Toward the Total Synthesis of Amphidinolide N: Synthesis of the C8–C29 Fragment

A synthesis of the C8–C29 fragment of amphidinolide N, a potent cytotoxic macrolide isolated from the marine dinoflagellate Amphidinium sp., has been achieved. The key features of the synthesis involve a convergent union of the C9–C15 and C16–C29 fragments by Steglich esterification and the construction of a pyran unit through a Tebbe methylenation/ring-closing metathesis sequence.