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Chemoenzymatic Synthesis of Sertraline
Author(s) -
Marx Lisa,
RíosLombardía Nicolás,
Süss Philipp,
Höhne Matthias,
Morís Francisco,
GonzálezSabín Javier,
Berglund Per
Publication year - 2020
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201901810
Subject(s) - chemistry , enantiopure drug , reductive amination , yield (engineering) , sodium borohydride , diastereomer , ketone , tetralone , sertraline , organic chemistry , enantioselective synthesis , imine , alcohol , amination , catalysis , materials science , neuroscience , biology , hippocampus , metallurgy , antidepressant
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.