Stability and Cleavage Conditions of (2-Furyl)-L-Alanine-Containing Peptides

The furyl group of (2-furyl)-L-alanine-containing peptides obtained from Fmoc solid-phase synthesis is partially degraded to several by-products during the final TFA-mediated deprotection in the presence of cation scavengers such as ethanedithiol and propanedithiol. The major by-product corresponds to a bis-dithioacetale formed after acidic hydrolysis of the furyl group. We examined several cleavage conditions and found that cleavage cocktails containing water and triisopropylsilane or 3,6-dioxa-1,8- octanedithiol (DODT) in trifluoroacetic acid are sufficient to minimize the side reaction.