This thesis firstly describes a synthesis of the natural product taurospongin A, a potent DNA polymerase beta inhibitor. Sharpless asymmetric dihydroxylation on olefin <b>E-1.60</b> followed by selective deoxygenation at C(2) via Barton‒McCombie reaction delivers the desired C(1)–C(10) carboxylic acid core. Subsequent esterification of the C(1)–C(10) fragment with C(1′)–C(25′) fatty acid furnishes the natural product in 13.5% yield. The structure of an unnamed natural product <b>2.14</b> isolated in 1974 is proven to be misassigned by previous studies within the Robertson group. As described in this thesis, two proposed structures A and B are obtained via total synthesis in order to reveal the identity of the natural product. A synthesis of key intermediate spirocycles <b>2.148</b> and <b>2.158</b> with desired trans- diol moiety is described by a dihydroxylation reaction on an electron deficient gamma-keto unsaturated acid with subsequent spirocyclisation reaction. Finally, methodology for generating high-value synthetic intermediates by an asymmetric, one-pot enzymatic di/polycarbonyl reduction is described. The concept of such methodology is first proven by the synthesis of (3R)-hydroxybutyl (3R)-hydroxybutanoate <b>3.20</b>. This thesis then describes substrate scope studies and corresponding stereochemical proof to provide more information about this methodology.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:565957 |
| Date | January 2017 |
| Creators | Wu, Boshen |
| Contributors | Robertson, Jeremy |
| Publisher | University of Oxford |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://ora.ox.ac.uk/objects/uuid:37a34bc4-efb4-4a6b-9d44-a3ad1c8ae0be |
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