Cyclic α‐Amino Acids as Proline Mimetics

Research oriented to the design, synthesis and applications of cyclic and bicyclic amino acids as proline analogues during recent decades has demonstrated a constant interest in constrained structures capable of functioning as peptidomimetics with high rigidity and chemical diversity. This chapter presents the panorama of peptidomimetic scaffolds as proline surrogates, taking into account the structural diversity given by cyclic and bicyclic scaffolds. An example of nitrogen-containing proline mimetics consists of synthesis and application of pyrazolidine-carboxylic acid as an azaproline scaffold. Detailed conformational analysis of selected scaffolds in model or bioactive peptides indicates the role of these bicyclic structures in limiting the conformational access of peptidic fragments. Bicyclic α-amino acids are carriers of pharmacological activities, and have been used as building blocks for the synthesis of conformationally constrained peptides.