Asymmetric synthesis of (+)-aspicilin

Aspicilin (1), an eighteen membered macrolide with four stereocenters, was synthesized using (3R,4R)- 1,5-hexadiene-3,4-diol and (S)-propylene oxide as the starting materials. Sharpless epoxidation on the protected dienediol generated the required three consecutive stereocenters, and malonic ester synthesis added the acetyl unit. Yamaguchi protocol was applied to form the key ester with two terminal olefins ready for the ring-closing metathesis. RCM, hydrogenation, selenylation, oxidation and deprotections gave aspicilin with 4.7% total yield.