Application of the allyloxycarbonyl protecting group for the indole of Trp in solid-phase peptide synthesis.

Abstract

The synthesis and stability of allyloxycarbonyl (Aloc) indole-protected Trp derivatives and their application in solid-phase peptide synthesis are reported. The study shows that the Aloc protection on the indole moiety is suitable for orthogonal protection in the Fmoc/tBu strategy if the Fmoc group is cleaved with DBU. Several tryptophan-containing peptides have been synthesized including dynorphin A-(1-13), which has been intensively studied with respect to side reactions during the final TFA cleavage procedure. The results demonstrate the protective function of the Aloc group on the Trp during final deprotection. Furthermore, it could be demonstrated that Trp(Aloc)-containing peptides can be isolated and that the Aloc group can then be removed in a second step. The synthesis of phosphorylated delta sleep inducing peptide (P-DSIP) using the global phosphorylation approach provides another example in which Trp indole protection by Aloc prevents the formation of oxidative side products.