Condensation with pyruvate

Pyruvic Acid Compounds.—Lubrzynska and Smedley have recently shown that a number of aldehydes such as heliotropin, anisic aldehyde, benzaldehyde, and cinnamic aldehyde, condense with pyruvic acid in slightly alkaline solution, with the formation of )8-unsaturated-a-ketonic acids. For example, if heliotropin and pyruvic acid in alkaline solution be left standing for about eight days at ordinary temperature, dihydroxy-methylene-benzal-pyruvic acid is formed. This body forms yellow needles, melting at 163° Similarly, anisic aldehyde yields methoxy-benzal-pyruvic acid, melting at 130° and cinnamic aldehyde yields cinnamal-pyruvic acid, melting at 73°. 

Likewise, such functional derivatives of V-acetylmannosamine as the 6-acetate (16), the 6-(L-lactate) 17, and the 4- and 6-methyl ethers, 18 and 19, condensed with pyruvate, gave,20 in good yields, acids 20, 21, 22, and 23. 

Condensations with pyruvate in the presence of V-acylneuraminate pyruvate lyase immobilized on agarose. 

The S-methyl compound (140) (R = Me), when treated with aminoacetal 152, yielded imidazodiazocine 153 (R = H). If, in addition, various electrophiles are added, such as aroyl isothiocyanates and aroyl chlorides, N-substituted compounds 153 (R = CONHC6H3R2 (R2 = Cl, Me) 3,4,5-(OMe)3C6H2CO, and 5-N02-2-furyl] are obatined [761JC(B)773]. Reaction of isoureas 113 (R = Me, Et) or isothioureas 140 (R = Me, Et) with hydrazine gave 106 (R = NH2). The latter compound was condensed with pyruvate or 2-ketophenylacetate esters to afford diazocino-l,2,4-triazinones 154 (R = Me, Ph) (72LA112). 

In the search for antimalarial products and other biologically active compounds unsubstituted isatin 7 and its derivatives 59 were brought into condensation with pyruvic acid, resulting in the synthesis of the diacids 60 [7, 15, 45-47],... 

Disposition in the Body. Acetaldehyde is a major intermediate metabolite of ethanol and is also a metabolite of metaldehyde, paraldehyde, and phenacetin. It undergoes further metabolism by oxidation to acetic acid and, eventually, to carbon dioxide and water. A minor pathway involves condensation with pyruvic acid to form acetoin. 

R, = OH, Rj = H, R2 = OH, R4 = CHjOH in Table 3), the enantiomeric compound of the one just reported could be easily prepared. Aldol condensation products were obtained as diastereomeric mixtures from L-sugars, such as L-fucose, L-xylose, L-lyxose, and o-sugars epimeric to o-mannose relative to the 3-position, such as D-allose and o-gulose [46-48]. Table 4 lists the corresponding aldol condensation products isolated as diastereomeric mixtures. Also, 3-deoxy-D-mannose by condensation with pyruvate gave a diastereomeric mixture of 6-deoxy-KDN furanose derivatives [43]. All these results confirm that sialic acid aldolase, similar to other aldolases, exhibits broad specificity toward the electrophilic acceptor on the other hand, only pyruvate was reported acceptable as the donor [10]. But very recently, in contradiction to that, 3-fluoro-Neu5Ac and 3-fluoro-KDN could be prepared by the sialic acid aldolase-catalyzed condensation of 3-fluoropyruvate and Af-acetylmannosamine or o-mannose (Scheme 5) [47]. 

Pyruvate ketals can be synthesized [161] by direct condensation of a pyruvate ester with a diol in the presence of a Lewis acid, but this is less preferred because of the electron-withdrawing effect of the adjacent carboxylate group [162,163]. Therefore, several indirect methods for the acetalization have been introduced including condensation with pyruvate derivatives [164,165] or generation of the carboxylate group by oxidation of a suitable precursor [166,167,168,169]. A more efficient route to pyruvic acid acetals starts from silylated diols [170] or by the reaction between diols and methyl pyruvate dialkyl dithioacetal [171,172] activated by methyl triflate, dimethyl(methylthio)sulfonium trifluoromethane sulfonate (DMTST), nitroso tetraflu-oroborate (NOBF4), S02Cl2-trifluoromethanesulfonic acid, or Al-Iodosuccinimide (NIS) and trifluoromethanesulfonic acid [173] (O Scheme 24). 

Further experiments with threonine and isoleucine have been carried out in Senecio magnificus Both [2- " C]- and [6- " C]-isoleucine were incorporated into senecic acid (21) and degradation gave a pattern of incorporation consistent with biosynthesis from two isoleucine units (Scheme 5). [ /- " CJ-L-Threonine was equally well incorporated into senecic acid, which was shown to contain essentially no activity at C-2 and C-8, consistent with the way in which threonine condenses with pyruvic acid to give isoleucine the route from threonine to senecic acid is illustrated (Scheme 6). In these three feeding experiments the incorporation of radioactivity into the main alkaloidal component of this plant, retronecine, was very low. 

Similarly, the Doebner reactionl >i b condenses aromatic amines and aldehydes and pyruvic acid derivatives. Reaction of p-toluidine with pyruvic acid (266) gave the aminopyruvic acid (267) in situ and subsequent cyclization and air oxidation under Friedel-Crafts conditions generated the 4-carboalkoxy-quinoline (268).Presumably, the reaction proceeds via initial imine formation (via reaction with benz-aldehyde) followed by condensation with pyruvate (in its enol form).l l Similar cyclization occurs with imines and pyruvate derivatives. ... 

Although a great number of alkaloids having a /8-carboline structure have been found in nature, very few reports have been published about their biogenesis, and these are concerned only with the plant material. From among the alkaloids mentioned above only harman (180) and 4,5-dihydrocanthin-6-one (181) were demonstrated in feeding experiments with H- and C-labeled precursors to be derived biosynthetically from tryptophan. In the case of harman, tryptamine is probably condensed with pyruvic acid to give l-methyl-l,2,3,4-tetrahydro-j8-carboline-l-carboxylic... 

Taking advantage of Harlan Wood s discovery that carbon dioxide itself enters the metabolic pool by condensing with pyruvate to produce oxalacetate, R. C. Greu-... 

In this pathway (Pig. 88.4), D-glyceraldehyde-3-phosphate initially condenses with pyruvate to yield l-deoxy-D-xylulose-5-phosphate (DOXP) through... 

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