Sheludko, Yuriy V. ; Slagman, Sjoerd ; Gittings, Samantha ; Charnock, Simon J. ; Land, Henrik ; Berglund, Per ; Fessner, Wolf‐Dieter (2022)
Enantioselective Synthesis of Pharmaceutically Relevant Bulky Arylbutylamines Using Engineered Transaminases.
In: Advanced Synthesis & Catalysis, 2022, 364 (17)
doi: 10.26083/tuprints-00022896
Artikel, Zweitveröffentlichung, Verlagsversion
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Kurzbeschreibung (Abstract)
ATAs engineered for having an enlarged small binding pocket were applied for the synthesis of enantiomerically pure (R)‐benzo[1,3]dioxol‐5‐yl‐butylamine, a chiral component of human leukocyte elastase inhibitor DMP 777 (L‐694,458). Kinetic resolution of the racemic amine was performed by using the L59A variant of the (S)‐selective ATA from Chromobacterium violaceum (Cv‐ATA), providing the residual (R)‐enantiomer in excellent yield and >99% ee. At moderate enzyme loading and absence of co‐solvent, high volumetric productivity of 0.22 mol L⁻¹ h⁻¹ (42.5 g L⁻¹ h⁻¹) was achieved. Complementarily, the (S)‐enantiomer was generated via kinetic resolution using the (R)‐selective ATA‐117‐Rd11 from Arthrobacter sp. with acetone as the amino acceptor. In an alternative approach, we employed ATA‐117‐Rd11 for the asymmetric amination of the prochiral ketone precursor, which at 86% conversion gave the (R)‐benzo[1,3]dioxol‐5‐yl‐butylamine with excellent >99% ee. We further evaluated the utility of Cv‐ATA L59A for the asymmetric synthesis of pharmaceutically relevant (S)‐1‐phenylbutan‐1‐amine, a chiral component of the deubiquitinase inhibitor degrasyn (WP1130). The enzyme showed good tolerance to high concentrations of isopropylamine, producing (S)‐1‐phenylbutan‐1‐amine in enantiomerically pure form (>99% ee).
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2022 |
| Autor(en): | Sheludko, Yuriy V. ; Slagman, Sjoerd ; Gittings, Samantha ; Charnock, Simon J. ; Land, Henrik ; Berglund, Per ; Fessner, Wolf‐Dieter |
| Art des Eintrags: | Zweitveröffentlichung |
| Titel: | Enantioselective Synthesis of Pharmaceutically Relevant Bulky Arylbutylamines Using Engineered Transaminases |
| Sprache: | Englisch |
| Publikationsjahr: | 2022 |
| Ort: | Darmstadt |
| Publikationsdatum der Erstveröffentlichung: | 2022 |
| Verlag: | Wiley-VCH |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | Advanced Synthesis & Catalysis |
| Jahrgang/Volume einer Zeitschrift: | 364 |
| (Heft-)Nummer: | 17 |
| DOI: | 10.26083/tuprints-00022896 |
| URL / URN: | https://tuprints.ulb.tu-darmstadt.de/22896 |
| Zugehörige Links: | |
| Herkunft: | Zweitveröffentlichung DeepGreen |
| Kurzbeschreibung (Abstract): | ATAs engineered for having an enlarged small binding pocket were applied for the synthesis of enantiomerically pure (R)‐benzo[1,3]dioxol‐5‐yl‐butylamine, a chiral component of human leukocyte elastase inhibitor DMP 777 (L‐694,458). Kinetic resolution of the racemic amine was performed by using the L59A variant of the (S)‐selective ATA from Chromobacterium violaceum (Cv‐ATA), providing the residual (R)‐enantiomer in excellent yield and >99% ee. At moderate enzyme loading and absence of co‐solvent, high volumetric productivity of 0.22 mol L⁻¹ h⁻¹ (42.5 g L⁻¹ h⁻¹) was achieved. Complementarily, the (S)‐enantiomer was generated via kinetic resolution using the (R)‐selective ATA‐117‐Rd11 from Arthrobacter sp. with acetone as the amino acceptor. In an alternative approach, we employed ATA‐117‐Rd11 for the asymmetric amination of the prochiral ketone precursor, which at 86% conversion gave the (R)‐benzo[1,3]dioxol‐5‐yl‐butylamine with excellent >99% ee. We further evaluated the utility of Cv‐ATA L59A for the asymmetric synthesis of pharmaceutically relevant (S)‐1‐phenylbutan‐1‐amine, a chiral component of the deubiquitinase inhibitor degrasyn (WP1130). The enzyme showed good tolerance to high concentrations of isopropylamine, producing (S)‐1‐phenylbutan‐1‐amine in enantiomerically pure form (>99% ee). |
| Freie Schlagworte: | Aminotransferase, Biocatalysis, Chiral amines, Kinetic resolution, Protein engineering |
| Status: | Verlagsversion |
| URN: | urn:nbn:de:tuda-tuprints-228969 |
| Sachgruppe der Dewey Dezimalklassifikatin (DDC): | 500 Naturwissenschaften und Mathematik > 540 Chemie |
| Fachbereich(e)/-gebiet(e): | 07 Fachbereich Chemie 07 Fachbereich Chemie > Clemens-Schöpf-Institut 07 Fachbereich Chemie > Clemens-Schöpf-Institut > Fachgebiet Organische Chemie |
| Hinterlegungsdatum: | 23 Dez 2022 13:28 |
| Letzte Änderung: | 02 Aug 2024 12:47 |
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| Suche nach Titel in: | TUfind oder in Google |
Verfügbare Versionen dieses Eintrags
- Enantioselective Synthesis of Pharmaceutically Relevant Bulky Arylbutylamines Using Engineered Transaminases. (deposited 23 Dez 2022 13:28) [Gegenwärtig angezeigt]
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