1-Aminobicyclo[2.2.2]octane-2-carboxylic Acid and Derivatives As Chiral Constrained Bridged Scaffolds for Foldamers and Chiral Catalysts

ConspectusThe improvement of molecular diversity is one the major concerns chemists since continuous development original synthetic molecules provides unique scaffolds usable in organic and bioorganic chemistry. The challenge to develop versatile platforms with highly controlled chemical three-dimensional space thanks chirality conformational restraints. In this respect, cyclic ?-amino acids are great interest applications various fields addition their intrinsic biological properties, they important precursors for synthesis new generations bioactive compounds such as antibiotics, enzyme inhibitors, antitumor agents. They have also been involved asymmetric efficient organo-catalysts free form derivatives. Finally, constrained incorporated into oligomers successfully stabilize structures foldamer science recent successes health, material science, catalysis. Over last ?10 years, we focused on bicyclic possessing a bicyclo[2.2.2]octane structure. This latter structural key element numerous families biologically active natural products an interesting template synthesis. Nonetheless, reported studies carbo-bridged rather limited compared those bicyclic-fused heterobridged Account, particularly 1-aminobicyclo[2.2.2]octane-2-carboxylic acid, named, ABOC, its sterically hindered bridgehead primary amine endocyclic chiral center, displays drastically reduced freedom. addition, high bulkiness strongly impacts spatial orientation appended functionalities conformation adjacent building blocks. Thus, first expanded fundamental work by wide ranging study field foldamers, design stable peptide/peptidomimetic helical incorporating ABOC residue (11/9-, 18/16-, 12/14/14-, 12/10-helices). was fully compatible stabilized canonical oligourea helix, whereas very few oligoureas. pursued some derivatives, particular 1,2-diaminobicyclo[2.2.2]octane diamine, named DABO, investigation catalytic systems. Covalent organo-catalysis aldol reaction using ABOC-containing tripeptide catalysts provided range enantioselectivity. Moreover, double reductive condensation DABO aldehydes allowed ligands that proved efficiency copper-catalyzed Henry reaction.