ChemInform Abstract: Practical Synthesis of α-Amino Acid N-Carboxy Anhydrides of Polyhydroxylated α-Amino Acids from β-Lactam Frameworks. Model Studies Toward the Synthesis of Directly Linked Peptidyl Nucleoside Antibiotics.

Abstract

A straightforward method for the synthesis of polyhydroxylated α-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 β-lactams through the highly diastereoselective Staudinger reaction of hydroxyketene equivalents with chiral α-oxyaldehyde-derived imines, followed by TEMPO radical assisted cycloexpansion to the corresponding NCA and subsequent peptide coupling with α-amino acid esters. The method has been applied to the synthesis of short peptide segments derived from carbamoylpolyoxamic acid, some glycoglycines, as well as C2 symmetric hydroxy amino acids.