Selective Access to All Four Diastereomers of a 1,3-Amino Alcohol by Combination of a Keto Reductase- and an Amine Transaminase-Catalysed Reaction
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
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.
amine transaminase, amino alcohols, enzyme catalysis, keto reductase
IdentifiersURN: urn:nbn:se:kth:diva-172237DOI: 10.1002/adsc.201500214ISI: 000355235700020ScopusID: 2-s2.0-84930202995OAI: oai:DiVA.org:kth-172237DiVA: diva2:848442
QC 201508252015-08-252015-08-142015-08-25Bibliographically approved