Aldose equilibrium

Another kind of intervention in the anhydrohexose aldose equilibrium has been described for l,6-anhydro-/3-D-gulopyranose. The action of 40% aqueous hydrogen bromide and bromine at 80° causes simultaneous hydrolysis and oxidation to D-gulono-1,4-lactone.122... 

Aldoses exist almost exclusively as their cyclic hemiacetals very little of the open chain form is present at equilibrium To understand their structures and chemical reac tions we need to be able to translate Fischer projections of carbohydrates into their cyclic hemiacetal forms Consider first cyclic hemiacetal formation m d erythrose To visualize furanose nng formation more clearly redraw the Fischer projection m a form more suited to cyclization being careful to maintain the stereochemistry at each chirality center... 

Treatment of an aldose or ketose with NaBH4 reduces it to a polyalcohol called an alditol. The reduction occurs by reaction of the open-chain form present in the aldehyde/ketone hemiacetal equilibrium. Although only a small amount of the open-chain form is present at any given time, that small amount is reduced, more is produced by opening of the pyranose form, that additional amount is reduced, and so on, until the entire sample has undergone reaction. 

Commercial A -acetylneuraminic acid aldolase from Clostridium perfringens (NeuAcA EC 4.1.3.3) catalyzes the addition of pyruvate to A-acetyl-D-mannosamine. A number of sialic acid related carbohydrates are obtained with the natural substrate22"24 or via replacement by aldose derivatives containing modifications at positions C-2, -4, or -6 (Table 4)22,23,25 26. Generally, a high level of asymmetric induction is retained, with the exception of D-arabinose (epimeric at C-3) where stereorandom product formation occurs 25 2t The unfavorable equilibrium constant requires that the reaction must be driven forward by using an excess of one of the components in order to achieve satisfactory conversion (preferably 7-10 equivalents of pyruvate, for economic reasons). 

NeuA, has broad substrate specificity for aldoses while pyruvate was found to be irreplaceable. As a notable distinction, KdoA was also active on smaller acceptors such as glyceraldehyde. Preparative applications, for example, for the synthesis of KDO (enf-6) and its homologs or analogs (16)/(17), suffer from an unfavorable equilibrium constant of 13 in direction of synthesis [34]. The stereochemical course of aldol additions generally seems to adhere to a re-face attack on the aldehyde carbonyl, which is complementary to the stereoselectivity of NeuA. On the basis of the results published so far, it may be concluded that a (31 )-configuration is necessary (but not sufficient), and that stereochemical requirements at C-2 are less stringent [71]. 

Amino-2-deoxy aldoses. The behaviour of O-unprotected sugars is exemplified in D-gluco series after basic hydrolysis of the starting 2-benzamidoglycoside followed by buffering the medium with carbon dioxide and treatment with thiophosgene, an intermediate isothiocyanate was obtained.320 However, NMR revealed a temperature-dependent equilibrium of this isothiocyanate with a trans-fused OZT (Scheme 5). 

Xylose isomerases with higher thermostability were found in the strains of Streptomyces and relaxed Actinoplanaceae (which includes the generdLAmpullariella and Actinopianes). High thermo-tolerance is desirable for production of HFCS because at equilibrium, as the temperature of the enzyme reaction is increased, the ketose/aldose ratio increases proportionately 30). In addition, reactors running at higher temperatures have less risk of microbial contamination, allowing for less frequent and less costly enzyme replacement. 

However, the applicability of this strategy is limited by the substrate specificity of the isomerases so that only a fraction of the ketoses that can be obtained from the aldose-catalyzed reaction can be enzymatically isomerized to the corresponding aldose. Moreover, the isomerization reaction is reversible and, as a ketone is generally more stable than an isomeric aldehyde, the equilibrium produces substantial aldose isomer only if the aldose sugar can exist in a very stable aldopyra-nose form [38b]. 

In the production of the sweetener high fructose com symp (HFCS), glucose isomerase is used to convert glucose into fmctose (equilibrium mixture appr. 50 50) since fmctose is nearly three times as sweet as glucose. The enzyme belongs to the subclass intramolecular oxidoreductases interconverting aldoses and ketoses (EC 5.3.1). About 8 million tonnes pr. year of glucose is treated in this way. For further details, see Chapter 4. 

Alkoxy-5,6-dihydro-2/7-pyrans are readily hydrolyzed8889 in dilute, aqueous acids to fnms-a./J-unsaturated aldehydes (206). Hydrolysis in a neutral medium leads to an equilibrium mixture of 5,6-dihy-dro-2ff-pyran-2-ol (207) and the corresponding cis-aldebyde 208. (For syntheses of stereoisomerie deoxy-DL-aldoses from aldehyde 79, see Section II.) The thermal isomerization of 193 has been investigated.1 "... 

Problem 22.7 (a) Explain how in basic solution an equilibrium is established between an aldose, its C epimer (a diastereomer with a different configuration at one chiral C) and a 2-ketose. (b) Will fructose give a positive Fehling s test which is done in a basic solution <4... 

These reactions are typical of the —CHO group. The Schiff and bisulfite reactions are reversible, and the equilibrium favors unreacted hemiacetal. Since osazone and Fehling reactions are irreversible, equilibrium is shifted to restore the low concentration (0.02%) of open-chain aldehyde as soon as some reaction occurs, and eventually all the aldose reacts. 

The proportion of the acyclic form also increases with increasing temperature this is true for aldoses and ketoses,16,31 as well as for simple hydroxyketones.74 This would be expected from considerations of entropy, as the acyclic form has a greater degree of freedom, but studies on y- and d-hydroxyketones show that change in enthalpy contributes even more to the changing position of the equilibrium with increasing temperature. Evidently, cyclization of hydroxyketones is exothermic, and is favored by lower temperatures.74... 

Most, if not all, of the stable forms of crystalline aldose and ketose monosaccharides exist in the pyranose structure. Each in solution, as with D-glucose, exists as an equilibrium mixture of open chain and of a- and / -anomers of the cyclic forms. The cyclic five- and six-membered structures formulated below are an illustrative selection of monosaccharides. 

In general, a six-membered pyranose form is preferred over a five-membered furanose form because of the lower ring strain, and these cyclic forms are very much favoured over the acyclic aldehyde or ketofte forms. As can be seen in Table 1.3, at equilibrium, the anomeric ratios of pyranoses differ considerably between aldoses. These observations are a direct consequence of differences in anomeric and steric effects between monosaccharides. The amount of the pyranose and furanose present in aqueous solution varies considerably for the different monosaccharides. Some sugars, such as D-glucose, have undetectable amounts of furanose according H-NMR spectroscopic measurements whereas others, such as D-altrose, have 30% furanose content under identical conditions. 

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