The Azirine/Oxazolone Method in Peptide Chemistry: Synthesis of Tripeptide Models

Article abstract of DOI:10.1002/hlca.19880710118

Tripeptides 5, containing an α,α-disubstituted α-amino acid and ethyl p-aminobenzoate, were synthesized in high yield by application of the azirine/oxazolone method (Table 2).In this versatile approach for the incorporation of disubstituted residues into the peptide chain, N-protected peptides or amino acids are coupled with 2,2-dialkyl-3-amino-2H-azirines and, after the selective hydrolysis of the newly formed C-terminal amid bond, further condensed with amino components via in situ generated oxazole-5(4H)-ones in the presence of additives (Scheme 1).A comparison with conventional procedures clearly demonstrates the advantages of this new method that works equally well with β-branched, cyclic, or acyclic disubstituted amino acids.