PUB - Publikationen an der Universität Bielefeld

The combination of the biocatalytic halogenation of l-tryptophan with subsequent chemocatalytic Suzuki-Miyaura crosscoupling 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 O-2. 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.