Cleavage and Final Deprotection with Dilute HCl in Fluoro Alcoho

New TFA-Free Cleavage and Final Deprotection in Fmoc Solid-Phase Peptide Synthesis: Dilute HCl in Fluoro Alcohol
P. Palladino and D. A. Stetsenko, Org. Lett., Article ASAP DOI: 10.1021/ol303124r
Publication Date (Web): December 4, 2012
Copyright © 2012 American Chemical Society

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.