Synthesis of glycidol- and sugar-derived bicyclic β- and γ/δ-amino acids for peptidomimetic design

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. (c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)