The natural alkaloid himbacine 1, first isolated in 1955 from Galbulimina baccata Bail, has attracted attention as a potential therapetic agent for Alzheimer's disease. It is proposed that a late stage in the biosynthesis of this compound may proceed via an iminium ion mediated Diels-Alder reaction (Scheme 1), which would yield the related alkaloid himgravine 2, which can be reduced to himbacine 1. Precident for the iminium ion mediated Diels-Alder reaction has been provided by a related oxonium ion mediated cycloaddition reaction (Scheme 2). Confirmation of the stereochemistry of the product of this reaction has been obtained by X-ray crystallography of the tricyclic alcohol. Studies towards the synthesis of the iminium ion have been undertaken. Piperidine sulfone has been synthesised in a 17% yield over 16 linear steps, and a synthesis of dihydrofuran has been investigated involving an enyne metathesis reaction. Additionally, methodology has been developed for a Julia coupling to join piperidine sulfone to dihydrofuran, and a Polonovski reaction for generation of the required iminium ion.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:362005 |
| Date | January 1997 |
| Creators | Parker, 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:16cdefc3-e9e6-4686-983d-a0bd73b6d716 |
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