Dimethyl fumarate
Encyclopedia
Dimethyl fumarate is the methyl ester
of fumaric acid
.
and an α,β-unsaturated
electrophilic compound, undergoing reactions typical to them. It is also a diene acceptor in the ordinary Diels-Alder reaction
, where the reactivity of its vinylidenic bond is enchanced by the two electron-withdrawing ester groups. Due to the geometry of the starting ester, the Diels-Alder product will have a trans configuration.
. It is a lipophilic, highly mobile molecule in human tissue. However, as an α,β-unsaturated ester, dimethyl fumarate reacts rapidly with the detoxifying agent glutathione
by Michael addition. When administered orally, it does not survive long enough to be absorbed into blood.
Another use for dimethyl fumarate is mold inhibition, mostly for leather products. But see below for the problems this has caused.
Tests in mouse models have been conducted with the aim of using it as part of a specific cancer treatment.
Dimethyl fumarate has been shown to provide benefit in a mouse model of multiple sclerosis and phase III clinical trials in patients are in progress As BG-12 it has shown good results with relapsing-remitting multiple sclerosis.
that is difficult to treat. Concentrations as low as 1 ppm may produce allergic reactions. There are only a handful of equally potent sensitizers.
The extreme sensitizing risk was brought to public attention by the "poison chair" incident, where Chinese manufacturer Linkwise produced two-seater sofas with dimethyl fumarate sachets inside to inhibit mould while they were in storage or transport. In Finland where the chairs were sold from 2006–2007, sixty users were given serious rashes. The cause was identified as dimethyl fumarate-induced allergic reaction by Tapio Rantanen, M.D. from Finland, and his original article became the cover story in the July issue of British Journal of Dermatology. In the United Kingdom, sofas sold by Argos
, Land of Leather
and Walmsley Furnishing containing the chemical caused over a hundred injuries. Argos withdrew the sofas from stores and contacted buyers to collect those that had been sold — with Land of Leather withdrawing the sofas without notifying buyers and Walmsley saying they had removed the sachets from sofas they sold after the danger came to light. Complaints have been made that dates on the sofas were altered and sofas containing the sachets sold. Land of Leather and Walmsley are facing a ₤10 million class action suit over their reaction to the incident, joining the manufacturer in denying the sofas are connected to their customers injuries. The danger came to public attention when the BBC Watchdog
program alerted consumers to the sofas.
In the European Union
the use of dimethyl fumarate for consumer products has been forbidden since 1998, and since January 2009 the import of products containing dimethyl fumarate is also forbidden.
The EU Commission Decision 2009/251 of 17 March 2009 requiring Member States to ensure that products containing the biocide
dimethylfumarate are not placed or made available on the market has definitely forbidden any marketing of products containing dimethyl fumarate into the European Union. The ban on dimethyl fumarate as laid down in Decision 2009/251 establishes a maximum concentration of dimethyl fumarate in products of 0.1 ppm. Products containing more than 0.1 ppm dimethyl fumarate shall be withdrawn from the market and recalled by consumers as of 1 May 2009.
Ester
Esters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...
of fumaric acid
Fumaric acid
Fumaric acid or trans-butenedioic acid is the chemical compound with the formula HO2CCH=CHCO2H. This white crystalline compound is one of two isomeric unsaturated dicarboxylic acids, the other being maleic acid. In fumaric acid the carboxylic acid groups are trans and in maleic acid they are cis...
.
Reactions
Dimethyl fumarate is an esterEster
Esters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...
and an α,β-unsaturated
Enone
An enone is an unsaturated chemical compound or functional group consisting of a conjugated system of an alkene and a ketone. The simplest enone is methyl vinyl ketone or CH2=CHCOCH3....
electrophilic compound, undergoing reactions typical to them. It is also a diene acceptor in the ordinary Diels-Alder reaction
Diels-Alder reaction
The Diels–Alder reaction is an organic chemical reaction between a conjugated diene and a substituted alkene, commonly termed the dienophile, to form a substituted cyclohexene system. The reaction can proceed even if some of the atoms in the newly formed ring are not carbon...
, where the reactivity of its vinylidenic bond is enchanced by the two electron-withdrawing ester groups. Due to the geometry of the starting ester, the Diels-Alder product will have a trans configuration.
