONFIGURATION, AND PHOSPHODIESTERASE INHIBITORY ACTIVITY OF CLOPENTYLOXY)-4-METHOXYPHENYL)-PYRROLIDIN-2-ONE())

Chiral HPLC resolution of the phosphodiesterase IV (PDE IV) inhibitor rolipram (1) provided (-)-1, and this enantiomer was converted into it s 1-(4-bromobenzyl) derivative, (+)-2. X-ray structural analysis of ()-2 established the absolute configuration as R, which provides the fi rst direct evidence for a previously assumed assignment of configurati on. The crystal structure of (+)-2 and the PDE inhibitory activity of both enantiomers of 2 are discussed in the context of a previously pro posed topological model.