Oxalacetic acid decarboxylation

In the experience of the present author, minor deviations from this procedure may result in decreased yields. Oxalacetic acid of high quality is essential, and this should be verified by a melting-point determination prior to use. Decarboxylation of oxalacetate has been reported111 to occur rapidly at pH 7, and it should be kept to a minimum by maintaining the pH as close to 10 as possible when dissolving the oxalacetic acid. A modification of the Comforth reaction is the co-balt(II)-ion-catalyzed condensation of D-erythrose 4-phosphate with oxalacetate to give 3-deoxyheptulosonic acid 7-phosphate112 (as a mixture of the arabino and ribo isomers). Other procedures for the preparation of KDO will be discussed in subsections 3 and 4 of this Section. 

A modified poly(ethylenimine) also acts as an efficient catalyst for decarboxylation (Suh et al., 1976 Spetnagel and Klotz, 1976). In particular, the partially quaternized polymer [SS] catalyzed the decarboxylation of oxalacetic acid in a bifunctional manner (Spetnagel and Klotz, 1976), as shown in (18). The decarboxylation is thought to occur via pre-equilibrium... 

C-kinetic isotope effects have been used to determine the degree of C —C breakage in metal and non-metal catalyzed decarboxylation of oxalacetic acid. (Sec. 2.2.2). 

Figure 4. Effect of metal ions on nonenzymatic decarboxylation of oxalacetic acid (41)...

However, if a further donor group is introduced, a chelate may be formed that does not involve the carboxylate group to be lost. In these cases, the decarboxylation is dramatically enhanced in the presence of metal ions. This is exactly the situation which pertains with oxalacetic acid, which undergoes a facile metal-promoted decarboxylation (Fig. 5-23). The rate of decarboxylation of oxalacetic acid is accelerated some ten thousand times in the presence of copper(n) salts. The metal ion is thought to play a variety of roles, including the stabilisation of the enolate that is produced after loss of carbon dioxide. 

Figure 5-23. The rate of decarboxylation of oxalacetic acid is accelerated many thousands of times in the presence of metal ions.

Precursors. Precursors for this reaction are compounds exhibiting keto-enol tau-tomerism. These compounds are usually secondary metabolites derived from the glycolysis cycle of yeast metabolism during fermentation. Pyruvic acid is one of the main precursor compounds involved in this type of reaction. During yeast fermentation it is decarboxylated to acetaldehyde and then reduced to ethanol. Acetone, ace-toin (3-hydroxybutan-2-one), oxalacetic acid, acetoacetic acid and diacetyl, among others, are also secondary metabolites likely to participate in this kind of condensation reaction with anthocyanins. 

The introduction of the a-keto acid function on the way to the ulosonic acids is a main problem of their syntheses. By analogy with the biosynthetic pathway, the aldol reaction between sugar aldehydes and a pyruvate equivalents seems to be the most simple and versatile. As it has been demonstrated by Comforth [74] in the first chemical synthesis, the reaction of arabinose and oxalacetic acid as pyruvate equivalent, followed by decarboxylation afforded KDO, albeit in low yield. This condensation has been optimized by use of Ni(II) catalyst for the decarboxylation [75], In this case, reaction of D-mannose and oxalacetic acid gave KDN (11) and its D-manno epimer 37 in 70% yield [75] (Scheme 12). 

In chloroplasts oxalacetic acid could be reduceo to malic acid (by NADP-malate dehydrogenase) and this acid could be decarboxylated and will regenerate the substrate for PEPCase. Another reaction is also possible - oxalacetic acid to be directly decarboxylated by oxalacetate decarboxylase. In either case the decarboxylase reactions will strengthen the flow of CO2 to RuBPCase and will contribute to the better operation of Calvin cycle. 

Scheme 7.3 Equilibria involved with oxaloacetic acid, and the metal ion promoted decarboxylation. A = dianion of oxalacetic acid...

The decarboxylation of oxalacetic acid was postulated by Wood and Werkman to participate in the fermentation process of Propionobacteria. They postulated that a reversal of this decarboxylation resulted in the fixation of CO2 by these bacteria, and the name, Wood-Werkman reaction, was used to identify this postidated mechanism for the first fixation of CO in carbon chains to be demonstrated in heterotrophic organisms. [C. H. Werkman and H. G. Wood, Advances in Emytnol. 2, 136 (1942).] The fixation of CO in succinate observed by these workers may be explained by the reactions discussed on p. 148. 

