Studies toward the total synthesis of phorboxazole A
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 tetrahydro...
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| Language: | en_US |
| Published: |
2012
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| Online Access: | http://hdl.handle.net/1957/30861 |
| Summary: | 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 |
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