Oxalacetic acid reaction

The reaction probably proceeds through oxalacetic acid as an intermediate HOOCCH(OH)CH OH)COOH HOOCC(OH)=CHCOOH ... 

Make acid yields coumaUc acid when treated with fuming sulfuric acid (19). Similar treatment of malic acid in the presence of phenol and substituted phenols is a facile method of synthesi2ing coumarins that are substituted in the aromatic nucleus (20,21) (see Coumarin). Similar reactions take place with thiophenol and substituted thiophenols, yielding, among other compounds, a red dye (22) (see Dyes and dye intermediates). Oxidation of an aqueous solution of malic acid with hydrogen peroxide (qv) cataly2ed by ferrous ions yields oxalacetic acid (23). If this oxidation is performed in the presence of chromium, ferric, or titanium ions, or mixtures of these, the product is tartaric acid (24). Chlorals react with malic acid in the presence of sulfuric acid or other acidic catalysts to produce 4-ketodioxolones (25,26). 

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. 

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. 

Acetylneuram nic acid. The yield and stereoselectivity of the aldol condensation of 2-acetamido-2-dc.soxy-r>-manno.sc (1) with oxalacetic acid (2) to give N-acetyl-ncuraminic add (3) are improved by adding sodium tetraborate to (he reaction, which is carried out in aqueous solution at pH 10. Thus in the absence of borate ion, yields of (3) ofl 1.5 % have been reported, whereas addition of borate improves the yield to 21.6%. I he borate ion inhibits the alkaline cpimerization of various 2-acylamino-2-desoxy-aldoses. 

The assimilation of CO2 by bacteria was first demonstrated by Wood and Werkman who observed that during the fermentation of glycerol by propionic acid bacteria there was an over-all uptake of COj and that the amount of product (succinic acid) formed corresponded to the CO which was taken up. Since pyruvic acid was known to be present it was proposed that pyruvic acid condenses with CO to produce oxalacetic acid (Fig. 3, Wood-Werkman reaction) which is subsequently converted to succinic acid. 

In 1941, Krampitz and Werkman separated an enzyme preparation (oxalacetate /3-carboxylase) from Micrococcus lysodeikiicus which decar-boxylates oxalacetic acid to form pyruvic acid. Cocarboxylase was not required for this reaction. When oxalacetate, the enzyme and magnesium ions were incubated in the presence of until approximately half of the oxalacetate disappeared, was found in the remaining oxalacetate. The isotope was found exclusively in the carboxyl group adjacent to the methylene group. Since the reaction medium contained only oxalacetate and CO2, and since the only products formed were pyruvic acid and COs, it was concluded that this reaction was reversible. 

Aldol reactions of this type, involving 2-acetamido-2-deoxyaldohexoses, have been studied in connection with the chemical synthesis of A -acetyl-neuraminic acid (50) and related substances, and, for this reason, the choice of the dicarbonyl compound has thus far been limited to oxalacetic acid and its esters. Oxalacetic acid condenses readily with 2-acetamido-2-deoxyaldohexoses in aqueous solution at pH 11. Under these conditions, acetamido sugars partially epimerize, and the aldol reaction takes place for both of the 2-acetamido-2-deoxyaldohexoses present. The complexity of the reaction is further increased by the formation of asymmetric centers at carbon atoms 3 and 4 of the condensation products, namely, diacids (45) and (48), and this can result in the formation of four diastereo-isomers from each sugar. The reaction using 2-acetamido-2-deoxy-o-rnannose (47) has been the one most extensively studied. In this... 

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. 

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. 

This acetylpyridone diester 15 was conveniently synthesized in 60% yield by reacting acetoacetamide with ethoxy-methylene oxalacetic acid diethyl ester 14 in ethanol in the presence of sodium acetate (13). Compound 14 was prepared according to the procedure of R. G. Jones by condensing ethyl oxalacetate with ethyl orthoformate in the presence of acetic anhydride (14). It was found that purified compound 14 gave the best yield (60%) of acetylpyridone diester 15, but as a matter of convenience, crude 14 gave product 15 in up to 40% yield. Isolation of 15 was expedited by the precipitation of its sodium salt from the reaction mixture. 

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. 

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