2-Ketohexose, -fructose

Problem 34.7 When the ketohexose ( - )-fructose is treated with phenylhydrazine, it yields an osazone that is identical with the one prepared from either (+)-glucose or (+)-mannose. How is the configuration of (-)-fructose related to those of (+)-glucose and (+)-mannose ... 

The forms of glucose in aqueous solution are quite complex and small proportions exist as furanose structures. These arise from the reaction between the OH group at C-4 and the aldehyde group in aldoses. The five-membered ring system is quite stable but pyranose forms are favoured over furanose forms by most monosaccharides notable exceptions are the ketohexose fructose and the aldopentose ribose. Too much strain would be involved in reducing bond angles to produce smaller rings, so trioses and tetroses do not form intermolecular cyclic systems. 

Fructose is a monosaccharide. It contains six carbons and a ketone group, classifying it as a ketohexose. Fructose is present as the free sugar in many fruits, and it is also derived from hydrolysis of sucrose (see Figure 13.12). 

A hexulose or ketohexose, fructose (IV). A glycoside with the common mixed full-acetal ring formula (V) and with the Haworth acetal ring formula (VI) R is an alkyl or aryl group. 

The separation on several columns of the isomeric forms of several aldohexoses and the four ketohexoses (fructose, psicose, sorbose and tagatose) as their pertrimethylsilyl ether derivatives has been reported, and a mathematic approach used in an attempt to relate retention times to structures. 

The fructokinase of rat liver does not react with glucose, mannose, and galactose, but does react with the ketohexoses, fructose, L-sorbose, and D-tagatose. Evidence has been obtained to show that the product of sorbose phosphorylation is probably sorbose-l-phosphate. The enzyme in liver homogenates is considerably more reactive aerobically than anaerobically—a curious and as yet unexplained phenomenon. liver fructokinase requires Mg++ or Mn++ ions for its activity, and evidence has been obtained that Mg++ in combination with ATP is a cosubstrate for the enzyme. Potassium ion in very high concentration increases the rate of the transphosphorylation. 

Glucose and fructose are structural isomers— they both have the same formula (C6H12O6), but they have different structures. Fructose is a ketose, a sugar that is a ketone. Since fructose has six carbon atoms, it is a ketohexose. Fructose, often called fruit sugar, is in many fruits and vegetables and is a major component of honey. 

Hexoses.—CgH Og.—Out of twenty-four possible hexoses, only four are capable of utilisation by higher animals. These are the aldohexoses, glucose, mannose, and galactose, and the ketohexose fructose. All are D-sugars, being related structurally to d-glycerose. 

Important monosaccharides are the aldohexoses, glucose and galactose, and the ketohexose, fructose. 

D Fructose (a 2 ketohexose also known as levulose it IS found in honey and IS signficantly sweeter than table sugar)... 

From a structural point of view, the carbohydrate template can have either furan or pyran rings although in some cases open chain structures can be formed. A large variety of aldopentoses (e.g. d- and L-arabinose, D-ribose, D-xylose), aldohexoses (e.g. D-glucose, D-mannose, D-galactose) as well as ketohexoses (e.g. D-fructose, L-sorbose) can be used as scaffolds. 

The in vitro bioassays allowed to determine the inhibition constant of D-fructose transport by the CHO cells. This measure is carried out by competition with radioactive D-fructose. The study put in evidence that pentose-OZT derivatives are not recognized by the protein transporter. Only the ketohexose-OZT derivatives expressed some inhibition of GLUT5. These inhibition constants showed to be much effective with L-Sor derivatives than with D-Fru derivatives and even better than D-fructose itself (Kt = 15.5 mM) (Table 2). 

These blocked structures gave a picture of the interaction of D-fructose with the protein. It is assumed that a ketohexose C-l additional arm (absent in pentose series), is required in order to achieve some inhibition, but a certain freedom of substitution is possible (OBn, OA11 or OH). Comparison of D-Fru- and L-Sor-OZTs showed that substituted derivatives are better... 

It is noteworthy that D-fructose, which has a pyranose structure in the free crystalline state, assumes a furanose configuration whenever it combines with another sugar to form an oligosaccharide or polysaccharide. Apparently the ketohexose L-sorbose shows the same behavior. 

