Removal of t-butyl and t-butoxycarbonyl protecting groups with trifluoroacetic acid. Mechanisms, biproduct formation and evaluation of scavengers.
The trifluoroacetic acid-mediated removal of t-butyl groups in protected amino acids leads to the formation of t-butyl trifluoroacetate. This t-butyl ester alkylates in trifluoroacetic acid methionine and tryptophan. The t-butyl trifluoroacetate ester can be destroyed by scavengers commonly employed for t-butyl cations, and the reaction rates of the scavengers with the ester are used in the evaluation of scavengers. Scavengers of sulphide structure react with t-butyl trifluoroacetate to form sulphonium compounds, which possess alkylating properties. In the presence of a scavenger during acidolysis, the trifluoroacetic acid and the scavenger will compete in reacting with the t-butyl cations. Kinetic studies show comparable reaction rates with thiophenol as scavenger. The usefulness of adding scavengers to trifluoroacetic acid in deblocking reactions is due to the removal of t-butyl trifluoroacetate in addition to the removal of t-butyl cations. Isobutene reacts with trifluoroacetic acid and yields t-butyl trifluoroacetate. The reaction reaches an equilibrium displaced in favour of the ester at room temperature. Hence no isobutene can be expected to escape during a deblocking reaction in trifluoroacetic acid.
D000478:Alkylation; D055598:Chemical Phenomena; D002621:Chemistry; D005463:Fluoroacetates / Q000031:analogs & derivatives; D008715:Methionine; D010455:Peptides; D013452:Sulfonium Compounds; D014269:Trifluoroacetic Acid; D014364:Tryptophan; D014443:Tyrosine
D005463:Fluoroacetates; D010455:Peptides; D013452:Sulfonium Compounds; D014443:Tyrosine; D014364:Tryptophan; D008715:Methionine; D014269:Trifluoroacetic Acid