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New TFA-free cleavage and final deprotection in fmoc solid-phase peptide synthesis: dilute HCl in fluoro alcohol
Pasquale Palladino1, Dmitry A Stetsenko
1Department of Chemistry, University of Reading, P.O. Box 224, Whiteknights, Reading RG6 6AD, UK.
Abstract:
A novel method for cleaving from resin and removing acid-labile protecting groups for the Fmoc solid-phase peptide synthesis is described. 0.1 N HCl in hexafluoroisopropanol or trifluoroethanol cleanly and rapidly removes the tert-butyl ester and ether, Boc, trityl, and Pbf groups and cleaves the common resin linkers: Wang, HMPA, Rink amide, and PAL. Addition of just 5-10% of a hydrogen-bonding solvent considerably retards or even fully inhibits the reaction. However, a non-hydrogen-bonding solvent is tolerated.
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