Anomeric effect carbohydrate reactivity

The anomeric effect is of prime consideration in synthetic carbohydrate chemistry in fact, some of the most important problems in this area, for example, the synthesis of oligosaccharides and carbohydrate-containing antibiotics, involve an understanding of the reactivity and properties of the anomeric center. In a detailed article concerned with the influence of reactant structure and solvent on glycoside synthesis, Schuerch explores how the anomeric effect of a number of reactants influences the course of kinetically controlled glycosidations. 

The stereofacial differentiation of the diastereotopic sides of nitrones by removable auxiliaries demands the positioning of the chiral group to be within the fV-substituent. In order to exhibit a spatial differentiation, a preferred conformation of this substituent is crucial. Carbohydrates, due to their exo-anomeric effect revealed to be efficient auxiliaries for these transformations. So far the reactivity and efficiency of more than 40 carbohydrate compounds have been examined. When optically active nitrones from inexpensive carbohydrates are applied, generally the optically purities of the N-substituted isoxazolidines are determined after removal of the chiral auxiliary. 

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, orientatiom 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 effect, because it involves a substituent at the anomeric position in carbohydrate pyranose rings. Scheme 3.1 lists... 

Quantum mechanical methods have been applied to carbohydrates and their fragments, especially for the purpose of understanding anomeric effects. Semiempirical techniques such as AMI and PM3 have been applied a number of times, even to molecules as large as cyclooctaamylose, which contains 168 atoms. Although these methods are often the only viable alternatives for studying chemical reactivity, they do not enjoy a reputation for accuracy sufficient to answer many questions. Density functional theory and ab initio methods have also been applied, again with geometry optimization. Solvation has also been included in some of these studies, based on continuum methods, which continue to be developed. ... 

Cooperativity/competUion among acceptors (armed/disarmed carbohydrates) Cleavage of the C-X bond at the anomeric position proceeds via evolution of the anomeric n o C-X interaction that culminates in the oxocarbenium ion. This carbocation is so strongly stabilized by n j- p interaction that this interaction is commonly described as a dative it-bond. Because oxacarbenium ions are strongly stabilized, their formation is relatively facile. In cross-coupling glycosylalion reactions, however, it is beneficial to differentiate the reactivity of two saccharides for the selectivity reasons. The competition and cooperativity between stereoelectronic effects can be used to fine-tune the reactivity of anomeric systems. 

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