Total synthesis of leukotrienes from butadiene

The total synthesis of leukotrienes has been achieved starting from butadiene by a palladium-catalyzed telomerization at room temperature. A Sharpless catalytic asymmetric epoxidation generated the asymmetric centers with >94% ee. Simple transformations of the key intermediate 15 produced the leukotrienes LTA₄ methyl ester (4), LTC₄ (1), LTD₄ (2) and LTE₄ (3), as well as (14S, 15S)-LTA₄ methyl ester (24) and the novel [²H₂]-LTA₄ methyl ester (28). The use of the opposite chiral director in the Sharpless catalytic asymmetric epoxidation gave the key intermediate 15a that has been used in the synthesis of the double epimers of the leukotrienes as well as LTB₄.