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

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. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.