Recent Advances in the Synthesis of Peptidomimetics via Ugi Reactions

Peptidomimetics have been extensively explored in many area due to their ability to improve pharmacological qualities and interesting biological activities. Cycles could be incorporated in peptides to reduce their flexibility, often enhancing the affinity for a certain receptor. Many efforts have been made to synthesize various peptidomimetics. Among them, the Ugi reaction is a popular way for the synthesis of peptidomimetics because it provides peptide-like products. The Ugi reaction consists of the condensation of an aldehyde or ketone, a carboxylic acid, an amine, and an isocyanide usually giving a linear peptidomimetic. In order to obtain other linear, cyclic or polycyclic peptidomimetics, the acyclic products have to undergo additional transformations or cyclizations. This review covers the years from 2018-2023, regarding the synthesis of linear, cyclic and polycyclic peptidomimetics, employing Ugi reactions eventually followed by post-Ugi transformations. Organo-catalyzed reactions, base-promoted reactions, and metal-free reactions toward peptidomimetics are highlighted. This review summarizes the recent development for the construction of peptidomimetics via Ugi reactions or post-Ugi transformations. By the combination of Ugi reaction and transition metal catalysis such as gold, palladium, rhodium and copper, as well as metal-free strategies, devise linear, cyclic and polycyclic peptidomimetics are prepared in a rapid, highly efficient and step-economical manner.image