Highly efficient and enantioselective synthesis of β-heteroaryl amino alcohols <i>via</i> Ru-catalyzed asymmetric hydrogenation

Wu, Chao; Ma, Baode; Chen, Gen‐Qiang; Zhang, Xumu

doi:10.1039/d2cc03701g

Cited by 7 publications

(2 citation statements)

References 41 publications

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“…Recently, the enantioselective synthesis of β ‐heteroaryl amino alcohols has been reported through Ru‐catalyzed asymmetric hydrogenation 7 . However, many of these approaches utilize highly expensive and environmentally unsafe chiral reagents that limit their usage on a large scale.…”

Section: Introductionmentioning

confidence: 99%

Biocatalytic enantioselective synthesis of cenobamate, an antiepileptic drug

Haritha,

Deepthi,

Gundamalla

et al. 2024

Chirality

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A green and efficient process for the synthesis of cenobamate has been accomplished in 70% yield and >99% ee through the bio‐reduction of β‐ketotetrazole using Daucus carota whole plant cells. The corresponding β‐hydroxytetrazole was isolated in 60% yield and >98% ee. This is the first report on the biocatalytic reduction of β‐ketotetrazole using plant enzymes derived from D. carota root cells with excellent enantioselectivity.

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Section: Introductionmentioning

confidence: 99%

Biocatalytic enantioselective synthesis of cenobamate, an antiepileptic drug

Haritha,

Deepthi,

Gundamalla

et al. 2024

Chirality

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“…1–3 These compounds are also privileged scaffolds in the field of peptidomimetics and molecular recognition. 4 In fact, β-aminocarbonyl compounds are valuable intermediates in organic synthesis, especially in the production of β-amino alcohols, 5 β-amino acids, 6 and lactams, 7 which are crucial in various pharmaceutical and natural product synthesis. 8 Due to the wide range of applications of β-aminocarbonyls, there is an ongoing effort to develop new synthetic methods for preparing these compounds.…”

Section: Introductionmentioning

confidence: 99%

Sustainable continuous flow synthesis of β-aminocarbonyls via acid-catalyzed hydration of N-Boc-2-azetines

Andresini,

Colella,

Dibenedetto

et al. 2023

React. Chem. Eng.

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A Three‐Step Chemoenzymatic Cascade Synthesis of Miconazole Analogues Based on the Asymmetric Synthesis of β‐Heteroaryl Amino Alcohols via Ketoreductases

Fang,

Xu,

Ren

et al. 2023

Adv Synth Catal

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Chiral β‐heteroaryl amino alcohols play a crucial role as intermediates in the synthesis of numerous bioactive pharmaceuticals, including cenobamate, oteseconazole, and miconazole. Nevertheless, there is a lack of literature documenting the establishment of a versatile approach for the synthesis of β‐heteroaryl amino alcohols and the aforementioned drugs. In this study, we successfully asymmetrically synthesized 50 pairs of chiral β‐heteroaryl amino alcohols using two engineered ketoreductases (KREDs) with opposite stereopreference. Based on this achievement, we developed a three‐step chemoenzymatic cascade route for synthesizing of chiral miconazole analogues from commercially available 2‐bromoacetophenone derivatives. By optimizing the solvent for the synthesis of α‐imidazolyl ketones in the first step, followed by the reduction of α‐imidazolyl ketones using KREDs in the second step and etherification in the third step, we obtained 20 chiral miconazole analogues with promising yields (26–84%) and impressive stereoselectivities (up to >99% ee). Notably, this route eliminates the need for the isolation of ketone and alcohol intermediates, and avoids the use of metal catalysts in the synthesis of chiral miconazole analogues. Furthermore, we successfully scaled up the preparation of (S)‐miconazole, achieving a 30% isolated yield and >99% ee. This method presents a novel synthetic approach for production chiral ether drugs and chiral β‐heteroaryl amino alcohols, offering new possibilities in pharmaceutical synthesis.

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Highly efficient and enantioselective synthesis of β-heteroaryl amino alcohols via Ru-catalyzed asymmetric hydrogenation

Abstract: Chiral β-heteroaryl amino alcohols are key fragments of many bioactive compounds and antibiotics, and the development of efficient synthetic methods for these compounds is of great value. The highly enantioselective...

Cited by 7 publications

References 41 publications

Biocatalytic enantioselective synthesis of cenobamate, an antiepileptic drug

Biocatalytic enantioselective synthesis of cenobamate, an antiepileptic drug

Sustainable continuous flow synthesis of β-aminocarbonyls via acid-catalyzed hydration of N-Boc-2-azetines

A Three‐Step Chemoenzymatic Cascade Synthesis of Miconazole Analogues Based on the Asymmetric Synthesis of β‐Heteroaryl Amino Alcohols via Ketoreductases

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