Combining ketoreductase and amine transaminase for 4-aminocyclohexanol synthesis

Dissertation, Mathematisch-Naturwissenschaftliche Fakultät der Universität Greifswald, 2020

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Bibliographische Detailangaben
1. Verfasser: Sviatenko, Olha (VerfasserIn)
Körperschaft: Universität Greifswald (Grad-verleihende Institution)
Weitere Verfasser: Höhne, Matthias (AkademischeR BetreuerIn), Lavandera, Iván García (AkademischeR BetreuerIn)
Format: UnknownFormat
Sprache:eng
Veröffentlicht: Greifswald Mai 2020
Schlagworte:
Hochschulschrift > Amine > Cyclohexanol > Transaminasen > Ketone > Reductasen > Enzym > Alkohol > Enzymkatalyse > Asymmetrische Synthese > Katalyse > Biokatalyse > Enzymatische Reduktion
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Zusammenfassung:Dissertation, Mathematisch-Naturwissenschaftliche Fakultät der Universität Greifswald, 2020
Biokatalyse, Enzym, Alkohol, Amine, Enzymkatalyse, Asymmetrische Katalyse, Amine transaminase, ketoreductase
The aim of our research is a stereoselective synthesis development of 4-aminocyclohexanol by the application of a keto reductase (KRED) and an amine transaminase (ATA). 4-Aminocyclohexanol is a valuable precursor for active pharmaceutical ingredients, for example, lomibuvir (a HCV protease inhibitor), ambroxol (a secretolytic agent) and other bioactive molecules. Today, the trans-4-aminocyclohexanol is accessed via Ni-catalyzed synthetic procedure giving moderate yields. In our project we perform cis- and trans-4-aminocyclohexanol synthesis from 1,4-cyclohexanedione (a bio-based precursor) by an one-pot approach combining sequentially a KRED and an ATA as catalysts. For this, we envisaged two multistep enzymatic procedures. The route A would involve 4-hydroxycyclohexanone formation from 1,4-cyclohexanedione via a KRED-catalyzed monoreduction and a further transamination mediated by an ATA towards 4-aminocyclohexanol. The route B would consist of switching the steps of the previous sequential approach, that is, a monoamination of the diketone to yield 4-aminocyclohexanone, and the subsequent reduction of the remaining carbonyl group. Only route A turned out to be feasible, and we performed 4-aminocyclohexanol synthesis at the preparative scale in the sequential and tandem modes. Depending on the ATA, both isomers can be obtained.
Beschreibung:Literaturverzeichnis: Seite 110-120
Beschreibung:157 Seiten
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