The Chemistry of Carbohydrates

Many aspects of the chemistry of carbohydrates are not specihc to this class of compounds, but are merely examples of the simple chemical reactions we have already met. Therefore, against usual practice, we have not attempted a full treatment of carbohydrate chemistry and biochemistry in this chapter. We want to avoid giving the impression that the reactions described here are something special to this group of compounds. Instead, we have deliberately used carbohydrates as examples of reactions in earlier chapters, and you will find suitable cross-references. 

Nagwa Rashed graduated from Alexandria University in 1974 (M.Sc. in 1977 and Ph.D. in 1981 under the supervision of Professor E. S. H. El Ashry). She currently works on the chemistry of carbohydrates, nucleosides, and heterocycles. She has to her credit about 80 publications besides 10 review articles. 

Since 1895, when Emil Fischer1 described the reaction of aldehydes and ketones with glycoses, an impressive part of the chemistry of carbohydrates has dealt with acetals, and especially cyclic acetals (mainly 1,3-dioxolanes and 1,3-dioxanes). There are probably relatively few studies on the synthetic chemistry of monosaccharides that do not describe at least one acetal of a carbohydrate, be it for routine protection, or for use in an original synthesis. At least, in this Series, three articles have appeared on the cyclic acetals of the aldoses and aldosides2,3 and of the ketoses4, one article dealt with acetals of tetri-... 

The chemistry of enolates has provided excellent routes to highly complex structures, in particular in the total synthesis of natural products. Because of the highly oxygenated structures of carbohydrates, enolate formation could easily result in p-elimination of a suitably located oxygenated group (ethers, esters, and such) to provide enone. For these reasons, the chemistry of carbohydrate enolates has been poorly documented. 

Structural studies of glycosphingolipids involves determination of the structure of the oligosaccharide chain and of the lipid moiety. For the oligosaccharide chain, it is necessary to determine the composition, molar ratio, and sequence of the monosaccharides, their pyranose or furanose nature, and the position of glycosidic bonds and their configuration for the lipid moiety, the composition of the fatty acids and sphingosine bases must be determined. Used for these purposes are the classical, chemical methods, conventionally accepted in the chemistry of carbohydrates and lipids and based on the degradation of compounds, enzymic, and physicochemical methods, primarily mass spectrometry and n.m.r. spectroscopy. 

Of these research topics, the most beloved one for Professor Bognar was still the chemistry of carbohydrates. He was extremely productive in this field, and so, only the most important results of his contribution to carbohydrate chemistry can be discussed here. 

Hemiacetals and acetals play an important role in the chemistry of carbohydrates. Consider what would happen, for example, if the —OH group on the fifth carbon atom in a glucose molecule attacked the aldehyde at other end of this molecule. 

The descriptive term alkali-sensitive glycoside has special significance to one concerned with a study of the chemistry of carbohydrate substances, for experience often refutes the generalization that the gly-cosidic linkage is stable to alkalis. The acid-catalyzed hydrolysis of glycosides is well known, and is characteristic of the acetal structure they possess.1 However, it is not practical to assume that most glycosides have... 

M. Engel, The chemistry of carbohydrates and Emil Fischer in the view of a French chemist , Mitt.-Ges. Dtsch. Chem., Fachgruppe Gesch. Chem., 1994, 10, 46-50. 

However, if the literature is relatively abundant concerning classical organic chemistry in the presence of such catalytic materials, this is not the case in the chemistry of carbohydrates, where enzymes are often the preferred and most appropriate catalysts. 

To avoid misunderstandings it must be added that many cases are known, e.g., from the chemistry of carbohydrates, where the intermediates are so stable that the above-mentioned method is inapplicable. 

To understand the chemistry of these more complex carbohydrates, we must first learn the principles of carbohydrate structure and reactions, using the simplest monosaccharides as examples. Then we will apply these principles to more complex disaccharides and polysaccharides. The chemistry of carbohydrates applies the chemistry of alcohols, aldehydes, and ketones to these polyfunctional compounds. In general, the chemistry of biomolecules can be predicted by applying the chemistry of simple organic molecules with similar functional groups. 

