Removal of acid-labile protecting or anchoring groups in the presence of polyfluorinated alcohol: Application to solid-phase peptide synthesis

Abstract

We describe herein a new method for cleaving from resin and removing acid-labile protecting groups in solid-phase peptide synthesis in the presence of a polyfluorinated alcohol (either trifluoroethanol, TFE, or hexafluoroisopropanol, HFIP). It was shown that 0.1 M HCl in hexafluoroisopropanol or trifluoroethanol removes the acid-labile protecting groups commonly used in Fmoc SPPS for the protection of amino acid side-chains, such as t-butyl ester and ether, Boc, trityl, and Pbf groups including the most acid-resistant p-hydroxymethylphenoxyacetyl group (HMPA), p-benzyloxy benzyl ester (Wang resin), Rink amide, and peptide amide linker (PAL). The addition of 5–10% of a hydrogen-bonding solvent was shown to considerably retard or even fully inhibit the reaction. However, nonhydrogen-bonding solvents, such as dichloromethane, do not slow down the reaction.