A anomer

The syn-anti conformational problem of a- and /3-pyrazofurins (756 one of the rare naturally occurring pyrazole compounds, see Section 4.04.4.4.3), which involves a rotation around a pyrazolic sp carbon atom and a sugar sp carbon atom, has been studied theoretically using the PCILO method (81MI40403). In agreement with the experimental observations, the /3 anomer is energetically more favourable than the a anomer, the preferred conformations being anti and syn, respectively. 

LiBF4, CH3CN, 70°, 3-8 h, 81-90% yield. This system of reagents also cleaves benzylidene acetals. Conventional reagents failed to cleave these glycosides. It is interesting to note that the /3-anomers are cleaved more rapidly than the a-anomers and that the furanoside derivatives are not cleaved. 

The rules previously mentioned for assignment of a- and /3-configurations can be readily applied to Haworth projection formulas. For the D-sugars, the anomeric hydroxyl group is below the ring in the a-anomer and above the ring in the /3-anomer. For L-sugars, the opposite relationship holds. 

The a-anomer gives better selectivity for the 2-OH than does the /3-anomer (3 2). Note that the conditions used to remove the 4,6-O-benzylidene group are sufficiently mild to retain the sulfate. ... 

Reaction of 3-amino-1-propanol and 5-bromo-5-deoxy-D-furanoxylose (25) in D2O was monitored by NMR (Scheme 4). The a-anomer of trihydroxypyridoPd-f l-LbSloxazine 26 formed 20 times faster, but the /3-anomer 27 was more stable (A / 7.3). The faster formation of the Q -anomer is a consequence of a kinetic anomeric effect that destabilizes the transition state for equatorial A -alkylation and formation of the /3-anomer 27 (OOJOC889). 

In similar manner 3,6-dideoxyhexoses have been prepared from esteri-fied 6-deoxy-2-hydroxyglycals. 2,3,4-Tri-0-acetyl-6-deoxy-2-hydroxy-D-glucal was converted into the a and / forms of l,2,4-tri-0-acetyl-2,3-didehydro-3,6-dideoxy-D-en/t/iro-hexose. The a anomer was the main product (77%, 55% isolated crystalline) and, in addition to the ft anomer (19%), a small amount (4%) of saturated products was obtained. On hydrogenation, the major product also suffered some hydrogenolysis but afforded two tri-0-acetyl-3,6-dideoxyhexoses which were shown by NMR spectroscopy to be present in the ratio 12 13 and to have the a configuration. Deacetylation of the reduction products gave... 

Both anomers of o-glucopyranose can be crystallized and purified. Pure a-n-glucopyranose has a melting point of 146 °C and a specific rotation, lo-Jn, of +112.2 pure /3-D-glucopyranose has a melting point of 148 to 155 °C and a specific rotation of +18.7. When a sample of either pure anomer is dissolved in water, however, the optical rotation slowly changes and ultimately reaches a constant value of +52.6. That is, the specific rotation of the a-anomer solution decreases from +112.2 to +52.6, and the specific rotation of the /3-anomer solution increases from +18.7 to +52.6. Called mutarotation, this change in optical rotation is due to the slow conversion of the pure anomers into a 37 63 equilibrium mixture. 

Each of these compounds, 53-56, was shown to be a very effective competitive inhibitor of the enzyme with respect to the fructose 1,6-diphosphate, whereas several other analogs, including acyclic structures, had no effect. These and other results suggest that the furanose form of the sugar diphosphate is the active form in the enzymatic reaction (105). More recent studies using rapid quenching techniques and C-nmr measurements have confirmed this hypothesis and indicate that the enzyme uses the a anomer 52 much more rapidly than the 3 anomer 50 and probably uses the a anomer exclusively (106). 

Scheme 1 The reaction catalyzed by influenza viras sialidase. The initially formed a-anomer 3a undergoes rapid equilibration with the 3-anomer 3b...

The Noyori procedure was applied to a total synthesis of baiyunoside, a sweet principle, using 2,3,4-tri-<9-benzyl-D-xylopyranosyl fluoride (18 see Table 1), and a synthesis of glycotriosyl ceramide. A model experiment for the synthesis, using 18, showed a solvent dependence for the a ratio of the products. In this case, the use of acetonitrile, oxolane, or ether gave the a anomer (1,2-a.v), and the use of toluene or hexane gave the P anomer (1,2-trans), preponderantly. 

Preparation of 2-fluorofuranoses is also important in relation to the synthesis of biologically active 2 -fluoro derivatives of nucleosides (see Section 111,4). Su and coworkers prepared the 2-triflates 236 and 239 through acid-catalyzed methanolysis of 3,5-di-O-benzyl-1,2-(9-isopropylidene-a-D-ribofuranose [to give 235 (major) and 238] and subsequent triflylation. On treatment with fluoride ion, the anomer 236 afforded exclusively the furan derivative 237, whereas the a anomer 239 gave the 2-fluoro compound 240... 

Perfluoroalkyl)-5 -deoxy-5 -fluoro- and 5-(perfluoroalkyl)-2, 5 -di-deoxy-5 -fluoro-uridines were prepared " from 840 and 834, respectively, using perfluoroalkyl-copper complexes. Among them, 5 -deoxy-5 -fluoro-(846) and 2, 5 -dideoxy-5 -fluoro-5-(perfluoroethyl)uridine (839) were particularly effective against Ehrlich ascites carcinoma. 5-Hydroxyl (847) and 5-amino or 5-alkylamino (5-NHMe, -NHBu, -NHCH2Ph, -morpholino, -piperidino, and -pyrrolo) analogs (848) of 840 were prepared. The a anomer of 5 -deoxy-5 -fluorouridine (840) was also synthesized. "... 

The a anomers of 2-acetamido-2-deoxy-D-glucose and 2-acetamido-2-deoxy-D-galactose have the same nir c.d. bands in 1 1 methanol-water at 0° as the anomeric mixtures have in aqueous solution. This indicates that the anomeric configuration has little influence on the nir c.d. band. 

The carboxyl chromophore is axial for the a anomer and equatorial for the p anomer. The sugar was studied as the carboxylate anion as it has a (low) piC of 2.6, and the compound is degraded in acidic solution. The c.d. spectrum of this compound contains contributions from the carboxylate n-jr at 217 nm, the amide n-tr at 210 nm, and the amide 7T7r at 190 nm. Apparently, all of these bands are positive, giving rise to a c.d. spectrum (see Fig. 29) having " a maximum at 199 nm and a shoulder at 210 nm. The c.d. spectra of a number of derivatives confirmed these assignments. 

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