Anomeric effect furanose rings

The furanose ring of ribose or deoxyribose is flexible and can be interconverted smoothly among an infinite number of envelope (E) and skew or twist (T) conformations. See Chapter 4, Section A,2. However, there are limits set by steric and anomeric effects.27 62-64 Conformations are often described as in Fig. 5-10 by stating which atom in an envelope conformation lies mostly out of the plane of the other four atoms. If this atom lies above the ring, i.e., toward the base, the ring... 

The conformational effects arising from the endoanomeric effect are for furanoses much less profound and as a result relatively little research has been performed in this area. The puckering of the furanose ring of an a and a P anomer usually adjusts the anomeric substituent in a quasi-axial orientation and hence both anomers experience a similar stereoelectronic effect. On the other hand, the conformational preference of the exocyclic C—O bond is controlled by the exoanomeric effect in the usual way. 

The marked stereoselectivity of these radical reactions must be ascribed to the effect of the bulk of the protecting groups. However, the radicals that were manipulated may have also shown an anomeric effect due to the vicinal oxygen. In a furanose sugar it is not easy to evaluate the anomeric effect without ESR, and also, the molecules concerned have two fused five-membered rings. This fixes the conformation into a V-shape. Such molecules are well known to have exo-reactivity and the formation of endo-bonds is difficult. All these effects may be acting together to make this nucleoside chemistry especially stereospecific. 

The conformational analysis of monosaccharides, disaccharides, and ohgosaccharides is reviewed. Conformational terms are introduced through examination of the conformations of cyclohexane and cyclopentane then applied to the pyranose, furanose, and septanose rings. Concepts such as the anomeric effect are discussed. Topics of current interest, such as hydroxymethyl group and hydroxyl group rotation and disaccharide conformations are summarized. Physical methods for studying conformation are outlined. 

Furanose rings possess considerable conformational flexibility. The configurations assumed by the rings are important stereochemical characteristics of the three-dimensional structure of DNA and RN A molecules. Statistical analysis of x-ray data has determined the probabilities of alternative conformations of the furanose ring in nucleosides and nucleotides and the free-energy difference <87AX(C)275). However, steric effects alone cannot entirely account for the conformational behavior of various furanose moieties in (modified) nucleosides, and the gauche and anomeric effects are... 

Because five-membered rings are more flexible than six-membered, the anomeric effect is less important in furanose than in pyranose forms. 

As we saw in Section 23.14, the preparation of glycosides by acid-catalyzed condensation of a carbohydrate with a simple alcohol—the Fischer glycosidation—is thermodynamically controlled and favors the formation of pyranose over furanose rings. The anomeric effect causes the a stereoisomer to predominate over the p. 

We will discuss later in more detail the anomeric effect in nucleosides, nucleotides, and nucleic acids and its influence on the conformation of the furanose ring and the chemical consequences due to its presence. 

The stereoselectivity of the cycloaddition reaction most likely depends upon the ring oxygen of the five-membered ring furanose. As a matter of fact, in the transition state of cycloaddition, the stereoelectronic effect could be expected to become operational which will, similarly to the anomeric effect, be based upon... 

In general, a six-membered pyranose form is preferred over a five-membered furanose form because of the lower ring strain, and these cyclic forms are very much favoured over the acyclic aldehyde or ketofte forms. As can be seen in Table 1.3, at equilibrium, the anomeric ratios of pyranoses differ considerably between aldoses. These observations are a direct consequence of differences in anomeric and steric effects between monosaccharides. The amount of the pyranose and furanose present in aqueous solution varies considerably for the different monosaccharides. Some sugars, such as D-glucose, have undetectable amounts of furanose according H-NMR spectroscopic measurements whereas others, such as D-altrose, have 30% furanose content under identical conditions. 

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