Synthesis of a constrained tricyclic scaffold based on trans-4-hydroxy-l-proline

Drug discovery research has taken advantage of peptidomimetic chemistry in order to achieve new leads possessing structural and functional characteristics of bioactive peptides together with enhanced metabolic resistance towards proteases. Herein is reported the synthesis of a tricyclic peptidomimetic scaffold derived from the combination of trans-4-hydroxy-l-proline and tartaric acid derivatives by means of amidation and acid trans-acetalisation reactions. Further manipulations of the hydroxylic function on the pyrrolidine ring gave access to a new set of amino acid scaffolds possessing high rigidity and a fixed arrangement of the functional groups.