Enediolate intermediate

Aldoses are reducing sugars because they possess an aldehyde function m then-open chain form Ketoses are also reducing sugars Under the conditions of the test ketoses equilibrate with aldoses by way of enediol intermediates and the aldoses are oxidized by the reagent... 

There is another reaction available to the enediol intermediate Proton transfer from water to C 1 converts the enediol not to an aldose but to the ketose d fructose... 

The results supported the proposal of Glu-165 as the general base and suggested the novel possibility of neutral histidine acting as an acid, contrary to the expectation that His-95 was protonated [26,58]. The conclusion that the catalytic His-95 is neutral has been confinned by NMR spectroscopy [60]. The selection of neutral imidazole as the general acid catalyst has been discussed in terms of achieving a pX, balance with the weakly acidic intermediate. This avoids the thermodynamic trap that would result from a too stable enediol intermediate, produced by reaction with the more acidic imidazolium [58]. 

Because the configuration at C-2 is lost on enolization, the enediol intermediate can revert either to D-glucose or to D-mannose. Two stereoisomers that have multiple chirality centers but differ in configuration at only one of them are refened to as... 

The addition of COg to ribulose-l,5-bisphosphate results in the formation of an enzyme-bound intermediate, 2-carboxy,3-keto-arabinitol (Figure 22.24). This intermediate arises when COg adds to the enediol intermediate gener-... 

This enzyme interconverts ribulose-5-P and ribose-5-P via an enediol intermediate (Figure 23.30). The reaction (and mechanism) is quite similar to the phosphoglucoisomerase reaction of glycolysis, which interconverts glucose-6-P and fructose-6-P. The ribose-5-P produced in this reaction is utilized in the biosynthesis of coenzymes (including N/ DH, N/ DPH, F/ D, and Big), nucleotides, and nucleic acids (DNA and RNA). The net reaction for the first four steps of the pentose phosphate pathway is... 

This reaction converts ribulose-5-P to another ketose, namely, xylulose-5-P. This reaction also proceeds by an enediol intermediate, but involves an inversion at C-3 (Figure 23.31). In the reaction, an acidic proton located a- to a carbonyl carbon is removed to generate the enediolate, but the proton is added back to the same carbon from the opposite side. Note the distinction in nomenclature here. Interchange of groups on a single carbon is an epimerization, and interchange of groups between carbons is referred to as an isomerization. 

FIGURE 23.30 The phosphopei merase reaction involves an enediol intermediate. 

FIGURE 23.31 The phosphopentose epimerase reaction interconverts ribulose-5-P and xylulose-5-phosphate. The mechanism involves an enediol intermediate and occurs with inversion at C-3. 

The reversible reactions are initiated by an equilibrium between neutral and ionized forms of the monosaccharides (see Fig. 6). The oxyanion at the anomeric carbon weakens the ring C-O bond and allows mutarotation and isomerization via an acyclic enediol intermediate. This reaction is responsible for the sometimes reported occurrence of D-mannose in alkaline mixtures of sucrose and invert sugar, the three reducing sugars are in equilibrium via the enediol intermediate. The mechanism of isomerization, known as the Lobry de Bruyn-... 

The mechanism of HMF formation from D-fructose and sucrose was reviewed by Antal et a/.48 Several arguments were advanced for favoring a mechanism involving furanose rings and a fructose oxocarbonium ion over an open-chain [3-elimination mechanism that proceeds via an enediol intermediate to a... 

Figure4.18 DKR of acyloins through meso-enediol intermediates.

D-xylose was converted into 2-furaldehyde in acidified, tritiated water, no carbon-bound isotope was detected. This suggested that the 1,2-enediol (2) reacted immediately, as otherwise, tritium would have been detected at the aldehydic carbon atom of 2-furaldehyde, as a result of aldose-ketose interconversion.An acidic dehydration performed with d-[2- H]xylose showed that an intramolecular C-2-C-1 hydrogen transfer had actually occurred. Thus, these data indicated that an intramolecular hydride shift is more probable than the previously accepted step involving a 1,2-enediol intermediate. 

