Guanacastepene A 1 is a diterpene natural product, which showed excellent antibiotic activity against both Methicillin resistant <i>Straphylococcus aureus </i>(MRSA) and Vancomycin resistant <i>Enterococcus faecium </i>(VREF). The novel tricyclic structure and biological activity make it an excellent target for synthetic chemists, with over fifteen approaches reported in the literature to date. Our retrosynthetic analysis is based on the rearrangement of epoxy ketone 360, to afford the hydro-azulene core in a single transformation. Initial efforts on our racemic approach confirmed a photochemical rearrangement strategy as a suitable method for the synthesis of the natural product. A chiral variant, based on Jacobsen’s asymmetric conjugate addition, with malononitrile 366 afforded nitrile 395 in > 99% e.e. The serendipitous discovery of a diastereoselective nitrile reduction afforded the corresponding aldehyde, which was subjected to an intramolecular Barbier-Aldol annulation strategy to synthesise the key intermediate, hydro-naphthalene 380.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:666221 |
| Date | January 2007 |
| Creators | McGowan, Craig |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/15338 |
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