Efficient and practical synthesis of both enantiomers of 3-phenylcyclopentanol derivatives

Abstract

An efficient, multigram scale synthesis of the respective optical isomers of 3-(substituted-phenyl) cyclopentanols was achieved by a lipase-catalyzed transesterification (kinetic resolution) in organic medium. This enzymatic reaction proceeded with great efficiency as measured by chemical yield and enantioselectivity. The racemic cis-alcohol 3 was successfully resolved to yield (1 R,3 S)-acetate 7 and the corresponding (1 S,3 R)-alcohol 3 . The utility of this procedure was demonstrated by the practical syntheses of the biologically active compounds. The (1 R,3 S)-acetate 7 and the (1 S,3 R)-alcohol 3 were converted into orally active 5-lipoxygenase inhibitors, respectively, without loss of optical purity.