Pyranose to furanose interconversion

Pyranose to Furanose Interconversion as a Function of Time and Water... 

The influence of pyranose to furanose interconversion on the observed stability constants (iifobs) of boronic acid complexes can be effectively demonstrated in the fluorescence response of boronic acid appended sensors with disaccharides. In examining the stabilities of disaccharides with the 5-indolylboronic acid 38, Aoyama and co-workers noted that for non-reducing sugars the observed stability constants (Aiobs) were significantly reduced or zero. This phenomenon was ascribed to the lack of an anomeric hydroxyl, which inhibited the... 

Scheme 37 The pyranose to furanose interconversion of the glucose ring in melibiose.

Specific rotation [ajD —132° to —92° (2% w/v aqueous solution). Note that fructose shows rapid and anomalous mutarotation involving pyranose-furanose interconversion. 

The observation that mutarotation of monosaccharides is retarded significantly by such solvents as l r,i f-dimethylformamide and methyl sulfoxide induced Kuhn and coworkers to investigate the pyranose-furanose interconversion more closely. Indeed, the rrii mechanism (normal a-/3 interconversion) is completely suppressed in these solvents, and the Isbell conversion (the rri2 mechanism) can be followed according to the equation ... 

Isbell and Pigman112 showed that the activation energies for a /8-pyranose anomerizations are usually higher than those for pyranose-furanose interconversions. Thus, the values of E given in Table VI (see page 53 of Part I) range from 18.6 to 14.2 kcal. mol-1 for the a-/8-pyranose anomerizations and from 15.8 to 10.7 kcal. mol-1 for... 

The above equilibria are confirmed by the complex, positive mutarotation in ethanol. First, a slow 3-D-furanose interconversion to equilibrium occurs, and then a very slow interconversion to equilibrium with the -D-pyranose form. The crystalline compound is, therefore, a /3-d anomer. This compound is interesting in that the identity of the forms taking part in the mutarotation can be ascertained, and the relative amounts of each determined, by nuclear magnetic resonance spectroscopy. Furthermore, the compound is unusual in existing in solution as the furanose forms, mostly. 

Hemiacetals in five- and six-membered rings are considerably more stable than acyclic hemiacetals. They constitute the form in which many saccharides exist under biological conditions. Glucose exists primarily in its pyranose (six-membered ring) form, although furanose (five-membered ring) forms are present also. Both the pyranose and furanose forms have anomeric isomers, known as a and p. These are shown below for the pyranose form. The open chain form is present in neutral water at ambient temperature only to an extent of approximately 0.003% of the total equilibrium. In the context of saccharides, interconversion between the hemiacetals and the open chain forms occurs in a reaction called mutarotation (see below). This reac-... 

As discussed above (see Section 4.10, The Importance of Pyranose to Fura-nose Interconversion, page 75) current thinking requires that we consider saccharidic forms where a 5yn-periplanar arrangement of the anomeric hydroxyl pair can be attained. Generally, this requires formation of the furanose form of the saccharide. However, computational work has shown that in the case of D-galactose the a-D-furanose form of the saccharide is not the only species that can be considered with a syn-periplanar alignment of the anomeric hydroxyl pair (Figure 32). 

Because six-membered rings aie nonnally less strained than five-membered ones, pyranose forms are usually present in greater anounts than furanose forms at equilibrium, and the concentration of the open-chain form is quite small. The distribution of carbohydrates among then- various herniacetal forms has been examined by using H and NMR spectroscopy. In aqueous solution, for exanple, D-ribose is found to contain the various a- and p-furanose and pyranose forms in the amounts shown in Figure 25.5. The concentration of the open-chain form at equilibr ium is too small to measure directly. Nevertheless, it occupies a central position, in that interconversions of a and p anorners and furanose and pyranose forms take place by way of the open-chain form as an intermediate. As will be seen later, certain chemical reactions also proceed by way of the open-chain form. 

Monosaccharides have many structural variations that correspond to local minima that must be considered. Acyclic carbohydrates can rotate at each carbon, and each of the three staggered conformers is likely to correspond to a local minimum. The shapes of sugar rings also often vary. Furanose rings usually have two major local minima and a path of interconversion. Experimental evidence shows a clear preference for only one chair form for some pyranose rings, but others could exist in several conformers. For exanqple, the and conformers must all be considered as possible structures for L-iduronate, as discussed by Ragazzi et al. in this book. 

Several monosaccharides mentioned in this Section are present in polysaccharide chains not only as pyranoses but also as furanoses. From the biogenetic point of view, a furanosidic form of a monosaccharide must be considered to be an additional component, as no ready interconversions of cyclic forms may be expected for monosaccharide residues incorporated into oligosaccharide chains, or in the activated form used for their formation. 

An extension of the simple mechanism in which ring forms are interconverted via a central, aldehydo intermediate includes direct pathways for the interconversion of the two pyranoses on one hand, and the two furanoses on the other. The existence of such direct pathways would permit a starting pyranose anomer to be converted rapidly to the other pyranose, as observed, even though the rate constant for the closure of the aldehydo form to the furanose ring were much greater than that for closure to the pyranose ring. 

The rate of the interconversion may also be followed by measuring the change in volume or in refractive index. Such measurements give rate coefficients identical with those obtained by the polarimetric method. In Table XVIII, rate coefficients for the mutarotation of a number of sugars are listed. The rates of mutarotation of several sugars (for example, D-ri-bose, D-galactose, and all the ketoses) do not obey the first-order law. Their complex mutarotations result from the presence in solution, in appreciable concentrations, of more than two species. In addition to pyranoses, there must be present either furanoses or acyclic forms, or both. 

Although no mutarotation was observed with the first small sample of D-altrose, its [a]D value of +32.6° in water was in agreement with the equilibrium rotation —32.3° recorded by Austin and Humoller for L-altrose. When a larger amount of the sugar became available, D-altrose was found to exhibit a complex mutarotation. From calculations of the velocity coefficients it would appear that the mutarotation consists of a very rapid interconversion of furanose and pyranose modifications, followed by a slower interconversion of o and /3 pyranose modifications. 

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