A fast and efficient synthetic route was developed for the synthesis of a novel class of enone-containing alpha-amino acid. An amino acid-derived beta-ketophosphonate ester was subjected to Horner-Wadsworth-Emmons conditions using a variety of aldehydes to produce a diverse library of alpha,beta-unsaturated amino acids. E-Configured enone-containing amino acids were also deprotected using a two-stage approach to give the parent alpha-amino acids. A minor modification to the route enabled the synthesis of Z-configured enones via the Still-Gennari reaction. A small library of Z-enones was produced using various aldehydes. Enone-functionalised alpha-amino acids were employed as substrates for an intramolecular cyclisation reaction to generate 6-substituted-4-oxopipecolic acids. A diastereoselective one-pot reductive amination/cyclisation strategy was developed to gain access to the anti-diastereomer of the chiral N-heterocycles. A small selection of 6-substituted-4-oxopipecolic acids was synthesised. 6-Substituted-4-oxopipecolic acids were also reduced diastereoselectively to generate 4- hydroxypipecolic acid analogues.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:547559 |
| Date | January 2011 |
| Creators | Fowler, Lindsay S. |
| Publisher | University of Glasgow |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://theses.gla.ac.uk/2524/ |
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