ENANTIOSELECTIVE SYNTHESIS OF AN UNNATURAL BIPYRIDYL AMINO-ACID AND ITS INCORPORATION INTO A PEPTIDE

The synthesis of a bipyridyl amino acid, 2-amino-3-(4'-methyl-2,2'-bip yridin-4-yl) propanoic acid, is described. A short three step synthesi s from commercially available 4,4'-dimethyl-2,2'-bipyridine provides t he amino acid in 65% enantiomeric excess (ee). An enzyme-mediated chir al resolution increases the ee to 95% in two additional steps. The ami no acid was incorporated into a 22 amino acid peptide composed predomi nantly of alanine. The peptide was found to be 88% alpha-helical in aq ueous solution at 1 degrees C by circular dichroism (CD) spectropolari metry, indicating a high helical propensity for this amino acid. This amino acid can provide a means to incorporate a metal into structure-f orming peptides. (C) 1998 Elsevier Science Ltd. All rights reserved.