Gram‐Scale Synthesis of a Hexapeptide by Fragment Coupling in a Ball Mill

Yves Yeboue (1) , Nadia Rguioueg (1) , Gilles Subra (1) , Jean Martinez (1) , Frédéric Lamaty (1) , Thomas-Xavier Métro (1)

1 IBMM - Institut des Biomolécules Max Mousseron [Pôle Chimie Balard]

Synthesis of long peptides is generally considered as being a challenge to peptide chemists, in addition to producing significant amounts of toxic waste, such as DMF. Here we show that using solvent-less methods, such as ball milling, enabled the production of the hexapeptide Boc-(Ala-Phe-Gly)2-OBn at the gram scale with high overall yield (77%, 5 linear steps). This is the longest peptide chain synthesized in a ball mill to date, in which the amino acid sequence is precisely controlled. This study complements the current fundamental knowledge required to synthesize longer and more difficult peptide chains (or small proteins) by using peptide fragment couplings in a ball mill.

Domaines: Chimie organique

Yves Yeboue, Nadia Rguioueg, Gilles Subra, Jean Martinez, Frédéric Lamaty, et al.. Gram‐Scale Synthesis of a Hexapeptide by Fragment Coupling in a Ball Mill. European Journal of Organic Chemistry, 2021, ⟨10.1002/ejoc.202100839⟩. ⟨hal-03348943⟩