Synthesis and preliminary biological evaluation of new phenolic and catecholic dehydroamino acid derivatives

Abstract A library of N -phenolic and N -catecholic dehydroamino acid derivatives was prepared using an innovative synthetic strategy that involves mild reaction conditions and simple work-up procedures. The method comprises coupling of phenolic or catecholic acids with β-hydroxyamino acids followed by tert -butyloxycarbonylation of all hydroxyl groups using tert -butyldicarbonate and 4-dimethylaminopyridine as catalyst. Treatment of these amino acids with N,N,N′,N′ -tetramethylguanidine affords the corresponding O - tert -butyloxycarbonyldehydroamino acid derivative. Deprotection of the aromatic hydroxyl groups is carried out with trifluoroacetic acid. This synthetic strategy can be applied in a one-pot procedure and yields compounds that can be easily inserted into peptides or other biomolecules after cleavage of the C-protecting group. Preliminary studies of cell viability show that these new compounds display very low or no toxicity. These dehydroamino acids with a phenolic or catecholic moiety can have intrinsic biological activity or used to prepare new hydrogels that mimic mussel adhesive proteins.