Modular Combination of Enzymatic Halogenation of Tryptophan with Suzuki–Miyaura Cross‐Coupling Reactions. Issue 10 (6th May 2016)

• Record Type: Journal Article
• Authors: Frese, Marcel; Schnepel, Christian; Minges, Hannah; Voß, Hauke; Feiner, Rebecca; Sewald, Norbert
• Is Part Of: ChemCatChem. Volume 8:Issue 10(2016)
• Page Start: 1799
• Page End: 1803
• Publication Date: 2016-05-06
• Subjects: biocatalysis -- enzyme catalysis -- cross-coupling -- multicomponent reactions -- palladium; Catalysis -- Periodicals; 541.39505
• DOI: 10.1002/cctc.201600317
• Languages: English
• ISSNs: 1867-3880

Abstract

Abstract: The combination of the biocatalytic halogenation ofl ‐tryptophan with subsequent chemocatalytic Suzuki–Miyaura cross‐coupling reactions leads to the modular synthesis of an array of C5, C6, or C7 aryl‐substituted tryptophan derivatives. In a three‐step one‐pot reaction, the bromo substituent is initially incorporated regioselectively by immobilized tryptophan 5‐, 6‐, or 7‐halogenases, respectively, with concomitant cofactor regeneration. The halogenation proceeds in aqueous media at room temperature in the presence of NaBr and O2 . After the separation of the biocatalyst by filtration, a Pd catalyst, base, and boronic acid are added to the aryl halide formed in situ to effect direct Suzuki–Miyaura cross‐coupling reactions followed by tert ‐butoxycarbonyl (Boc) protection. After a single purification step, different Boc‐protected aryl tryptophan derivatives are obtained that can, for example, be used for peptide or peptidomimetic synthesis. Abstract : Putting the pieces together : By combining the enzymatic halogenation ofl ‐tryptophan using flavin adenine dinucleotide dependent halogenases with Pd‐catalyzed Suzuki–Miyaura cross‐coupling reactions in water, the C5‐, C6‐, or C7‐position of the indole ring can be brominated regioselectively in situ and functionalized chemocatalytically in a stepwise one‐pot reaction.