Synthesis of Enantiomerically Pure Stereomers of Rosaprostol

Enantiopure stereomers of rosaprostol 1, an antiulcer drug, were synthesized from diastereomeric building blocks (-)-5a and (+)-5b. Conversion of (-)-5a into rosaprostol stereomer (-)-(1S,2R,5R)-1a was accomplished in nine steps in 18% overall yield. In this sequence, fully diastereoselective hydrogeneration of the endocyclic carbon double bond in the cyclopentenone ring was key, generating a new stereogenic center (C-2 in 1a). C-5 epimeric rosaprostol (-)-(1S,2R,5S)-1b was obtained from (-)-1a in 72% yield by a two-reaction sequence involving methylation and one-pot Mitsunobu esterification-hydrolysis.