Toward the Total Synthesis of Amphidinolide O: An Enantioselective Synthesis of C3-C8 Fragment

The methyl ester 4, a C3-C8 fragment of am-phidinolide O (1), was prepared enantioselectively via 11 steps in 14% overall yields. The diastereoselective Ireland-Claisen rearrangement of 5 via the corresponding (E)-enolate intermediate was used as a key step in order to implement the C4 and C5 chiral centers. Retrosynthetic analysis was described in Figure 1. Amphi-dinolide O (1) might be assembled from two intermediates 2 and 3 via esterification and ring closing metathesis as key steps. Intermediate 4, a precursor to 3 as well as the target molecule in this paper, involves the γ,δ-unsaturated ester moiety along with α,β-chiral substituents with anti-stereochemical relationship