Abstract
A crush on sweetness ! A novel solvent-free methodology for the synthesis of peptides was developed: the coupling of an urethane protected N-carboxy anhydride (UNCA) of an aminoacid with another aminoacid derivative gave a protected dipeptide in very high yield under ball-milling conditions. The reaction is taking place in the solid state. This solvent-free synthesis was applied to the preparation of dipeptides and tripeptides, and exemplified in the preparation of Aspartame, in three steps, using the UNCA route, without any organic solvent and purification.