Synthesis and Biological Evaluation of (−)-Laulimalide Analogues

The syntheses of five laulimalide analogues are described, incorporating modifications at the C16−C17-epoxide, the C20-alcohol, as well as the C1−C3-enoate of the parent natural product. The resultant analogues are active in drug-sensitive HeLa and MDA-MB-435 cell lines. Significantly, like laulimalide, these analogues are poor substrates for the drug transport protein P-glycoprotein (Pgp) and are thus effective against Taxol-resistant cell lines.