Design, synthesis, and biological evaluation of simplified analogues of (+)-discodermolide. Additional insights on the importance of the diene, the C7 hydroxyl, and the lactone.

[structure: see text] The design, synthesis, and biological evaluation of seven totally synthetic analogues of the antitumor agent (+)-discodermolide are reported. Saturation of the terminal diene system, alteration of the substituents on the lactone, and alkylation of the C7-hydroxyl group reveal significant structure-activity relationships.