Enzyme catalysis is gaining increasing importance in synthetic chemistry. Nowadays, the growing number of biocatalysts accessible by means of bioinformatics and enzyme engineering opens up an immense variety of selective reactions. Biocatalysis especially provides excellent opportunities for late‐stage modification often superior to conventional de novo synthesis. Enzymes have proven to be useful for direct introduction of functional groups into complex scaffolds, as well as for rapid diversification of compound libraries. Particularly important and highly topical are enzyme‐catalysed oxyfunctionalisations, halogenations, methylations, reductions, and amide bond formations due to the high prevalence of these motifs in pharmaceuticals. This Review gives an overview of the strengths and limitations of enzymatic late‐stage modifications using native and engineered enzymes in synthesis while focusing on important examples in drug development.

D-Tryptophan and its derivatives are important precursors of a wide range of indole-containing pharmaceuticals and natural products. Here, we developed a one-pot biocatalytic process enabling the synthesis of D-tryptophans from indoles in good yields and high enantiomeric excess (91% to >99%). Our method couples the synthesis of L-tryptophans catalyzed by Salmonella enterica tryptophan synthase with a stereoinversion cascade mediated by Proteus myxofaciens L-amino acid deaminase and an aminotransferase variant that we engineered to display native-like activity toward D-tryptophan. Our process is applicable to preparative-scale synthesis of a broad range of D-tryptophan derivatives containing electron-donating or -withdrawing substituents at all benzene-ring positions on the indole group.

Six chemo-enzymatic routes for the synthesis of a trifluorinated d-phenylalanine have been described and compared, including the first example of a fully biocatalytic d-hydroamination.

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Biokatalytische Modifikationen bieten attraktive Methoden für die selektive Funktionalisierung von komplexen Molekülen. Inmitten einer ständig wachsenden Zahl von Enzymen sind heute modulare Werkzeugkästen enzymatischer Transformationen in der Synthese verfügbar. Eine große Zahl von Biokatalysatoren ist in der Lage, vielzählige Diversifikationen vorzunehmen, z. B. für die Wirkstoffentwicklung. In ihrem Aufsatz auf S. 16962 stellen Nicholas J. Turner, Christian Schnepel et al. die derzeitige Bandbreite enzymatischer Modifikationen vor.