Sequential Two-Step Stereoselective Amination of Allylic Alcohols through the Combination of Laccases and Amine Transaminases |
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Authors: | Jesús Albarrán-Velo Dr. Iván Lavandera Dr. Vicente Gotor-Fernández |
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Affiliation: | Organic and Inorganic Chemistry Department, University of Oviedo, Avenida Julián Clavería 8, 33006 Oviedo, Spain |
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Abstract: | A sequential two-step chemoenzymatic methodology for the stereoselective synthesis of (3E)-4-(het)arylbut-3-en-2-amines in a highly selective manner and under mild reaction conditions is described. The approach consists of oxidation of the corresponding racemic alcohol precursors by the use of a catalytic system made up of the laccase from Trametes versicolor and the oxy-radical TEMPO, followed by the asymmetric reductive bio-transamination of the corresponding ketone intermediates. Optimisation of the oxidation reaction, exhaustive amine transaminase screening for the bio-transaminations and the compatibility of the two enzymatic reactions were studied in depth in search of a design of a compatible sequential cascade. This synthetic strategy was successful and the combinations of enzymes displayed a broad substrate scope, with 16 chiral amines being obtained in moderate to good isolated yields (29–75 %) and with excellent enantiomeric excess values (94 to >99 %). Interestingly, both amine enantiomers can be achieved, depending on the selectivity of the amine transaminase employed in the system. |
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Keywords: | allylic amines amine transaminases asymmetric synthesis biotransformations laccases |
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