Efficient and Scalable Asymmetric Total Synthesis of (−)-Emetine with Pharmaceutical Grade Quality; First Multigram Scale Synthesis

Yamada, Masatoshi; Azuma, Kazuki; Takizawa, Iori; Ejima, Yuki; Yamano, Mitsuhisa; Satoh, Kimio; Doi, Takayuki; Ueda, Hirofumi; Tokuyama, Hidetoshi

doi:10.1021/acs.oprd.2c00355

Cited by 6 publications

(3 citation statements)

References 22 publications

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“…Ligand screening indicated ( R )-DADMP-BINAP ( L37 ) to be the most suitable chiral ligand for the asymmetric allylation of 6,7-dimethoxy-3,4-dihydroisoquinoline ( 212 ) at a hundred-gram scale (Scheme ). In the presence of 0.5 mol % CuCl and 0.6 mol % of ( R )-DADMP-BINAP, the reaction provided crude isoquinoline 213 in high conversion and 84.4% ee. Subsequent crystallization further increased the optical purity of this chiral intermediate to 98.9% ee.…”

Section: Asymmetric Transition Metal Catalysismentioning

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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Section: Asymmetric Transition Metal Catalysismentioning

confidence: 99%

Enantioselective Transformations in the Synthesis of Therapeutic Agents

Yang

Stolarzewicz

et al. 2023

Chem. Rev.

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“…Preliminary experiments were performed either in a continuous-flow system or as batch reactions, while the preparative-scale resolution was carried out in two steps with VA, Et 3 N, and Na 2 SO 4 in toluene at 3 • C, as a batch reaction (Scheme 3). The furnished amino alcohol (S)-7 and amino ester (R)-8 (ee ≥ 94%) were separated by column chromatography (silica, elution with n-hexane:EtOAc (2:1) (yields ≥ 32%) and they were then transformed (treatment with 18% HCl, followed by 5% NaOH) into the desired homocalycotomine (S)-9 (the intermediate of emetine [51]) and (R)-9 (ee ≥ 94%, yields ≥ 71%).…”

Section: Kr Through O-acylationmentioning

confidence: 99%

Lipase-Catalyzed Strategies for the Preparation of Enantiomeric THIQ and THβC Derivatives: Green Aspects

Orsy,

Forró

2023

Molecules

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This report reviews the most important lipase-catalyzed strategies for the preparation of pharmaceutically and chemically important tetrahydroisoquinoline and tetrahydro-β-carboline enantiomers through O-acylation of the primary hydroxy group, N-acylation of the secondary amino group, and COOEt hydrolysis of the corresponding racemic compounds with simple molecular structure, which have been reported during the last decade. A brief introduction describes the importance and synthesis of tetrahydroisoquinoline and tetrahydro-β-carboline derivatives, and it formulates the objectives of this compilation. The strategies are presented in chronological order, classified according to function of the reaction type, as kinetic and dynamic kinetic resolutions, in the main text. These reactions result in the desired products with excellent ee values. The pharmacological importance of the products together with their synthesis is given in the main text. The enzymatic hydrolysis of the hydrochloride salts as racemates of the starting amino carboxylic esters furnished the desired enantiomeric amino carboxylic acids quantitatively. The enzymatic reactions, performed in tBuOMe or H2O as usable solvents, and the transformations carried out in a continuous-flow system, indicate clear advantages, including atom economy, reproducibility, safer solvents, short reaction time, rapid heating and compression vs. shaker reactions. These features are highlighted in the main text.

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“…Enantioenriched homoallylic amines are important building blocks that are widely used in the synthesis of N -containing molecules due to the versatile transformations of the olefinic moieties . The transition-metal-catalyzed asymmetric allylation of imines is one of the most straightforward methods to access chiral homoallylic amines, and many elegant methodologies have been established in this area .…”

Section: Introductionmentioning

confidence: 99%

Copper-Catalyzed Asymmetric Allylation of N-Aryl Aldimines

Deng,

Yan,

Zhang

et al. 2023

J. Org. Chem.

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The copper-catalyzed enantioselective allylation reaction of N-aryl aldimines has been developed using a combination of Cu(OAc) 2 and SPINOL-based phosphonamidite. This protocol significantly broadens the substrate scope, such that imines bearing various ortho-substituents on the N-aryl were converted smoothly into homoallylic amines in up to 99% yield and 98% ee. Taking advantage of the diversity of the N-aryl motif, three kinds of N-heterocyclic compounds were constructed, respectively, from the corresponding homoallylic amines in merely one step.

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Efficient and Scalable Asymmetric Total Synthesis of (−)-Emetine with Pharmaceutical Grade Quality; First Multigram Scale Synthesis

Cited by 6 publications

References 22 publications

Enantioselective Transformations in the Synthesis of Therapeutic Agents

Enantioselective Transformations in the Synthesis of Therapeutic Agents

Lipase-Catalyzed Strategies for the Preparation of Enantiomeric THIQ and THβC Derivatives: Green Aspects

Copper-Catalyzed Asymmetric Allylation of N-Aryl Aldimines

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