Constrained Cyclic β,γ‐Diamino Acids from Glutamic Acid: Synthesis of Both Diastereomers and Unexpected Kinetic Resolution

Abstract

We describe here an efficient synthesis of both diastereomers of cyclic β,γ‐diamino acids starting from l‐glutamic acid, based on the Blaise reaction. We show that by changing the protecting group, we can access either the five‐membered‐ring lactam, which can be used as a β‐amino acid, or the six‐membered‐ring lactam, as a γ‐amino acid. We also discovered an interesting kinetic resolution during the synthesis that allowed easier separation of diastereomers. The products can be easily used in peptide synthesis, and a tetramer with alternating trans cyclic γ‐amino acid and AIB (2‐aminoisobutyric acid) residues was synthesized.