Chemoselective Nitrile Oxide–Alkyne 1,3-Dipolar Cycloaddition Reactions from Nitroalkane-Tethered Peptides

Abstract

Synthesis and incorporation of a new amino acid with a nitroalkane side chain into peptides, in situ transformation of a nitroalkane side chain into nitrile oxide, and chemoselective 1,3-dipolar cycloaddition reactions between in situ generated nitrile oxide and different alkynes are reported. The nitroalkane-mediated nitrile oxide–alkyne cycloaddition was found to be orthogonal to the copper(I)-catalyzed azide–alkyne cycloaddition reaction. The combination of orthogonal nitrile oxide–alkyne and azide–alkyne cycloaddition reactions can be explored to tailor different 1,2,3-triazole and 3,5-isoxazoles, respectively, on the peptide backbone.