Conformational isomers glycosides

A kinetic study of the methyl glycosidation of D-mannose was also made by Mowery.48 The more stable anomer, the a-D-mannofuranoside, was formed at a higher initial rate (see Table III) the proportions of both furanosides in the final equilibrium mixture was too small to permit accurate comparison of isomer distribution. The conformational stability of the D-mannofuranosides may be compared with that of the D-lyxo-furanosides the furanoid structures are similar, except for the bulky two-carbon group at 04 of the hexoside. This similarity is shown in the very small proportion of n-lyxofuranosides (see Table V) and of D-manno-furanosideo (see Table III) in the final equilibrium mixtures, and also in the initial formation of D-mannopyranosides48 and of D-lyxofuranosides.u... 

On the basis of the above results and discussion, the glycosides can now be considered. Efforts have been made previously to evaluate the magnitude of the anomeric effect by undertaking equilibration studies between equatorial and axial isomers at the anomeric center in carbohydrates (48), in monosubstituted 2-alkoxytetrahydropyrans (49, 50) and in more rigid systems (51). The anomeric effect has been evaluated to be of the order of 1.2 to 1.8 kcal/mol from these studies. In these evaluations, the conformation of the OR group in the axial and in the equatorial isomer was not considered the influence of the exo-anomeric effect was therefore neglected (3). Nevertheless, these studies demonstrated the importance of the anomeric effect. 

The proposal of a conformation at the glacosidic bond with an upside down orientation of the two monomeric constituents has its support from experimental data of completely different origin. Thiem et al. were able to show that the kinetic isopropyli-denation of cellobiose in refluxing pyridine yields an isomer in low yield which has the glycosidic bond fixed via an isopropylidene bridge across the rings from OS to 06. This implies an upside down orientation of both rings compared to its normal conformation [91, 92]. 

The p anomers of sugars are generally oxidized more rapidly than the a anomers (see later), a similar pattern is seen in the faster oxidation of /1-glycosides. The different rates of oxidation of /1-D-glucopyranosides and their a-D anomers have been attributed to the equatorial orientation of the anomeric hydroxyl group in the 4Ci conformation of the former. Other compounds have shown a similar behavior.10 Thus, the relative rate of oxidation of cw-2-tert-butylcyclohexanol (HO-axial) with respect to the trans isomer (HO-equatorial) is approximately 5 1. 

The 5 -triphosphate deoxynucleoside derivatives of pyrrole-3-carboxamide and pyrrole 3,4-dicarboxamide have been incorporated into DNA with DNA polymerases. They are preferentially incorporated with Klenow fragment where they are incorporated as either dA or dC. The base analogue 1,2,4-triazole-3-carboxamide (124) can exist in four different conformations by rotation about the glycosidic or carboxamide bonds, and thus can in principle behave as a universal base. The analogue has been examined by NMR in duplexes opposite G and T where it is anticipated that it would adopt syn and anti conformations, respectively. NMR showed that in both duplexes, the complementary nucleotide adopted a syn conformation, and the carboxamide group is able to adopt two rotational isomers. 

Calculations predicted that lone-pair interactions in the (ap, ap) conformation corresponding to )S-glycosides are larger than in the (jc, sc) conformation representing a-glycosides, and thus, the increase of nucleophilicity in the former isomers should be higher. The enhancement of oxygen nucleophilicity can be demonstrated in several, simple reactions. A suitable measure of nucleophilicity of the 0-1 atom is its rate of protonation in... 

In order to compare the structure of this polysaccharide to its glycosidic isomer polysaccharide, Ogawa s data was used to generate a model for the conformation of a single chain.(36)... 

NMR is also a non-destructive technique, and a small number of sequential applications have been published. Wilson and co-workers [147] used HPLC-DAD-NMR-MS to characterize plant extracts. Hanson and co-workers [148] used a similar approach to examine another plant extract of pharmaceutical interest. In both cases, the complementary nature of the data provided quantitation of both major and minor constituents and aided in the structural identification of several of the minor components, including chiral isomers. Lommen et al. [149] describe a similarly configured system. The DAD and MS outputs were used to detect peaks, which were then transferred for NMR. They examined glycosides found in apple peel. They identified six quercetin glycosides and two phloretin glycosides, with the NMR data providing the definitive conformational data to differentiate the isomers. 

The solution conformations of the C-linked lactose analogues 32-34, and in particular the flexibility of the interglycosidic linkages, have been examined by NMR spectroscopy, as well as computational methods. Compound 32 is very similar to natural lactose around the glycosidic bond but more flexible about the aglyconic bond. Analogue 33 is similar to 32, its isomer 34, however, is more... 

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