This thesis is divided into two parts: Part One describes synthetic approaches to the naturally occurring antibiotic Lactivicin (1) and its acylamino derivatives, involving the condensation of protected L-cycloserine with 2-oxoglutaric acid. The phenoxyacetyl-amino derivative (2) exhibited antibacterial activity. A method was developed for the selective deprotonation of the endocyclic amide of the protected cycloserine; the resulting anion was then quenched with various electrophiles. In this manner, the Lactivicin analogues (3) and (4) were prepared. Whilst (3) was biologically inactive, (4) showed appreciable antibacterial activity. [See pdf file for chemical structures (1)-(4)]. Part Two details the use of N-benzoylamino-2-bromoglycine methyl ester, a glycidyl radical precursor, as a novel a-amino acid synthon. Its synthetic utility in free radical reactions was demonstrated with 2-functionalised allylstannanes as allyl transfer reagents, to produce a range of substituted a-allylglycines. Using this procedure, the naturally occuring amino acid, 4-methyleneglutamic acid, was prepared in its racemic form. Studies on the extension of this methodology to the asymmetric synthesis of a-amino acids are also described. A synthesis of (alpha)-allenylglycine, a previously undocumented amino acid, was developed. The synthetic route involves the Lewis acid mediated reaction of propargyltriphenylstannane with N-benzoylyamino-2-bromoglycine methyl ester, followed by aqueous acidic deprotection.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:291654 |
| Date | January 1989 |
| Creators | Lowe, Christopher |
| Contributors | Baldwin, Jack E. |
| Publisher | University of Oxford |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://ora.ox.ac.uk/objects/uuid:e1648252-c0dc-42af-a11a-03df8ecb83c1 |
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