Synthesis of unnatural enone-containing α-amino acids: precursors to chiral N-heterocycles

Fowler, Lindsay S. (2011) Synthesis of unnatural enone-containing α-amino acids: precursors to chiral N-heterocycles. PhD thesis, University of Glasgow.

Abstract

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.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: amino acid, nitrogen, heterocycle, pipecolic acid, horner wadsworth emmons, cyclisation, enone
• Subjects: Q Science > QD Chemistry
• Colleges/Schools: College of Science and Engineering > School of Chemistry
• Supervisor's Name: Sutherland, Dr. Andrew
• Date of Award: 2011
• Depositing User: Miss Lindsay S Fowler
• Unique ID: glathesis:2011-2524
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 05 Mar 2012
• Last Modified: 10 Dec 2012 13:56
• URI: https://theses.gla.ac.uk/id/eprint/2524