Carbohydrates anomeric effect

It IS not possible to tell by inspection whether the a or p pyranose form of a par ticular carbohydrate predominates at equilibrium As just described the p pyranose form IS the major species present m an aqueous solution of d glucose whereas the a pyranose form predominates m a solution of d mannose (Problem 25 8) The relative abundance of a and p pyranose forms m solution depends on two factors The first is solvation of the anomeric hydroxyl group An equatorial OH is less crowded and better solvated by water than an axial one This effect stabilizes the p pyranose form m aqueous solution The other factor called the anomeric effect, involves an electronic interaction between the nng oxygen and the anomeric substituent and preferentially stabilizes the axial OH of the a pyranose form Because the two effects operate m different directions but are com parable m magnitude m aqueous solution the a pyranose form is more abundant for some carbohydrates and the p pyranose form for others... 

Anomeric effect (Section 25 8) The preference for an elec tronegative substituent especially a hydroxyl group to oc cupy an axial orientation when bonded to the anomeric carbon m the pyranose form of a carbohydrate Anti (Section 3 1) Term describing relative position of two substituents on adjacent atoms when the angle between their bonds is on the order of 180° Atoms X and Y m the structure shown are anti to each other... 

An electronegative substituent adjacent to a ring oxygen atom also shows a preference for an axial orientation. This is known as the anomeric effect , and is particularly significant to the conformations of carbohydrates (B-71MI20100, B-83MI20100). 

Anomeric effect (Section 25.8) The preference for an electronegative substituent, especially a hydroxyl group, to occupy an axial orientation when bonded to the anomeric carbon in the pyranose form of a carbohydrate. 

The first interpretation of the conformational anomeric effect, given by Edward,2 invoked more favorable electrostatic interactions in the axial anomers than in the equatorial anomers of carbohydrates (Fig. 8). 

Anhydrous hydrogen fluoride, application of for the structural analysis of polysaccharides, 47, 167-202 Anomeric and exo-anomeric effects in carbohydrate chemistry, 47, 45-123 Anomeric-oxygen activation for glycoside synthesis, trichloroacetimidate method, 50,21-123... 

Carba-sugars (pseudo-sugars) and their derivatives, chemistry of, 48, 21 - 90 Carbohydrate chemistry anomeric and exo-anomeric effects in, 47, 45-123... 

Two characteristics of carbohyhdrate structure are often given special attention when constructing potential functions. Although hydrogen bonding and "anomeric effects" are certainly in ortant in other compounds, they are thought to be especially important for carbohydrates. 

Carbohydrates have been included in the wide range of molecules used in the parameterization of MM2 and of MM3. Alcohol and ether parameters have usually been determined from simple alcohols and ethers themselves. However, carbohydrates contain some unusual features in the acetal linkages, and in the many vicinal hydrogen-bonded hydroxyl groups. The "anomeric effect", first discovered by Edward (15) and popularized by Lemieux (16.), is best known in carbohydrates, although, of course, it occurs in other classes of compounds as well. One apparent result of this effect is that an axial alkoxy substituent is often more stable than the corresponding equatorial substituent when attached at the Cl position of a tetrahydropyranyl ring. This effect can be... 

Two recent versions of MM2, MMP2(85) and MM2(87), automatically compensate for the anomeric effects that are important for sugars. Accomodations for carbohydrates are discussed further in the chapter in this book by French,... 

Similar comments apply to cyclic systems (Table 8-2). SYBYL molecular mechanics is completely unsatisfactory for establishing relative conformer stabilities, while MMFF appears to be quite well suited for this purpose. The only unsatisfactory case for the MMFF model is 2-chlorotetrahydropyran, where the noted preference for an axial chlorine (usually attributed to the anomeric effecF) is not reproduced. Caution should be exercised in the application of MMFF to carbohydrates where the anomeric effect may lead to significant conformational preferences. 

