A CONCISE BETA-LACTAM ROUTE TO SHORT PEPTIDE SEGMENTS CONTAINING BETA,BETA-DISUBSTITUTED BETA-AMINO ACIDS

An efficient epimerization-free route toward beta,beta-disubstituted b eta-amino acid-containing peptides is described. The methodology invol ves the use of 4,4-disubstituted-N-Boc beta-lactams as acylating agent s, which upon coupling with amino acid esters, promoted by potassium c yanide, give rise to dipeptides with no appreciable racemization. By t his procedure short peptide segments containing a four-, five-, or six -membered ring at the beta-position of the beta-amino acid residue hav e been prepared. The method has also proven to be valuable for the pre paration of tripeptides. In addition the sterically hindered amino ter minus of the beta-amino acid can undergo peptide couplings under stand ard conditions.