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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
Author(s) -
Kohls Hannes,
Anderson Mattias,
Dickerhoff Jonathan,
Weisz Klaus,
Córdova Armando,
Berglund Per,
Brundiek Henrike,
Bornscheuer Uwe T.,
Höhne Matthias
Publication year - 2015
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201500214
Subject(s) - transamination , diastereomer , chemistry , ketone , amine gas treating , kinetic resolution , alcohol , enantiomer , stereochemistry , enantioselective synthesis , organic chemistry , catalysis , enzyme
The biocatalytic synthesis of chiral amines has become a valuable addition to the chemists’ toolbox. 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 (2 R ,4 R )‐ and (2 R ,4 S )‐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 (2 S ,4 R )‐ and (2 S ,4 S )‐diastereomers, respectively.