Desulfation vs. deprotection: direct solid-phase synthesis of Tyr(SO3 H)-containing peptides using the Sn1-type deprotection procedure

Recent advances in the Fmoc-chemistry made the direct synthesis of the sulfated peptide possible using the solid-phase method, however, even when the Fmocstrategy is adopted, conditions for the final cleavage/deprotection with acidic reagents becomes very crucial. During the course of our efforts to find a general synthetic method for the Tyr(SO3 H)-containing peptides, we noticed that TFA is not a destructive acid towards Tyr(SO3 H) as long as the treatment is conducted at low temperature [1]. Based on this finding, we used 90% aqueous TFA at low temperature as the deprotection system for Tyr(SO3 H)-containing peptides. In this study, we also performed kinetic studies on the desulfation reaction and the deprotection reactions to understand this deprotection system.