SN 1 and SN 2 mechanisms for the deprotection of synthetic peptides by hydrogen fluoride

Abstract

Studies on the side reaction leading to ring alkylation during HF deprotection of tyrosine revealed that under S_N 1 conditions the formation of by-product can be reduced by using protecting groups that either provide only weakly electrophilic carbocations or give rise to an intermediate that deactivates the tyrosine ring and allows scavengers to suppress the formation of 3-alkyltyrosine. The effectiveness of the scavenger can be qualitatively predicted by its pKa value. A new reagent (HF: dimethylsulfide, 1:3, v/v) provides an S_N 2 cleavage mechanism that removes the danger of carbocation formation and suppresses the electrophilic alkylation side reaction.