Hydroxypyruvic aldehyde

Furthermore, a base-catalyzed transformation by OH from the reaction medium between glycerate and hydroxypyruvate aldehyde (or hydroxypyruvic acid) could be excluded, while hydroxyacetone and glyceraldehyde interconversion was possible (Scheme 11.11). The existence of two major routes, of which hydroxyacetone and glyceric aldehyde are the primary oxidation products and glycolic and oxalic acid are the end-members, respectively, is now firmly established. Clearly, rapid oxidation of glyceraldehydes favors glyceric acid rather than hydroxyacetone formation. 

This dialdehyde was then hydrolyzed to hydroxypyruvic aldehyde and glycolaldehyde, which were identified as the dinitrophenylosazones. These data prove the pyranoside structure of methyl a-L-sorboside. 

Aldehydes have been formed from alcohols by the use of other oxidizing agents. Dihydroxyacetone has been oxidized with excess cupric acetate to hydroxypyruvic aldehyde in 87% yield. p-Cyanobenzyl alcohol treated at 0° with a chloroform solution of nitrogen tetroxide gives practically pure p-cyanobenzaldehyde (90%). Aromatic alcohols containing nitro groups have been oxidized to the corresponding nitro aldehydes with concentrated nitric acid, e.g., o- and p-nitrobenzaldehydes (80-85%). m-Nitrobenzenesulfonic acid in basic media has been used for the oxidation of substituted benzyl alcohols, most satisfactorily for the water-soluble phenolic benzyl alcohols. Selenium dioxide, or less effectively tellurium dioxide, oxidizes benzyl alcohol slowly to benzaldehyde. ... 

The simplest osone, glycerosone or hydroxypyruvic aldehyde, has been prepared by the oxidation of dihydroxyacetone. This compound is enolic in character, reducing cold Fehling solution and forming acidic aqueous solutions 160). It exists normally as the trimer. 

A number of lyases are known which, unlike the aldolases, require thiamine pyrophosphate as a cofactor in the transfer of acyl anion equivalents, but mechanistically act via enolate-type additions. The commercially available transketolase (EC 2.2.1.1) stems from the pentose phosphate pathway where it catalyzes the transfer of a hydroxyacetyl fragment from a ketose phosphate to an aldehyde phosphate. For synthetic purposes, the donor component can be replaced by hydroxypyruvate, which forms the reactive intermediate by an irreversible, spontaneous decarboxylation. 

D-erythro-Pentulose 5-phosphate (XLIV) has been formed by the action of transketolase on hydroxypyruvate (XLII) and D-glycerose 3-phosphate, the hydroxypyruvate being decarboxylated196 to active glycolaldehyde which then reacts with the triose phosphate by an acyloin reaction.28 The active glycolaldehyde is also formed from L-glycero-tetrulose, d-altro-heptulose 7-phosphate, D-fructose 6-phosphate, and D-i/ireo-pentulose 5-phosphate and it reacts with various aldehydes (acceptors) to give ketoses.198, 200 Thus, substitution of L-gfh/cero-tetrulose for hydroxypyruvate in the above experiment also resulted in formation of D-en/i/iro-pentulose... 

In a critical study of the periodate oxidation of raffinose and related oligosaccharides, Courtois and Wickstrom showed78 that 1 mole of raffinose reduces 5 moles of periodate, with the formation of 2 moles of formic acid plus a hexaldehyde. Conversion of the aldehyde to the hexa-carboxylic acid, followed by hydrolysis, gave the expected amounts of glyoxylic acid, glyceric acid, hydroxypyruvic acid, and glycolaldehyde (by decarboxylation of hydroxypyruvic acid). 

Figure 2.2.12 Reaction network of glycerol oxidation (GLY, glycerol DHA, dihydroxyace-tone GLA, glyceric aldehyde GLS, glyceric acid HBT, hydroxypyruvic acid MOS, mesoxalic acid TS, tartronic acid GOX, glyoxal GOS, glycolic acid GYS, glyoxylic acid OS, oxalic acid).

Sucrose was oxidized by Fleury and Courtois, who obtained a tetra-aldehyde (87) which was oxidized by bromine, in the presence of strontium or barium carbonate, to the corresponding tetracarboxylic acid salt the latter compound was hydrolyzed with acid to yield D-glyceronic acid, glyoxylic acid, and hydroxypyruvic acid, which spontaneously decomposed into carbon dioxide and glycolaldehyde. It was found that oxysucrose shows four aldehyde groups from hypoiodite estimation, but only two from mercurimetry the latter result was attributed to steric hindrance, but it would seem more likely that, under the conditions of the determination. 

This enzyme catalyzes the reversible transfer of the hydroxyketo group of a ketose phosphate to an aldose phosphate. The cofactor thiamine pyrophosphate (TPP) is associated with the enzyme and activates the ketose (Scheme 7). Most known donor ketoses (xylulose 5-phosphate, sedoheptulose 7-phosphate, fructose 6-phosphate, L-erythrose) have a trans arrangement of hydroxy groups at C-3 and C-4 hydroxypyruvate is an exception. A range of aldehydes (such as o-glyceraldehyde 3-phosphate, D-ribose 5-phosphate, o-erythrose 4-phosphate, glycoaldehyde) are acceptors. Transketolase has been... 

