Access to α,α-Disubstituted Disilylated Amino Acids and Their Use in Solid-Phase Peptide Synthesis

Roberto Fanelli (1) , Khoubaib Ben Haj Salah (2) , Nicolas Inguimbert (2) , Claude Didierjean (3) , Jean Martinez (1) , Florine Cavelier (1)

1 IBMM - Institut des Biomolécules Max Mousseron [Pôle Chimie Balard]
2 CRIOBE - Centre de recherches insulaires et observatoire de l'environnement
3 CRM2 - Cristallographie, Résonance Magnétique et Modélisations

A concise synthetic pathway yielding to hydrophobic α,α-disubstituted disilylated amino acids based on a hydrosilylation reaction is described. As a first example of utilization in solid-phase peptide synthesis, TESDpg was introduced in replacement of Aib in an alamethicin sequence, leading to analogues with modified physicochemical properties and conserved helical structures. This study highlights the potential of these new amino acids as tools for peptide modulation.

Domains: Organic chemistry

Roberto Fanelli, Khoubaib Ben Haj Salah, Nicolas Inguimbert, Claude Didierjean, Jean Martinez, et al.. Access to α,α-Disubstituted Disilylated Amino Acids and Their Use in Solid-Phase Peptide Synthesis. Organic Letters, 2015, 17 (18), ⟨10.1021/acs.orglett.5b02175⟩. ⟨hal-01212249⟩