Synthesis of 3-Oxo-2,3-dihydro-pyrrole Amino Acids as Chiral Dipeptidomimics

Abstract

We describe the synthesis of a novel chiral dipeptide β-sheet mimic based on aminomethyl-3-oxo-2,3-dihydropyrrole carboxylic acids. The synthesis uses a palladium-catalyzed allylation with the chiral Trost ligand as a key step for the construction of a quaternary chiral center. This allows the enantioselective conversion of 2-carboxy-3-hydroxy-pyrrole into 3-oxo-2,3-dihydropyrrole-2-allyl-2-carboxylate. The allyl group is subsequently converted into an aldehyde or ester group. Peptide coupling of the 3-oxo-2,3-dihydropyrrole amino acid leads to more extended systems with partially constrained dipeptide units.