Synthesis of Six-Membered-Ring Analogues of 6α-Carba-PGI2

Article abstract of DOI:10.1021/jo00143a027

To further develop our understanding of prostacyclin (PGI₂, 1) structure-activity relationships, we have prepared the six-membered-ring analogues of 6α-Carba-PGI₂ (carbacyclin, 3).An intramolecular alkylation of 1,3-dithiane was utilized as the critical reaction for securing the key cyclohexanone intermediate 8.The carboxyl side chains were attached to 8 by using conventional Wittig chemistry.Acid removal of the tetrahydropyranyl protective groups and separation of the resulting E and Z isomers afforded the 7a-homo-6α-Carba-PGI₂ analogues 6 and 7.The reactions described are simple to perform and useful for preparetive purposes.The six-membered-ring carbacyclins reported were found to be much less active than parent carbacyclin in inhibiting human platelet aggregation.