| The amphidinolides are a class of macrolide natural products isolated from symbiotic marine dinoflagellates of the genus Amphidinium, which are associated with the Okinawan flatworm Amphiscolops sp. Amphidinolide C has displayed exceptional antineoplastic activity against NCI tumor cell lines. Biological studies have been hindered by extremely limited quantities of the natural product. The unique structural features of Amphidinolide C, and the exceptional antineoplastic activity, have inspired our studies toward the total synthesis. To achieve this goal, an enantioselective strategy directed towards the preparation of four fragments was envisioned. This highly convergent strategy is also applicable for the synthesis of other amphidinolide metabolites such as Amphidinolide F, C2 and C4. The enantiocontrolled synthesis of each of the nonracemic fragments, comprising of all 41 carbons is described. New methodology has been developed for the construction of enantio-enriched 2,5- trans and 2,5-cis fused tetrahydrofurans. |
