(University Honors College Middle Tennessee State University, 2020-12-02)
Teeples, Charles
The nitrile oxide-alkyne 1,3-dipolar cycloaddition reaction is a concerted reaction
between a nitrile oxide, which is usually generated in situ, and an alkyne to afford an
isoxazole. This reaction has been previously used in post-synthetic modification of
nucleic acids. This work examines the potential utility of the nitrile oxide-alkyne 1,3-
dipolar cycloaddition reaction in the synthesis of stapled peptides. Stapled peptides, or
hydrocarbon cross-linked peptides, show potential as drugs to target protein-protein
interactions in the body. The nitrile oxide-alkyne cycloaddition, if efficient, could solve
some of the issues currently present in stapled peptide synthesis, including the use of
toxic copper catalysts in the more common azide-alkyne 1,3-dipolar cycloaddition.
Multiple nitrile oxide-alkyne cyclization attempts proved successful with simple starting
materials. Subsequently, two amino acids, one containing an aldehyde and another
containing an alkyne, were synthesized. The amino acids were not able to successfully
participate in the nitrile oxide-alkyne cycloaddition. More research is required to
optimize the procedure for this reaction before it can be used in a stapled peptide.