The Development of a Practical Total Synthesis of Discodermolide, a Promising Microtubule-Stabilizing Anticancer Agent

Marine organisms provide an important source of natural product diversity with an associated range of significant biological activities. Discodermolide, isolated in microscopic quantities from a deep-water sponge, shares the same microtubule-stabilizing mechanism as Taxol and has a promising antitumor profile. There is, however, a chronic supply problem hampering clinical development and so a practical total synthesis of discodermolide is an important goal. This review highlights the completed total syntheses of discodermolide, focusing on the various methods and strategies employed for achieving stereocontrol and realising the pivotal fragment couplings. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)