Trabectedin (TBD)

Trabectedin is composed of 3 tetrahydroisoquinoline moieties, 8 rings including one 10-membered heteocyclic ring containing a cysteine residue, and 7 chiral centers. The biological mechanism of action is believed to involve the production of superoxide near the DNA strand, resulting in DNA backbone cleavage and cell apoptosis. The actual mechanism is not yet known, but is believed to proceed from reduction of molecular oxygen into superoxide via an unusual auto-redox reaction on a hydroxyquinone moiety of the compound following. There is also some speculation the compound becomes """activated""" into its reactive oxazolidine form. The biosynthesis of trabectedin is believed to involve the dimerization of two tyrosine residues to form the pentacyclic core of the molecule.  A separate synthetic process also involved the Ugi reaction to assist in the formation of the pentacyclic core.