TRIFLUOROACETYLATION OF AMINO-ACIDS AND PEPTIDES BY ETHYL TRIFLUOROACETATE

Although the trifluoroacetyl group has not found general use as an N-protecting group in peptide synthesis, it has nevertheless continued to prove useful in certain special circumstances. For example, we recently capitalized on its ready enzymatic removal to develop a new synthesis of azaserine, a compound of interest as an antitumor agent and pancreatic carcinogen. Methods for the introduction of the trifluoroacetyl group into amino acids and peptides include reaction with trifluoroacetic anhydride alone or in trifluoroacetic acid solution, reaction with aqueous S-ethyl trifluorothioacetate in mildly alkaline medium, reaction with phenyl trifluoroacetate in phenol, and reaction with sym-trichlorotrifluoroacetone in Me2SO. The use of high boiling solvents, or odoriferous or strongly electrophilic reagents, can be disadvantageous. Trifluoroacetic anhydride, for example, can cause peptide bond cleavage, while Panetta's Me2SO procedure requires chromatographic separation of the trifluoroacetyl derivative from the solvent and tends to give poor or mediocre yields. Our finding that serine can be trifluoroacetylated with methyl trifluoroacetate in methanol in the presence of triethylamine prompted us to examine the generality of this method, with the results reported herein. © 1979, American Chemical Society. All rights reserved.