Design, synthesis, and evaluation of analogues of (+)-14- normethyldiscodermolide

The design, syntheses, and biological evaluation of nine totally synthetic analogues of the microtubule-stabilizing agent (+)-14-normethyldiscodermolide (2) are reported. Simplification at the C(21)−C(24) terminal diene and at the C(1)−C(5) lactone moieties reveals significant structure−activity relationships.