2756-87-8 Usage
Description
Monomethyl fumarate (MMF), a bioactive metabolite of fumaric acid ester, is an immunotherapy for psoriasis that causes decreased production of Th1 cytokines and lymphocytopenia. Monomethyl fumarate was shown to decrease DC response to LPS and decreased IL-12p70 and IL-10 production.
Chemical Properties
Off-White Solid
Uses
Monomethyl fumarate is used to treat the relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease. This medicine will not cure MS, but it may slow some of the disabling effects and decrease the number of relapses of the disease.Fumaric Acid Monomethyl Ester is one of the most bioactive anti-psoriatic fumaric acid ester metabolite. Fumaric Acid Monomethyl Ester is potent nicotinic acid receptor agonist. Fumaric Acid Monomethy l Ester has also been shown to selectively stimulate of T helper 2 cytokine response.
Application
mono-Methyl fumarate can be used as a reactant to synthesize:Jumonji C domain-containing histone demethylases (JCHDMs) inhibitor.(?)-Xylariamide A, a fungal metabolite.(±)-Methoxyfumimycin ethyl ester, a potential bacterial peptide deformylase inhibitor.It is also a wide spectrum antibacterial agent with a powerful antioxidant activity.
Preparation
Monomethyl fumarate was synthesized by maleic anhydride and methanol. monomethyl fumarate could inhibit the growth of mold, and the storage time of feed could be prolonged.
Synthesis Reference(s)
The Journal of Organic Chemistry, 23, p. 1559, 1958 DOI: 10.1021/jo01104a608
Biological Activity
Monomethyl fumarate is an active metabolite of the immune modulator dimethyl fumarate (Item No. 14714) that is rapidly formed from dimethyl fumarate by hydrolysis. It is an agonist of the hydroxycarboxylic acid 2 (HCA2) receptor/GPR109A with an EC50 value of 9.4 μM for inducing calcium accumulation in CHO cells expressing the receptor. Monomethyl fumarate reduces neutrophil adhesion to endothelial cells stimulated with TNF, decreases CXCL2-directed neutrophil migration, and increases the expression of the Nrf2 target gene NQO1 in wild-type but not HCA2-/- macrophages. It inhibits proliferation and induces differentiation in keratinocytes, as well as decreases the levels of TNF-α induced by phorbol 12-myristate 13-acetate (TPA; Item No. 10008014) in keratinocytes when used at a concentration of 1 mM. Monomethyl fumarate (1 mg/day) reduces symptoms of experimental autoimmune encephalomyelitis (EAE) in mice and isolated natural killer cells from these mice induced cytotoxicity in previously isolated immature and mature dendritic cells. Formulations containing monomethyl fumarate have been used in the treatment of multiple sclerosis.
Clinical claims and research
Mono Methyl Fumarate (MMF) is an active component of Fumaria sp. methanolic extract. In Iranian traditional medicine, Fumitory is used widely as a remedy for several diseases including liver dysfunction. The effect of monomethyl fumarate and Fumaria extract was investigated by Moghaddam et al. (2012) against APAP-induced acute liver damage and compared to a known hepatoprotective plant, Silybum marianum and its active ingredient, SM. APAP produced acute toxicity at the dose of 640 mg/kg in mice while pretreatment and posttreatment of animals (i.p., twice daily for 48 h) with monomethyl fumarate, SM (25, 50, and 100 mg/kg) or the plant extracts (300 and 500 mg/kg) significantly lowered the rise of ALT, AST, LDH, ALKP, and bilirubin (total and direct) in serum. In addition, both the compounds and the plant extracts significantly increased GSH content and reduced MDA level of the liver.
Check Digit Verification of cas no
The CAS Registry Mumber 2756-87-8 includes 7 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 4 digits, 2,7,5 and 6 respectively; the second part has 2 digits, 8 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 2756-87:
(6*2)+(5*7)+(4*5)+(3*6)+(2*8)+(1*7)=108
108 % 10 = 8
So 2756-87-8 is a valid CAS Registry Number.
InChI:InChI=1/C5H6O4/c1-9-5(8)3-2-4(6)7/h2-3H,1H3,(H,6,7)/b3-2+
2756-87-8Relevant articles and documents
Dimethyl Fumarate: Heterogeneous Catalysis for the Development of an Innovative Flow Synthesis
Dedè, Fabiana,Piccolo, Oreste,Vigo, Daniele
, p. 292 - 299 (2021)
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.
Isolation and structure elucidation of the new fungal metabolite (-)-xylariamide A
Davis, Rohan A.
, p. 769 - 772 (2005)
Chemical investigations of the terrestrial microfungus Xylaria sp. have afforded the new natural product (-)-xylariamide A (1). The gross structure of 1 was determined by interpretation of 1D and 2D NMM, UV, IR, and MS data. Confirmation of the structure and the absolute stereochemistry of 1 were determined by the total synthesis of (4-)-xylariamide A (2). Synthetic 2 was produced by N,O-bis(trimethylsilyl)-acetamide-induced coupling of 3-chloro-L-tyrosine (3) with (E)-but-2-enedioic acid 2,5-dioxo-pyrrolidin-1-yl ester methyl ester (4). Optical rotation comparison of 1 with 2 indicated that the natural product (1) contained 3-chloro-D-tyrosine. Both enantiomers of xylariamide A were tested in a brine shrimp lethality assay, and only the natural product (1) showed toxicity.
Continuous-flow synthesis of dimethyl fumarate: A powerful small molecule for the treatment of psoriasis and multiple sclerosis
Lima, Marcelo T.,Finelli, Fernanda G.,De Oliveira, Alline V. B.,Kartnaller, Vinicius,Cajaiba, Joa? F.,Lea?, Raquel A. C.,De Souza, Rodrigo O. M. A.
, p. 2490 - 2494 (2020/02/03)
Dimethyl fumarate (DMF) is a methyl ester of fumaric acid and has recently gained attention due to its use as a pro-drug in different pharmaceutical preparations, besides the low price of the final molecule and no active patents being available for the synthesis of DMF, the prices of multiple sclerosis treatment are still high. In our continuous effort for the development of process intensification strategies towards the synthesis of active pharmaceutical ingredients, here we present our work on a cascade methodology for dimethyl fumarate synthesis in short reaction times and quantitative yields.
AN IMPROVED PROCESS FOR THE SYNTHESIS OF DIMETHYL FUMARATE
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Paragraph 0027, (2017/05/10)
The present invention describes an improved process for the industrial scale production of dimethyl fumarate. The process involves a one-pot ring opening reaction of maleic anhydride to monomethyl maleate and isomerization into the corresponding monomethyl fumarate in presence of a Lewis acid. Finally the mono methyl fumarate was converted into the dimethyl fumarate by an acid catalyzed esterification reaction.
