Cleavage and deprotection of peptide resins using chloro- and bromotrialkylsilanes.

Abstract

The cleavage of a peptide resin attached to a phenylacetomidomethyl (PAM) resin was investigated using bromotrimethylsilane (TMSBr) with thioanisole in trifluoroacetic acid (TFA), and by chlorotrimethylsilane (TMSCl) in the same reagents with lithium bromide. Both TMSBr and TMSCl cleaved the peptide from the resin, but TMSCl required elevated temperature (50 degrees C) to effect the cleavage. Procedures were investigated for the deprotection and cleavage of either N(g)-tosyl (Tos)- or mesitylenesulfonyl (MTS)-arginine residues attached to 4-methylbenzylhydrylamine (MBHA) resin, and of a peptide containing an MTS-arginine residue attached to MBHA resin, using either TMSCl or TMSBr as cleavage reagents. The MTS group is cleanly removed from arginine using TMSBr with thioanisole in TFA and by TMSCl in the same reagents with lithium bromide.