Discodermolide structure/isolation

The natural product eleutherobin (1) was isolated in 1994 by Fenical et al. from a marine soft coral from an Eleutherobia species and its structure was elucidated shortly afterwards (Figure 1) [1]. Eleutherobin is a diterpene glycoside that possesses remarkable cytotoxicity against a wide variety of cancer cells, which is likely to be based on binding to tubulin and stabilization of microtubules [2, 3]. Mitosis is interrupted and the cell division cycle is terminated. The mechanism of action of eleutherobin is comparable to that of highly potent cytostatic agents such as paclitaxel (Taxol), nonataxel, epothilones, and discodermolide. 

ABSTRACT Discodermolide and pironetin are two immunosuppressive agents with antitumor activity. The isolation, structure elucidation, biological activity are reported as well as the synthetic routes to these two compounds. Five syntheses of discodermolide and seven syntheses of pironetin are described. 

The combination of NMR spectroscopy and X-ray crystallographic analysis revealed a novel polypropionate structure for discodermolide (104) [114], a polyhydroxylated lactone isolated from Discodermia... 

Discodermolide (36) is a cytotoxic polyketide isolated in low yield from the Caribbean sponge Discodermia dissoluta 44), The recent discovery that discodermolide shares the same microtubule-stabilising mechanism of antimitotic action as the clinically important anticancer drug, Taxol (paclitaxel), and retains activity against Taxol -resistant cancer cells has stimulated considerable interest (45,46). Due to the scarce supply of the natural material, the development of an efficient total synthesis (47-52) of (+)-discodermolide is needed to provide useful quantities for further testing, as well as enabling access to structurally simplified analogues. 

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