Hydroxy pyruvate

Table 5. Transketolase Catalyzed Preparative Aldol Additions with Hydroxy-pyruvate...

Based on the stereospecific transketolase-catalyzed ketol transfer from hydroxy-pyruvate (20) to D-glyceraldehyde 3-phosphate (18), we have thus developed a practical and efficient one-pot procedure for the preparation of the valuable keto-sugar 19 on a gram scale in 82% overall yield [29]. Retro-aldolization of D-fructose 1,6-bisphosphate (2) in the presence of FruA with enzymatic equilibration of the C3 fragments is used as a convenient in-situ source of the triose phosphate 18 (Scheme 2.2.5.8). Spontaneous release of CO2 from the ketol donor 20 renders the overall synthetic reaction irreversible [29]. 

The transketolase (TK EC 2.2.1.1) catalyzes the reversible transfer of a hydroxy-acetyl fragment from a ketose to an aldehyde [42]. A notable feature for applications in asymmetric synthesis is that it only accepts the o-enantiomer of 2-hydroxyaldehydes with effective kinetic resolution [117, 118] and adds the nucleophile stereospecifically to the re-face of the acceptor. In effect, this allows to control the stereochemistry of two adjacent stereogenic centers in the generation of (3S,4R)-configurated ketoses by starting from racemic aldehydes thus this provides products stereochemically equivalent to those obtained by FruA catalysis. The natural donor component can be replaced by hydroxy-pyruvate from which the reactive intermediate is formed by a spontaneous decarboxylation, which for preparative purposes renders the overall addition to aldehydic substrates essentially irreversible [42]. 

Nondirected probes O 0 cl -x N vif-N>r hrvcoNH2 H ° v Oxidoreductases Enoyl-CoA hydratases Glutathione-S- transferases (GSTs) Hydroxy pyruvate reductase GSTs [27. 43. 44] [45]... 

The action of transketolase generates vicinal diols having the same stereochemistry as the products of RAMA-catalyzed condensation. The enzyme, however, has two signiHcant advantages over RAMA the reaction docs not require DHAP, and the products arc not phosphorylated. The ketose functionality can be replaced by hydroxy pyruvate, which provides a hydroxyketo equivalent after decarboxylation. No other hydroxy acid has yet been found that is accepted by transketolase. Although the enzyme is absolute in its requirement for the R configuration of the hydroxy functionality at C2 of the aldehyde, there seem to be no other stereochemical requirements. Transketolase accepts a range of aldoses as substrates, and should be a useful enzyme for carbohydrate synthesis (Table 1) (37). 

The above structure is confirmed by the results obtained by periodic acid oxidation 93), Sucrose consumes three moles of periodic acid, and one mole of formic acid is formed. (See earlier discussion in this chapter.) After bromine oxidation of the tetraaldehyde and subsequent hydrolysis, hydroxy-pyruvic, D-glyceric, and glyoxylic acids are obtained. (For a discussion of this method see p. 215.)... 

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 ... 

Although the native substrate for the enzyme is pyruvate, the enzyme is capable of decarboxylation of a number of other substrates such as hydroxy pyruvate, acetaldehyde, aliphatic a-keto acids, and p-substituted a-keto acids [11,21]. It has been reported that pyruvate decarboxylase decarboxylates higher homologues of pyruvate up to 2-oxohex-anoate, also at a rate decreasing with chain length. The enzyme is activated by its substrate, pyruvate, but is practically inactive when the substrate concentration approaches zero [22]. 

Transketolase (TKase, EC 2.2.1.1) essentially catalyzes the transfer of C-2 unit from d-xylulose-5-phosphate to ribose-5-phosphate to give D-sedoheptulose-7-phosphate, via a thiazolium intermediate as shown in Eq. (26). An important discovery was that hydroxy-pyruvate (74) works as the donor substrate and the reaction proceeds irreversibly via a loss of carbon dioxide [111] [Eq. (27)]. In this chapter, we put emphasis on the synthesis with hydroxyp5nnvate, as it is a typical TPP-mediated decarboxylation reaction of a-keto acid [112]. 

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