Synthesis of Glycidol- and Sugar-Derived Bicyclic beta- and gamma/delta-Amino Acids for Peptidomimetic Design

摘要

Constrained bicyclic beta- and gamma/delta-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 beta- or gamma/delta-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.