Synthesis of 7-Thiaprostaglandin E₁ Congeners : Potent Inhibitors of Platelet Aggregation

Abstract

Novel 7-thiaprostaglandin E₁ derivatives and congeners were synthesized by a stepwise three-component coupling process, which involves the introduction of α-side chains (thiols) and β-side chains (organocopper reagents) into (R)-4-tert-butyldimethylsilyloxy-2-cyclopentenone. Several acid derivatives of 7-thiaprostaglandin E₁ were also prepared either by enzymatic or by chemical methods. The stereochemistry of these products was assigned on the basis of the results with chiral protected cyclopentenones and chiral ω-side chains. Some of these 7-thiaprostaglandin E₁ congeners were found to exhibit more potent platelet aggregation-inhibitory activity than PGE₁. The structure-activity relationship of these congeners is discussed.