Scalable synthesis and coupling of quaternary α-arylated amino acids: α-aryl substituents are tolerated in α-helical peptides. Issue 27 (16th June 2021)

• Record Type: Journal Article
• Authors: Leonard, Daniel J.; Zieleniewski, Francis; Wellhöfer, Isabelle; Baker, Emily G.; Ward, John W.; Woolfson, Derek N.; Clayden, Jonathan
• Is Part Of: Chemical science. Volume 12:Issue 27(2021)
• Page Start: 9386
• Page End: 9390
• Publication Date: 2021-06-16
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/d1sc01378e
• Languages: English
• ISSNs: 2041-6520

Abstract

Abstract : Both R and S enantiomers of Fmoc-protected amino acids bearing α-aryl substituents may be made on gram scale. Solid-phase synthesis leads to helical peptides unperturbed by the presence of these additional α-aryl groups. Abstract : Quaternary amino acids are important tools for the modification and stabilisation of peptide secondary structures. Here we describe a practical and scalable synthesis applicable to quaternary alpha-arylated amino acids (Q4As), and the development of solid-phase synthesis conditions for their incorporation into peptides. Monomeric and dimeric α-helical peptides are synthesised with varying degrees of Q4A substitution and their structures examined using biophysical methods. Both enantiomers of the Q4As are tolerated in folded monomeric and oligomeric α-helical peptides, with the ( R )-enantiomer slightly more so than the ( S ).