Pyruvic acid esters

Especially high optical inductions have been achieved with catalysts which contain BPPM (13), PPM (14) or (15) as chiral ligands. Pyruvic acid esters were usually hydrogenated to lactic acid esters in quantitative chemical yield with an enantiomeric excess of 65-75%41 a,53). However, this method is not of technical significance, since chiral lactic acid derivatives may be produced more conveniently by biotechnological processes. 

This method has been developed especially by workers in the rubber industry (249) since many of these products are important vulcanization accelerators. The use of halo acetyl acetic acid esters, halo diketones or halo pyruvic acid esters allows thiazoline-2-thiones to be prepared with carbonyl or carboxyl substitution. These are also useful vulcanization accelerators (99, 101,102,103). 

Later, a modified version of the synthesis was reported, in which the important secodine precursor is a tetrahydro-jS-carboline derivative, such as 557-559, rather than an indoloazepine ester, as in 560. This led to a simpler synthesis, the tetrahydro-/3-carboline derivatives required for the preparation of 557-559 being obtained directly from the appropriate trypt-amine derivative and pyruvic acid ester. By this route, ( )-vincadifformine (76), ( )-minovine (A g-methylvincadifformine) and ( ) ervinceine (87) were synthesized in comparatively high yield, and in essentially two stages from the starting tryptamine (330). 

Treatment of aryl(aroyl)pyruvic acid ester metal chelates with ortho-phenylene-diamine and ethylenediamine is accompanied by an attack at the a-ketoester fragment, forming quinoxalones and piperazinones, respectively (95ZOR266, 99JFC(96)87) (Scheme 60). 

Besides several diastereoselective heterogeneous catalytic hydrogenations [1-3] only two enantioselective hydrogenation reactions are known the reduction of p-keto-esters with Raney-nickel modified by tartaric acid and of pyruvic acid esters with Pt modified by cinchona alkaloids. Garland and Blaser [4] described the reduction of pyruvic acid ester as a "ligand-accelerated" reaction with the adsorption of the modifier new active sites are generated on the catalyst surface. On these new centers the selective reaction is faster and the increased reaction rate is accompanied by greater enantioselectivities. 

The differences between the two systems are (i) the reaction on modified sites is faster then on unmodified ones (Pt-cinchonidine) (ii) the hydrogenation of pyruvic acid ester is enantioselective even if the cinchonidine is only solved in the reaction mixture without premodification of the catalyst. 

Although cinchona alkaloids and especially cinchonidine, Cnd, proved to be the most effective chiral modifier for the catalytic system of Pt-alumina, in the liquid phase enantioselective hydrogenations of the carbonyl group in pyruvic acid esters, efforts to understand the mechanism of action of this catalyst system has continued to the present. The efforts may be divided into two categories finding natural modifiers other than cinchona alkaloids and examining new effective amino alcohols, which are modeled after the structure of known cinchona modifiers. 

A little dichlorotitanium diisopropoxide in toluene added to a mixture of activated, powdered, 4A molecular sieves and a little (R)-2,2 -dihydroxy-1,1 -binaphthyl in methylene chloride at room temp, under argon, the mixture stirred for 1 h, cooled to — 70°, isobutylene and methyl glyoxylate added, warmed to — 30°, and stirred for 8 h - (R)-product. Y 72% (e.e. 95%). Molecular sieves facilitate ligand exchange on the metal and play a role in maximizing the stereodifferentiating ability of the catalyst (e.e. ca. 20% without sieves). F.e.s. K. Mikami et al., J. Am. Chem. Soc. Ill, 1940-1 (1989) from chiral pyruvic acid esters with TiCl4 cf. J.K. Whitesell et al., J. Org. Chem. 54, 2258-60 (1989) review of C2-symmetry and asym. induction s. Chem. Rev. 89, 1581-90 (1989). 

Most syntheses of iminocarboxylic acid derivatives start from a-keto acids or a-amino acids. Thus Appel and Hauss 12) described the formation of a-iminopropionic acid ester by treatment of pyruvic acid ester with triphenylphosphine imine. This product was however not isolated, but hydrogenated directly to the corresponding alanine ester. 

