From Total Synthesis to Diverted Total Synthesis: Case Studies in the Amphidinolide Series

Amphidinolides are a class of structurally rather unique macrolides of marine origin which stimulated a lot of creative work in the total synthesis arena over the last decade. This review summarizes the strategies and tactics pursued by our group en route to various amphidinolides of the B, G, H, T, V, X, and Y series. These projects were invariably benefitting from the power of transition metal catalysis, with olefin and alkyne metathesis, palladium- and iron cross-coupling, as well as asymmetric oxidation and reduction chemistry playing particularly prominent roles. Once the total syntheses were completed, the flexibility of the underlying blueprints enabled the extension of our program toward the preparation of non-natural analogues for biological testing, all of which feature deep-seated structural modifications in keeping with the logic of diverted total synthesis.