A convergent synthesis of epothilone B that generates all seven of its
asymmetric centers in a completely stereoselective fashion has been
completed. Key reactions include an anti-Felkin aldol condensation to
set the C6 and C7 stereochemistry, a directed α-hydroxylation to install
the C15 (S)-hydroxyl substituent, and a Wittig condensation to join two
main subunits via C-C bond formation at C9-C10. In addition, through
modifications to the C9-C10 region of the macrolide, several novel and
cytotoxic epothilone analogues were synthesized. Bioassay data
comparing the antiproliferative activity and tubulin polymerization of the
analogues with epothilone B, epothilone D, and paclitaxel showed that
the synthetic analogues were less potent than their natural
counterparts. / Graduation date: 2005
| Identifer | oai:union.ndltd.org:ORGSU/oai:ir.library.oregonstate.edu:1957/29006 |
| Date | 18 January 2005 |
| Creators | Sundermann, Kurt F. |
| Contributors | White, James D. |
| Source Sets | Oregon State University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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