From β-lactams to α- and β-amino acid derived peptides

The potential of beta-lactams as intermediates for the access to alpha- and beta-amino acid-derived peptides is shortly reviewed, with major focus on the technologies developed in our group. The two general strategies lie, on one side, in the oxidative ring expansion of 3-hydroxy beta-lactams to N-carboxy alpha-amino acid anhydrides or Leuch's anhydrides and subsequent coupling with alpha-amino acid esters and, on the other side, in the nucleophilic ring opening of N-Boc-beta-lactams. Both approaches have been successfully applied to the synthesis of alpha,beta-diamino acid, alpha-amino-beta-hydroxy acid, polyhydroxylated alpha-amino acid, alpha,alpha-disubstituted alpha-amino acid, beta-amino acid, beta-amino-alpha-hydroxy acid and beta,beta-disubstituted beta-amino acid derived peptides. Because of the mild reaction conditions needed for the above transformations and the highly stereoselective procedures employed for the construction of the starting beta-lactam ring, the whole process allows the production of optically pure final products.