Issue 31, 2018

Formation of Nα-terminal 2-dialkyl amino oxazoles from guanidinated derivatives under mild conditions

Abstract

Oxazole-containing peptides are an important class of molecules in medicinal chemistry programs. Here we describe a convenient solid-phase synthesis of Nα-terminal oxazole peptides. The strategy took advantage of an intramolecular rearrangement side reaction that occurred during the guanidination of the Nα-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.

Graphical abstract: Formation of Nα-terminal 2-dialkyl amino oxazoles from guanidinated derivatives under mild conditions

Supplementary files

Article information

Article type
Paper
Submitted
21 Jun 2018
Accepted
16 Jul 2018
First published
17 Jul 2018

Org. Biomol. Chem., 2018,16, 5661-5666

Formation of Nα-terminal 2-dialkyl amino oxazoles from guanidinated derivatives under mild conditions

S. A. H. Abdel Monaim, J. T. Mhlongo, A. Kumar, A. El-Faham, F. Albericio and B. G. de la Torre, Org. Biomol. Chem., 2018, 16, 5661 DOI: 10.1039/C8OB01463A

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