Methylsuccinic acid has been prepared by the pyrolysis of tartaric acid from 1,2-dibromopropane or allyl halides by the action of potassium cyanide followed by hydrolysis by reduction of itaconic, citraconic, and mesaconic acids by hydrolysis of ketovalerolactonecarboxylic acid by decarboxylation of 1,1,2-propane tricarboxylic acid by oxidation of /3-methylcyclo-hexanone by fusion of gamboge with alkali by hydrog. nation and condensation of sodium lactate over nickel oxide from acetoacetic ester by successive alkylation with a methyl halide and a monohaloacetic ester by hydrolysis of oi-methyl-o -oxalosuccinic ester or a-methyl-a -acetosuccinic ester by action of hot, concentrated potassium hydroxide upon methyl-succinaldehyde dioxime from the ammonium salt of a-methyl-butyric acid by oxidation with. hydrogen peroxide from /9-methyllevulinic acid by oxidation with dilute nitric acid or hypobromite from /J-methyladipic acid and from the decomposition products of glyceric acid and pyruvic acid. The method described above is a modification of that of Higginbotham and Lapworth. ... 

Only in the case of the pyruvic acid condensation product was it possible to isolate the corresponding ethyl ester under these conditions. This, on mild hydrolysis, reverted to 1-methyl-1,2,3,4-tetrahydro-j8-carbohne-1-carboxylic acid, identical with the starting material, which therefore had the assigned structure 26 (R = CH3) and was not the SchiflF s base 25 (R = CH3). Alkaline hydrolysis of the ester was accompanied by decarboxylation. ... 

Catalytic reduction of the nitrile 79 in the presence of semicarbazide affords initially the semicarbazone of 80. Hydrolysis-interchange, for example in the presence of pyruvic acid, gives the aldehyde 80. Condensation with the half ester of malonic acid leads to the acrylic ester 81 the double bond is then removed by means of catalytic reduction (82). Base catalyzed reaction of the... 

Addition of 2-pyrazolines to tetrazines gave 330 (84AP237 88CZ17). The pyrazolotriazine derivative 331 was prepared (76MI6) by treating diamino guanidine with acetyl pyruvic acid ethyl ester in either acid or neutral aqueous solution (Scheme 70). 

Ethyl bromopyruvate Pyruvic acid, bromo-, ethyl ester (8) Propanoic acid, 3-bromo-2-oxo-, ethyl ester (9) (70-23-5)... 

A. Phosphoenolpyruvate.—The mechanisms of hydrolysis of phosphate esters of phosphoenol pyruvic acid (33) have been described in detail, and 0 studies confirm an earlier postulate that attack by water on the cyclic acyl phosphate (34) occurs at phosphorus and not at carbon. In the enolase reaction, the reversible interconversion of 2-phosphoglyceric acid(35)... 

Nef prepared acetol in several ways, the more important of which depended upon the reaction between bromoacetone and potassium or sodium formate or acetate, and the subsequent hydrolysis of the ester by methyl alcohol.1 2 Acetol is also formed, together with pyruvic acid, by the direct oxidation of acetone by Baeyer and Villiger s acetone-peroxide reagent.3... 

METHYL PYRUVATE (Pyruvic acid, methyl ester)... 

A solution of 88 g. (l mole) of freshly distilled pyruvic acid, 1 128 g. (4 moles) of absolute methanol, 350 ml. of benzene, and 0.2 g. of -toluenesulfonic acid is placed in a 1-1. round-bottomed flask connected through a ground-glass joint (Note 1) to a methyl ester column shown in Fig. 1 2 (Note 2). The column is fitted at... 

Methyl pyruvate has been prepared from the silver salt of pyruvic acid and methyl iodide,3 and from the free acid by the alcohol-vapor method without a catalyst.4 Pyruvic esters have also been prepared by the dehydrogenation of lactic acid esters.5... 

Phenylethyl Alcohol Pyruvic Acid Oxalylacetic Acid Dihydroxytartaric Acid Dihydroxymaleio Add Acetonedicarboxylic Acid (ethyl ester) Muoonio Acid... 

Once the phosphate ester is hydrolysed, there is an immediate rapid tautomerism to the keto form, which becomes the driving force for the metabolic transformation of phosphoenolpyruvic acid into pyruvic acid, and explains the large negative free energy change in the transformation. This energy release is coupled to ATP formation (see Box 7.25). 

This is another exampie of substrate-level phosphorylation, but differs from the earlier example that involved hydrolysis of a mixed anhydride. Here, we have merely the hydrolysis of an ester, and thus a much lower release of energy. In fact, with 1,3-diphosphoglycerate, we specifically noted the difference in reactivity between the anhydride and ester groups. So how can this reaction lead to ATP synthesis The answer lies in the stability of the hydrolysis product, enolpyruvic acid. Once formed, this enol is rapidly isomerized to its keto tautomer, pyruvic acid, with the equilibrium heavily favouring the keto tautomer (see Section 10.1). The driving force for the substrate-level phosphorylation reaction is actually the position of equilibrium in the subsequent tautomerization. 

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