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.
journal_name
Medchemcommjournal_title
MedChemCommauthors
Henry JL,Wilson MR,Mulligan MP,Quinn TR,Sackett DL,Taylor REdoi
10.1039/c9md00164fsubject
Has Abstractpub_date
2019-04-09 00:00:00pages
800-805issue
5eissn
2040-2503issn
2040-2511pii
c9md00164fjournal_volume
10pub_type
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