The Conformations of Discodermolide in DMSO

(+)-Discodermolide (1), a polyhydroxylated lactone isolated from the marine sponge Discodermia dissoluta,1 is currently a high-profile substance for its promise as an immunosuppressive agent1,2 and an anti-cancer drug. The compound induces apoptosis in human breast cancer cells,3 inhibits the in vitro proliferation of murine P388 leukemia cells,1 and combines synergistically with Taxol to suppress the proliferation of human carcinoma cells.4 Biomechanistically, discodermolide resembles Taxol and epothilone in its ability to bind to microtubules, effect tubulin polymerization, and promote mitotic arrest.5 Not surprisingly, these optimistic findings have stimulated a number of laboratories to pursue the total synthesis of the compound.6,7