Total Synthesis of Exiguamines A and B Inspired by Catecholamine Chemistry

The evolution of a total synthesis of the exiguamines, two structurally unusual natural products that are highly active inhibitors of indolamine‐2,3‐dioxygenase (IDO), is described. The ultimately successful strategy involves advanced cross‐coupling methodology and features a potentially biosynthetic tautomerization/electrocyclization cascade reaction that forms two heterocycles and installs a quaternary ammonium ion in a single synthetic operation. Be inspired: The presented biomimetic total synthesis of exiguamines A and B draws inspiration from catecholamine chemistry and is heavily influenced by biosynthetic considerations, in particular with respect to pericyclic reactions. The key steps are a challenging biaryl coupling, oxidation of a phenol to a para‐quinone, and a cascade reaction in the final step.