Many amino ketoacid derivatives are potent inhibitors of proteases (thrombin, calpain, cathepsin, HIV protease) and display antithrombotic, anti-tumoral and antiviral activity, among others. Therefore, the derivatives of peptidyl beta-keto acids have elicited much interest. In contrast, little work has been reported about the biological activity of gamma-amino alpha-ketoacids and their peptide derivatives. Herein we report a methodology for the direct transformation of alpha-amino acids into gamma-amino alpha-ketoesters, using a new sequential process, where the oxidative radical decarboxylation of commercial amino acids or small peptides is followed by the addition of C-nucleophiles (silyl enol ether derivatives of ketoesters). In this way, a single starting peptide can generate a library of amino ketoester derivatives, which can be used as building blocks of more complex peptide chains. The resulting libraries enable structure-activity studies.

To programs CTQ2009-07109 and SAF2013-48399-R, Ministerio de Economía y Competitividad, and European Funds FEDER/FSE. Dácil Hernández thanks her JAE postdoctoral contract to CSIC.

Trabajo presentado en "Peptides in Paris Symposium PIPS" celebrado en París del 5 al 8 de octubre de 2014.

Peer Reviewed