October 3, 2006

Building Functionalized Peptidomimetics: Use of Electroauxiliaries for Introducing N-Acyliminium Ions into Peptides

Haizhou Sun, Connor Martin, David Kesselring, Rebecca Keller, and Kevin D. Moeller
J. Am. Chem. Soc., 2006, 128 (42), 13761–13771

A series of silyl-substituted amino acids have been synthesized, inserted into peptides, and then employed as precursors for oxidatively generating reactive N-acyliminium ions. Both electrochemical and chemical oxidation procedures have been employed. N-Acyliminium ion generation in a solid-phase substrate as well as application to a small library of functionalized dipeptides has been demonstrated. Limitations in terms of how electron-rich the silyl groups can be as well as the compatibility of multiple silyl groups within a longer peptide are defined.