Acetone dicarboxylic acid, decarboxylation

Further studies by Spenser demonstrated that l,2-13C-labeled acetate (13) was incorporated into lycopodine but gave a distribution of the labels that did not account for the pelletierine-route that was hypothesized (Scheme 6.2) [11]. An intact 3-carbon unit was desired for testing, but labeled acetoacetate (l,2,3,4-13C-acetoacetate (14), which could undergo decarboxylation to provide an intact 3-carbon unit) was found to give the same incorporation pattern as acetate (and therefore must have been cleaved to acetate prior to uptake). In addition, feeding studies using deuterated, 13C-labeled acetate provided a loss or washout of deuterium at the C16 methyl group. This could only occur if an intermediate had formed that would provide for facile enolization. Both the equal distribution of the 13C labels and loss of the deuteriums led the researchers to propose that the intermediate was symmetric, such as acetone dicarboxylic acid (15). 

The authors point out that other possibilities for the catabolism of glutarate are (1) a direct splitting of the molecule into a 2- and 3-carbon fragment (2) /3-oxidation to acetone dicarboxylic acid followed by decarboxylation to acetoacetate or (3) direct decarboxylation to butyrate. 

Because citric acid is considered as relatively cheap and abundant material, it was catalytically dehydrated to aconitic acid in the 120-150 °C temperature range by Umbdenstock and Bruin [61]. Aconitic acid can be readily decaiboxylated to a mixture of isomeric itaconic acids (itaconic, citraconic and mesaconic acids). These acids and their esters are nsed to produce alkyl resins and plasticizers. The mechanism of thermal rearrangement of citraconic acid to itaconic acid in aqueous solution was in a great detail investigated by Sakai [62]. In some cases, the applied catalyst caused excessive pyrolysis of citric acid and in the dehydration and decarboxylation reactions acetone dicarboxylic acid (P-ketoglutaric acid) was initially formed and from it acetone. The catalytic pyrolysis of citric acid monohydrate heated up to 140 °C to obtain itaconic and citraconic acids was reported by Askew and Tawn [63],... 

Citric dehydrogenase, from liver, muscle and vegetable extracts, converts citric acid into acetone dicarboxylic acid, which by a second decarboxylation gives rise to acetoacetic acid. 

Regioselectivity of C—C double bond formation can also be achieved in the reductiv or oxidative elimination of two functional groups from adjacent carbon atoms. Well estab llshed methods in synthesis include the reductive cleavage of cyclic thionocarbonates derivec from glycols (E.J. Corey, 1968 C W. Hartmann, 1972), the reduction of epoxides with Zn/Nal or of dihalides with metals, organometallic compounds, or Nal/acetone (seep.lS6f), and the oxidative decarboxylation of 1,2-dicarboxylic acids (C.A. Grob, 1958 S. Masamune, 1966 R.A. Sheldon, 1972) or their r-butyl peresters (E.N. Cain, 1969). 

When citric acid is exposed to permanganate in sulfuric acid, it is oxidized to formic acid and 1,3-dicarboxylic acid acetone, and the latter is changed, through decarboxylation caused by heat, into formic acid and acetone (Figure 3.17.5). 

This reaction was initially reported by Franchimont in 1872. It is a condensation of two a-bromocarboxylic acids in absolute alcohol in the presence of sodium cyanide to give 1,2-dicarboxylic acids after hydrolysis and decarboxylation. In the case of a-bromoketones, 1,4-diketones are produced similarly after hydrolysis with phosphoric acid. It was found that the bulky group at the ester end prevents condensation, as in the case of phenyl and naphthyl esters. Although the substituent at j0-position does not prevent such condensation, it reduces the overall yield. In addition, a compound with two ester groups at proper position will form cyclic diacid under such reaction conditions and cyclobutane, " cyclopentane and cyclohexane dicarboxylic acid have been prepared in such a way. In the case of l,4-dibromo-l,4-dibenzoylbutane, a derivative of cyclopentanone is produced after acidic hydrolysis. It should be pointed out that other common solvents—including acetone, ether, and acetonitrile- are not good for this reaction. ... 

An extended NeuAc analogue 49 has been prepared by the reaction of 5,6-0-isopropylidene-A-acetylmannosamine with disodium acetone dicarboxylate in the presence of nickel acetate the C-5 and C-6 epimers of 49 were also formed. Deprotection of 49 by hydrogenolysis gave the free acid which decarboxylated readily. 9 Treatment of the Wittig product 50 under Wacker-type conditions led to the glycoside 51 of a 3-ulosonic acid (Scheme 7). ... 

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