A convergent, stereocontrolled total synthesis of psymberin, an architecturally complex marine antitumor agent, has been achieved in 27 steps from the known aldehyde 8. Highlights of this synthesis include a novel and efficient transannular Michael addition/lactone reduction sequence to construct the highly substituted 2,6- trans-tetrahydropyran, a diastereoselective IBr-induced iodocarbonate cyclization to introduce the C17 stereogenic center, and a Diels-Alder/aromatization reaction to install the highly substituted aromatic ring.