Abstract:

This thesis describes progress toward the total synthesis of three architecturally complex natural products: lyconadins A–E, cyclobutastelletolide B, and diplopyrone. Our unified approach to the lyconadins features a key Diels-Alder/ring-expansion sequence to construct their characteristic seven-membered ring. Efforts toward cyclobutastelletolide B centered on a [2+2] ene–ketene cycloaddition strategy and enabled scalable access to a key intermediate, though the final cyclization remained elusive. To address the unresolved stereochemistry of diplopyrone, we developed an expedient, modular synthesis capable of accessing all 16 possible diastereomers via cobalt-mediated cyclization.