Synthesis and Biological Evaluation of
(-)-Laulimalide Analogues
Paul A. Wender,*Sayee G. Hegde,Robert D. Hubbard,Lei Zhang, and
Susan L. Mooberry*
Department of Chemistry, Stanford University, Stanford, California 94305, and
Department of Physiology and Medicine, Southwest Foundation for Biomedical
Research, San Antonio, Texas 78245
wenderp@stanford.edu; smooberry@sfbr.org
Received July 18, 2003
Abstract:
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.
