A Straightforward Access to Enantiopure 4‐Hydroxy‐pipecolic Acid Peptidomimetics by aza‐Prins Cyclization/LiNTf ₂ ‐Promoted Aminolysis of Lactones

Abstract Peptidomimetics, that can take advantage of bioavailability and metabolic stability, are considered as an important class of molecules and constitute thus a large research field in medicinal chemistry. With the aim of obtaining constrained examples for drug discovery, we designed a two‐step synthesis of cis‐4‐hydroxy pipecolic acid derivatives as pseudodipeptides mimics. This straightforward procedure concerns the coupling of amino acid‐derived homoallylic amines with glyoxylic acid via an aza‐Prins cyclization to deliver piperidine‐lactones, followed by LiNTf 2 ‐promoted aminolysis of the lactone with various amino acids. The 4‐hydroxy pipecolic acid peptidomimetics are obtained as single enantiomers and with a high diastereomeric control and they represent original and modular scaffolds for drug discovery.