Side Reactions in Peptide Synthesis

The base catalyzed ring closure in t-Boc-Asp-X beta-napthylamides was examined in a series of 2-peptide derivatives in which position X was occupied by the neutral and acidic amino acid residues that occur in proteins. Bulkiness and functional groups in the side chain of X have a major effect on the rate of cyclization, e.g. acidic groups slow down the formation of aminosuccinyl derivatives. Rate-enhancing effect can be observed in serine and threonine, while the side reaction is unexpectedly slow when X is methionine.