477211-58-8Relevant articles and documents
FUMARATE COMPOUNDS, PHARMACEUTICAL COMPOSITIONS THEREOF, AND METHODS OF USE
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Paragraph 0309-0313, (2016/11/17)
Fumarate compounds, pharmaceutical compositions comprising the fumarate compounds, and methods of using fumarate compounds and pharmaceutical compositions for treating neurodegenerative, inflammatory, and autoimmune disorders including multiple sclerosis, psoriasis, irritable bowel disorder, ulcerative colitis, arthritis, chronic obstructive pulmonary disease, asthma, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis are disclosed.
Photochemical cleavage and release of carboxylic acids from α-keto amides
Ma, Chicheng,Steinmetz, Mark G.,Kopatz, Erica J.,Rathore, Rajendra
, p. 4431 - 4442 (2007/10/03)
In aqueous media, α-keto amides LGCH2COCON(R)CH(R′) CH3 (1a, R = Et, R′ = H; 1b, R = iPr, R′ = Me; 1c, R = Ph, R′ = H) with various carboxylate leaving groups (LG) at the C-3 position undergo photocleavage and release of carboxylic acids with formation of diastereomeric 5-hydroxyoxazolidin-4-ones 2a,c in the cases of 1a,c or 5-methyleneoxazolidin-4-ones 3b in the case of 1b. For 1a,b, Φ(photocleavage) = 0.24-0.38, whereas Φ(photocleavage) = ca. 0.05 for 1c. The proposed mechanism involves transfer of hydrogen from an N-alkyl group to the keto oxygen to produce zwitterionic intermediates 4a-c that eliminate carboxylate anions. The resultant imminium ions, H2C=C(OH)CON +(R)=C(R′)CH3 5a-c, cyclize intramolecularly to 3b or undergo intermolecular addition of water followed by tautomerization and cyclization to give 2a,c. These inter- or intramolecular trapping reactions of 5 release protons that decrease the pH and cause bleaching of the 620 nm band of the pH indicator, bromocresol green. Determination of the bleaching kinetics by laser flash photolysis methods in the case of 1a gives time constants of 18-137 μs, depending on the leaving group ability of the carboxylate anion, whereas amides 1b show only a small leaving group effect. For 1a, the large leaving group effect is consistent with rate-limiting carboxylate elimination from 4a, whereas the proton release step would be largely rate determining for 1b. Photolyses of 1a (LG = CH3CO2-, PhCH 2CO2-) in neat CH3CN results in carboxylate elimination to form imminium ion 5a, followed by internal return to give aminals.
Osmium-Catalyzed Dihydroxylation of Olefins in Acidic Media: Old Process, New Tricks
Dupau, Philippe,Epple, Robert,Thomas, Allen A.,Fokin, Valery V.,Sharpless, K. Barry
, p. 421 - 433 (2007/10/03)
A screen of over 500 diversely functionalized additives in osmium-catalyzed dihydroxylation has uncovered that electron-deficient olefins are converted into the corresponding diols much more efficiently when the pH of the reaction medium is maintained on the acidic side. Further studies have identified citric acid as the additive of choice, for it allows preparation of very pure diols in yields generally exceeding 90%. As described here, a much wider range of olefin classes can now be successfully dihydroxylated. The process is experimentally simple, in most cases involving little more than dissolving the reactants in water or a waler/tertbutyl alcohol mixture, stirring them, and filtering off the pure diol product.
