Synthesis of 3-Oxo-2,3-dihydropyrrole 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.

Key words

pyrroles - 3-oxo-2,3-dihydropyrrole - allylations - amino acids - catalysis - palladium

References

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15

The ¹H NMR coupling constant (³ J) between NH of the peptide bond and the α-CH shows a value of 5.9 Hz which indicates free rotation of the 3-oxo-2,3-dihydropyrrole moieties around the connecting single bond.