Design, Total Synthesis, and Evaluation of C(13)−C(14) Cyclopropane Analogues of (+)-Discodermolide

The design, total synthesis, and biological evaluation of two C(13)−C(14)-cyclopropyl analogues [(+)-1 and (+)-2] of (+)-discodermolide have been achieved. Key features of the syntheses include highly stereoselective, hydroxyl-directed cyclopropanations of vinyl iodides and higher order cuprate-mediated cross-coupling reactions between cyclopropyl iodides and alkyl iodides. Biological evaluation revealed that neither orientation of the cyclopropyl methylene completely substitutes for the C(14) methyl found in (+)-discodermolide (3).