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.
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.
Palomo
Claudio
C
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.
Oiarbide
Mikel
M
Esnal
Aitor
A
Landa
Aitor
A
Miranda
José I.
JI
Linden
Anthony
A