title: 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.
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.
authors.affiliation: 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.
authors.forename: Claudio
authors.initials: C
authors.lastname: Palomo
authors.forename: Mikel
authors.initials: M
authors.lastname: Oiarbide
authors.forename: Aitor
authors.initials: A
authors.lastname: Esnal
authors.forename: Aitor
authors.initials: A
authors.lastname: Landa
authors.forename: José I.
authors.initials: JI
authors.lastname: Miranda
authors.forename: Anthony
authors.initials: A
authors.lastname: Linden