Synthesis of Glycidol-and Sugar-derived Bicyclic beta- and gamma/delta-Amino Acids for Peptidomimetic Chemistry

Constrained bicyclic β‐ and γ/δ‐amino acids using glycidol and sugar derivatives were developed. The synthetic strategies involved epoxide ring opening of a glycidol derivative, and subsequent coupling with sugar‐derived amines, leading to di‐ or trisubstitued bicyclic scaffolds after cyclisation with trifluoroacetic acid. Achievement of β‐ or γ/δ‐amino acids was accomplished by changing the protecting group strategy of the starting materials. Compatibility of the scaffold with solid‐phase peptide synthesis was assessed by preparing model peptidomimetics using acid‐ and base‐labile resins, thus giving a new tool for peptidomimetic design.