Figure 4.17 The trioses D-glyceraldehyde (aldose) and dihydroxyacetone (ketose), the pentose D-ribose, the hexoses D-galactose and D-glucose (aldoses) and the ketohexose D-fructose in their open chain forms. The configuration of the asymmetrical hydroxyl group on the carbon, the furthest away from the aldehyde or ketone group, determines the assignment of D- or L-configuration.

The substantial amounts of this ketohexose are mainly prepared by base-catalyzed isomerization of starch-derived glucose, yet may also are generated by hydrolysis of inulin, a fructooligosaccharide. An aqueous solution of fructose—consisting of a mixture of all four cyclic tautomers (Figure 2.5), of which only the (3-D-pyranose ((3-p) form present to about 73% at room temperature is sweet — about 1.5 times sweeter than an equimolar solution of sucrose hence, it is widely used as a sweetener for beverages ( high fructose syrup ). 

The carbonyl group in glucose and ribose is an aldehyde such compounds are termed aldoses. Fructose, by contrast, has a ketone group and is therefore classified as a ketose. Glucose could also be termed an aldohexose and fructose a ketohexose, whereas ribose would be an aldopentose, names which indicate both the number of carbons and the nature of the carbonyl group. Another aspeet of nomenclature is the use of the suffix -ulose to indicate a ketose. Fructose could thus be referred to as a hexulose, though we are more likely to see this suffix in the names of specific sugars, e.g. ribulose is a ketose isomer of the aldose ribose. 

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. 

Phosphoric acid esters of the ketopentose D-ribulose (2) are intermediates in the pentose phosphate pathway (see p.l52) and in photosynthesis (see p.l28). The most widely distributed of the ketohexoses is D-fructose. In free form, it is present in fruit juices and in honey. Bound fructose is found in sucrose (B) and plant polysaccharides (e.g., inulin). 

Since mannose and glucose are C epimers, they are identical at the C, C. C, and C" portions of the molecule, which are unaltered during osazone formation. The chiral C , which differs in each hexose, loses chirality in the osazone and becomes identical for both mannose and glucose. 2-Ketohexoses give osazones in which the C CH,OH is oxidized. Since C, C, C and C of fructose and glucose are identical (Problem 22.8), fructose also gives the same osazone. Identical portions are in the boxes below. 

Problem 22.34 (a) Write shorthand structures for the three o-2-ketohexoses other than o-fructose. (b) Which one does not give a meso alditol on reduction (c) Which one gives the same osazone as does D-galactose (Problem 22.22)7 <... 

Pentoses and hexoaes could be distinguished readily with phenylhydra-zine. The compound hitherto called isodulcitol was identified as a sugar by means of phenylhydrazine, and was designated as rhamnose from that time on. Glucose and fructose (which H. Kiliani had discerned to be an aldohexose and a ketohexose, respectively) and mannose were found to give one and the same phenylosazone the three sugars, therefore, have the same configuration at carbon atoms 3, 4, and 5. 

The ketohexoses identified as components of bacterial polysaccharides include D-fructose, found in Vibrio lipopolysaccharide167 and Hemophilus influenzae capsular polysaccharide,252 and D-xylulose (d- riireo-2-pen-tulose), identified in Pseudomonas lipopolysaccharide.253 Activated forms of the monosaccharides were not determined. 

To be consistent with the relationship between a mono- and a disaccharide, some authorities do not term a tetrose or a pentose a monosaccharide. By combining the aid- and ket- prefixes, certain compounds then may be called aldohcxoses. such as glucose and galactose, or ketohexoses. such as fructose and sorbose. 

The saccharides have long and awkward names by the IUPAC system, consequently a highly specialized nomenclature system has been developed for carbohydrates. Because this system (and those like it for other natural products) is unlikely to be replaced by more systematic names, you will find it necessary to memorize some names and structures. It will help you to remember the meaning of names such as aldopentose and ketohexose, and to learn the names and details of the structures of glucose, fructose, and ribose. For the rest of the carbohydrates, the nonspecialist needs only to remember the kind of compounds that they are. 

The common six-carbon sugars (hexoses) are D-glucose, D-fructose, D-galactose, and D-mannose. They all are aldohexoses, except D-fructose, which is a ketohexose. The structures of the ketoses up to Cf) are shown for reference in Figure 20-2. The occurrence and uses of the more important ketoses and aldoses are summarized in Table 20-1. 

---