化学
对映体药物
还原胺化
产量(工程)
硼氢化钠
非对映体
酮
四氢萘酮
舍曲林
有机化学
对映选择合成
亚胺
酒
胺化
催化作用
生物
海马体
抗抑郁药
材料科学
冶金
神经科学
作者
Lisa Marx,Nicolás Ríos‐Lombardía,Philipp Süss,Matthias Höhne,Francisco Morís,Javier González‐Sabín,Per Berglund
标识
DOI:10.1002/ejoc.201901810
摘要
A chemoenzymatic approach has been developed for the preparation of sertraline, an established anti‐depressant drug. Ketoreductases (KREDs) were employed to yield a key chiral precursor. The bioreduction of the racemic tetralone exhibited excellent enantioselectivity (>99 % ee ) and diastereomeric ratio (99:1) at 29 % conversion (the maximum theoretical yield is 50 %) after 7 hours. The resulting ( S , S )‐alcohol was efficiently oxidized to an enantiopure ( S )‐ketone, an immediate precursor of sertraline, by using sodium hypochlorite as oxidant and 2‐azaadamantane N ‐oxyl (AZADO) as organocatalyst. Alternative routes aiming at the direct biocatalytic amination using imine reductases and transaminases were unsuccessful.
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