Asymmetric synthesis of amino acids: new concepts and applications

Our group is interested in the design of new asymmetric synthetic methods to access to non proteinogenic amino acids, starting from natural alpha-amino acids. We have thus developed an enantioselective synthesis of quaternary alpha-amino acids through enolate alkylation based on Memory of Chirality (MOC), exploiting the dynamic axial chirality of tertiary aromatic amides. The unique source of chirality was in that case the initial chirality of the starting tertiary alpha-amino acid despite this stereogenic center is temporarily destroyed during enolization. We have successfully adapted this reaction to a flow based system. We also developed MOC aldol reaction and oxidative coupling on enolates. We have then extended this method to an absolute asymmetric synthesis of tertiary alpha-amino acids, by applying the Frozen Chirality principle, which uses only the homochirality in a crystal. In another field, we have also developed a diastereoselective synthesis of beta,gamma-diamino acids and we have included them in hybrid alpha/gamma-peptides. These peptides are able to adopt various conformations and we have recently used them to build analogues of Gramicidin S, a very active cyclic antimicrobial peptide, but with high haemolytic activity. An overview of all these results will be provided.