Anomeric effect on conformation

Paulsen H, Gyorgydeak M, Friedmann M (1974) Conformational analysis. V. Influence of the anomeric and reverse anomeric effect on conformational equilibria on N-substituted N-pentopyranosides. Chem Ber 107 1590... 

The incorporation of heteroatoms can result in stereoelectronic effects that have a pronounced effect on conformation and, ultimately, on reactivity. It is known from numerous examples in carbohydrate chemistry that pyranose sugars substituted with an electron-withdrawing group such as halogen or alkoxy at C-1 are often more stable when the substituent has an axial, rather than an equatorial, orientation. This tendency is not limited to carbohydrates but carries over to simpler ring systems such as 2-substituted tetrahydropyrans. The phenomenon is known as the anomeric ect, because it involves a substituent at the anomeric position in carbohydrate pyranose rings. Scheme 3.1 lists... 

Other examples of the application of calculations of spin-spin coupling constants by means of the PCM/DFT model for chemical problems using the IEF-PCM approach are studies of the spin-spin coupling constants in the keto and enol forms of monosubstituted 2-OH-pyridines [83], of the anomeric effect on the 27HH and 37HH coupling constants in 2-methylthiirane and 2-methyloxirane [83], and of the conformation of pyridine aldehyde derivaties [84], In these studies, PCM has been used to obtain a more realistic... 

The 2D-NMR NOESY correlations determined the absolute configuration (3S) for spirodioxocin 641a, which could adopt different conformations whose relative populations depended on steric factors, anomeric, and related effects and intramolecular //-bonding. In the preferred conformation of 641a, both endocyclic oxygen atoms were disposed in equatorial position relative to the other cycle and, therefore, such a structure was not stabilized by a conformational anomeric effect. The conformation (3Y)-641 a that disposed both endocyclic oxygen atoms in an axial position, which was stabilized by a double conformational anomeric effect, would imply chair-chair conformation for... 

Although the origin and nature of the anomeric and exo-anomeric effects appear well appreciated, the importance of these effects on conformational equilibria, especially with regard to the influence of the exo-anomeric effect on the conformational preferences about glycosidic linkages, is not well appreciated. This paper is concerned with experimental investigations which were designed to help clarify this situation. 

In the solid state, tri-O-acetyl-p-D-xylopyranosyl halides adopt the all-equatorial 4Ci conformation, -whereas tri-O-benzoyl-p-D-xylopyranosyl halides crystallize in the all-axial 1C4 conformation, except for tri-O-benzqyl-p-D-xylopyranosyl chloride, which adopts the (skew) conformation. The variations of bond lengths to the anomeric carbon atom are discussed with regard to the anomeric effect. By comparative studies of the conformational equilibria of acetylated and benzoylated 1,5-anhydropentitols on the one hand, and pentopyranoses exhibiting the anomeric effect on the other, data for the non-bonding interactions may be derived. Based on the principle of additivity of these factors, the conformational distribution of structurally related compound may be estimated. In connection with these results, it is noted that two benzoyl groups show a smaller 1,3-diaxial interaction than two acetyl groups the difference between these interactions is about... 

Definitions based on Eqs. 1,3, and 4 should, in principle, also apply for the exo-anomeric and reverse anomeric effects. There are, however, some problems with the practical application of Eq. 1 in the case of the exo-anomeric effect, because the AG values are largely not available. For the exo-anomeric effect, the conformational equiUbrium is specified by two dihedral angles, 6 and d>, and the value of AG° is needed for all six individual con-formers shown in Fig. 3. Because rotation around the exocychc bond by angle O is much less restricted in comparison with rotation by angle 6, a mixture of conformers was experimentally observed, with a difficult resolution of AG2 into individual components. If the exo-anomeric effect is treated by Eq. 3, the extra term AE(AE2) should be redefined for the whole range of values of the torsional angle O. Due to the lack of experimental data on AG or AE , for each conformer in Fig. 3, the energy values calculated correctly , for example by some molecular orbital method, are used, instead of... 

