Synthesis of Peptides by Reactive Extrusion. Application to the Continuous and Solventless Preparation of Aspartame.

The solventless synthesis of peptides from unactivated amino acids was optimized in a twin‐screw extruder (TSE). The general method enabled the preparation of dipeptides and tripeptides with no epimerization. This flow mechanochemistry approach was applied to the synthesis of aspartame, a synthetic dipeptide, prepared in a continuous mode on large scale and with high productivity.