Synthesis of (9S,12S)-cycloisodityrosine and its unnatural (9R,12S)-diastereomer

A synthesis of the (9S,12S)-cycloisodityrosine derivatives and their unnatural (9R,12S)-diastereomers are disclosed. The approach is based on an intramolecular aromatic nucleophilic substitution reaction for formation of the macrocyclic biaryl ether and includes the documentation of a remarkably facile base-catalyzed epimerization.