Effective stereoselective total synthesis of 16,16-dimethyl prostaglandin E₂

The first stereoselective synthesis of the specific EP₁ receptor agonist, 16,16-dimethyl prostaglandin E₂ 1, is described. The key- intermediate 3 was obtained from the E-allyl alcohol 6 via Sharpless epoxidation followed by stereospecific transformations to the γ-iodo vinyl compound 3. Two component coupling of 2 and 3, using the dilithiocyanocuprate technology, gave the 1,4-addition product. Mild desilylation and enzymatic ester cleavage produced the optically pure prostaglandin 1 in high yield.