Total Synthesis of (+)-12- epi -Fischerindole U Isonitrile and Its Activity as a Substrate of the Halogenase WelO5

-fischerindole G (FIG). Researchers have proposed that a dynamic reconfiguration of the WelO5 active site governs the selective halogenation of FIUI. Unfortunately, the requirements of spectroscopic and structural methods for large amounts of fully assembled samples of protein-substrate complexes impede the investigation of such reconfiguration. In this work, we describe a synthesis of (+)-FIUI that makes use of the Baran group's strategy for coupling of indoles with carbonyl compounds. We apply EPR and LC-MS methods to demonstrate the ability of WelO5 to bind the synthetic (+)-FIUI and subsequently convert it to FIG.