A number of amino acids containing terminal five- and six-membered heterocyclic substituents have been synthesised using a strategy in which a 6-oxopipecolate system is 'ring switched'. Functionalisation of the protected (2S)-6-oxopipecolate at C-5 with methyl formate, or with allyl bromide followed by ozonolysis, have provided the important 5-formyl-6-oxopipecolate and its' homologue as intermediates. Reaction of these intermediates with hydrazine gave a successful 'ring switching' reaction, yielding a pyrazolone and a pyridazin-6-one, which were deprotected to give the free amino acids. Alkylation of the homodehydro-6-oxopipecolate system at C-4 by Michael addition with allyl cuprate, followed by ozonolysis, provided the important 4-formyl-6- oxopipecolate intermediate. Reaction with hydrazine gave a successful 'ring switching' reaction yielding a pyridazin-6-one, which was deprotected to the free amino acid. Attempts to apply the 'ring switching' reaction to morpholinones, thiazanes, azepanes, thiazepines and were unsuccessful. The amino acids synthesised are currently being examined in a high throughput screen at Glaxo-Wellcome
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:288834 |
| Date | January 1999 |
| Creators | Philps, Oliver James |
| Publisher | University of Sussex |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
Page generated in 0.0021 seconds