The preparation of racemic and optically active beta-amino-acids and their utilisation in peptide formation.

Mtetwa, Eli

Abstract

B-Amino acids are being isolated from biologically active peptide antibiotics with increasing frequency nowadays. Recognition of the importance of these amino acids, has led to their incorporation into synthetic peptide analogues and into polymers. The main part of this thesis reports the successful preparation of linear and cyclic peptides of racemic and optically active B-aminobutyric acid. B-Amino acid cyclisation studies by Barker 84 had led to the conclusion that oxazinones could only be obtained from saturated B-benzamido—acids containing quaternary B-cabon atoms, while other saturated B-benzamido-acids (eg. B-aminobutyric acid) yield only symmetrical anhydrides. However, in this work oxazinones of both racemic and optically active B-aminobutyric acid were isolated, charaterised, and used as peptide coupling intermediates. A chiral oxazinone has thus been isolated for the first time, and used as a coupling intermediate 85 for the preparation of optically active peptides. Transacylation 89, of B-benzamidobutyric acid was encountered, during treatment of this compound with acetic anhydride under reflux conditions. While the use of isobutyl chloroformate allowed obtention of oxazinone in high yield at temperatures below-10°, its use at temperatures around 0° led to esterification of oxazinone by isobutyl alcohol. Arndt-Eistert Synthesis using N-tosyl derivatives led to the isolation of a chiral B-lactam during Wolff rearrangement in an inert solvent. Elsewhere in this thesis, it has been demonstrated that the formation of cyclohexylamide 89 as a side-product during peptide coupling of B-amino- pivalic acid with the acid of DCCI is due to alkaline cleavage of N-acylurea.

Citation

MTETWA, E. 1978. The preparation of racemic and optically active beta-amino-acids and their utilisation in peptide formation. Robert Gordon's Institute of Technology, PhD thesis. Hosted on OpenAIR [online]. Available from: https://doi.org/10.48526/rgu-wt-1993212

• Thesis Type: Thesis
• Deposit Date: Oct 18, 2024
• Publicly Available Date: Oct 18, 2024
• DOI: https://doi.org/10.48526/rgu-wt-1993212
• Public URL: https://rgu-repository.worktribe.com/output/1993212
• Award Date: Jan 31, 1978