Bioreductive production of enantiopure (S)-duloxetine intermediates catalyzed with ketoreductase ChKRED15

Ren, Zhiqiang; Liu, Yan; Pei, Xiaokun; Wang, Haibo; Wu, Zhong‐Liu

doi:10.1016/j.molcatb.2015.01.008

Cited by 19 publications

(9 citation statements)

References 36 publications

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“…It depicts that the single stereocenter has an S -conformation, and through a retrosynthetic strategy, enantiopure ( S )- 4k′ is proved to be an excellent building block for the synthesis of ( S )-duloxetine. Only the S -enantiomer of duloxetine is pharmaceutically active for the treatment of anxiety, diabetes-related pain, chronic musculoskeletal pain, etc . Since it has been proposed that N , N -disubstitution can be used to modify amide- O -metal coordination, N , N -dimethyl-3-oxo-3-phenylpropanamide ( 3r ) was prepared and tested for a similar asymmetric reduction, and the corresponding β-hydroxyamide ( S )- 4r was isolated with 63% yield and 96% ee (Scheme ).…”

Section: Resultsmentioning

confidence: 99%

Chiral Vanadyl(V) Complexes Enable Efficient Asymmetric Reduction of β-Ketoamides: Application toward (S)-Duloxetine

et al. 2020

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High-valent chiral oxidovanadium(V) complexes derived from 3,5-substituted-N-salicylidene-L-tert-leucine were used as catalysts in asymmetric reduction of N-benzyl-βketoamides. Among six different solvents, three different alcohol additives, and two different boranes examined, the use of pinacolborane in tetrahydrofuran (THF) with a t-BuOH additive led to the best results at −20 °C. The corresponding βhydroxyamides can be furnished with yields up to 92% and an enantiomeric excess (ee) up to 99%. We have successfully extended this catalytic protocol for the synthesis of an (S)-duloxetine precursor.

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Section: Resultsmentioning

confidence: 99%

Chiral Vanadyl(V) Complexes Enable Efficient Asymmetric Reduction of β-Ketoamides: Application toward (S)-Duloxetine

et al. 2020

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“…CA49 [21]. This inventory of recombinant KREDs has been applied in the bioreduction of a spectrum of chiral alcohols with excellent stereoselectivity [22][23][24][25]. We first evaluated the ability of those KREDs to catalyze the bioreduction of N-Boc-piperidin-3-one to afford (S)-NBHP (Fig.…”

Section: Screening Of the Target Enzymementioning

confidence: 99%

Efficient bioreductive production of (S)-N-Boc-3-hydroxypiperidine using ketoreductase ChKRED03

Wang

2016

Process Biochemistry

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“…Chirality is a key property of organic fine chemicals in the field of agrochemical [1], pharmaceutical [2,3] and food industries [4,5]. Consequently, there is an ever increasing demand for optically pure final products especially by active pharmaceutical ingredients [6][7][8] where particularly hydroxyl [9,10] and amine [11] functions or their derivatives [12] are bound to the center of asymmetry. Asymmetric techniques, such as aldol reaction [13], epoxide opening [14], ketone reduction [15] or kinetic resolution of racemic mixtures [16] are well known methods to produce pure enantiomers of alcohols.…”

Section: Introductionmentioning

confidence: 99%

Lipase B from Candida antarctica Immobilized on Epoxy-functionalized Hollow Silica Microspheres: Efficient Biocatalysts for Enantiomer Selective Acylation of Alcohols and Amines

Olah

Suba

Boros³

et al. 2018

Period. Polytech. Chem. Eng.

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Hollow silica microspheres with promising physical properties (MAT540TM) as support for enzyme immobilization and biocatalyst were investigated in this study. The amine-functionalized MAT540TM was activated by six bisepoxides inclosing different spacers and used as epoxy-functionalized carrier for immobilization of lipase B from Candida antarctica (CaLB). The novel, covalently fixed CaLB biocatalysts were compared in kinetic resolution (KR) of racemic 1-phenyethanol rac-1 and five racemic amines rac-3a-e using shaken flasks and continuous-flow packed-bed microreactors. Mechanic stability, re-usability and the effect of temperature (0–90 °C) on productivity and enantiomer selectivity of the covalently immobilized CaLB were investigated. The best performing CaLB biocatalyst showed good mechanic stability after 24 h operation time in continuous-flow mode at 60 °C and provided in KRs of racemic 1-phenyethanol rac-1 with vinyl acetate and of five racemic amines with isopropyl 2-ethoxyacetate as acylating agent the non-reacted (S)-alcohol [(S)-1] or (S)-amines [(S)-3a-e] and the forming (R)-ester [(R)-2] or (R)-amide [(R)-4a-e] in good yields with high enantiomeric excess (ee > 99 %, for all).

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Bioreductive production of enantiopure (S)-duloxetine intermediates catalyzed with ketoreductase ChKRED15

Cited by 19 publications

References 36 publications

Chiral Vanadyl(V) Complexes Enable Efficient Asymmetric Reduction of β-Ketoamides: Application toward (S)-Duloxetine

Chiral Vanadyl(V) Complexes Enable Efficient Asymmetric Reduction of β-Ketoamides: Application toward (S)-Duloxetine

Efficient bioreductive production of (S)-N-Boc-3-hydroxypiperidine using ketoreductase ChKRED03

Lipase B from Candida antarctica Immobilized on Epoxy-functionalized Hollow Silica Microspheres: Efficient Biocatalysts for Enantiomer Selective Acylation of Alcohols and Amines

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