Continuous-flow synthesis of dimethyl fumarate: a powerful small molecule for the treatment of psoriasis and multiple sclerosis

Lima, Marcelo T.; Finelli, Fernanda G.; Oliveira, Alline V. B. de; Kartnaller, Vinicius; Cajaiba, João; Leão, Raquel A. C.; Souza, Rodrigo O. M. A. de

doi:10.1039/c9ra09119j

Cited by 16 publications

(8 citation statements)

References 10 publications

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“…De Souza and colleagues reported a continuous flow process for the preparation of dimethyl fumarate, an API for treating psoriasis and multiple sclerosis. 876 The process relied on the Fischer esterification of fumaric acid with methanol, catalyzed by sulfuric acid. 98% yield was obtained in flow under optimized conditions, corresponding to 10.2 kg day −1 productivity.…”

Section: Upgrading Of Carboxylic Acidsmentioning

confidence: 99%

Continuous Flow Upgrading of Selected C₂–C₆Platform Chemicals Derived from Biomass

et al. 2020

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The ever increasing industrial production of commodity and specialty chemicals inexorably depletes the finite primary fossil resources available on Earth. The forecast of population growth over the next 3 decades is a very strong incentive for the identification of alternative primary resources other than petro-based ones. In contrast with fossil resources, renewable biomass is a virtually inexhaustible reservoir of chemical building blocks. Shifting the current industrial paradigm from almost exclusively petro-based resources to alternative bio-based raw materials requires more than vibrant political messages; it requires a profound revision of the concepts and technologies on which industrial chemical processes rely. Only a small fraction of molecules extracted from biomass bears significant chemical and commercial potentials to be considered as ubiquitous chemical platforms upon which a new, bio-based industry can thrive. Owing to its inherent assets in terms of unique process experience, scalability, and reduced environmental footprint, flow chemistry arguably has a major role to play in this context. This review covers a selection of C2 to C6 bio-based chemical platforms with existing commercial markets including polyols (ethylene glycol, 1,2-propanediol, 1,3-propanediol, glycerol, 1,4-butanediol, xylitol, and sorbitol), furanoids (furfural and 5-hydroxymethylfurfural) and carboxylic acids (lactic acid, succinic acid, fumaric acid, malic acid, itaconic acid, and levulinic acid). The aim of this review is to illustrate the various aspects of upgrading bio-based platform molecules toward commodity or specialty chemicals using new process concepts that fall under the umbrella of continuous flow technology and that could change the future perspectives of biorefineries.

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Section: Upgrading Of Carboxylic Acidsmentioning

confidence: 99%

Continuous Flow Upgrading of Selected C₂–C₆Platform Chemicals Derived from Biomass

et al. 2020

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“…Most recently, de Souza and co-workers [37] reported two continuous flow synthesis strategies of dimethyl fumarate 54 (Figs. 26 and 27), a prodrug used in the treatment of psoriasis and multiple sclerosis.…”

Section: Dimethyl Fumaratementioning

confidence: 99%

“…26 and 27), a prodrug used in the treatment of psoriasis and multiple sclerosis. The prices of treating multiple sclerosis are high reaching 75,000 USD/annum for 87 g dimethyl fumarate (862 USD/g) [37] thus inaccessible to most patients in developing economies. The authors demonstrated two strategies towards dimethyl fumarate starting from either fumaric acid or maleic anhydride.…”

Section: Dimethyl Fumaratementioning

confidence: 99%

Flow Chemistry Supporting Access to Drugs in Developing Countries

Sagandira

Watts

2021

Topics in Medicinal Chemistry

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Herein, we assess how developing economies can take advantage of the limited existing batch manufacturing infrastructure to set up state-of-the-art continuous flow manufacturing infrastructure to enable local pharmaceutical manufacturing as well as support access to drug discovery. This potentially provides paradigm shift in developing countries' pharmaceutical industry that could lead to better drug discovery access as well as enabling local drug manufacturing with the consequence of improving access to medicines.

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“…Over time, different strategies were developed for the production of DMF, exploiting different catalysts, in some cases using different raw materials ( e . g ., maleic anhydride) and also using the CF technology. , In most cases, these alternative strategies do not fully address the reported drawbacks and their actual industrial advantage can be considered really limited.…”

Section: Introductionmentioning

confidence: 99%

Dimethyl Fumarate: Heterogeneous Catalysis for the Development of an Innovative Flow Synthesis

Dedè¹,

Piccolo²,

Vigo³

2021

Org. Process Res. Dev.

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The present work describes the development of an improved synthesis of the active pharmaceutical ingredient (API) dimethyl fumarate. The use of continuous flow technology and the newly developed methylation conditions solve some of the issues of previous commercial production strategies, e.g., reaching complete conversion and avoiding the formation of toxic impurities. The optimization was carried out using the design of experiment approach and afforded a very efficient, sustainable process, suitable for the industrial application.

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Continuous-flow synthesis of dimethyl fumarate: a powerful small molecule for the treatment of psoriasis and multiple sclerosis

Abstract: Dimethyl fumarate (DMF) has recently gained attention due to its use as a pro-drug in different pharmaceutical preparations, here in we present our work on a cascade methodology in short reaction times and quantitative yields.

Cited by 16 publications

References 10 publications

Continuous Flow Upgrading of Selected C₂–C₆Platform Chemicals Derived from Biomass

Continuous Flow Upgrading of Selected C₂–C₆Platform Chemicals Derived from Biomass

Flow Chemistry Supporting Access to Drugs in Developing Countries

Dimethyl Fumarate: Heterogeneous Catalysis for the Development of an Innovative Flow Synthesis

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Continuous-flow synthesis of dimethyl fumarate: a powerful small molecule for the treatment of psoriasis and multiple sclerosis

Abstract: Dimethyl fumarate (DMF) has recently gained attention due to its use as a pro-drug in different pharmaceutical preparations, here in we present our work on a cascade methodology in short reaction times and quantitative yields.

Cited by 16 publications

References 10 publications

Continuous Flow Upgrading of Selected C2–C6Platform Chemicals Derived from Biomass

Continuous Flow Upgrading of Selected C2–C6Platform Chemicals Derived from Biomass

Flow Chemistry Supporting Access to Drugs in Developing Countries

Dimethyl Fumarate: Heterogeneous Catalysis for the Development of an Innovative Flow Synthesis

Contact Info

Product

Resources

About

Continuous Flow Upgrading of Selected C₂–C₆Platform Chemicals Derived from Biomass

Continuous Flow Upgrading of Selected C₂–C₆Platform Chemicals Derived from Biomass