Evaluation of gaseous hydrogen fluoride as a convenient reagent for parallel cleavage from the solid support

We have tested the limits of gaseous hydrogen fluoride as an agent for para llel detachment of organic molecules from the solid support. Peptides were chosen as relatively sensitive models for this reaction. Acid-catalyzed ami de bond hydrolysis, side chain modification (tryptophan and other unnatural amino acids) by the protecting group residues as well as dehydration of se rine and asparagine was followed. The technique of cleavage of side chain p rotection prior to the resin cleavage has given satisfactory results. Two-s tep deprotection and cleavage from benzhydrylamine resin by TFA and HF was compared to the deprotection and cleavage by TFA from Knorr resin.