Uses
Dimethyl fumarate is used to treat psoriasisPsoriasis
Psoriasis is an autoimmune disease that appears on the skin. It occurs when the immune system mistakes the skin cells as a pathogen, and sends out faulty signals that speed up the growth cycle of skin cells. Psoriasis is not contagious. However, psoriasis has been linked to an increased risk of...
. It is a lipophilic, highly mobile molecule in human tissue. However, as an α,β-unsaturated ester, dimethyl fumarate reacts rapidly with the detoxifying agent glutathione
Glutathione
Glutathione is a tripeptide that contains an unusual peptide linkage between the amine group of cysteine and the carboxyl group of the glutamate side-chain...
by Michael addition. When administered orally, it does not survive long enough to be absorbed into blood.
Another use for dimethyl fumarate is mold inhibition, mostly for leather products. But see below for the problems this has caused.
Tests in mouse models have been conducted with the aim of using it as part of a specific cancer treatment.
Dimethyl fumarate has been shown to provide benefit in a mouse model of multiple sclerosis and phase III clinical trials in patients are in progress As BG-12 it has shown good results with relapsing-remitting multiple sclerosis.
Risks
Dimethyl fumarate has been found to be an allergic sensitizer at very low concentrations, producing extensive, pronounced eczemaEczema
Eczema is a form of dermatitis, or inflammation of the epidermis . In England, an estimated 5.7 million or about one in every nine people have been diagnosed with the disease by a clinician at some point in their lives.The term eczema is broadly applied to a range of persistent skin conditions...
that is difficult to treat. Concentrations as low as 1 ppm may produce allergic reactions. There are only a handful of equally potent sensitizers.
The extreme sensitizing risk was brought to public attention by the "poison chair" incident, where Chinese manufacturer Linkwise produced two-seater sofas with dimethyl fumarate sachets inside to inhibit mould while they were in storage or transport. In Finland where the chairs were sold from 2006–2007, sixty users were given serious rashes. The cause was identified as dimethyl fumarate-induced allergic reaction by Tapio Rantanen, M.D. from Finland, and his original article became the cover story in the July issue of British Journal of Dermatology. In the United Kingdom, sofas sold by Argos
Argos (retailer)
Argos is the largest general-goods retailer in the United Kingdom and Ireland with over 800 stores. It is unique amongst major retailers in the UK in that it is a catalogue merchant...
, Land of Leather
Land of Leather
Land of Leather was a furniture retail store based in Northfleet, Kent in the United Kingdom. It operated in the United Kingdom and the Republic of Ireland.- History :...
and Walmsley Furnishing containing the chemical caused over a hundred injuries. Argos withdrew the sofas from stores and contacted buyers to collect those that had been sold — with Land of Leather withdrawing the sofas without notifying buyers and Walmsley saying they had removed the sachets from sofas they sold after the danger came to light. Complaints have been made that dates on the sofas were altered and sofas containing the sachets sold. Land of Leather and Walmsley are facing a ₤10 million class action suit over their reaction to the incident, joining the manufacturer in denying the sofas are connected to their customers injuries. The danger came to public attention when the BBC Watchdog
Watchdog (TV series)
Watchdog is a BBC television series that investigates viewers' reports of problematic experiences with traders, retailers, and other companies around the UK...
program alerted consumers to the sofas.
In the European Union
European Union
The European Union is an economic and political union of 27 independent member states which are located primarily in Europe. The EU traces its origins from the European Coal and Steel Community and the European Economic Community , formed by six countries in 1958...
the use of dimethyl fumarate for consumer products has been forbidden since 1998, and since January 2009 the import of products containing dimethyl fumarate is also forbidden.
The EU Commission Decision 2009/251 of 17 March 2009 requiring Member States to ensure that products containing the biocide
Biocide
A biocide is a chemical substance or microorganism which can deter, render harmless, or exert a controlling effect on any harmful organism by chemical or biological means. Biocides are commonly used in medicine, agriculture, forestry, and industry...
dimethylfumarate are not placed or made available on the market has definitely forbidden any marketing of products containing dimethyl fumarate into the European Union. The ban on dimethyl fumarate as laid down in Decision 2009/251 establishes a maximum concentration of dimethyl fumarate in products of 0.1 ppm. Products containing more than 0.1 ppm dimethyl fumarate shall be withdrawn from the market and recalled by consumers as of 1 May 2009.
External links
- Dimethyl fumarate Material Safety Data Sheet (MSDS)