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-a mino acid N-carboxy anhydrides (NCAs) is described as the means by whi ch short peptide segments comprised of a polyhydroxylated chain are ea sily affordable. The entire sequence lies in the preparation of nonrac emic 3-hydroxy beta-lactams through the highly diastereoselective Stau dinger reaction of hydroxyketene equivalents with chiral alpha-oxyalde hyde-derived imines, followed by TEMPO radical assisted cycloexpansion to the corresponding NCA and subsequent peptide coupling with alpha-a mino acid esters. The method has been applied to the synthesis of shor t peptide segments derived from carbamoylpolyoxamic acid, some glycogl ycines, as well as C-2 symmetric hydroxy amino acids.