Electrochemical α-acyloxylation of dibenzoylmethane with C-terminal carboxylic acids for peptide and drug diversification.

Carboxylic acids are common functional handles in peptides and drug molecules, but their direct use for DBM derivatization remains limited. Herein, a bromide-mediated electrochemical α-acyloxylation of dibenzoylmethane (DBM) with amino acid-, peptide-, and drug-derived carboxylic acids is described. The reaction proceeds in an undivided cell under mild conditions, providing DBM-amino acid, DBM-peptide, and DBM-drug conjugates through C-O bond formation. Various amino acids, DBM derivatives, drug acids, dipeptides, and bioactive peptides are tolerated. Mechanistic studies support α-bromination of DBM followed by carboxylate substitution. Representative peptide conjugation improves the aqueous behaviour of DBM.