Abstract
For the past three decades, chemists have sought to synthesise oligomeric structures that adopt single, well-defined conformations in solution. Known as foldamers, these structures have the potential to be able to replicate and perhaps even improve upon the function of biopolymers, with applications in areas such as catalysis and information storage. Peptidomimetic foldamers – those that mimic the structure and behaviour of natural peptides– have received a great deal of attention in particular, with the synthesis and use of extended, unnatural amino acids a common method in order to access molecules with novel secondary structures.This thesis first describes the synthesis of novel, cyclically-constrained δ-amino acid monomers. Two δ-amino acid targets were synthesised, with the required stereochemistry embedded via previously described organocatalytic procedures. The trans monomer was achieved in an overall yield of 4%, whilst the cis monomer was achieved in a 29% overall yield.
The cis monomer was then incorporated into a series of α/δ foldamers, which were subsequently characterised in order to probe their secondary structure. The 1:1 α/δ foldamers with D-Alanine α-residues showed a strong propensity for folding and were found to populate either a 13/11- or 11/13-helical conformation, depending on their length.
Finally, the syntheses of two previously described cyclically-constrained γ-amino acid precursors was optimised, after which they were incorporated into a series of novel dipeptide building blocks that could be used to for the construction of potentially catalytic α/γ foldamers.
| Date of Award | 1 May 2023 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Andre Cobb (Supervisor) & Manuel Muller (Supervisor) |