Development of a Chemoenzymatic Route to (<i>R</i>)-Allyl-(3-amino-2-(2-methylbenzyl)propyl)carbamate

Lindhagen, Marika; Klingstedt, Tomas; Andersen, Sebastian; Mulholland, Keith R.; Tinkler, Laura; McPheators, Gary; Chubb, Richard W. J.

doi:10.1021/acs.oprd.5b00326

Cited by 10 publications

(3 citation statements)

References 14 publications

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“…Industrial researchers developed the kilogram synthesis of (R)-allyl-3-amino-2-(2-methylbenzyl)propylcarbamate to support preclinical and clinical studies in an internal drug discovery program (Scheme 19). With that purpose, the alkoxycarbonylation of 2-(2-methylbenzyl)propane-1,3-diamine with allyl carbonate was studied, finding Amano PS as the best commercially available enzyme (Lindhagen 2016). Best conditions at preparative scale were found at 30 ºC and using 2-methyltetrahydrofuran (2-Me-THF) as environmentally friendly solvent, yielding the (R)-carbamate in 82% ee, although its optical purity was improved to 88% ee after crystallisation as tartrate salt.…”

Section: Scheme 15 Ple-catalysed Hydrolytic Desymmetrisation Of Cis-mentioning

confidence: 99%

Stereoselective biocatalysis: A mature technology for the asymmetric synthesis of pharmaceutical building blocks

Albarrán-Velo

González‐Martínez

Gotor‐Fernández

2017

Biocatalysis and Biotransformation

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Biocatalysis is gaining increasing attention in the academic and industrial sector due to the possibility of developing highly stereoselective transformations in a sustainable manner. The creation of stereogenic centers in organic synthesis is not trivial and multiple approaches have been disclosed based on 2 organometallic and organocatalytic methods with the use of day by day more complex catalysts to induce asymmetry in selected transformations. The intrinsic chirality of enzymes makes them powerful tools for the development of stereoselective transformations, catalysing a wide range of chemical reactions due to the high abundance and diversity of enzymes in nature. In addition, the enormous advances in rational design and molecular biology methods have opened up the possibility to create more robust and versatile biocatalysts, which have improved the initial activities displayed by wild-type enzymes. Therefore, their applicability has been widely increased in terms of reaction conditions, substrate specificity, activity and selectivity among others. All these properties have attracted the industrial sector, which has taken advantage of the enzyme selectivities in multiple scenarios. Herein, the focus has been put in recent developments of stereoselective transformations for the synthesis of valuable building blocks towards the production of pharmaceuticals and biologically active natural products.

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Section: Scheme 15 Ple-catalysed Hydrolytic Desymmetrisation Of Cis-mentioning

confidence: 99%

Stereoselective biocatalysis: A mature technology for the asymmetric synthesis of pharmaceutical building blocks

Albarrán-Velo

González‐Martínez

Gotor‐Fernández

2017

Biocatalysis and Biotransformation

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“…During the course of our recent study seeking efficient methods for catalytic hydration of unsaturated organic compounds, we found that the use of palladium chloride and carboxamide − allows the hydration of acetone cyanohydrin ( 1a ). The conversion of nitriles to amides by palladium chloride and acetamide was initially described by Maffioli et al as a reverse reaction of the dehydration of amides to nitriles .…”

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confidence: 99%

Catalytic Transfer Hydration of Cyanohydrins to α-Hydroxyamides

2018

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We report the palladium(II)-catalyzed transfer hydration of cyanohydrins to α-hydroxyamides by using carboxamides as water donors. This method enables selective hydration of various aldehyde- and ketone-derived cyanohydrins to afford α-mono- and α,α-disubstituted-α-hydroxyamides, respectively, under mild conditions (50 °C, 10 min). The direct conversion of fenofibrate, a drug bearing a benzophenone moiety, into a functionalized α,α-diaryl-α-hydroxyamide was achieved by means of a hydrocyanation–transfer hydration sequence. Preliminary kinetic studies and the synthesis of a site-specifically 18O-labeled α-hydroxyamide demonstrated the carbonyl oxygen transfer from the carboxamide reagent into the α-hydroxyamide product.

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“…Lindhagen and co-workers optimized the desymmetrization reaction of 2-(2-methylbenzyl) propane-1,3-diamine 291 using Amano PS-IM lipase in the presence of diallyl carbonate, delivering the desired product 292 as the D-tartrate salt in 62% yield and 88% ee (Scheme 64). 200 This methodology also provides a convenient and efficient synthesis of chiral 1,3-diamines, which are bidentate ligands in various asymmetric transformations.…”

Section: Lipases-catalyzed Hydrolysis and Relatedmentioning

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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Development of a Chemoenzymatic Route to (R)-Allyl-(3-amino-2-(2-methylbenzyl)propyl)carbamate

Cited by 10 publications

References 14 publications

Stereoselective biocatalysis: A mature technology for the asymmetric synthesis of pharmaceutical building blocks

Stereoselective biocatalysis: A mature technology for the asymmetric synthesis of pharmaceutical building blocks

Catalytic Transfer Hydration of Cyanohydrins to α-Hydroxyamides

Enantioselective Transformations in the Synthesis of Therapeutic Agents

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