2-Oxoadipic acid

Carboxy-4-methyl-5-pentyl-2-furanpropanoic acid (273), isolated from blood and urine, is a hitherto unknown class of metabolic compound. The structure of (273) has recently been confirmed by synthesis (80CB699). 2,4,5-Trialkyl substituted furan-3-carboxylic acids have been synthesized from acyloin and /3-ketoesters by treatment with zinc chloride. By analogy with this synthetic route, the reaction of acetoin with 3-oxoadipic acid dimethyl ester was found to yield the 2,3-dimethylfuran (274). The dimethyl ester (275) was prepared by condensation of 3-chloro-2-octanone with 3-oxoadipic acid dimethyl ester and was shown to be identical with the dimethyl ester of the natural product. 

There is a substantial literature on the transformation of simple phenolic acids by microorganisms.2,7,11,16,18,20,22,25,29,44 For example, ferulic acid is transformed by fungi to either caffeic acid or vanillic acid, and these are transformed to protocatechuic acid. Next the ring structure of protocatechuic acid is broken to produce 3-carboxy-c/s,c/s-muconic acid, which is then converted to (3-oxoadipic acid (Fig. 3.1), which in turn is broken down to acetic acid and succinic acid, and these ultimately are broken down to C02 and water.11,18,29 Flowever, distribution of residual 14C-activity after growth of Hendersonula toruloidea, a fungus, in the presence of specifically 14C-labeled ferulic acid ranged from 32 to 45% in C02, 34 to 45% in cells, 9 to 20% in humic acid and 4 to 10% in fulvic acid.29 Thus, a considerable portion of the ferulic-acid carbon was bound/fixed over a 12-week period, and the initial ferulic acid transformation products (e.g., caffeic acid, vanillic acid and protocatechuic acid) were clearly of a transitory nature. Similar observations have also been made for other simple phenolic acids 22,23 however, the proportions metabolized to C02 and fixed into cells and the soil... 

Schulze-Bergkamen A, Okun JG, Spiekerkotter U, et al (2005) Quantitative acylcarnitine profiling in peripheral blood mononuclear cells using in vitro loading with palmitic and 2-oxoadipic acids biochemical confirmation of fatty acid oxidation and organic acid disorders. Pediatr Res 58 873-880... 

The overall sequence is illustrated for the preparation of 2-oxoadipic acid in Scheme 36 and the methodology was also successfully applied in carbohydrate chemistry [38]. 

The semialdehyde is subsequently oxidized to 2-ami-noadipic acid, which is transaminated to 2-oxoadipic acid. Further degradation, via glutaiyl-CoA to acet-yl-CoA is identical with the final stages of i-trypto-phan degradation (see t-Ttyptophan). An alternative pathway (Fig. 2) of Lys degradation in mammals (also in yeast) involves acetylated intermediates ey-... 

Approximately thirteen cases of 2-aminoadipic aciduria have been reported in the literature. Nine of the reported patients excreted in addition more or less significant amounts of 2-oxoadipic acid, some also 2-hydroxy-adipic acid and variable amounts of glutaric acid. The latter results obviously from spontaneous decarboxylation of 2-oxoadipic acid. 

In all cases, the starting material has been the bromide (3). The first method of synthesis via the diester (156) was originally developed on the basis of the 3-desmethoxy analog of the bromide (3) as early as 1934 [275, 276] and was improved in 1951 [195]. The ketodiester (156) was formed by the alkylation of the bromide (3) with the diester of )S-oxoadipic acid its cyclization and hydrolysis led to the diacid (157). Pyrolysis of the latter over lead carbonate enabled the 18-nor derivative (158) to be obtained. ... 

The use for alkylation of the diester of ce-methyl-jS-oxoadipic acid [195] led through the keto diester (159) and the lactone-ester (160) to A " -de-hydro-equilenin (33), the hydrogenation of which (Scheme 4) has given equilenin. 

Carboxyethylquinoxalinol and 3-carboxypropylquinoxalinol, formed from 2-oxoglutaric and 2-oxoadipic acids respectively, are reported to be stable to decarboxylation (Langenbeck et aL, 1975), and the derivatives form a useful group of compounds for the determination of most 2-oxocarboxylic acids. However, other carboxylic acids cannot be determined simultaneously as is usual when oxime and substituted oxime derivatives (Section 3.2.1) are used, although it may be advantageous occasionally to determine the 2-oxo acids separately in this way. 

Fig. 13.5 Mass spectra of the trimethylsilyl derivative of (a) 2-hydroxyadipic acid and the ethoxime-trimethylsilyl derivative of (b) 2-oxoadipic acid.

Biological. Benzoic acid may degrade to catechol if it is the central metabolite whereas, if protocatechuic acid (3,4-dihydroxybenzoic acid) is the central metabolite, the precursor is 3-hydroxybenzoic acid (Chapman, 1972). Other compounds identified following degradation of benzoic acid to catechol include cis,c/5-muconic acid, (+)-muconolactone, 3-oxoadipate enol lactone, and 3-oxoadipate (quoted, Verschueren, 1983). Pure microbial cultures hydroxylated benzoic acid to 3,4-dihydroxybenzoic acid, 2- and 4-hydroxybenzoic acid (Smith and Rosazza, 1974). In activated sludge, 65.5% mineralized to carbon dioxide after 5 d (Freitag et al., 1985). 

Oxoadipate enol lactone, see Benzoic acid (4-Oxo-3//-l,2,3-benzotriazin-3-yl)methanesulfonic... 

This compound (4) was prepared both by Holker132, and Buchi et al.55), in connection with studies done to help elaborate the structures of the B and G series of toxins. Condensation of phloroglucinol dimethyl ether (39)133 with diethyl j3-oxoadipate (sulfuric acid) gave the coumarin (6), after a hydrolysis-cyclization (phosphoric acid) sequence. Compound (4) was then able to be obtained by catalytic hydrogenation of(6). 

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