Solvent‐Free Synthesis of Peptides

Abstract

A crush on sweetness! The coupling of a urethane-protected N-carboxyanhydride of an amino acid with another amino acid derivative under ball-milling conditions gives a protected dipeptide in very high yield (see scheme; PG: protecting group). The reaction takes place in the solid state. The synthesis was applied to the preparation of a tripeptide and the sweetener aspartame, without any organic solvent or purification. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.