Furanoses anomeric effect

On account of the more favorable anomeric effect,12 as well as of the larger nonbonding interactions of vicinal, synclinal substituents in furanoses as compared to pyranoses, jS-D-glucofuranose,13 /3-D-glucofuranurono-6,3-lactone, and their derivatives are of higher thermodynamic stability than their respective a-D anomers. 

As conformational anomeric effects represent only a fraction (—1 to —3 kcal/mol) of the global enthalpic anomeric effect or gem-dioxy stabilizing effect (—6 to —17 kcal/mol), additional factors have to be taken into account. Depending on substitution, steric factors can affect the relative stability of acetal conformers. Dubois et al.2S have demonstrated that in furanose pyranose derivatives a bulky substituent at the furanose... 

A similar series of reactions was performed on a 6-azido-6-deoxy-2-ketose.246,252 In most of the foregoing syntheses, the piperidine formed is accompanied by the tautomeric furanose. The tautomers can, however, be separated without occurrence of equilibration (which can be induced by changing the pH of the medium). For the ketose derivative 183, the equilibrium mixture includes246 compound 184 and a dehydration product (182). The conformation and anomeric effect in these piperidines have been studied by n.m.r. spectroscopy,253 and their fragmentation pathways have been determined by mass spectrometry.254... 

The only systematic study published on the influence of solvents on the solution equilibria of sugars is contained in two articles by Perlin.51-57 This work showed that, in other solvents, the a / -pyranose ratio is higher than in water (if the a-anomeric hydroxyl group is axial), and that there is a greater proportion of the furanose forms. The increase in the a-pyranoses is caused by the increased anomeric effect the possible reason for the increase in the furanose forms has been discussed in Section III, 1. The anomeric effect becomes particularly important in nonpolar solvents for example, in a chloroform solution of evernitrose... 

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... 

Most furanoses prefer the envelope conformation and it appears that a quasi-equatorial exocyclic side chain and a quasi-axial C(l)—0(1) bond (anomeric effect) are equally important stabilising factors (Figure 1.8). 

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. 

The cyclic hemiacetal (or hemiketal) can react with an alcohol to form an acetal (or ketal), called a glycoside. If the name pyranose or furanose is used, the acetal is called a pyranoside or a furanoside. The bond between the anomeric carbon and the alkoxy oxygen is called a glycosidic bond. The preference for the axial position by certain substituents bonded to the anomeric carbon is called the anomeric effect. If a sugar has an aldehyde, ketone, hemiacetal, or hemiketal group, it is a reducing sugar. 

Soon, it was pointed out by Fuchs et al. (89) that the equivalence of oxygen lone electron pairs is not consistent with X-ray structures of carbohydrates. They scrutinized 111 structures and found torsion angles O in Oendo—C—O—R fragments appreciably larger than 60°. If lone pairs were equivalent, one might expect 0 = 60° to be preferred whereas nonequivalence implies 0 > 60°. Indeed, Cosse-Barbi et al. (69,257) have recently shown that the endo anomeric effect is stronger in furanoses than in pyranoses. They... 

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. 

Chattopadhyaya et al. [8] have shown based upon thermodynamic estimates on a set of four isomeric 273 -deoxynucleosides that the net result of the gauche effect and the anomeric effect is of major importance in determining the overall furanose conformation. Many qualitative studies have been conducted [83-88] to understand how the electronic nature, protonation state [89], bulkiness or substitution pattern [90-95], and configuration of the nucleobases [96-115] or Cl substituent [116] modulate the sugar conformation in nucleosides and nucleotides, as well as furan-osides [117-121]. The conformational analysis [122] in solution of a dimer containing a 4 -oxofuran derivative [123], based upon the analysis of vicinal Jhh. has shown that the modified nucleoside adopts exclusively (89 %) the S-type puckered geometries, as a result of the cooperative drive by the 05 -C4 -04 anomeric effect and the [03 -C3 -C4 -04 ] gauche effect. 

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... 

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... 

The foregoing indicates that the anomeric effect can be relied upon to confer a high degree of stereochemical and conformational homogeneity upon pyranose structures. Furanose derivatives also exhibit preferences (87), although to a lesser degree. 

---