Anomeric substituents

It IS not possible to tell by inspection whether the a or p pyranose form of a par ticular carbohydrate predominates at equilibrium As just described the p pyranose form IS the major species present m an aqueous solution of d glucose whereas the a pyranose form predominates m a solution of d mannose (Problem 25 8) The relative abundance of a and p pyranose forms m solution depends on two factors The first is solvation of the anomeric hydroxyl group An equatorial OH is less crowded and better solvated by water than an axial one This effect stabilizes the p pyranose form m aqueous solution The other factor called the anomeric effect, involves an electronic interaction between the nng oxygen and the anomeric substituent and preferentially stabilizes the axial OH of the a pyranose form Because the two effects operate m different directions but are com parable m magnitude m aqueous solution the a pyranose form is more abundant for some carbohydrates and the p pyranose form for others... 

T—temporary anomeric substituent Scheme 1.8 Linear oligosaccharide synthesis. 

The limit of this modification lies on the impossibility to mime the anomeric substituent, which makes these compounds not really useful as carbohydrate mimics. 

The occurrence of some substitution in the deamination of 2-amino-2-deoxy-/3-D-mannopyranosides131 152 (72), and its absence in the reaction of the a-D-pyranoside150 69, must be due to the steric effect of the axial anomeric substituent which (in the a-D-pyran-oside) hinders the approach of the nucleophile (water) to either the C-2 carbonium ion or to C-2 of the diazonium ion. The glucose and glucitol tentatively detected as minor products in the deamination of 72 (R = D-glucose residue and R = D-glucitol residue) presumably arose by way of a hydride shift of H-l to C-2. 2-Deoxy-D-glucono-1,5-lactone (75) was not detected, as it would probably have. o,... 

The many carbohydrate compounds to have been examined (see Section II) clearly raise the interesting question of the combined effects of the ring-oxygen atoms and of the other substituents on radicals formed at C-l and at C-4 and C-5 for furanoid and pyranoid compounds, respectively. The several acetylated / -D-glucopyranosyl derivatives (100) to have been studied are particularly suitable compounds for examination in this regard, since, because of their near-symmetry, the effects of the anomeric substituent (X) in respect of its ability to facilitate photobromination at C-l can be compared closely with the effect of the substituent (CH2OAc) at C-5. 

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. 

FIGURE 1.10 The anomeric effect, (a) The n-o interaction stabilizes the a anomer. (b) The P anomer experiences unfavorable dipole-dipole interaction that is reduced in the a anomer. (c) Greater electrostatic repulsion between the lone-pair electrons of the endocyclic oxygen and the electronegative anomeric substituent in the (1 anomer. 

On the basis of these and related results, and because variation of the oxidant did not produce the clear-cut differences in the steric course of oxidation observed with thianes, it was suggested66 that control of the S-oxidation of derivatives of 2-hydroxy-l,4-oxathiane is best achieved by changing the configuration at the anomeric center an axially attached substituent such as methoxyl or acetoxyl engenders equatorial S-oxygenation, whereas an equatorially attached, anomeric substituent leads to an axial S-oxide. 

Osborn, H M I, Brome, V A, Harwood, L M, Suthers, W G, Regioselective C-3-O-acylation and 0-methylation of 4,6-0-benzylidene-(3-D-gluco- and galactopyranosides displaying a range of anomeric substituents, Carbohydr. Res., 332, 157-166, 2001. 

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