Immobilized whole cells of Rhodotorula rubra MIM147 were used in a packed bed flow reactor for the enantioselective reduction of β-ketonitriles and for the efficient production of a key building block for the synthesis of the antidepressant drug duloxetine. A choline chloride-glucose natural deep eutectic solvent (NADES) was employed with a dual function, as a co-solvent and as a source of glucose, fundamental for cofactor regeneration. To develop a fully automated protocol, an in-line purification procedure was also developed. Firstly, an in-line liquid-liquid extraction of the desired β-hydroxynitriles was performed with a flow stream of ethyl acetate, then the unreacted ketone was trapped by a polymer-supported benzylamine. The optimized protocol allowed the obtainment of (S)-β-hydroxynitriles in 80 minutes of residence time with >95% conversion and excellent e.e. (96-99%). This journal is

Continuous-flow stereoselective reduction of prochiral ketones in a whole cell bioreactor with natural deep eutectic solvents / F. Annunziata, A. Guaglio, P. Conti, L. Tamborini, R. Gandolfi. - In: GREEN CHEMISTRY. - ISSN 1463-9262. - 24:2(2022 Jan 24), pp. 950-956. [10.1039/d1gc03786b]

Continuous-flow stereoselective reduction of prochiral ketones in a whole cell bioreactor with natural deep eutectic solvents

F. Annunziata
Primo
;
P. Conti;L. Tamborini
Penultimo
;
R. Gandolfi
Ultimo
2022

Abstract

Immobilized whole cells of Rhodotorula rubra MIM147 were used in a packed bed flow reactor for the enantioselective reduction of β-ketonitriles and for the efficient production of a key building block for the synthesis of the antidepressant drug duloxetine. A choline chloride-glucose natural deep eutectic solvent (NADES) was employed with a dual function, as a co-solvent and as a source of glucose, fundamental for cofactor regeneration. To develop a fully automated protocol, an in-line purification procedure was also developed. Firstly, an in-line liquid-liquid extraction of the desired β-hydroxynitriles was performed with a flow stream of ethyl acetate, then the unreacted ketone was trapped by a polymer-supported benzylamine. The optimized protocol allowed the obtainment of (S)-β-hydroxynitriles in 80 minutes of residence time with >95% conversion and excellent e.e. (96-99%). This journal is
Settore CHIM/08 - Chimica Farmaceutica
Settore CHIM/11 - Chimica e Biotecnologia delle Fermentazioni
24-gen-2022
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/905160
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