Rubriflordilactones A and B are highly oxygenated nortriterpenoid natural products isolated from Schisandra rubriflora. The latter is of particular biological interest as it shows significant anti-HIV activity. Two transition metal-catalysed cascade cyclisation approaches for the formation of the CDE rings of the rubriflordilactones were developed. Palladium-catalysed cyclisation of bromoenediynes and cobalt-catalysed triyne cyclotrimerisation both transform acyclic precursors into 7,6,5-bisannelated arenes in a single step. Two enantioselective syntheses of the AB ring fragment common to both rubriflordilactones, with bromoene or alkyne functional groups required for the respective cyclisation methods, are described; along with the refinement of a route to the CDE diyne fragment of rubriflordilactone A. From these fully functionalised bromoenediyne and triyne substrates, both metal-catalysed cyclisation methods were successful; these strategies converged on a late-stage intermediate bearing the ABCDE ring system of rubriflordilactone A. Construction of the F ring, followed by attachment of the G ring by an intriguing oxo-carbenium ion addition reaction completed two enantioselective total syntheses of (+)-rubriflordilactone A.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:711854 |
| Date | January 2015 |
| Creators | Goh, Simin Shermin |
| Contributors | Anderson, Edward |
| Publisher | University of Oxford |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | https://ora.ox.ac.uk/objects/uuid:796adfdf-b4d5-474d-85a6-d2e19c1085db |
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