LAUSR

Amphidinolide U is a cytotoxic marine macrolide isolated from Amphidinium sp., sharing 75% of amphidinolide C backbone. We report here a synthetic study of the C1-C12 fragment of amphidinolide U. The C6-C12 pattern was built using consecutive regioselective ring-opening of epoxides, a directed reaction to control newly formed stereogenic centers. In parallel, the C1-C5 moiety was constructed by taking advantage of a symmetrical diol. Attempts to cross-couple C1-C5 and C6-C12 fragments were performed but led to poor conversion rates using Suzuki cross-coupling reaction. The same transformation on a close substrate model used during past studies on the total synthesis of amphidinolides F and C2 was successful. These contrasted results could be explained by a presumably steric hindrance of the protecting group adjacent to the vinyl function involved in the cross-coupling reaction. Our investigations will stimulate the optimization of Csp2-Csp3 cross-coupling reactions with bulky substrates, aiming to achieve the total synthesis of amphidinolide U.