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Modular Combination of Enzymatic Halogenation of Tryptophan with Suzuki–Miyaura Cross‐Coupling Reactions
Author(s) -
Frese Marcel,
Schnepel Christian,
Minges Hannah,
Voß Hauke,
Feiner Rebecca,
Sewald Norbert
Publication year - 2016
Publication title -
chemcatchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.497
H-Index - 106
eISSN - 1867-3899
pISSN - 1867-3880
DOI - 10.1002/cctc.201600317
Subject(s) - chemistry , halogenation , aryl , tryptophan , substituent , combinatorial chemistry , coupling reaction , catalysis , organic chemistry , suzuki reaction , amino acid , alkyl , biochemistry
The combination of the biocatalytic halogenation of l ‐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 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.