The synthesis of antibiotics and amino acids
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.