Stereoselective Synthesis of Proline‐Derived Dipeptide Scaffolds (ProM‐3 and ProM‐7) Rigidified in a PPII Helix Conformation

Abstract

Abstract Following a peptide coupling/metathesis‐based strategy, the two diastereomeric scaffolds ProM‐3 and ProM‐7 were stereoselectively synthesized (as 9‐fluorenylmethoxycarbonyl derivatives), and their configuration was unambiguously proven by means of X‐ray crystallography. The required dehydroisoleucine building blocks were prepared by applying the enantioselective Kazmaier–Claisen rearrangement. The target compounds represent dipeptide analogs rigidified in a PPII helix conformation, which are of interest for the development of new proteomimetics that selectively bind to protein domains specialized in the recognition of ligands adopting a PPII helix secondary structure.