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The total synthesis of furano-epothilone D by a convergent route is reported. The key fragments are available on a large scale to provide sufficient material for biological evaluation. The approach involves a palladium-catalyzed coupling that generates a highly functionalized aldehyde which is connected in a stereoselective aldol reaction to yield the framework of furano-epothilone D. Finally, a macrolactonization provides furano-epothilone D.

Members of a new class of macrolide—the so-called epothilones (1)—showing a taxol-like biological activity have recently been isolated. A convergent approach to 1 is presented, and the asymmetric syntheses of the three key intermediates 3, 4, and 8 are reported.