Syntheses of Discodermolides Useful for Investigating Microtubule Binding and Stabilization

Discodermolide is a marine natural product reported to inhibit the proliferation of T cells and exhibit immunosuppresive activity. Total syntheses of the natural antipode of discodermolide and several variants are reported. These studies provide reagents to investigate discodermolide's recently discovered ability to bind and stabilize microtubules in cells. Retrosynthetically, the polypropionate is divided into three fragments of approximately equal complexity. This modular strategy provides convergency in the synthesis and facilitates the preparation of discodermolide-based reagents.