Carbohydrates are the most abundant of all organic compounds in the biosphere. Many members of the carbohydrate class have the empirical formula Cx(H20)y, and are literally hydrates of carbon. The fundamental units of the carbohydrate class, the monosaccharides, are polyhydroxy aldehydes or ketones and certain of their derivatives. As with other classes of biologically important compounds, much of the function of the carbohydrates derives from the ability of the monosaccharides to combine, with loss of water, to form polymers oligosaccharides and polysaccharides. The chemistry of carbohydrates is, at its core, the chemistry of carbonyl and hydroxyl functional groups, but these functional groups, when found in the same compound, sometimes exhibit atypical properties. The discussion that follows is designed to review the aspects of carbohydrate chemistry that are especially important for isolation, analysis, and structure determination of biologically important carbohydrates. 

An effort has been made to collect information that would not come to light in a literature search this has met with partial success. The main aim, namely, to determine what non-aqueous solvents have been specifically investigated for their solvating power for carbohydrates, has resulted in such an interesting array of compounds, both inorganic and organic, that the author ventures to hope that further interest in the chemistry of carbohydrates in non-aqueous solvents will be generated. 

Guthrie, R. D., and Honeyman, J. 1968. "Introduction to the Chemistry of Carbohydrates. 3rd ed. Clarendon Press, Oxford, England. 

An old problem in the chemistry of carbohydrates has been the synthesis of oligosaccharides from monosaccharides, if possible in a way which proves the structure and configuration of the oligosaccharides. This problem has been solved in some instances with starting materials made available through tritylation. 

The field of monosaccharides, disaccharides and polysaccharids contains many industrial examples of semi-synthesis, which have entered chemical history, such the hydrolysis of starch to form D-glucose, the esterification of cellulose, the chemistry of rayon and, more recently, advances in the chemistry of carbohydrate surfactants (ref.83). 

RajanBabu et al. has deeply explored the chemistry of carbohydrate phosphinite complexes [84, 95]. While the carbohydrate backbone provided the necessary stereochemical diversity, substitution patterns around phosphoms were used to vary the steric and electronic properties of the ligand. 

Kenner, J. 1955. The alkaline degradation of carbonyl oxycelluloses and the significance of saccharinic acids for the chemistry of carbohydrates, Chem. Ind., pp. 727-730. 

The chemistry of carbohydrate radicals is dominated by loss of vicinal substituents which can leave as relatively stable anions and molecules. The attack of OH from the Ti °-H202 system on myo-inositol at pH 4 yields the radicals 1, 2, 3 and 4 shown in Figure 7.27 in the expected 2 2 1 1 ratio, as judged from ESR signal intensities. At lower pH values, acid-catalysed loss of OH became apparent, with the reaction of radical 1 occurring with a second-order rate constant of 2.8 x 10 M s at 20 °C, 11 times faster than the loss of equatorial OH from, for example, radical 3. ° The preferential loss of the axial OH is probably a least-motion effect of the type held to support ALPH. 

Hemiacetal formation is fundamental to the chemistry of carbohydrates (see Section 11.1). Glucose, for example, contains an aldehyde and several alcohol groups. The reaction of the aldehyde with one of the alcohols leads to the formation of a cyclic hemiacetal (even without acid catalysis) in an intramolecular reaction. 

When making comparisons, it is important that the two substances should have the same physical state. Furthermore, any mono- or oligosaccharide used as a model substance in interpreting the spectrum of the crystalline portion of a polysaccharide should have the same unit cell as the polymer. In this connection, attention should be drawn to the facts that (a) additional complications are introduced into the spectra of crystals, and into those of the crystalline fraction of polymers, by interactions between vibrations in neighboring unit cells, and (b) differences in the degree of order (crystalline, noncrystalline) within polymers also produce complications in the spectra. A detailed discussion of such complexities would be out of place here, as they are probably of primary interest to those engaged in fine-structure examination of polysaccharides rather than to investigators of the chemistry of carbohydrates. 

Chapter 22 introduces you to the chemistry of carbohydrates, the most abundant class of compounds in the biological world. First you will learn about the structures and reactions of monosaccharides. Then you will see how they are linked to form disaccharides and polysaccharides. A wide variety of carbohydrates found in nature will be discussed. 

The first encounter that the young Wolfrom had with the chemistry of carbohydrates came at the end of his sophomore year, when Professor C. W. Foulk recommended him for a post of student research assistant to Professor William Lloyd Evans of the Department of Chemistry. The stipend was 250 per year, and Wolfrom put in all of the extra time that he had on the work. During his junior year, he carried out quantitative oxidations of maltose with permanganate at various temperatures and concentrations of alkali. In his senior year, he attempted unsuccessfully to synthesize amino acid esters of glycerol. None of this work was published, but it was a good introduction to chemical research. Professor Evans, a student of J. U. Nef s, was very research-minded and inspirational. 

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