학술논문
Chemoenzymatic Synthesis of Sertraline
Document Type
Author
Source
European Journal of Organic Chemistry. 2020(4):510-513
Subject
Language
English
ISSN
1434-193X
Abstract
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 (>99â% ee) and diastereomeric ratio (99:1) at 29â% conversion (the maximum theoretical yield is 50â%) 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.