Carbonate anomeric effects

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... 

The magnitude of the anomeric effect depends on the nature of the substituent and decreases with increasing dielectric constant of the medium. The effect of the substituent can be seen by comparing the related 2-chloro- and 2-methoxy-substituted tetrahydropy-rans in entries 2 apd 3. The 2-chloro compound exhibits a significantly greater preference for the axial orientation than the 2-methoxy compound. Entry 3 also provides data relative to the effect of solvent polarity it is observed that the equilibrium constant is larger in carbon tetrachloride (e = 2.2) than in acetonitrile (e = 37.5). 

Compounds in which conformational, rather than configurational, equilibria are influenced by the anomeric effect are depicted in entries 4—6. Single-crystal X-ray dilfiaction studies have unambiguously established that all the chlorine atoms of trans, cis, ira j-2,3,5,6-tetrachloro-l,4-dioxane occupy axial sites in the crystal. Each chlorine in die molecule is bonded to an anomeric carbon and is subject to the anomeric effect. Equally striking is the observation that all the substituents of the tri-0-acetyl-/ -D-xylopyranosyl chloride shown in entry 5 are in the axial orientation in solution. Here, no special crystal packing forces can be invoked to rationalize the preferred conformation. The anomeric effect of a single chlorine is sufficient to drive the equilibrium in favor of the conformation that puts the three acetoxy groups in axial positions. 

Several structural factors have been considered as possible causes of the anomeric effect. In localized valence bond terminology, it can be recognized that there will be a dipole-dipole repulsion between the polar bonds at the anomeric carbon in the equatorial conformation. This dipole-dipole interaction is reduced in the axial conformation, and this factor probably contributes to the solvent dependence of the anomeric effect. 

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 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. 

A number of explanations have been offered for the anomeric effect. The one ° that has received the most acceptance is that one of the lone pairs of the polar atom connected to the carbon (an oxygen atom in the case of 93)... 

The turning of the key once the complex has formed is a separate issue. In this regard, Lemieux (47) has pointed out that rotation about the glycosidic bond must weaken the exo-anomeric effect and thereby importantly activate the anomeric carbon to nucleophilic attack. Therefore, it seems likely that the role of the key hydroxyl group of the aglycon is to accommodate the rotation prior to the attack by water to form / -D-glucopyranose, which is the first product of the reaction. 

Another anomeric effect is that acetal C-0 bonds, and to a lesser extent, the bonds between acetal carbons and ether oxygens, are shortened or elongated as a function of their associated torsional angles. Jeffrey and Taylor modified MMl to account for these anomeric effects (17) and similar additions were put in the standard 1985 version of MM2 (11). The parameterization of MM3 for anomeric effects is preliminary, with recent (18-20) results being monitored. 

By definition, a generalized anomeric effect is observed at carbon of an XCY system when a molecule preferentially adopts a conformation that optimizes a secondary, stabilizing electronic interaction involving overlap between the lone pair on one heteroatom with the a orbital of the bond between the central carbon atom and the second heteroatom . Figure 5a illustrates that in XNY systems, as with anomeric carbon centres, two anomeric interactions are possible and involve either an ny-CT x ° nx-o NY overlap where nx and ny represent the p-type lone pairs on X and Y and NX and NY represent the N—X and N—Y a orbitals. In either case, the result is a net stabilization of the lone pair of electrons (Figure 5b). Except where the nitrogen is symmetrically substituted, one of these interactions will be strongest. 

In addition to solvolysis and nitrenium ion formation, Af-aLkoxy-A-chloroamides (2) also undergo bimolecular reactions with nucleophiles at nitrogen. Not only is the configuration destabilized by the anomeric effect, it also parallels that of a-halo ketones, where halogen on an sp carbon is activated towards reactions by the adjacent carbonyl. This rate-enhancing effect on 8 /2 processes at carbon is well-known, and has been attributed to conjugation of the p-orbital on carbon with the carbonyl jr-bond in the S 2 transition state stabilization of ionic character at the central carbon as outlined by Pross as weU as electrostatic attraction to the carbonyl carbon. The transition states are also affected by the nature of the nucleophile. ... 

A parameter that has been useful for defining the anomeric stereochemistry of glycopyranosides is the chemical shift of the anomeric carbon atom, C-l. Similarly, the 13C NMR shifts of C-l in methyl septanosides also diagnostic for their anomeric configuration. In general, the Sc.i values for a-septanosides are slightly upfield (99-104 ppm in completely deprotected septanosides) relative to (S-septanosides (104-111 ppm) (Table I). This distribution of chemical shifts mirrors the trends for pyranosides namely, the C-l chemical shifts for a-pyranosides lie upfield from those of p-pyranosides. This observation suggests that the anomeric effect is operative in... 

The gauche effect — which has the same electronic origin as that of the anomeric effect—is able to stabilize a conformation that should, a priori, be disfavored by steric factors. Thus, the gauche effect prevents the trans antiperiplanar conformation of two electronegative substituents borne by two vicinal carbon atoms (Figure 3.2). ° ... 

This is exactly the reverse situation found in dealing with attachment of two methoxy groups or two fluorines (a acceptors and n donors) onto a tetrahedral carbon, also known as the anomeric effect, yet leads to exactly the same energetic consequences. 

An alkyl group located on a carbon a to a hetero atom prefers the equatorial position, which is of course the normally expected behavior, but a polar group in such a location prefers the axial position. An example of this phenomenon, known as the anomeric effect,24 is the greater stability of a a-glucosides over p-glucosides. A number of explanations have... 

Annelida (segmented worms) 24 Annexins 316,422, 571 Anomeric carbon atom 162 Anomeric effect 166 Antagonists 479 Antamanide 414... 

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