The above analysis gains support from the cyclization results of the compounds 238 and 240. The compound 238 furnished the conformer 239a rather than 239b. In the conformer 239a, each heteroatom exerts an anomeric effect on the other heteroatom, whereas only the sulfur atom exerts an anomeric effect on the oxygen atom in the conformer 239b. 

Box based his explanation (8, 14) of the reverse anomeric effect on the lone-pair interaction model analogous to that presented earlier by Finch and Nagpurkar vide supra). The observed conformational behavior is a result of an interplay of stabilizing and destabilizing interactions. The former consist of attractive, stabilizing interactions between the lone pairs of the 0(1) oxygen and the electron deficient r, or n, orbitals of a substituent, which are favorable in 76e, as shown in Figure 9. The normal steric requirements of... 

This anomeric (n->CT ) interpretation, employing an electron-delocalization model, is the basis of the phosphorus app lone-pair hypothesis (PAPH). This hypothesis is completed by integration of two observations from the theoretical calculations discussed above (I) bond-weakening effects are calculated to be greater for apical than equatorial P—O bonds and (2) effects on conformational energy and electron distribution are amplified in pentacoordinate transition-state structures. 

Dithiaspiro[5.5]undecane can exist in the three conformations 64A, 64B, and 64C (Fig. 11). Conformer 64A which has the two sulfurs axially oriented can have two anomeric effects, conformer 64C which has the two sulfurs equa-torially oriented has no anomeric effects and conformer 64B with one sulfur axially oriented has only one anomeric effect. Taking Into account the ster-1c effects (0.9 kcal/mol for a gauche form of butane and 0.4 kcal/raol for a gauche form of S-CH2 X-CH2) and an anomeric effect of 1.4 kcal/mol. the relative stabilities 64A, 64B, and 64C are 0, 2.4, and 4.8 kcal/mol. On that basis, this compound must be essentially conformationally rigid existing in the conformation 64A only. This prediction was verified experimentally (25, 62), and further confirmation was found by the study of the acid catalyzed cyclization of ketone dithiol 65. This compound can give either isomer 66 or 67 which can take two different conformations each. 

Koole LH, Buck HM, Nyilas A, Chattopadhyaya J (1987) Structural properties of modified deoxyadenosine structures in solution. Impact of the gauche and anomeric effects on the furanose conformation. Can J Chem 65 2089-2094... 

Diene (47) displays notable diastereofacial discrimination in Diels-Alder reactions which has been ascribed to a reacting conformation determined by the exo-anomeric effect on the basis of an... 

Paulsen has discussed the influence of jy/z-l,3-diaxial interactions and the anomeric effect on the conformations of various pyranoid derivatives. High proportions of the C4 forms, indicating that there are strong syn-d ax a interactions in the Ci forms, were observed for 2,4-diazido-2,4,6-trideoxy-a-D-idopyranoside and the corresponding 2,4-diamino dihydrochloride derivative. Strong 5y -diaxial interactions in the usual chair forms of l,6-anhydro-2,4-... 

Modified Deoxyadenosine Structures in Solution. Impact of the Gauche and Anomeric Effects on the Furanose Conformation, Can. J. Chem. 65 2089 (1987). 

The general features of the monensin synthesis conducted by Kishi et al. are outlined, in retrosynthetic format, in Scheme 1. It was decided to delay the construction of monensin s spiroketal substructure, the l,6-dioxaspiro[4.5]decane framework, to a very late stage in the synthesis (see Scheme 1). It seemed reasonable to expect that exposure of the keto triol resulting from the hydrogen-olysis of the C-5 benzyl ether in 2 to an acidic medium could, under equilibrating conditions, result in the formation of the spiroketal in 1. This proposition was based on the reasonable assumption that the configuration of the spiroketal carbon (C-9) in monensin corresponds to the thermodynamically most stable form, as is the case for most spiroketal-containing natural products.19 Spiro-ketals found in nature usually adopt conformations in which steric effects are minimized and anomeric effects are maximized. 

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