Recall that in the latter, certain types of substituents adjacent to oxygen in the ring actually prefer axial arrangements. This observation has been codified in what is commonly referred to as the anomeric effect and is responsible in part for the conformations of carbohydrates. Is it possible that conformational preferences seen in substituted tetrahydropyrans will carry over into preferences in transition-state geometries for Claisen rearrangements ... 

D. P. Curran and Y. Suh, Selective mono-Claisen rearrangement of carbohydrate glycals. A chemical consequence of the vinylogous anomeric effect, Carbohydr. Res. 777 161 (1987). 

It is to be emphasized that, in the absence of elements of symmetry, as is the case for carbohydrates, determination of the molecular structure should be based on both the experimental, vibrational spectra and the calculated frequencies. In order to minimize the differences between experimental and calculated results, the structure factors utilized in the calculation should take into account the previous conformational studies. The peculiarities of carbohydrate structures, such as anomeric and exo-anomeric effects, are revealed by bond shortening and torsion-angle modifications. These modifications are accompanied by a change in the vibrational-energy level, and hence, by the corresponding information in their infrared or Raman spectra. 

On the basis of the above results and discussion, the glycosides can now be considered. Efforts have been made previously to evaluate the magnitude of the anomeric effect by undertaking equilibration studies between equatorial and axial isomers at the anomeric center in carbohydrates (48), in monosubstituted 2-alkoxytetrahydropyrans (49, 50) and in more rigid systems (51). The anomeric effect has been evaluated to be of the order of 1.2 to 1.8 kcal/mol from these studies. In these evaluations, the conformation of the OR group in the axial and in the equatorial isomer was not considered the influence of the exo-anomeric effect was therefore neglected (3). Nevertheless, these studies demonstrated the importance of the anomeric effect. 

Stereoelectronic effects have long been recognized to influence the configuration and the conformation of acetals, particularly in carbohydrates where these effects were first discovered and discussed in terms of the anomeric and the exo-anomeric effects (1-3). The term anomeric effect introduced by Lemieux in 1958 (A) refers to the tendency of an alkoxy group at C-l of a pyranose ring to assume the axial rather than the equatorial orientation despite unfavorable steric interactions, whereas the term exo-anomeric effect also introduced by the same author (5) concerns the preferred orientation of the 0-R bond of the alkoxy group at the anomeric center. 

The Contribution of the Exo-Anomeric Effect to the Conformation Preferences Exhibited for Methyl a-Maltoside and Methyl a-Maltotrioside. E. Alvarado, A. J. Ragauskas, and R. U. Lemieux, Abstr. XHIth Int. Carbohydr. Symp., August 10-15, (1986). Ithaca, N.Y. U.S.A., p.133. 

D-(+)-galactose (15) is an example of the consecutive numbering of the carbon ring atoms in a monosaccharide (disaccharide see p. 253). Carbohydrates can exist in a cyclic and an acyclic structure. For this reason there is a special position in the structure of a monosaccharide, the carbon atom C-l and so called anomeric center. You can see that there is an equilibrium between er-anomer a-15 and / -anomer /3-15 of D-(+)-glucopyranose over the acyclic aldehyde structure 16. Both are cyclic hemi-acetals. The /Tanomer is the preferred conformation, but there are a few effects, like sterical or stereoelectronical effects (anomeric effect, inverse anomeric effect), which have influence on the a /i rate. 

The anomeric effect, a stereoelectronic effect, is explained in terms of lone pair-lone pair repulsion, dipole-dipole interactions and by M.O. theory. The equatorial positions of a carbohydrate are favored by sterically demanding substituents. However, electronegative groups at the anomeric center prefer the axial position because of the stereoelectronic effects. This fact is known as the anomeric effect.13 If there is a positive charge at the anomer substituent of a carbohydrate, the equatorial conformation is preferred. To explain this result a reverse anomeric effect was proposed and first detected at A-(tt-glycopyranosyl)pyridinium ions 31 and 32.14... 

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