N-carboxy-α-amino acid anhydrides (NCAs) are amino acid derivatives discovered by Leuch in 1906. Ever since, they have found invaluable use in the preparation of peptide drugs and polypeptides. NCAs are generally synthesised using phosgene; however, due to the hazardous nature of this chemical, safer method of synthesis using protected amino acids in the presence of activating reagents such as P2O4, T3P, HBTU and BOP-Cl were investigated, where a protonated oxazolone intermediate is dealkylated to generate the corresponding amino acid NCA. After the successful synthesis of a variety of NCAs, starting from Boc-protected amino acids and using T3P, we attempted to work out a new method of sequential peptide synthesis using NCAs in a controlled way. The challenge involved in the use of NCAs in the synthesis of peptides is to prevent decarboxylation of the intermediate products, which lead to the generation of unwanted peptide oligomers. An elegant way to prevent the decarboxylation was studied in this work, which consists of the stabilisation of the carbamate intermediates using an appropriate receptor. We prepared several carbamate receptors and tested them in model reactions using amines and NCAs under various conditions. Despites partial success in limiting the amount of oligomerisation, we were never able to prevent it completely, and could not established conditions to prepare peptides in good purity.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:655680 |
| Date | January 2015 |
| Creators | Nneoyi-Egbe, Ada Francesca |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=226984 |
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