I hereby declare that I am the sole author of this thesis. This is a true copy of the thesis, including any required final revisions, as accepted by my examiners.I understand that my thesis may be made electronically available to the public.

The aminohydroxylation of various alkenes using FmocNHCl as a nitrogen source is reported. In general, in the absence of a ligand, the reaction provided racemic Fmoc-protected amino alcohols with excellent regioselectivity but in low to moderate yields. However, in some instances, the yield of an amino alcohol product and the regioselectivity could be altered by the addition of a catalytic amount of triethylamine (TEA). The Sharpless asymmetric variant of this reaction (Sharpless asymmetric aminohydroxylation (SAAH)), using (DHQD)2PHAL (DHQD) or (DHQ)2PHAL (DHQ) as chiral ligands, proceeded more readily and in higher yield compared to the same reaction in the absence of a chiral ligand. The enantiomeric ratios (er) of all but two examples exceeded 90:10 with many examples giving er values of 95:5 or higher, making FmocNHCl a highly practical reagent for preparing chiral amino alcohols. The SAAH reaction using FmocNHCl was used for the preparation of d-threo-β-hydroxyasparagine and d-threo-β-methoxyaspartate, suitably protected for Fmoc solid phase peptide synthesis.

Biaryl and heterobiaryl-containing cyclic peptides represent promising scaffolds in the development of bioactive molecules. The incorporation of heterobiaryl motifs continues to pose synthetic challenges, which is partially due to the difficulties in effecting late-stage metal-catalyzed cross-couplings. We report a new strategy to form heterobiaryls that is based on trapping nitrilium ions. The sequence is exemplified using oxadiazole- and oxazole-containing biaryl linkages. NMR analysis and molecular dynamics simulations reveal structural control elements common to each member of the heterobiaryl containing peptide family in this study. Strategic substitutions on the C-terminal aminobenzoic acid moiety paired with installation of oxadiazole or oxazole heterobiaryl backbone linkages allow for the modulation of peptide backbone conformation, which should assist efforts to optimize the biophysical properties of peptide macrocycles.

Biaryl and heterobiaryl-containing cyclic peptides represent promising scaffolds for the development of bioactive molecules. The incorporation of heterobiaryl motifs continues to pose synthetic challenges, which is partially due to the...