Novel Arylindigoids by Late‐Stage Derivatization of Biocatalytically Synthesized Dibromoindigo

Indigoids represent natural product‐based compounds applicable as organic semiconductors and photoresponsive materials. Yet modified indigo derivatives are difficult to access by chemical synthesis. A biocatalytic approach applying several consecutive selective C−H functionalizations was developed that selectively provides access to various indigoids: Enzymatic halogenation of l‐tryptophan followed by indole generation with tryptophanase yields 5‐, 6‐ and 7‐bromoindoles. Subsequent hydroxylation using a flavin monooxygenase furnishes dibromoindigo that is derivatized by acylation. This four‐step one‐pot cascade gives dibromoindigo in good isolated yields. Moreover, the halogen substituent allows for late‐stage diversification by cross‐coupling directly performed in the crude mixture, thus enabling synthesis of a small set of 6,6’‐diarylindigo derivatives. This chemoenzymatic approach provides a modular platform towards novel indigoids with attractive spectral properties.