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(+)-Discodermolide is a recently discovered polyketide natural product found to be a potent inhibitor of tumor cell growth. The molecule's carbon skeleton is made up of eight polypropionate and four acetate units with 13 stereocenters.

History
Discodermolide was first isolated in 1990 from the Caribbean marine sponge Discodermia dissoluta by chemist Dr. Sarath Gunasekera and biologist Dr. Ross Longley, scientists at the Harbor Branch Oceanographic Institution. The sponge contained 0.002% of discodermolide (7 mg/434 g of sponge). Since the compound is light-sensitive, the sponge must be harvested at a minimum depth of 33 meters. Discodermolide was initially found to have immunosuppressive and antifungal activities.

Mechanism of action and structure
Discodermolide has been shown to inhibit the proliferation of human cells by arresting the cell cycle in G2- and M-phase. It hyper-stabilizes microtubules, especially prevalent during cell division. Hyper-stabilization of the mitotic spindle causes cell cycle arrest and cell death by apoptosis. Over a variety of cell lines, activity has been measured at IC50 = 3-80 nM.

Discodermolide competes with paclitaxel for microtubule binding, but with higher affinity and is also effective in paclitaxel- and in epothilone-resistant cancer cells.. Discodermolide also seems to demonstrate a remarkably consistent 3D molecular conformation in the solid-state, in solution and when bound to tubulin; molecules with the conformational flexibility of discodermolide usually present very different conformations in different environments.

Biosynthesis
Many marine-derived polyketides that are often found in sponges cannot be cultured out of their natural environment.Finding the genes responsible for the biosynthesis of a sponge derived polyketides is a difficult task to accomplish because of the sponges’ colonial nature. Scientists are not yet able to culture the sponges; therefore, the genes for the biosynthesis of (+)-discodermolide have not yet been discovered.

Total syntheses
Several total syntheses have been published to date by Schreiber, Smith, Paterson, Marshall, and Myles. A review of the various synthetic approaches has also been published.

Clinical development
The Harbor Branch Oceanographic Institution licensed (+)-discodermolide to Novartis, which began a phase 1 clinical trial in 2004. Patient accrual was halted due to drug toxicity. Amos B. Smith's research group, in collaboration with Kosan Biosciences, has a preclinical drug development program ongoing.

The compound supply necessary for complete clinical trials cannot be met by harvesting, isolation, and purification. As of 2005, attempts at synthesis or semi-synthesis by fermentation have proven unsuccessful. As a result, all discodermolide used in preclinical studies and clinical trials has come from large-scale total synthesis.

The chemistry of palladium-catalyzed reactions developed by professor Richard F. Heck, Ei-ichi Negishi and Akira Suzuki, allowed chemists to carry out key coupling steps on-route to the final product; discodermolide. These three gentelmen were recognized for their ground breaking work with the Nobel prize in 2010.