Anomeric glycosides

The reactions of protected carbohydrates with and in anhydrous hydrogen fluoride have been well investigated and arc covered by some excellent reviews29,33 34"277 279 288 289 (see also Flouben-Weyl, Vol. E14a/3, pp 627-646). The anomeric (glycosidic) center is as a rule the most reactive position of a carbohydrate moiety. Practically all functional groups located in... 

Little difference in reaction rates was observed between the anomeric glycosides or between the corresponding methyl and phenyl glycosides.97 118 This point might bear re-examination in view of the extensive side-reactions encountered in almost all of the oxidations, for, with the anomeric 2-deoxy-... 

Dais and Perlin90 have invoked the molecular-weight dependence of the 7, values in conjunction with solvent effects in order to explain the dynamic behavior of a pair of anomeric glycosides, namely methyl a-D- (5a) and methyl j8-D-gluco-pyranoside (5b) in a group of solvents that represent an extended range of such properties as viscosity and dielectric constants. 

The aforementioned procedure was also applied to P-anomer P-276 (Scheme 10.90). In this case, the cyclization after mercuration was less diastereoselective (3 1 dr). After separation of the diastereomers, the major diastereomer was converted into (5 )-1,2-propanediol (S)-27S with more than 99% ee. The advantage of this method is that both configurations of the product can be synthesized from one chiral auxiliary by separation of the anomeric glycosides and transformation of each anomer into the corresponding diol with excellent enantioselectivity. 

Like D-(+)-glucose, other monosaccharides exist in anomeric forms capable of mutarotation, and react with alcohols to yield anomeric glycosides. 

Although Koenigs and Knorr isolated a small yield of methyl /3-n-gluco-pyranoside (as such) from a solution of tetra-O-acetyl-a-D-glucopyranosyl bromide in methanol that had stood at room temperature for several days, it is customary to add an acid acceptor to speed up the reaction and to prevent deacetylation of the product. Silver, in the form of the oxide or a salt, was the first acid acceptor to be employed, and is still the one in most common use. Unless the aglycon is a simple alcohol, it is usual to dissolve the reactants in a solvent, which is often an organic base to act as an additional acid acceptor. Walden inversion at Cl is almost the invariable rule when the reaction is done in the presence of silver ion. Under special circumstances, however, both anomeric glycoside acetates may be obtained. ... 

The anomeric oxygen activations described above could not fulfill the requirements put forward. Either they failed to provide both activated intermediates or both anomeric glycosides were not obtained. Obviously, for a stereocontrolled activation of the anomeric oxygen, the anomerisation of the 1-OH, or the 1-0", group in the presence of base has to be taken into account (Scheme 16). Thus, in a reversible activation process and with the help of kinetic and thermodynamic reaction control both activated anom-ers should eventually be obtainable. 

The first lipophilicity-activity relationship was published by Charles Richet in 1893, exactly 100 years ago. From his quantitative investigations of the toxicities of ethanol, diethyl ether, urethane, paraldehyde, amyl alcohol, acetophenone, and essence of absinthe ( ) he concluded plus Us sont solubles, mains Us sont toxiques (the more they are soluble, the less toxic they are). One year later Emil Fischer derived the lock and key model of ligand-enzyme interactions from his results on the stereospecificity of the enzymatic cleavage of anomeric glycosides. 

Augestad I, Berner E, Weigner E (1953) Chromatographic separations of anomeric glycosides. Chem Ind (Lond) 376-377... 

Augestad I, Berner E (1954) Chromatographic separation of anomeric glycosides. II. New crystalline methylfuranosides of galactose, arabinose, and xylose. Acta Chem Scand... 

Augestad 1, Berner E (1956) Chromatographic separation of anomeric glycosides. III. Crystalline methylfuranosides of L-fucose, D-ribose, and L-rhamnose. Acta Chem Scand 10 911-916... 

The product distribution is independent of the identity of the starting anomer-—that is, a-D-glucopyranose and (3-D-glucopyranose each yield the same ratio of anomeric glycosides when treated with an alcohol in acid-catalyzed conditions. Once isolated, the glycoside products are stable under neutral or basic conditions. However, upon treatment with aqueous acid, they are readily converted back to a hemiacetal. 

The anomeric glycosides are diastereomers with different physical properties. Like ordinary acetals and ketals, they are stable in neutral or basic solution. Therefore, they are not reducing sugars because they do not hydrolyze to form a free aldehyde group in Benedicts solution, which is basic. However, glycosides are hydrolyzed in acid solution by the reverse of the reactions shown in Figure 26.7. 

The influence of pK and the insensitivity to steric hindrance is seen from the gly-cosylation of fluorinated alcohols (Figure Ic) [18]. Glycosidation of trifluoroetha-nol, hexafluoro-2-propanol, and hexafluoro-tert-butanol by one equivalent of the diazirine 7 in dioxane yielded the anomeric glycosides in yields of 70-74% and in P-d/u-d ratios ranging from 77 32 to 95 5. The solvent has an influence on the anomeric ratio, which changes for hexafluoro-tcrt-butanol from P-d/o-d = 84 16 (75%) in dichloromethane to 98 2 (80%) in DME. The formation, upon glycosidation in propionitrile at -60 °C, of the imino ether 31 (55%) besides the glycosides evidences the formation of an oxycarbenium cation, its solvation, and the preferred axial attack of the solvent. 

Introduction of a p-glycosidic linkage in native CDs with only a-anomeric glycosidic linkages was found to offer further advantage for the complexation with polymers, as a result of cavity shape being elliptical, which facilitated processes of polymer inclusion inside the cavity. Akashi and coworkers continued the previous finding that CDs... 

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