Marx, Lisa; Rí os‐ Lombardí a, Nicolá s; Sü ss, Philipp; Hö hne, Matthias; Morí s, Francisco; Gonzá lez‐ Sabí n, Javier; Berglund, Per
초록
<P>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 % <I>ee</I>) and diastereomeric ratio (99:1) at 29 % conversion (the maximum theoretical yield is 50 %) after 7 hours. The resulting (<I>S</I>,<I>S</I>)‐alcohol was efficiently oxidized to an enantiopure (<I>S</I>)‐ketone, an immediate precursor of sertraline, by using sodium hypochlorite as oxidant and 2‐azaadamantane <I>N</I>‐oxyl (AZADO) as organocatalyst. Alternative routes aiming at the direct biocatalytic amination using imine reductases and transaminases were unsuccessful.</P>