Protection and Activation of Hydroxycinnamic Acids in Water

Hydroxycinnamic acids such as p-coumaric, ferulic, sinapic and caffeic acids were protected as carbonates and activated as mixed carbonic anhydrides in water at RT by adding a base and isobutyl chloroformate. These anhydrides were used for amine and C-protected α-amino acid acylation to give O-carbonate protected phenolic amides. Acylation of free α-amino acids was performed in acetone-water in high yields producing the O- carbonate protected N-hydroxycinnamoyl-α-amino acids. Pure derivatives were obtained in many cases directly by crystallization. Free phenolic compounds were rapidly obtained by carbonate deprotection with piperidine. The method offers a novel route for amide bond formation in water and the direct functionalization of hydroxycinnamic acid families with free α- amino acids, providing a facile preparation of precious natural bioactive derivatives.