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

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.