More recently, Henning and Ammon (H19) described 10 aliphatic keto and aldehydic adds in normal urine. In addition to a-ketoglutaric, oxalacetic, pyruvic, glyoxylic, and a-ketoisocaproic acids, they found hydroxypyruvic, a-keto-y-methylthiobutyric, a-keto-fi-hydroxybutyric, a-keto-P-methylvaleric and a-keto-n-butyric acids, that is to say, the keto acids corresponding, respectively, to serine, methionine, threonine, isoleucine, and a-amino-n-butyric acid. They conclude that one finds in normal human urine the keto acids corresponding to all the amino adds normally present in urine, with the exception of those correspond-... 

An enzyme closely related to the aldolases is transketolase. The enzyme is commercially available (from baker s yeast) and can also be obtained from spinach leaves. Transketolase catalyses the stereospecific synthesis of C—C bonds using aldehydes as the electrophiles, with a suitable 2-carbon ketol donor [e.g. hydroxypyruvate (9)] as the nucleophile (Scheme 5.11). The use of hydroxypyruvate ensures that the reaction goes to completion, since carbon dioxide is evolved as the by-product, and hence the reaction is irreversible. In addition, both magnesium ions and catalytic thiamine pyrophosphate are required as co-factors. 

Transketolase requires an acceptor it cannot split a ketol to form aldehydes. Presumably an intermediate active glycolaldehyde" is formed by combination of the two-carbon unit with the enzyme. The enzyme will react with a number of aldehydes, and the reactions in many cases have been shown to be reversible. The donor requirements are not completely understood. Among the sugars only those with the hydroxyl on carbon 3 on the l side are substrates. Before the discovery of epimerase, ribulose-5-phosphate was thought to be a substrate, but it has been shown that a mixture of ribose and ribulose phosphates does not undergo the transketolase reaction until epimerase is added. Besides xylulose phosphate, fructose-6-phosphate, sedoheptulose-7-phosphate, and hydroxypyruvate are glycolaldehyde donors. 

The specificity of purified transketolase is rather broad, and several compounds have been shown (93) to act as donors of active glycolaldehyde. Included in these compounds are D-ribulose 5-phosphate, D-sedoheptulose 7-phosphate, D-fructose 6-phosphate, L-erythrulose, and hydroxypyruvic acid. A number of aldehydes have been shown to act as active glycolalde-... 

The transketolase enzyme of Racker el obtained in crystalline form from baker s yeast, catalyzes the cleavage of ribulose-5-phosphate, with the formation of D-glyceraldehyde-3-phosphate upon the addition of an acceptor aldehyde, such as ribose-5-phosphate or glycolaldehyde. The reaction of hydroxypyruvate with D-glyceraldehyde-3-phosphate as acceptor aldehyde leads to the decarboxylation of the hydroxypyruvate with the formation of ribulose-5-phosphate. The transketolase enzyme was demonstrated to have a requirement for thiamine pyrophosphate. ... 

The enzyme is of low specificity and it also acts on ribulose-5-P, sedo-heptulose-7-P, L-erythrulose, hydroxypyruvate and fructose-6-P. A rupture of the ketol bond occurs and the active glycolaldehyde formed is condensed with an acceptor aldehyde. When the acceptor is glyceralde-hyde 3-P, ribulose-5-P is formed. 

Transketolase from spinach leaves has been used in the stmeoq)ecific condensation of hydroxypyruvic acid with a variety of aldehydes, including free sugars, which gives ketoses with (5) configuration at the new chiral centre. An example is given in Scheme 1. ... 

The acceptor aldehyde can be glycolaldehyde, 3-p-glyceraldehyde, 5-p-ribose, or 5-p-desoxyribose. There are really two quite separate processes which are catalyzed by Racker s yeast enzyme first, a non-oxidative decarboxylation of hydroxypyruvic acid to active glycolaldehyde and CO2 second, a transketolation of active glycolaldehyde from the enzyme to the acceptor aldehyde. One must conceive of the enzyme as the bearer of a keto group (ECO) which reacts with hydroxy-pyruvate to form an acyloin, with CO2 being liberated in the process ... 

Transketolase from Different Sources Catalyzed Aldol Transfer of Hydroxyacetyl Moiety from Hydroxypyruvate to Aldehydes... 

Although this type of transfonnation has been exploited in a synthetic manner, the reaction can be made more generally useful by using hydroxypyruvic acid 70 (HPA) as the ketol donor. The use of HPA renders the reaction irreversible by the concomitant release of carbon dioxide as a by-product. This TK-catalyzed C C bond formation is both stereospecific and stereoselective leading to the (5)-enantiomer." A wide range of aldehyde acceptors can then be used (Scheme 28.30). 

The mechanism of formation of a,a -dihydroxy ketones by tertiary amine-catalysed reaction of aldehydes with lithium hydroxypyruvate proceeds with opportunity for facial stereodifferentiation as an intermediate adds to the aldehyde and can be achieved with up to 50% ee if catalysed by a quinine ether. i... 

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