The Modification of Tryptophyl Residues during the Acidolytic Cleavage of Boc-groups. I. Studies with Boc-Tryptophan

Abstract

The formation of a component, X, was observed when a reaction mixture of t-butyloxycarbonyl-tryptophan (Boc-Trp), trifluoroacetic acid (TFA), and 1,2-ethanedithiol was analyzed by cellulose TLC. The side product was isolated and further separated into two components by column chromatography on silica gel. The subsequent analysis of the NMR spectra of these components confirmed that they were Nin-But-Trp and Cin-But-Trp. The reaction of Boc-Trp with TFA and with anhydrous hydrogen fluoride (HF) was examined as model systems in order to determine conditions which would minimize the formation of the X component during the synthesis of peptides containing Trp. The addition of 10 molar equivalents of 1,2-ethanedithiol completely suppressed the formation of the X component in HF, but additives were less efficient in TFA. A combination of dimethyl sulfide and 1,2-ethanedithiol was the most effective method for suppressing the formation of the X component in TFA. The behavior of Nin- and Cin-But-Trp in acidic media was also investigated, and a possible pathway for the t-butylation of the tryptophyl residue will be proposed.