AbstractThe total syntheses of (+)‐9‐epi‐dictyostatin (1a) and (–)‐12,13‐bis‐epi‐dictyostatin (1b), diastereomers of the antimitotic marine sponge‐derived macrolide (–)‐dictyostatin (1), were achieved by creating 11 stereogenic centers and 4stereogenic double bonds with a high level of stereocontrol. The yield for the 29‐step longest linear sequence from Roche ester was 1.53 and 1.52 %, respectively. The final key steps to these unnatural products were the addition of vinylzincates C10‐C26 to aldehyde C1–C9 (leading surprisingly to complete stereoselectivity for the 9R‐configuration in 28a and for the 9S‐configuration in 12,13‐bis‐epimeric 28b), followed by Yamaguchi macrolactonization and global deprotection. (–)‐12,13‐Bis‐epi‐dictyostatin (1b) displayed a dramatic decrease of cytotoxicity and of the affinity toward the paclitaxel binding site of microtubules.