Note that harsher conditions may lead to further changes, e.g. epimerization at C-3 in fmctose, plus isomerization, or even reverse aldol reactions (see Section 10.3). In general, basic conditions must be employed with care if isomerizations are to be avoided. To preserve stereochemistry, it is usual to ensure that free carbonyl groups are converted to acetals or ketals (glycosides, see Section 12.4) before basic reagents are used. Isomerization of sugars via enediol intermediates features prominently in the glycolytic pathway of intermediary metabolism (see Box 10.1). 

Epimerization. In weakly alkaline solutions, glucose is in equilibrium with the ketohexose D-fructose and the aldohexose D-mannose, via an enediol intermediate (not shown). The only difference between glucose and mannose is the configuration at C-2. Pairs of sugars of this type are referred to as epi-mers, and their interconversion is called epimerization. 

Figure 2. Free energy profile for converting di hydroxy acetone phosphate, the substrate (abbreviated S) and glyceraldehyde 3-phosphate, the product (abbreviated P), with intermediate formation of the enedi-olate (abbreviated Z). Catalysis occurs either by a free carboxyl group (levels connected by dotted lines) or by triose-phosphate isomerase (levels connected by dashed lines). The vertical arrows show the limits of those states that are less well defined as a result of uncertainty in the experimental data. The transition state marked "e" refers to the exchange of protons between the solvent and the enzyme-bound enediol intermediate (EZ). Reproduced with permission of the authors and the American Chemical Society.

The interconversion of aldoses and the respective 2-ketoses in alkaline solution may be somewhat more complex than originally supposed, as it has been reported that a partial transfer of hydrogen from C-2 of the aldose to C-l of the corresponding ketose occurs during the reaction.29 This observation is not inconsistent with isomerizations that involve 1,2-enediol intermediates. The transfer could occur as a result of a rapid conversion in which some of the protons originally at C-2 of the aldose molecules are retained by the solvent cage that surrounds the intermediate 1,2-enediol, and are, therefore, available for addition to C-l of the resulting ketose. It should be noted that other interpretations, such as hydride-transfer mechanisms, are also possible. 

As shown in Fig. 2, two mechanisms involving an intermediate oxidation may be written for the epimerization at C-4". In the first one (A), the oxidation results in an a-D-xj/lo-hexopyranosyl-4-ulose derivative (96), which is then attacked by a hydride ion from the opposite side of the carbonyl group a change in conformation of the enzyme-intermediate complex seems necessary for such a process. The mechanism depicted under (B) postulates oxidation at C-3", and the resulting hexopyranosyl-3-ulose derivatives (54 and 97) then achieve equilibrium through the common enediol intermediate (98) before undergoing reduction at C-3". Compound 98 may also be formed from the hexopyranosyl-4-ulose ester 96, and in such a manner, both of the pathways may be linked. 

FIGURE 9 Isomerization and elimination reactions (a) The conversion of glucose 6-phosphate to fructose 6-phosphate, a reaction of sugar metabolism catalyzed by phosphohexose isomerase. (b) This reaction proceeds through an enediol intermediate. The curved blue ar-... 

In 1895, Emil Ficher proposed an enediol intermediate for this isomerization. As would be expected, the enzyme-catalyzed isomerization of glucose-6-phosphate in 2H20 is accompanied by incorporation of deuterium into the product fructose 6-phosphate at C-l. In the reverse reaction 2H-containing fructose 6-phosphate was found to react at only 45% of the rate of the 1H-containing compound. Thus, the primary deuterium isotope effect expected for a rate-limiting cleavage of the C-H bond was observed (see Chapter 12, Section B,3). 

The isomerization of D-glucose to D-fructose by way of an enediol intermediate is an important step in glycolysis, a complex process (11 steps) by which an organism converts glucose to chemical energy. The substrate is not glucose itself but its 6-phosphate ester. The enzyme that catalyzes the isomerization is called phosphoglucose isomerase. 

Demonstration that the enediol intermediate in aldose-ketose... 

As will be discussed in Chapter 16, the catalysis of a reaction by aldose-ketose isomerases involves an enediol intermediate in which the transferred proton (T in equation 8.18) remains on the same face of the intermediate. The stereochemistry of the products shows that the intermediate is syn rather than anti.9... 

---