Synthesis of conformationally restricted amino acids and their use in the preparation of biologically active peptides and peptidomimetics

摘要

A very efficiently synthetic strategy was developed aiming to obtain a series of amino acids containing the rigid azabicyclo[3.2.1]octane scaffold in few steps, multi gram scale, and starting from commercially available compounds. udFurthermore, enantiomerically pure azabicyclo[3.2.1]octane amino acids were also prepared using a very efficient protocol consisting in the use of an asymmetric synthesis or in the use of a chiral building block as resolving agent.udStudies of orthogonal deprotection of the amino and of carboxylic functions were also developed aiming to obtain useful compounds for different applications. udIn fact, these interesting amino acids were tested in a binding test as a rigid mimic of GABA, as a potential ligand for transition metals, and also as catalyst in asymmetric Diels-Alder and Staudinger reactions. The most promising application was found in the use of azabicyclo[3.2.1]octane amino acids as a alpha,alpha-disobstituted amino acids. These compounds are able to induce a well defined 310 helical structure when inserted in a short peptide sequence.udud