Asymmetric synthesis of syn-aryl-(2S,3R)-2-chloro-3-hydroxy esters via an engineered ketoreductase-catalyzed dynamic reductive kinetic resolution

Yue, Xiaoping; Li, Yitong; Sang, Di; Tao, Yuan; Huang, Zedu; Chen, Fen‐Er

doi:10.1016/j.cclet.2023.108178

Cited by 7 publications

(6 citation statements)

References 25 publications

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Section: Methodsmentioning

confidence: 99%

“…Compounds 3 and rac-2 were synthesized following literature procedures. [13,22] Unless otherwise specified, all other reagents were purchased from commercial sources and used without further purification.…”

Section: Strains Media and Chemicalsmentioning

confidence: 99%

“…The reaction conditions and workup conditions for this enzyme screening were the same as those reported previously by us. [13,22]…”

Section: Screening Ketoreductases For the Asymmetric Reduction Ofmentioning

confidence: 99%

“…The specific activity of the purified SSCR and its mutant V135A, Q245G, and V135A/Q245G toward the reduction of 3 was determined by following the similar protocols as we demonstrated previously. [13,22] The enzyme kinetic parameters were determined by measuring the initial velocities of the enzymatic reaction and curve-fitting to the Michaelis-Menten equation. The activity assay was conducted in a mixture with a varying concentration of 3 (0.03125-4 mM).…”

Section: Standard Enzyme Activity Assay and Kinetic Parametersmentioning

confidence: 99%

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Sustainable asymmetric synthesis of diltiazem precursor enabled by recombinant Escherichia coli whole cells co‐expressing an engineered ketoreductase and glucose dehydrogenase

Yue,

Li,

Yang

et al. 2023

Biotechnology Journal

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As a key synthetic intermediate of the cardiovascular drug diltiazem, methyl (2R,3S)‐3‐(4‐methoxyphenyl) glycidate ((2R,3S)‐MPGM) (1) is accessible via the ring closure of chlorohydrin (3S)‐methyl 2‐chloro‐3‐hydroxy‐3‐(4‐methoxyphenyl)propanoate ((3S)‐2). We report the efficient reduction of methyl 2‐chloro‐3‐(4‐methoxyphenyl)‐3‐oxo‐propanoate (3) to (3S)‐2 using an engineered enzyme SSCRM2 possessing 4.5‐fold improved specific activity, which was obtained through the structure‐guided site‐saturation mutagenesis of the ketoreductase SSCR by reliving steric hindrance and undesired interactions. With the combined use of the co‐expression fine‐tuning strategy, a recombinant E. coli (pET28a‐RBS‐SSCRM2/pACYCDuet‐GDH), co‐expressing SSCRM2 and glucose dehydrogenase, was constructed and optimized for protein expression. After optimizing the reaction conditions, whole‐cell‐catalyzed complete reduction of industrially relevant 300 g L−1 of 3 was realized, affording (3S)‐2 with 99% ee and a space‐time yield of 519.1 g∙L−1∙d−1, representing the highest record for the biocatalytic synthesis of (3S)‐2 reported to date. The E‐factor of this biocatalytic synthesis was 24.5 (including water). Chiral alcohol (3S)‐2 generated in this atom‐economic synthesis was transformed to (2R,3S)‐MPGM in 95% yield with 99% ee.

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Section: Methodsmentioning

confidence: 99%

Section: Strains Media and Chemicalsmentioning

confidence: 99%

“…The reaction conditions and workup conditions for this enzyme screening were the same as those reported previously by us. [13,22]…”

Section: Screening Ketoreductases For the Asymmetric Reduction Ofmentioning

confidence: 99%

Section: Standard Enzyme Activity Assay and Kinetic Parametersmentioning

confidence: 99%

See 2 more Smart Citations

Sustainable asymmetric synthesis of diltiazem precursor enabled by recombinant Escherichia coli whole cells co‐expressing an engineered ketoreductase and glucose dehydrogenase

Yue,

Li,

Yang

et al. 2023

Biotechnology Journal

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“…17 Our group has long-standing interest in the development and application of KRED-catalyzed stereoselective reduction to the synthesis of chiral pharmaceuticals and bioactive molecules. 15,[18][19][20][21] Within this context, we previously discovered a new ketoreductase named KmCR2 through genome mining, which was revealed to be active in the stereoselective reduction of a broad range of sterically hindered diaryl-and aryl(heteroaryl)methanones. 22 The corresponding products, chiral diaryl-and aryl(heteroaryl)methanols, along with their amine derivatives, are privileged structural motifs found in various pharmaceutical molecules.…”

Section: Introductionmentioning

confidence: 99%

Stereoselective reduction of diarylmethanones via a ketoreductase@metal–organic framework

Wu,

Ye,

Guo

et al. 2024

Org. Biomol. Chem.

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Enzymatic and Chemo–catalytic Redox Deracemization: Recent Progress

Wan,

Wang,

Sun

et al. 2024

ChemCatChem

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The precise synthesis of chiral small molecules is a core research area in chemical science. Deracemization, an appealing technology that converts racemate to its single enantiomer with the same constitution in theoretical 100% yield, appears as a straightforward and efﬁcient strategy in asymmetric synthesis. A cascading redox sequence was the most employed approach to drive deracemization through destroy and recreate the stereocenter in a given molecule. This review mainly focuses on the progress of redox deracemization driven by respective biocatalysis and chemo‐catalysis. In particular, each section will be subdivided according to the action modes, the respective substrate classes and perspectives on future development.

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Asymmetric synthesis of syn-aryl-(2S,3R)-2-chloro-3-hydroxy esters via an engineered ketoreductase-catalyzed dynamic reductive kinetic resolution

Cited by 7 publications

References 25 publications

Sustainable asymmetric synthesis of diltiazem precursor enabled by recombinant Escherichia coli whole cells co‐expressing an engineered ketoreductase and glucose dehydrogenase

Sustainable asymmetric synthesis of diltiazem precursor enabled by recombinant Escherichia coli whole cells co‐expressing an engineered ketoreductase and glucose dehydrogenase

Stereoselective reduction of diarylmethanones via a ketoreductase@metal–organic framework

Enzymatic and Chemo–catalytic Redox Deracemization: Recent Progress

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