Peptide cyclization strategies in confined spaces

Peptides play important roles in many biological processes. There are interesting differences in the properties of linear and cyclic peptides. The cyclic structure increases membrane permeability, increases resistance towards proteolytic degradation and leads to more rigidity of the molecule. Because of their wide range of biological activities, cyclic peptides have proved to be useful compounds for drug research. The synthesis of cyclic peptides is not always trivial and given the worldwide increase in antibiotic resistance, it is beneficial to expand the toolkit of the synthetic chemist in order to synthesize novel compounds with antibiotic potential.
The work in this thesis describes the exploration of several site-isolation strategies to facilitate difficult peptide cyclizations. The main pathway of realizing this is the suppression of oligomeric side-reactions by isolation of individual cyclic peptide precursors. Both covalent and supramolecular approaches to achieve this have been explored. Supramolecular approaches have the benefit of an easier synthesis, while the convenient self-assembly processes also restrict the range of conditions in which these systems can be employed. Covalent approaches generally benefit from more stability, but require a larger synthetic effort to realize.
The results in this thesis prove the possibility of supramolecularly controlling dipeptide cyclizations. The limitations and difficulties of the approaches are also discussed. The described work provides a basis on which further research can expand.