An entirely different sort of mechanism for the photochemical step in photosynthesis was suggested by Calvin and Barltrop (35). It had been observed that when algae in a steady state of photosynthesis were fed radioactive carbon dioxide, the radioactivity could not be found in those products characteristic of the tricarboxylic acid cycle (Fig. 11, p. 777). If the algae were allowed to undergo photosynthesis for a short time in the presence of radioactive carbon dioxide and then placed in the dark, the radioactive carbon was found to appear in the members of the tricarboxylic acid cycle. These results were interpreted in terms of the reactions known to be necessary for pyruvic acid to enter into the tricarboxylic acid cycle. The pyruvic acid is oxidatively decarboxylated to yield acetyl-coenzyme A and CO2. Acetyl-coenzyme A then enters the tricarboxylic acid cycle by condensing with oxalacetic acid. 

Sulfinylpyruvic acid accumulates as a result of the transaminating activity. It is an analog of oxalacetic acid, and like this compound, it is decomposed to pyruvate and SOs under the influence of Mn ". The reaction is analogous to the j3-decarboxylation of oxalacetate by Mn++. Mn++ also catalyzes the oxidation of SOj to S04 . As a consequence, reactions 5 and 6 of Fig. 2 are assumed to be nonenzymatic. 

Macrophomate synthase enzyme (MPHS), isolated from the fungus Macrophoma com-melinae, catalyzes the Diels-Alder cycloaddition between 2-pyrones 42 and decarboxylated oxalacetic acid 43 in aqueous buffered medium at pH 7.0, giving the benzoates 44 (Scheme 5.11). These types of aromatic compounds are commonlybiosynthesized by either a shiki-mate or polyketide pathway and therefore the reaction depicted in Scheme 5.11 supports the fact that the Diels-Alder reaction takes place in biosynthesis. 

Pantothenic acid, as a constituent of coenzyme A, is involved in several of the steps of the citric acid cycle these include the synthesis of citric acid from oxalacetic acid and its salts, and the oxidation by decarboxylation of a-keto-acids. 

Gelles E (1956) Kinetics of the decarboxylation of oxalacetic acid. J Chem Soc 4736-4739... 

Kochi JK (1965b) Formation of alkyl halides from acids by decarboxylation with lead(IV) acetate and halide salts. J Org Chem 22A 3265-3271 Kosicki GW, Kipovac SN (1964) The pH and pD dependence of the spontaneous and magnesium-ion-catalyzed decarboxylation of oxalacetic acid. Can J Chem 42 403-415 Kraeutler B, Bard AJ (1978) Heterogeneous photocatalytic decomposition of saturated carboxylic acids on Ti02 powder. Decarboxylative route to alkanes. J Am Chem Soc 100 5985-5992... 

Tsai CS (1967) Spontaneous decarboxylation of oxalacetic acid. Can J Chem 45 873-880 Virely C, Forissier M, Millet JM, Vedrine JC, Huchette D (1992) Kinetic study of isobutyric acid oxydehydrogenation on various Fe-P-O catalysts proposal for the reaction mechanism. J Mol Catal 71 119-213 Westheimer FH, Jones WA (1941) The effect of solvent on some reaction rates. J Am Chem Soc 63 3283-3286... 

The sugar 2-amino-2-deoxy-D-gluconic acid inhibits reduction of iron(III) by D-galacturonic acid. Decarboxylation of oxalacetic acid is the final step in a sequence of reactions with the C-bound chromium(III) complex, [(H20)5CrCH2CN] ". The initial steps are coordination and ring closure of the oxalacetate, both by displacement of coordinated H2O with rate constants 0.16 M s and 1 x 10 s respectively at 25.0 °C and 1.0 M ionic strenght. Decarboxylation takes place after protonation of the coordinated substrate. 

Biotin is a growth factor for many bacteria, protozoa, plants, and probably all higher animals. In the absence of biotin, oxalacetate decarboxylation, oxalosuccinate carboxylation, a-ketoglutarate decarboxylation, malate decarboxylation, acetoacetate synthesis, citrulline synthesis, and purine and pyrimidine syntheses, are greatly depressed or absent in cells (Mil, Tl). All of these reactions require either the removal or fixation of carbon dioxide. Together with coenzyme A, biotin participates in carboxylations such as those in fatty acid and sterol syntheses. Active C02 is thought to be a carbonic acid derivative of biotin involved in these carboxylations (L10, W10). Biotin has also been involved in... 

