Biocatalytic Approach to Chiral β-Nitroalcohols by Enantioselective Alcohol Dehydrogenase-Mediated Reduction of α-Nitroketones

Tentori, Francesca; Brenna, Elisabetta; Colombo, Danilo; Crotti, Michele; Gatti, Francesco G.; Ghezzi, Maria Chiara; Pedrocchi-Fantoni, Giuseppe

doi:10.3390/catal8080308

Cited by 16 publications

(7 citation statements)

References 50 publications

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“…Our group recently developed a ketoreductase‐catalyzed stereoselective reduction of α‐nitro ketones to chiral β‐nitro alcohols, which can be easily converted to β‐amino alcohols via the subsequent chemical reduction of the nitro group (Scheme 19). [32] Prior to our study, bioreduction of α‐nitro ketones was scarcely studied, with the only detailed study coming from the Brenna group, who reported the stereoselective reduction of α‐nitro ketones using commercial KREDs affording both enantiomers of β‐nitro alcohols with good‐to‐excellent ee values in most cases [33] . In contrast, the gene/protein sequences of the ketoreductases employed in our work are all publicly available.…”

Section: Creation Of One Stereocenter Through Kred‐catalyzed Reductionmentioning

confidence: 99%

Application of Ketoreductase in Asymmetric Synthesis of Pharmaceuticals and Bioactive Molecules: An Update (2018–2020)

Yang

Liu

et al. 2021

The Chemical Record

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With the rapid development of genomic DNA sequencing, recombinant DNA expression, and protein engineering, biocatalysis has been increasingly and widely adopted in the synthesis of pharmaceuticals, bioactive molecules, fine chemicals, and agrochemicals. In this review, we have summarized the most recent advances achieved (2018–2020) in the research area of ketoreductase (KRED)‐catalyzed asymmetric synthesis of chiral secondary alcohol intermediates to pharmaceuticals and bioactive molecules. In the first part, synthesis of chiral alcohols with one stereocenter through the bioreduction of four different ketone classes, namely acyclic aliphatic ketones, benzyl or phenylethyl ketones, cyclic aliphatic ketones, and aryl ketones, is discussed. In the second part, KRED‐catalyzed dynamic reductive kinetic resolution and reductive desymmetrization are presented for the synthesis of chiral alcohols with two contiguous stereocenters.

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Section: Creation Of One Stereocenter Through Kred‐catalyzed Reductionmentioning

confidence: 99%

Application of Ketoreductase in Asymmetric Synthesis of Pharmaceuticals and Bioactive Molecules: An Update (2018–2020)

Yang

Liu

et al. 2021

The Chemical Record

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“…Lipase, esterase, halohydrin dehalogenase, and HNL catalyzed retro-Henry reaction are used in the kinetic resolution of a racemic β-nitroalcohol or an epoxide. [12][13][14][15][16] Alcohol dehydrogenase catalyzed asymmetric reduction, [17][18][19][20] and HNL catalyzed nitroaldol reaction [21][22][23][24][25] are the other two routes. Both kinetic resolution and asymmetric reduction requires an additional step of substrate preparation, while the former could provide a maximum 50% theoretical yield.…”

Section: Introductionmentioning

confidence: 99%

One‐Pot Enzyme Cascade Catalyzed Asymmetrization of Primary Alcohols: Synthesis of Enantiocomplementary Chiral β‐Nitroalcohols

2021

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Biocatalytic asymmetrization of inexpensive and stable primary alcohols to prepare enantioenriched β-nitroalcohols is an important development in green chemistry for the production of chiral pharmaceutical intermediates. Herein, we report a one-pot, two-step cascade reaction sequence in which first benzylic alcohols were oxidized to produce corresponding benzaldehydes using horse liver alcohol dehydrogenase (HLADH). The in situ generated aldehydes were then reacted in a biphasic medium with nitromethane by Arabidopsis thaliana hydroxynitrile lyase (AtHNL) or Baliospermum montanum HNL (BmHNL) catalyzed Henry reaction to produce stereoselective β-nitroalcohols with (R) or (S) configuration, respectively. Using HLADH-AtHNL, (R)-β-nitroalcohols were obtained in up to 64% conversion, and HLADH-BmHNL, (S)-β-nitroalcohols in up to 70% conversion, while in both cases excellent stereoselectivity (up to > 99% ee) was achieved. The concept was proven by functionalization of sp 3 CÀ H bond of ten simple achiral benzylic alcohols to enantiocomplementary chiral β-nitroalcohols.

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“…Tentori et al . (2018) also reported two alcohol dehydrogenases (ADHs) for the reduction of aromatic and aliphatic nitroketone. The enantioselectivities of 62–99% e.e .…”

Section: Introductionmentioning

confidence: 99%

“…This enzyme coupled to an immobilized cofactor recycling partner was utilized for the quantitatively asymmetric reduction of rac-2-phenylpropanal to (R)-2-phenyl-1-propanol with an enantiomeric excess of 71%. Tentori et al (2018) also reported two alcohol dehydrogenases (ADHs) for the reduction of aromatic and aliphatic nitroketone. The enantioselectivities of 62-99% e.e.…”

Section: Introductionmentioning

confidence: 99%

Green and scalable synthesis of chiral aromatic alcohols through an efficient biocatalytic system

Han

Wang

Pei

et al. 2020

Microbial Biotechnology

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Summary Chiral aromatic alcohols have received much attention due to their widespread use in pharmaceutical industries. In the asymmetric synthesis processes, the excellent performance of alcohol dehydrogenase makes it a good choice for biocatalysts. In this study, a novel and robust medium‐chain alcohol dehydrogenase RhADH from Rhodococcus R6 was discovered and used to catalyse the asymmetric reduction of aromatic ketones to chiral aromatic alcohols. The reduction of 2‐hydroxyacetophenone (2‐HAP) to (R)‐(‐)‐1‐phenyl‐1,2‐ethanediol ((R)‐PED) was chosen as a template to evaluate its catalytic activity. A specific activity of 110 U mg−1 and a 99% purity of e.e. was achieved in the presence of NADH. An efficient bienzyme‐coupled catalytic system (RhADH and formate dehydrogenase, CpFDH) was established using a two‐phase strategy (dibutyl phthalate and buffer), which highly raised the tolerated substrate concentration (60 g l−1). Besides, a broad range of aromatic ketones were enantioselectively reduced to the corresponding chiral alcohols by this enzyme system with highly enantioselectivity. This system is of the potential to be applied at a commercial scale.

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Biocatalytic Approach to Chiral β-Nitroalcohols by Enantioselective Alcohol Dehydrogenase-Mediated Reduction of α-Nitroketones

Cited by 16 publications

References 50 publications

Application of Ketoreductase in Asymmetric Synthesis of Pharmaceuticals and Bioactive Molecules: An Update (2018–2020)

Application of Ketoreductase in Asymmetric Synthesis of Pharmaceuticals and Bioactive Molecules: An Update (2018–2020)

One‐Pot Enzyme Cascade Catalyzed Asymmetrization of Primary Alcohols: Synthesis of Enantiocomplementary Chiral β‐Nitroalcohols

Green and scalable synthesis of chiral aromatic alcohols through an efficient biocatalytic system

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