Versatility of beta-lactams in synthesis. Studies directed toward the synthesis of complex nucleoside antibiotics and some macrocyclic peptides

The diastereoselective [2+2] cycloaddition of alpha -hydroxyketene equivale nts with chiral alpha,omega -oxyaldehyde-derived imines followed by the 2,2 ,6,6-tetramethylpiperidinyl-1-oxyl (TEMPO)-promoted ring expansion of the r esulting alpha -hydroxy beta -lactam adducts provides an unconventional and short route to alpha -amino acid N-carboxy anhydrides (NCAs). The required enantiopure alpha,omega -oxyaldehydes were obtained either from the chiral pool or through the Sharpless AD methodology. Following the present strate gy, several nonproteinogenic NCAs were synthesized, which were further coup led with alpha -amino acid esters giving rise to key fragments of some nucl eoside antibiotics and macrocyclic peptides.