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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

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논문

Selective Access to All Four Diastereomers of a 1,3-Amino Alcohol by Combination of a Keto Reductase- and an Amine Transaminase-Catalysed Reaction

학술지

Advanced synthesis & catalysis

저자명

Kohls, Hannes; Anderson, Mattias; Dickerhoff, Jonathan; Weisz, Klaus; Có rdova, Armando; Berglund, Per; Brundiek, Henrike; Bornscheuer, Uwe T.; Hö hne, Matthias

초록

<P><B>Abstract</B></P><P>The biocatalytic synthesis of chiral amines has become a valuable addition to the chemists&rsquo; toolbox. However, the efficient asymmetric synthesis of functionalised amines bearing more than one stereocentre, such as 1,3&#8208;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&#8208;amino&#8208;1&#8208;phenylpentane&#8208;2&#8208;ol as a representative molecule bearing the 1,3&#8208;amino alcohol functionality. Starting from a racemic hydroxy ketone, a kinetic resolution using an (<I>S</I>)&#8208;selective KRED provided optically active hydroxy ketone (86% <I>ee</I>) and the corresponding diketone. Further transamination of the hydroxy ketone was performed by either an (<I>R</I>)&#8208; or an (<I>S</I>)&#8208;selective ATA, yielding the (2<I>R</I>,4<I>R</I>)&#8208; and (2<I>R</I>,4<I>S</I>)&#8208;1,3&#8208;amino alcohol diastereomers. The remaining two diastereomers were accessible in two subsequent asymmetric steps: the diketone was reduced regio&#8208; and enantioselectively by the same KRED, which yielded the (<I>S</I>)&#8208;configured hydroxy ketone. Eventually, the subsequent transamination of the crude product with (<I>R</I>)&#8208; and (<I>S</I>)&#8208;selective ATAs yielded the remaining (2<I>S</I>,4<I>R</I>)&#8208; and (2<I>S</I>,4<I>S</I>)&#8208;diastereomers, respectively.</P>

발행연도

2015

ISSN

1615-4150

ISSN

1615-4169

357

8

페이지

pp.1808-1814

주제어

amine transaminase; amino alcohols; enzyme catalysis; keto reductase

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논문; 2015-05-18

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