Glycoaldehyde phosphate

Eschenmoser and co-workers [35] studied the aldomerization of glycoaldehyde phosphate which led to mixtures containing mostly racemates of the two diastereomeric tetrose 2,4-di-phosphate and eight hexose 2,4,6-triphosphates (O Scheme 2, route A). At 20 °C in the absence of air, a 0.08-molar solution of glycolaldehyde phosphate 2 in 2-M NaOH gave 80% yield of a 1 10 mixture of tetrose 3 and hexose 4 derivatives with DL-allose 2,4,6-triphosphate comprising up to 50% of the mixture of sugar phosphate [36]. 

L-ribulose 5-phosphate 4-epimerase divalent metal (Mn2+ > Ni + > Ca + > Zn +) glycoaldehyde phosphate + metal-bound enolate retro-aldol C—C bond cleavage ... 

Another group of sugar epimerases, which uses a metal cofactor instead of NADH/NAD+, takes an entirely different approach to epimerization. L-ribulose 5-phosphate 4-epimerase, which is involved in the bacterial metabolism of arabinose, performs a retro-aldol cleavage of a C-C bond to yield a metal-stabilized enolate of dihydroxyacetone and glycoaldehyde phosphate, similar to the reaction catalyzed by class II aldolases [77-79]. The glycoaldehyde phosphate is thought to rotate, such that addition of the enolate generates the isomeric product. 

The first step is a retro-aldol of the Zn+ -coordinated l-ribulose-5-phosophate (150) induced by the enzyme to give the aldehyde 151A (glycoaldehyde phosphate) and the zinc-coordinated enolate anion 152 (dihydroxyacetone enolate). Before the aldol reaction occurs, there is a bond rotation to generate a different rotamer of the aldehyde, 151B (see Chapter 8, Section 8.1, for a discussion of rotamers). The aldehyde unit is not positioned differently, such that an aldol reaction will give the aldolate 153, but rather with a different absolute stereochemistry (Chapter 9, Section 9.3). The overall enzyme process leads to epimerization of the hydroxyl-bearing carbon. 

We have traced the metabolic pathways channelling metabolites towards the fluorometabolites in S. cattleya and an overview of these relationships is shown in Figure 13. We believe that the substrate for the fluorination process is either a C3 phosphorylated glycolytic intermediate such as dihydroxyacetone phosphate or glyceraldehyde-3-phosphate, or alternatively a C2 metabolite such glycoaldehyde phosphate, derived from these compounds. Fluoroacetaldehyde appears to be a strong candidate for the role of common intermediate to both fluoroacetate and 4-fluorothreonine. 

The compound (54) has been enzymatically converted into a phosphorylated derivative of (E)-2-methylbut-2-ene-l,4-diol, which most probably represents a novel intermediate in the methylerythritol phosphate pathway of isoprenoid biosynthesis. The use of a photolabile acetal protecting group enables the synthesis of glycoaldehyde di-, and triphosphates (55) and (56) respectively. 

Transketolase is a TPP-dependent enzyme found in the cytosol of many tissues, especially hver and blood cells, in which principal carbohydrate pathways exist. In the pentose phosphate pathway, which additionally supplies reduced nicotinamide-adenine dinucleotide phosphate (NADPH) necessary for biosynthetic reactions, this enzyme catalyzes the reversible transfer of a glycoaldehyde moiety from the first two carbons of a donor ketose phosphate to the aldehyde carbon of an aldose phosphate. 

Thiamine pyrophosphate is also an important cofactor for the transketolase reactions in the pentose phosphate pathway of carbohydrate metabolism (Fignre 15-3). These reactions are important in the reversible transformation of pentoses into the glycolytic intermediates fructose 6-phosphate and glyc-eraldehyde 3-phosphate. Again, it is the reactive carbon on the thiazole ring of TPP that reacts with a ketose phosphate (xylnlose 5-phosphate) to canse the release of an aldose phosphate with two fewer carbons (glyceraldehyde 3-phosphate). The TPP-bonnd glycoaldehyde unit is then transferred to a different aldose phosphate (ribose 5-phosphate or erythrose 4-phosphate) to produce a ketose phosphate that has two carbons more (sedoheptulose 7-phosphate or fructose 6-phosphate). 

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... 

Both L- and D-ribose occur in this complex mixture, but are not particularly abundant. Since all carbohydrates have somewhat similar chemical properties, it is difficult to envision simple mechanisms that could lead to the enrichment of ribose from this mixture, or how the relative yield of ribose required for the formation of RNA could be enhanced. However, the recognition that the biosynthesis of sugars leads not to the formation of free carbohydrates but of sugar phosphates, lead Albert Eschenmoser and his associates to show that under slightly basic conditions the condensation of glycoaldehyde-2-phosphate in the presence of formaldehyde considerable selectivity exist in the synthesis of ribose-2,4-diphosphate 54). This reaction has also been shown to take place under neutral conditions and low concentrations in the presence of minerals (55), and is particularly attractive given the properties of pyranosyl-RNA (p-RNA), a 2 ,4 -linked nucleic acid analogue whose backbone includes the six-member pyranose form of ribose-2,4-diphosphate 56). 

An exception is the dihydroxyacetone (DHA) utilizing aldolases such as the D-fructose-6-phosphate aldolase that also accepts hydroxyacetone, hydroxy-butanone, and glycoaldehyde. Such broad donor tolerance is almost unique among aldolases [8,82]. Aldolases can accept a broad structural variety of aldol acceptors, and this is what makes them highly important for synthetic applications. 

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