4- -4-oxobutyric acid derivatives

Acylation of 270 with certain cyclic anhydrides 433 in acetic acid affords 4-oxobutyric acid derivatives 434. Cyclocondensation of these acids with acetic anhydride gives pyridazino[l,2- ]indazole-6,9,ll-triones 435 (Scheme 70) <2003MI1>. 

A facile and efficient synthetic route to densely substituted thiophenes based on base induced cyclization reaction between thioamides derived from morpholine and a-haloketones has been reported. Thus, the thioamides 4 were subjected to treatment with the haloketones 5 (R = H, Ar, Me) under basic conditions to provide the tetrasubstituted thiophenes 6. Likewise, the reaction was also demonstrated to give good yields of thiophenes when the haloketones were replaced with 2-bromo-3-oxobutyric acid derivatives or propargyl bromide <04T6085>. 

Hofmann and Schieberle (1996) suggested hydroxyacetaldehyde and 2,3-butanedione as possible precursors of this odorant lactone. A mechanism of formation (in vin jaune ) has been proposed by Guichard et al. (1998) by transformation of threonine (present in coffee) into 2-oxobutyric acid (which can also be derived from carbohydrates), condensation with acetaldehyde and cyclization. 

Gas chromatography Acesulfame-K, aspartame, cyclamate, saccharin, and stevioside are determined by gas chromatography, but the main drawback of this technique is that a derivatization is required. Acesulfame-K is methylated with ethereal diazomethane, aspartame is converted into its N- 2-methylpropoxycarbonyl) methyl ester derivative, menthol and isobutyl chloroformate are used to convert aspartame to 3-[(isobutoxycarbonyl)amino]-4-[[a-(methoxycarbonyl)phenethyl]amino]-4-oxobutyric acid, cyclamate is determined as cyclohexene resulting from the reaction with nitrite, saccharin is converted to N-methylsaccharin, and stevioside is hydrolyzed. Detection is carried out utilizing flame-ionization, flame-photometric electron-capture detectors or nitrogen-phosphorus detection. 

L-Isoleucine originates from 2-oxobutyric acid, a threonine derivative and activated acetaldehyde (C 4) as outlined in Fig. 196. Both compounds condense to form tx-aceto-a-hydroxybutyric acid from which 2,3-dihydroxy-3-methyl-... 

The amino acid L-histidine is the assumed building block in the biosynthesis of pilocarpine (27) and other imidazolic alkaloids due to the presence of glyoxaline ring [8, 23]. First attempts to clarify this pathway were proposed by Boit and Leete that considered the phosphate derivative of 2-oxo-3-(5-imidazofyl)-propanol, also known as imidazole pyruvic acid, as imidazole ring precursor (Scheme 25.1-Pathway 1) [8]. This initial biosynthesis proposal was improved detailing the lactone ring formation by aldol condensation. Another biosynthetic approach suggested condensation of 2-oxobutyric acid (lactone moiety) with urocanic acid (imidazole moiety) (Scheme 25.1- Pathway 2) [8, 39]. 

A cold soln. of 2-oxobutyric acid in ethanol treated with L-(—)-a-methylhenzyl-amine in the same solvent, 10%-Pd-on-charcoal added, hydrogenated 10 hrs. at 30 /50 p.s.i. until 1 mole of has been absorbed, the catalyst removed by filtration, the filtrate coned., aq. 30%-alcohol and palladium hydroxide-on-charcoal added, then hydrogenated at 25 /50 p.s.i. until Hg-uptake ceases L-butyrine. Y 75.9-84.9% excess of enantiomorph 81.4%.— Debenzylation with other catalysts was not successful. Asym. induction occurs during reduction of the azomethine and debenzylation can be performed with little or no loss of configurational integrity. The configuration of the amino acids is the same as that of the a-methylbenzylamine from which it is derived. The magnitude of the induced asymmetry depends on the substrate and the catalyst. F. e. s. R. G. Hiskey and R. G. Northrop, Am. Soc. 83 4798 (1961) asym. synthesis of amino acids s. a. J. G. Sheehan and R. E. Chandler, Am. Soc. 83, 4795 (1961). 