In enzymic decarboxylations the mechanistic pathway seems to involve Schiff base formation between an —NH2 from a lysine residue and a C=0 of the keto acid.52 Likewise, with small-molecule primary amines, catalysis of decarboxylation of /3-ketoacids53-58 has been ascribed to a Schiff base intermediate. The overall reaction for oxalacetate is... 

The procedure reported in Scheme 13.11 describes deracemization of an amino acid involving oxidation with an L-specific enzyme and transamination with a D-amino transferase using D-aspartate 10, which is generated from L-aspartate 11 by aspartate racemase, as the amino donor. The oxidative enzyme is defined as an L-amino acid deaminase, a flavoprotein from Proteus myxofadens [34]. The transamination reaction is shifted towards the product since the oxalacetate 12 formed decarboxylates spontaneously to give pyruvate and carbon dioxide. 

COs to form oxalacetate which under anaerobic conditions is reduced to malate. The malate in turn may be converted to fumarate and succinate (Fig, 5). The last step in this series of reactions is blocked by malonate. The second pathway involves the aerobic condensation of pyruvate and oxalacetate followed by oxidation of the condensation product to form -ketoglutarate and succinate. Wood has proposed that the first condensation product of the aerobic tricarboxylic cycle is cfs-aconitic acid which is then converted to succinate by way of isocitric, oxalosuccinic, and a-ketoglutaric acids. The a-ketoglutarate is decarboxylated and oxidized to succinic acid. Isotopic a-ketoglutarate containing isotopic carbon only in the carboxyl group located a to the carbonyl would be expected to yield non-isotopic succinate after decarboxylation. This accounts for the absence of isotopic carbon in succinate isolated from malonate-poisoned liver after incubation with pyruvate and isotopic bicarbonate. 

Although citrate has been excluded as the primary condensation product of pyruvate and oxalacetate, no direct evidence bearing upon the nature of this product has as yet been obtained. The participation of cfs-aconitic and isocitric acids is speculative. Nor is there any evidence supporting the hypothesis that pyruvate and oxalacetate condense to form a hypothetical intermediate oxalcitraconic acid which can be oxidatively decarboxylated to citric acid. Since citrate, aconitate and isocitrate are in equilibrium with each other, the participation of the last two substances as intermediates of carbohydrate oxidation would, on the surface, appear to be doubtful. Krebs, however, believes that the conversion of cis-aconitate to a-ketoglutarate occurs so rapidly in liver that equilibrium with citrate is not attained. 

C Amino acid s Asn is hydrolyzed in one step to aspaartate, which in turn is transaminated in one step to oxalacetate. Threonine feeds into the TCA cycle through succinyl-CoA instead of oxalacetate. Thr is first deaminated via a dehydratase as seen earlier, then decarboxylated by Pyruvate DH Complex to give propionyl-CoA, which is then transformed via a series of steps to give succinyl-CoA. 

Kumagai and coworkers11131 developed an enzymatic procedure to produce d-alanine from fumarate by means of aspartase (E. C. 4.3.1.1), aspartate racemase, and D-amino acid aminotransferase (Fig. 17-12). Aspartase catalyzes conversion of fumarate into L-aspartate, which is racemized to form D-aspartate. D-Amino acid aminotransferase catalyzes transamination between D-aspartate and pyruvate to produce D-alanine and oxalacetate. This 2-oxo acid is easily decarboxylated spontaneously to form pyruvate in the presence of metals. Thus, the transamination proceeds exclusively toward the direction of D-alanine synthesis, and total conversion of fumarate into D-alanine was achieved. 

The 5,6,7,8-tetrahydro-7,7-dimethyl-2,5-dioxo-2H-l-benzopyran-4-carboxylic ester 435 was prepared from 1 and sodium diethyl oxalacetate in trifluoroacetic acid. Hydrolysis of the ester group in 435 gave 436 whose decarboxylation afforded the 7,8-dihydrobenzopyran 437 (72JOC1337). 

---