A Highly Stereoselective Total Synthesis of (+)-9-epi-Dictyostatin

The total synthesis of (+)-9-epi-dictyostatin (1b), a diastereomer of the antimitotic marine-sponge-derived macrolide (–)-dictyostatin (1a), was achieved by creating 11 stereogenic centers and 4 stereogenic double bonds with a high level of stereocontrol. The yield for the 29-step longest linear sequence from Roche ester was 1.53%. The final key steps to this unnatural product were the vinylzincate C10–C26 addition to aldehyde C1–C9 (leading surprisingly to a complete stereoselectivity for the 9R-epimer), followed by Yamaguchi macrolactonization and global deprotection.