N-Carboxyanhydrides directly from amino acids and carbon dioxide and their tandem reactions to therapeutic alkaloids

Abstract

We report on the preparation of synthetically versatile N-carboxyanhydrides (NCAs) directly from amino acids and CO₂ using n-propylphosphonic anhydride. Most of the NCAs were isolated with >95% purity after simple workup, avoiding the need for tedious purification procedures typically required using conventional methods. Because the reagents and conditions employed are mild, tandem reactions with moisture-sensitive NCAs were carried out to transform them into the medicinally active alkaloids tryptanthrin and phaitanthrin A in one pot. A qualitative analysis revealed that our NCA synthesis approach is more green than conventional methods, which all directly or indirectly use the highly poisonous gas phosgene.