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Updated: Oct 7, 2025

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Investigating Bicyclobutane-Triazolinedione Cycloadditions as a Tool for Peptide Modification
Brett D Schwartz1, Aidan P Smyth1, Philippe E Nashar1
1Research School of Chemistry, Australian National University, Canberra, ACT 2601, Australia.
Abstract:
Acyl bicyclobutanes are shown to engage in strain-promoted cycloaddition reactions with a diverse array of triazolinedione reagents. The synthesis of an orthogonally protected urazole building block enabled the facile preparation of amino acid- and peptide-derived triazolinediones that undergo cycloaddition reactions to afford novel peptide conjugates. The additive-free and fully atom-economical nature of the transformation is a promising starting point for the generalization of this cycloaddition reaction for the functionalization of biomolecules.
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