Synthesis, conformational preferences, and biological activity of conformational analogues of the microtubule-stabilizing agents, (-)-zampanolide and ...

Basic Information

ID: ALA4373650

Journal: Medchemcomm

Title: Synthesis, conformational preferences, and biological activity of conformational analogues of the microtubule-stabilizing agents, (-)-zampanolide and (-)-dactylolide.

Authors: Henry JL, Wilson MR, Mulligan MP, Quinn TR, Sackett DL, Taylor RE.

Abstract: Zampanolide and dactylolide are microtubule-stabilizing polyketides possessing potent cytotoxicity towards a variety of cancer cell lines. Using our understanding of the conformational preferences of the macrolide core in both natural products, we hypothesized that analogues lacking the C17-methyl group would maintain the necessary conformation for bioactivity while reducing the number of synthetic manipulations necessary for their synthesis. Analogues 3, 4 and 5 were prepared via total synthesis, and their conformational preferences were determined through computational and high-field NMR studies. While no observable activities were present in dactylolide analogues 3 and 4, zampanolide analogue 5 exhibited sub-micromolar cytotoxicity. Herein, we describe these efforts towards understanding the structure- and conformation-activity relationships of dactylolide and zampanolide.

CiteXplore: 31191870

DOI: 10.1039/C9MD00164F

Patent ID: