Towards a streamlined synthesis of peptides containing α,β-dehydroamino acids
- Resource Type
- Authors
- Joseph C. Chanthakhoun; Jaden D. Barfuss; Diego A. Moyá; Michael A. Lee; Steven L. Castle; Austin K. LeSueur; Daniel Joaquin
- Source
- Tetrahedron Lett
- Subject
- chemistry.chemical_classification
010405 organic chemistry
Alkene
Sulfonium
Organic Chemistry
Peptide
Oxazoline
010402 general chemistry
01 natural sciences
Biochemistry
Combinatorial chemistry
Article
0104 chemical sciences
chemistry.chemical_compound
Residue (chemistry)
chemistry
Drug Discovery
Peptide synthesis
Moiety
- Language
- ISSN
- 0040-4039
Investigation of a strategy to streamline the synthesis of peptides containing α, β -dehydroamino acids (ΔAAs) 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 ΔAA-containing azlactone dipeptides to facilitate coupling of these residues. Z-dehydroaminobutyric acid (Z-ΔAbu) could be constructed most efficiently via EDC/CuCl-mediated dehydration of Thr. Formation of Z-ΔPhe by this or other dehydration methods was unsuccessful. Production of the bulky ΔVal residue could be accomplished by DAST-promoted dehydrations of β -OHVal or by DBU-triggered eliminations of sulfonium ions derived from penicillamine derivatives. However, competitive formation of an oxazoline byproduct remains problematic.