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Selective Access to All Four Diastereomers of a 1,3-Amino Alcohol by Combination of a Keto Reductase- and an Amine Transaminase-Catalysed Reaction
KTH, School of Biotechnology (BIO), Industrial Biotechnology.
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2015 (English)In: Advanced Synthesis and Catalysis, ISSN 1615-4150, E-ISSN 1615-4169, Vol. 357, no 8, 1808-1814 p.Article in journal (Refereed) Published
Abstract [en]

The biocatalytic synthesis of chiral amines has become a valuable addition to the chemists' tool-box. However, the efficient asymmetric synthesis of functionalised amines bearing more than one stereocentre, such as 1,3-amino alcohols, remains challenging. By employing a keto reductase (KRED) and two enantiocomplementary amine transaminases (ATA), we developed a biocatalytic route towards all four diastereomers of 4-amino-1-phenylpentane-2-ol as a representative molecule bearing the 1,3-amino alcohol functionality. Starting from a racemic hydroxy ketone, a kinetic resolution using an (S)-selective KRED provided optically active hydroxy ketone (86% ee) and the corresponding diketone. Further transamination of the hydroxy ketone was performed by either an (R)- or an (S)-selective ATA, yielding the (2R,4R)- and (2R,4S)-1,3-amino alcohol diastereomers. The remaining two diastereomers were accessible in two subsequent asymmetric steps: the diketone was reduced regio- and enantioselectively by the same KRED, which yielded the (S)-configured hydroxy ketone. Eventually, the subsequent transamination of the crude product with (R)- and (S)-selective ATAs yielded the remaining (2S,4R)and (2S,4S)-diastereomers, respectively.

Place, publisher, year, edition, pages
2015. Vol. 357, no 8, 1808-1814 p.
Keyword [en]
amine transaminase, amino alcohols, enzyme catalysis, keto reductase
National Category
Chemical Sciences
Identifiers
URN: urn:nbn:se:kth:diva-172237DOI: 10.1002/adsc.201500214ISI: 000355235700020Scopus ID: 2-s2.0-84930202995OAI: oai:DiVA.org:kth-172237DiVA: diva2:848442
Note

QC 20150825

Available from: 2015-08-25 Created: 2015-08-14 Last updated: 2017-12-04Bibliographically approved
In thesis
1. Amine Transaminases in Multi-Step One-Pot Reactions
Open this publication in new window or tab >>Amine Transaminases in Multi-Step One-Pot Reactions
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Amine transaminases are enzymes that catalyze the mild and selective formation of primary amines, which are useful building blocks for biologically active compounds and natural products. In order to make the production of these kinds of compounds more efficient from both a practical and an environmental point of view, amine transaminases were incorporated into multi-step one-pot reactions. With this kind of methodology there is no need for isolation of intermediates, and thus unnecessary work-up steps can be omitted and formation of waste is prevented. Amine transaminases were successfully combined with other enzymes for multi-step synthesis of valuable products: With ketoreductases all four diastereomers of a 1,3-amino alcohol could be obtained, and the use of a lipase allowed for the synthesis of natural products in the form of capsaicinoids. Amine transaminases were also successfully combined with metal catalysts based on palladium or copper. This methodology allowed for the amination of alcohols and the synthesis of chiral amines such as the pharmaceutical compound Rivastigmine. These examples show that the use of amine transaminases in multi-step one-pot reactions is possible, and hopefully this concept can be further developed and applied to make industrial processes more sustainable and efficient in the future.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2017. 58 p.
Series
TRITA-BIO-Report, ISSN 1654-2312 ; 2017:3
Keyword
Biocatalysis, enzyme, amine transaminase, ω-transaminase, amination, primary amine, chiral amine, chemoenzymatic, green chemistry, synthesis, cascade
National Category
Biochemistry and Molecular Biology
Research subject
Biotechnology
Identifiers
urn:nbn:se:kth:diva-199646 (URN)978-91-7729-254-8 (ISBN)
Public defence
2017-02-17, Kollegiesalen, Brinellvägen 8, KTH, 10:00 (English)
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Supervisors
Note

QC 20170113

Available from: 2017-01-13 Created: 2017-01-12 Last updated: 2017-01-13Bibliographically approved

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Berglund, Per

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