Towards a streamlined synthesis of peptides containing α,β-dehydroamino acids

Investigation of a strategy to streamline the synthesis of peptides containing alpha,beta-dehydroamino acids (Delta AAs) is reported. The key step involves generating the alkene moiety via elimination of a suitable precursor after it has been inserted into a peptide chain. This process obviates the need to prepare Delta AA-containing azlactone dipeptides to facilitate coupling of these residues. Z-dehydroaminobutyric acid (Z-Delta Abu) could be constructed most efficiently via EDC/CuCl-mediated dehydration of Thr. Formation of Z-Delta Phe by this or other dehydration methods was unsuccessful. Production of the bulky Delta Val residue could be accomplished by DAST-promoted dehydrations of beta -OHVal or by DBU-triggered eliminations of sulfonium ions derived from penicillamine derivatives. However, competitive formation of an oxazoline byproduct remains problematic. (C) 2021 Elsevier Ltd. All rights reserved.

Automated summary

The study reports a strategy to streamline the synthesis of peptides containing alpha,beta-dehydroamino acids (Delta AAs) by generating the alkene moiety via elimination of suitable precursor. However, there are challenges in the production of certain amino acids during the process.