Late-Stage Diversification of Tryptophan-Derived Biomolecules.

Abstract

Gruß H, Sewald N. Late-Stage Diversification of Tryptophan-Derived Biomolecules. Chemistry - A European Journal. 2020;26(24):5328-5340.Pd-mediated reactions have emerged as a powerful tool for the site-selective and bioorthogonal late-stage diversification of amino acids, peptides and related compounds. Indole moieties of tryptophan derivatives are susceptible to C2 H-activation, whereas halogenated aromatic amino acids such as halophenylalanines or halotryptophans provide a broad spectrum of different functionalisations. The compatibility of transition-metal-catalysed cross-couplings with functional groups in peptides, other biologically active compounds and even proteins has been demonstrated. This Review primarily compiles the application of different cross-coupling reactions to modify halotryptophans, halotryptophan containing peptides or halogenated, biologically active compounds derived from tryptophan. Modern approaches use regio- and stereoselective biocatalytic strategies to generate halotryptophans and derivatives on a preparative scale. The combination of bio- and chemocatalysis in cascade reactions is given by the biocompatibility and bioorthogonality of Pd-mediated reactions. © 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA