Practical Synthesis of alpha-Amino Acid N-Carboxy Anhydrides of Polyhydroxylated alpha-Amino Acids from beta-Lactam Frameworks. Model Studies toward the Synthesis of Directly Linked Peptidyl Nucleoside Antibiotics

Claudio Palomo; Mikel Oiarbide; Aitor Esnal; Aitor Landa; José I. Miranda; Anthony Linden

doi:10.1021/jo980354x

Practical Synthesis of alpha-Amino Acid N-Carboxy Anhydrides of Polyhydroxylated alpha-Amino Acids from beta-Lactam Frameworks. Model Studies toward the Synthesis of Directly Linked Peptidyl Nucleoside Antibiotics

J Org Chem. 1998 Aug 21;63(17):5838-5846. doi: 10.1021/jo980354x.

Authors

Claudio Palomo¹, Mikel Oiarbide, Aitor Esnal, Aitor Landa, José I. Miranda, Anthony Linden

Affiliation

¹ Departamento de Química Orgánica, Facultad de Química, Universidad del País Vasco, Apdo 1072, 20080 San Sebastián, Spain, and Organisch-chemisches Institut der Universität Zürich, Winterthurerstrasse 190, CH-8057, Zürich, Switzerland.

PMID: 11672185
DOI: 10.1021/jo980354x

Abstract

A straightforward method for the synthesis of polyhydroxylated alpha-amino acid N-carboxy anhydrides (NCAs) is described as the means by which short peptide segments comprised of a polyhydroxylated chain are easily affordable. The entire sequence lies in the preparation of nonracemic 3-hydroxy beta-lactams through the highly diastereoselective Staudinger reaction of hydroxyketene equivalents with chiral alpha-oxyaldehyde-derived imines, followed by TEMPO radical assisted cycloexpansion to the corresponding NCA and subsequent peptide coupling with alpha-amino acid esters. The method has been applied to the synthesis of short peptide segments derived from carbamoylpolyoxamic acid, some glycoglycines, as well as C(2) symmetric hydroxy amino acids.