Development of a Novel Chemoenzymatic Process for (<i>S</i>)-1-(Pyridin-4-yl)-1,3-propanediol

Wang, Hongyi; Tang, Jiawei; Peng, Peng; Yan, Honggao; Zhang, Fuli; Chen, Shaoxin

doi:10.1021/acs.oprd.0c00403

Cited by 6 publications

(4 citation statements)

References 17 publications

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“…The pH and temperature greatly influence the enzymatic activity. − In the present study, a pH tolerance investigation of acylase was performed in the pH range of 5.5–8.5 (Figure a). The results demonstrate that when the pH was below 7, the catalytic activity of the enzymes decreased.…”

Section: Resultsmentioning

confidence: 99%

Development of a Novel Chemoenzymatic Process for 3-(Methylsulfonyl)-l-phenylalanine Phenylmethyl Ester─A Key Intermediate of Lifitegrast (Xiidra)

Wu,

Guo,

Tang

et al. 2024

Org. Process Res. Dev.

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In the present study, a practical chemoenzymatic method was developed for the synthesis of chiral phenylalanine derivative 1, which is the key intermediate of Lifitegrast. In this established process, a simple and effective Zn/HCl reduction system was employed to obtain N-acetyl-3-bromo-phenylalanine 6, which served as the substrate for the subsequent enzymatic resolution process. Then, the key chiral intermediate, 3-bromo-L-phenylalanine 7, could be obtained using acylase (ACY) AmACY. Upon process optimization, the chemical reaction was executed at a 300 g scale, with a notable substrate concentration reaching up to 100 g/L. The process achieved a yield of 40%, compared to a maximum theoretical yield of 50%, and exhibited an enantiomeric excess (ee) value reaching up to 99.9%. A simple and effective Zn/HCl reduction system was employed to obtain N-acetyl-3-bromophenylalanine 6, which served as the substrate for the subsequent enzymatic resolution process. This synthetic pathway was effectively executed, yielding 1•HCl with a purity of 99.7% and an ee value of 99.9%, culminating in an overall yield of 23.4%. Additionally, the undesired (D)-6 enantiomer was recycled to form (rac)-6, employing an acetanhydride/acetic acid (Ac 2 O/AcOH) system. This recycling process achieved a yield of 47.5%, relative to a maximum theoretical yield of 50%, and a purity level of 99.8%.

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Section: Resultsmentioning

confidence: 99%

Development of a Novel Chemoenzymatic Process for 3-(Methylsulfonyl)-l-phenylalanine Phenylmethyl Ester─A Key Intermediate of Lifitegrast (Xiidra)

Wu,

Guo,

Tang

et al. 2024

Org. Process Res. Dev.

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“…Chen and co-workers used ketoreductase EA from Exiguobacterium sp. F42 as the biocatalyst for the reduction of keto-ester 343 (Scheme b) . After the process was optimized, the reaction was performed on a 100-g scale with a substrate concentration of up to 150 g/L, providing chiral alcohol 344 in 93% yield and 99.9% ee.…”

Section: Biocatalysismentioning

confidence: 99%

Enantioselective Transformations in the Synthesis of Therapeutic Agents

Yang

Stolarzewicz

et al. 2023

Chem. Rev.

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The proportion of approved chiral drugs and drug candidates under medical studies has surged dramatically over the past two decades. As a consequence, the efficient synthesis of enantiopure pharmaceuticals or their synthetic intermediates poses a profound challenge to medicinal and process chemists. The significant advancement in asymmetric catalysis has provided an effective and reliable solution to this challenge. The successful application of transition metal catalysis, organocatalysis, and biocatalysis to the medicinal and pharmaceutical industries has promoted drug discovery by efficient and precise preparation of enantio-enriched therapeutic agents, and facilitated the industrial production of active pharmaceutical ingredient in an economic and environmentally friendly fashion. The present review summarizes the most recent applications (2008–2022) of asymmetric catalysis in the pharmaceutical industry ranging from process scales to pilot and industrial levels. It also showcases the latest achievements and trends in the asymmetric synthesis of therapeutic agents with state of the art technologies of asymmetric catalysis.

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“…Two or more different enzymes can be immobilised in a single CLEA to give the so-called combi-CLEAs. This approach has been employed for the obtaining of bi-enzymatic immobilisates, including magnetic combi-CLEAs (Chen et al, 2018) bearing the main ADH and the cofactor regenerating enzyme (Ning et al, 2014;Zhang J. et al, 2020;Xu et al, 2020). As an example, Su et al (2018) described the preparation of combi-CLEAs comprised of ketoreductase and GDH enzymes embedded with magnetic Fe 3 O 4 nanoparticles and their use in the obtaining of 1.98 g of enantiopure ethyl (S)-4-chloro-3-hydroxybutyrate from its corresponding ketoester in 15 h with a TTN of NADH of 11.880.…”

Section: Adh Immobilisationmentioning

confidence: 99%

“…Some new ADHs showing some potential for the selective monoreduction have been identified recently (Shanati et al, 2019). Similarly, β-hydroxy esters are accessible via various ADHs (Hummel et al, 2003;Muller, 2005;Zadlo et al, 2016;Wang et al, 2020) as well as ß-hydroxy ketones (Ludeke et al, 2009). The bioreduction of 1,4-diketones has been investigated for a long time already (Haberland et al, 2002a;Haberland et al, 2002b;Katzberg et al, 2009;Muller et al, 2010;Mourelle-Insua et al, 2018).…”

Section: Adh-catalysed Reduction Reactionsmentioning

confidence: 99%

Alcohol Dehydrogenases as Catalysts in Organic Synthesis

2022

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Alcohol dehydrogenases (ADHs) have become important catalysts for stereoselective oxidation and reduction reactions of alcohols, aldehydes and ketones. The aim of this contribution is to provide the reader with a timely update on the state-of-the-art of ADH-catalysis. Mechanistic basics are presented together with practical information about the use of ADHs. Current concepts of ADH engineering and ADH reactions are critically discussed. Finally, this contribution highlights some prominent examples and future-pointing concepts.

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Development of a Novel Chemoenzymatic Process for (S)-1-(Pyridin-4-yl)-1,3-propanediol

Cited by 6 publications

References 17 publications

Development of a Novel Chemoenzymatic Process for 3-(Methylsulfonyl)-l-phenylalanine Phenylmethyl Ester─A Key Intermediate of Lifitegrast (Xiidra)

Development of a Novel Chemoenzymatic Process for 3-(Methylsulfonyl)-l-phenylalanine Phenylmethyl Ester─A Key Intermediate of Lifitegrast (Xiidra)

Enantioselective Transformations in the Synthesis of Therapeutic Agents

Alcohol Dehydrogenases as Catalysts in Organic Synthesis

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