A new synthetic method of dehydropeptides

by direct coupling of N-protected amino acids or N-protected peptides with β-hydroxy -α-amino acid esters in the presence of three equivalents of each of triphenylphosphine

carbon tetrachloride

and triethylamine or ethyl diisopropylamine

was devcloped. Compounds synthesized by this method were Boc-DL-Ile-⊿But-oMe

Boc-DL-Ile-⊿Ala-oMe

Boc-DL-Val⊿Ala-OMe

Boc-L Ile-DL-Val(Thz)-⊿But-oMe

and Boc-L-Ile-DL-Val(Thz)-⊿Ala -oMe. In the case of L-threone methyl ester

only Z-dehydroamino acid residue was observed. A possible mechanism was proposed. It was believed that the Nprotected amino acid or N-protected peptide was coupled first with β-hydroxy -α-amino acid ester

forming a peptide having a β-hydroxyamino acid residue at the C terminal

and then dehydration of the newly formed peptide gave dehydropeptide. The same reagents were used to synthesize peptide oxazolines. The key factor affecting reaction directions was the acidity of the protons at the α-C-H bond and at the N-H bond.