Safe and efficient Boc-SPPS for the synthesis of glycopeptide-α-thioesters.

Abstract

Boc-solid phase peptide synthesis is useful for the preparation of peptide-α-thioesters. However, this strategy usually employs hydrogen fluoride for the final deprotection step. These strongly acidic conditions cannot be applied for the synthesis of acid-labile glycopeptide-α-thioesters. The protocol presented here is a modified in situ neutralization Boc-solid phase peptide synthesis employing 10% sulfuric acid/dioxane conditions for intermediate Boc removal and TfOH for the final side-chain deprotection step. These conditions were found to be applicable for the synthesis of acid-labile glycopeptide-α-thioesters. In this protocol, a glycopeptide is synthesized as α- thioester on a thiol linker, and the product glycopeptide-α-thioester is released from the resin by thiolysis after side-chain deprotection step with an acid cocktail containing TfOH instead of hydrogen fluoride.