Protection of 3,4-dihydroxyphenylalanine (DOPA) for Fmoc solid-phase peptide synthesis

Cyclic ethyl orthoformate (Ceof) was utilized as a protecting group to protect the catechol hydroxyl groups of 3,4-dihydroxyphenylalanine (DOPA). This protecting group is stable to strong bases and nucleophiles, and can be removed efficiently by 1 M trimethylsilyl bromide in trifluoroacetic acid in the presence of scavengers at 0°C for 60 min. Fmoc-DOPA(Ceof)-OH was synthesized in high yield and applied along with other Fmoc-amino acids to the solid-phase peptide synthesis of a DOPA-containing decapeptide from a mussel adhesive protein.