Title: Formation of N?-terminal 2-dialkyl amino oxazoles from guanidinated derivatives under mild conditions
Authors: Abdel Monaim SAH, Mhlongo JT, Kumar A, El-Faham A, Albericio F, de la Torre BG.
Journal: Org Biomol Chem,16(31):5661-5666 (2018)
Oxazole-containing peptides are an important class of molecules in medicinal chemistry programs. Here we describe a convenient solid-phase synthesis of N?-terminal oxazole peptides. The strategy took advantage of an intramolecular rearrangement side reaction that occurred during the guanidination of the N?-amino function of a peptide still anchored on the solid-support. The substitution map of the N,N-dialkylamino oxazole obtained using this strategy differed completely from the one achieved through the heterocyclization of the Ser or Thr side chain with the preceding carbonyl group, which is a common approach for the preparation of these compounds. This unexpected reaction was observed with N-terminal aromatic and aliphatic amino acids that have a Gly as the last before residue in both short as well as long peptides; however, it does not form the oxazole ring if Gly was substituted with other amino acids.