3- Oxoglutaric acid derivatives

N-Alkylated 2-oxoglutaric acid derivatives cyclize at neutral pH values to two epimeric 5-carboxy-5-hydroxy-2-oxopyrolidine structures (Chart 4). In this way, ot-hydroxycarboxylic acid groupings are formed that can act as ligand sites for Fe ". ... 

The sodium salt of the stabilized enolate derived from the heteroaryl-substituted 2-oxoglutaric acid ester (186) is reported to have the alkene geometry as shown in formula (187). Hnally, Collum et al. have reported the structure of the lithiated anion derived from the A, A -dimethylhydrazone of 2-methoxy-carbonylcyclohexanone (188). This enolate crystallizes as the dimeric, bis-THF-solvated aggregate (189). 

Some of the earliest kinetic studies on metal ion-promoted reactions were carried out on metal ion-promoted decarboxylations of j8-oxo acids. The literature on this topic up to about 1974 has been reviewed. Much of the work has centred on oxaloacetic acid (HO2CCOCH2CO2H = H20xac) and its derivatives, a,a-dimethyl oxaloacetic acid and fluorooxaloacetic acid. Studies have also been made with acetonedicarboxylic acid (3-oxoglutaric acid), " dihydroxyfumaric acid, dihydroxytartaric acid, acetosuccinic acid, oxalosuccinic acid and 2-oxalopropionic acid (Figure 6). The decarboxylation of )3-oxo acids is of considerable biological importance, and in a number of cases metalloenzymes are involved. Similarities in the enzymatic and chemical processes stimulated early interest in these reactions as models for the enzymatic systems. 

Various approaches to the synthesis of 2,7-naphthyridines are available. Thus, the dianilide of 3-oxoglutaric acid 133 reacted with malononitrile in the presence of sodium acetate to give pyridone derivative 134, whereas the reaction of 133 with ethyl cyano-acetate in pyridine afforded tetrahydropyridinedione derivative 135. The compounds 134 and 135 underwent cyclization upon heating with triethylamine in DMF to form substituted 2,7-naphthyridine-3,6-diones 136 and 137, respectively (1989JPR745). 

Thalictrum minus, T. minus var. adiantifolium, which contains thalifoline (2)/ Trichocereus werdermamianus and T. pachanoO The peyote cactus Lophophora williamsii) deserves special mention biogenetically important mescaline derivatives have been isolated the first N-ethylisoquinoline alkaloid (3) has been characterised and pyrrole derivatives, e.g., (4), have been identified. The isolation of (4) prompted the speculation that mescaline may incorporate a-oxoglutaric acid and thus may be involved in the Krebs cycle. ... 

Isoda, T., Ichikawa, A., and Shimamoto, T. (1958) Asymmetric synthesis. I. General conditions of asymmetric rednction of derivatives of oxoglutaric acid, Repts. Sci. (Res. Inst. Phys. Chem. Tokyo), 34, 134 -142. 

Phylloquinone and menaquinone are derived from chorismic acid, which results from 3-phosphoenolpyruvic acid (a product of glycolysis) and D-erythrose 4-phosphate (a product of the pentose and Calvin cycles) as a starting compound for the biosynthesis of phenylalanine, tyrosine and tryptophan. It is transformed into iso-chorismic acid other carbon atoms are derived from 2-oxoglutaric acid. The side chain is provided by ph)4yl diphosphate or by polyprenyl diphosphates, which are formed from geranylgeranyl diphosphate. The final reaction is a methylation at C-2. 

AcCoA is the building block of fatty acids, polyketides, and mevalonic acid (MVA), a cytosolic precursor of the C5 isoprene units for the biosynthesis of terpenes in the C,5 and Cj series (mind it is different from the MEP pathway, in product, and in cell location). Finally, AcCoA enters the citric acid or Krebs cycle, which leads to several precursors of amino acids. These are oxaloacetic acid, precursor of aspartic acid through transamination (thus toward lysine as a nitrogenated C N linear unit and methionine as a methyl supplier), and 2-oxoglutaric acid, precursor of glutamic acid (and subsequent derivatives such as ornithine as a nitrogenated C N linear unit). All these amino acids are key precursors in the biosynthesis of many alkaloids. 

Alkaloids Derived from the Krebs Cycle (Lysine and Ornithine Derived) As shown previously (Scheme 1.2), the Krebs cycle is a crucial metabolic process, which leads to a-ketoacids (oxaloacetic and 2-oxoglutaric acids). Their enzymatic transamination affords the two amino acids— aspartic acid and glutamic acid—which are the direct biosynthetic precursors of amino acids lysine and ornithine, respectively. These in turn produce cadaverine, a CjN unit, and putrescine, a C N unit, which are major components for the biosynthesis of important alkaloids, as will be discussed later (Scheme 1.6). Additionally, ornithine is a precursor of arginine, another important amino aeid. 

Fig. 5.18 Mass spectra of the trimethylsilyl derivatives of the oximes of (a) 2-oxo-isovaleric acid and (b) 3-phenylpyruvic acid, (c) the methyloxime of 2-oxoglutaric acid, and the ethyloximes of (d) 2-oxoglutaric acid and (e) 3-phenylpyruvic acid.

On heating the parent acid of ester VI (from condensation of D-glucose with diethyl 3-oxoglutarate) in aqueous solution,11 following the procedure employed to obtain the corresponding derivative of ethyl acetoacetate XXVI, a sirup results. However, its change in optical activity shows a parallelism with that in analogous cases where crystalline products are isolated, and apparently indicates anhydride formation (see the last line in Table V). 

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