A mechanistic study of acetophenone keto-enol tautomerism has been reported, and intramolecular and external factors determining the enol-enol equilibria in the cw-enol forms of 1,3-dicarbonyl compounds have been analysed. The effects of substituents, solvents, concentration, and temperature on the tautomerization of ethyl 3-oxobutyrate and its 2-alkyl derivatives have been studied, and the keto-enol tautomerism of mono-substituted phenylpyruvic acids has been investigated. Equilibrium constants have been measured for the keto-enol tautomers of 2-, 3- and 4-phenylacetylpyridines in aqueous solution. A procedure has been developed for the acylation of phosphoryl- and thiophosphoryl-acetonitriles under phase-transfer catalysis conditions, and the keto-enol tautomerism of the resulting phosphoryl(thiophosphoryl)-substituted acylacetonitriles has been studied. The equilibrium (388) (389) has been catalysed by acid, base and by iron(III). Whereas... 

Although pyruvate and 2-oxobutyrate are substrates of acetohydroxyacid synthase, measurements of the activity of this enzyme have been almost exclusively based on the production of acetolactate from pyruvate. This reaction product is readily decarboxylated under acidic conditions and the acetoin produced can be measured spectrophotometrically. However, ace-toin can be formed during reactions which need not be related to amino acid biosynthesis. Therefore it is unclear whether the enzyme activity characterized by Saytanarayana and Radhakrishnan (1963) can be completely ascribed to acetohydroxyacid synthase. Only a portion of the acetolactate forming activity measured in pea extracts was considered to represent the activity of this enzyme (Davies, 1964). However, the enzyme(s) isolated from barley was shown to facilitate formation of acetohydroxy derivatives of 2-oxobutyrate and pyruvate (Miflin, 1971). Mg or Mn " " as well as the substrate, hydroxyethylthiamine-pyrophosphate, was required for maximum enzyme activity. The fact that the acetolactate forming activity of the barley... 

Fig. 4.3 Chromatogram of standard oxo acids separated as their trimethysilyl-oxime derivatives on 3 per cent OV-17 using temperature programming from 110°C to 220°C. Peak identifications are 1, pyruvate 2, 2-oxobutyrate 3, 2-oxoisovalerate 4, 2-0X0valerate 5, L-2-oxo-3-methylvalerate 6, 2-oxoisocaproate plus 7, d-2-oxo-3-methylvalerate 8, 2-oxo-4-methylthiobutyrate 9, 2-oxoglutarate 10, phenylpyruvate. (Redrawn with modifications from Sternowsky etal., 1973)...

Fig. 10.1 Metabolites in the urine of an untreated patient with branched-chain keto aciduria (maple syrup urine disease). Extracted using ethyl acetate and separated as their trimethylsilyl-oxime derivatives on a 25 m SE-30 capillary column, using temperature programming from 80°C to 110°C at 0.5°C min and an injection split ratio 1 12 at a temperature of 250°C. The peaks marked R are due to solvent and reagents. Peak identifications are 1, lactic 2, 2-hydroxyisobutyric 3, 2-hydroxybutyric 4, pyruvic 5, 3-hydroxybutyric 6, 2-hydroxyisovaleric 7, 2-oxobutyric 8, 2-methyl-3-hydroxy-isovaleric 10, a and b, 2-oxoisovaleric 11, acetoacetic 12, 2-hydroxyisocaproic 13, 2-hydroxy-3-methyl- -valeric 14, 2-oxo-3-methyl-/i-valeric (14a L- 14b D-) 15, 2-oxoisocaproic acids. The internal standard was malonic acid. (Redrawn with modifications from Jellum etal., 1976)...

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