Studies toward the total synthesis of a highly potent cytotoxic marine
natural product, phorboxazole A, were conducted and resulted in a route to
an advanced intermediate, C4-C32, for this purpose. A key feature of our
approach is the stereoselective synthesis of two cis-2,6-disubstituted
tetrahydropyrans present in the macrolide portion of phorboxazole A by
palladium (II) mediated intramolecular alkoxy carbonylation. This provided
the C20-C32 and C9-C19 tetrahydropyran subunits of phorboxazole A. An
attempt at diastereoselective formation of the third C5-C9 trans-2,6-disubstituted tetrahydropyran by hydride reduction of a C9 hemiketal was
complicated by reduction of the C7 exocyclic olefin. However, the C5-C9
tetrahydropyran was constructed by an intramolecular etherification
sequence using a novel allylsilane as the source of C4-C8 of the
macrolactone. The studies carried out in the course of this thesis have set
in place a major segment of the phorboxazole A structure; they require only
the addition of the C1-C3 unit and minor functional group modifications to
complete the macrolide portion of the molecule. / Graduation date: 2004
| Identifer | oai:union.ndltd.org:ORGSU/oai:ir.library.oregonstate.edu:1957/30861 |
| Date | 06 January 2004 |
| Creators | Kuntiyong, Punlop |
| Contributors | White, James D. |
| Source Sets | Oregon State University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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