Dimethylmalic acid

With dimethylmalic acid lyase (EC 4.1.3.32) from Clostridium harkeri. an enzyme involved in nicotinic acid metabolism, propanoate can be added to pyruvate yielding stereospecifically the (2i ,3S)-dimethylmalic acid39. 

Homer and Roder also found that dimethylmaleic acid 112, R = H) and its methyl ester 112, R = CH3) are reduced stereospecifically to meso-2,3-di-methylsuccinic acid and its methyl ester, respectively 113, R = H and CH3)ll7>. 

These results, which correspond to stereospecific cis addition of hydrogen to the double bond, stand in direct contradiction to the report st> by Elving and coworkers that dimethylmaleic acid 112, R = H) affords dl-113 (R = H) exclusively and that dimethylfumaric acid affords only meso-113 (R = H). The latter results correspond of course to stereospecific tram addition of hydrogen across the double bond. Camilli, like Homer and R6der, however, observed c/s-addition of hydrogen, albeit in a slightly different system, 18> ... 

Meyer M, Zintchenko A, Ogris M, Wagner E (2007) A dimethylmaleic acid-melittin-polylysine conjugate with reduced toxicity, pH-triggered endosomolytic activity and enhanced gene transfer potential. J Gene Med 9 797-805... 

The formation of meso-dimethylsuccinic acid from dimethylmaleic acid and the racemic mixture from dimethylfumaric acid implies that both hydrogen atoms add to the same side of the unsaturated molecule 11). Bourguel (12) also noted that disubstituted acetylenes yielded initially cis-ethylenes but that trans isomers were formed if the hydrogenations were protracted. 

The degradation of nicotinic acid by Clostridium barkeri involves the cleavage of the intermediate 2,3-dimethylmalate 132 from which propionic and pyruvic acids are formed by a specific lyase (EC 4.1.3.32). In the reverse direction, the enzyme must have the unusual capacity to deprotonate propionic acid at the a-carbon instead of the carboxylic acid function, or next to an anionic car-boxylate. Purified dimethylmalic acid aldolase has been used to catalyze the stereospecific addition of 133 to the oxoacid acceptor, yielding the (2R,3S) configurated dimethylmalic acid 132 at the multi-gram scale [381]. The substrate tolerance of this enzyme has not yet been determined. 

The stereochemistry of cathodic hydrogenation is thus far not predictable or explainable. There is a preponderance for trans addition in the reduction of al-kynes, while cis addition occurs predominantly with cis- and trans-stilbene and maleic acid derivatives. On the other hand, dimethylmaleic acid and dimethyl-fumaric acid are exclusively hydrogenated to the trans products, meso- and dl-di-methylsuccinic acid 302 With a silver-palladium cathode in 5% aquous sulfuric acid triple bonds are reduced in a specific cis addition to double bonds 303 ... 

The rate of reaction decreases with increase in the number of substituents on the doubly bonded atoms. However, not all substituents have the same influence. Terminal double bonds react faster than those in the interior of a chain 112 and with further increase in the number of substituents on the double bond there may be no reduction at all. Relative rates of reaction measured by Hiinig et al.106 are maleic acid 10, methylmaleic acid 0.7, dimethyl-maleic acid 0, and ethylenetetracarboxylic acid (dicarboxymaleic acid 0.3). Nevertheless, under other conditions dimethylmaleic acid also can be reduced.109... 

Dimethylmaleic Acid (Qia-2-Bntylene-2 3-dicarboxylic acid, pyrocinchonic acid)... 

Evidence for Mn was also found in the oxidation of methylmaleic, methyl-fumaric, and dimethylmaleic acids. The rates were found to be pH-dependent in the range 0—5.0, resulting from reaction of permanganate with different protonated... 

The oxidation of dimethylmaleic acid (H2A) and anhydride obeys the rate law... 

Alder diadduct, 108 3,4-Dimethylhexane, 169 A, A -Dimethylhydrazine, reaction with MA, 84 )3(2,4-Dimethyl-6-hydroxybenzoyl)acrylic acid, 94 )3(2,6-Dimethyl-4-hydroxybenzoyl acrylic acid, 94 Dimethylmaleic acid, 238 Dimethylmaleic anhydride alternating copolymerization, 307 diazoalkane adducts, 222 MA in synthesis, 238 photochemical reactions, 182 polymerization attempts, 263 Dimethylmaleimide,A-(2-pyradinyl), MA in synthesis, 238... 

Diethyl acetylenedicarboxylate is reduced to diethyl fumarate. Dime thy Ifumaric acid is reduced to meso-dimethylsuccinic acid, and dimethylmaleic acid is reduced to racemic dimethylsuccinic acid. 

---