A NEW OUTLOOK ON CARBODIIMIDE-MEDIATED PEPTIDE-SYNTHESIS

Mechanistic studies on carbodiimide-mediated peptide synthesis show th at an O-acylisourea intermediate preserving its chiral integrity under goes fast transformation into optically pure N-acylurea by-product and symmetrical anhydride and 5(4H)-oxazolone. Although there is no direc t proof for the N-acylamino acid anhydride formation, some experimenta l results indicate that it may be responsible for extensive epimerizat ion of the peptide observed at the beginning of the reaction. The slow ramp in epimerization at prolonged reaction times is caused by 5(4H)- oxazolone.