2-Ketoses, enolization

Enolization of an aldose or a ketose gives an enediol Enediols can revert to aldoses or ketoses with loss of stereochemical integrity at the a carbon atom... 

Figure 25.8 Fructose, a ketose, is a reducing sugar because it undergoes two base-catalyzed keto-enol tautomerizations that result in conversion to an aldose.

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. 

Ketose Sugar N-Fructosylamine (if ketose is fructose) Enol 2-Amino-l-Keto Sugar... 

Elimination reactions (Figure 5.7) often result in the formation of carbon-carbon double bonds, isomerizations involve intramolecular shifts of hydrogen atoms to change the position of a double bond, as in the aldose-ketose isomerization involving an enediolate anion intermediate, while rearrangements break and reform carbon-carbon bonds, as illustrated for the side-chain displacement involved in the biosynthesis of the branched chain amino acids valine and isoleucine. Finally, we have reactions that involve generation of resonance-stabilized nucleophilic carbanions (enolate anions), followed by their addition to an electrophilic carbon (such as the carbonyl carbon atoms... 

The reactivity of carbohydrates is dominated by the reactivity of the aldehyde group and the hydroxyl on its next-neighbor (/ ) carbon. As illustrated by the middle row of Fig. 2.3, the aldehyde can be isomerized to the corresponding enol or be converted into its hydrate (or hemiketal) form upon reaction with water (or with an hydroxyl-group). These two reactions are responsible for the easy cycliza-tion of sugars in five- and six-membered rings (furanose and pyranose) and their isomerization between various enantiomeric forms and between aldehyde- and ketone-type sugars (aldose and ketose). 

These retro-Aldol and -Michael reactions can, obviously, follow an isomerization of the aldose to the corresponding ketose, leading thereby to different Aldol fragments or retro-Michael products. Keto-enol exchange as well as the retro-... 

Glucose 6-phosphate is then isomerized to fructose 6-phosphate. This conversion of an aldose sugar to a ketose sugar is easy to rationalize in terms of keto-enol tautomerism (see Box 10.1). 

Aldose-ketose interconversions, e.g. glucose 6-phosphate to fructose 6-phosphate (Figure 8.4), also proceed through a common enol intermediate. 

Generally useful reagent with a high silyl donor ability will not react with amino groups will not cause formation of enol-ether on unprotected ketone groups especially useful for ecdysones, norepinephrine, dopamine, steroids, sugars, sugar phosphates, and ketose isomers... 

Hodge7 has advanced several possible routes for the conversion of the enol form of the 1-amino-l-deoxy-2-ketose into melanoidin, and the evidence to support these mechanisms is considerable. Thus, the enol may be converted into the Schiff base of a furaldehyde, or to a reductone by loss of water. It may also be broken down into smaller fragments (for example, hydroxy-2-propanone or pyruvaldehyde), which react further with amino compounds. The enol may also react with an a-amino acid and be converted to an aldehyde by a Strecker degradation. The compounds thus formed from... 

With acid degradation, the first step appears to involve the formation of 1,2-enols from the aldose or ketose (7), followed by a series of dehydration reactions resulting in the formation of 5-hydroxymethyl-2-furfuraldehyde. If the initial sugar is a pentose, the final product is 2-furfuraldehyde. 

The resulting furfurals then can undergo a series of complicated polymerization reactions. Hodge (8) reported that these reactions include hydrolytic fission, fission of 2-ketoses, dehydration of triose, dismutation of biose, trioses, and tetroses, self- and cross-condensations of aldehydes and ketones, reversion of aldoses and ketoses to various oligosaccharides, dimerization of monosaccharides, cyclodehydration of aldoses followed by polymerization, and finally, the enolization and dehydration of formed oligosaccharides. 

It has been postulated (37) that lactulose is formed from lactose by the Lobry de Bruyn and Alberda van Ekenstein transformation, whereby glucose is isomerized to fructose via an enol intermediate. In turn, two mechanisms have been proposed for the degradation of this intermediate (38)- One involves the addition of a proton to the enediol resulting in epimeric aldoses and the original ketose, while the other involves 8-elimination to yield galactose and saccharinic acids. The authors experimental data would tend to better support the second pathway. 

Another base-catalyzed side reaction is the enediol rearrangement, which moves the carbonyl group up and down the chain, as shown in Mechanism 23-3. If the enolate ion (formed by removal of a proton on C2) reprotonates on the Cl oxygen, an enediol intermediate results. Removal of a proton from the C2 oxygen and reprotonation on Cl gives fructose, a ketose. 

Lobry de Bruyn-Alberta van Ekenstein reaction) A base-catalyzed tautomerization that interconverts aldoses and ketoses with an enediol as an intermediate. This enolization also epimer-izes C2 and other carbon atoms, (p. 1115)... 

Following the production of 1,2-enol forms of aldose and ketose amines, a series of degradations and condensations results in the formation of melanoidins. The a-fi-dicarbonyl compounds enter into aldol type condensations, which lead to the formation of polymers, initially of small size, highly hydrated, and in colloidal form. These initial products of condensation are fluorescent, and continuation of the reaction results in the formation of the brown melanoidins. These polymers are of nondistinct composition and contain... 

In addition to serving as structural motifs, enols and enolates are involved in diverse biological processes. Several enol/enolate intermediates have been proposed to be involved in glycolysis (Section IV.A), wherein c/ -enediol 21 is proposed to be an intermediate in the catalytic mechanism of phosphohexose isomerase and an enol-containing enamine intermediate (22) has been proposed in the catalytic pathway of class I aldolase. In the case of glucose-fructose (aldose-ketose) isomerization, removal of the proton on Cl-OH produces the aldose while deprotonation of C2-OH yields the ketose, which is accompanied by protonation at the C2 and Cl positions, respectively. There are several cofactors that are involved in various biological reactions, such as NAD(H)/NADP(H) in redox reaction and coenzyme A in group transfer reactions. Pyridoxal phosphate (PLP, 23) is a widely distributed enzyme cofactor involved in the formation of a-keto acids, L/D-amino... 

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