Aldopentopyranoses

Conformational Equilibria of Acylated Aldopentopyranose Derivatives and Favored Conformations of Acyclic Sugar Derivatives... 

T1he conformational studies (I) on acyclic sugar derivatives and on aldopentopyranose derivatives that have been conducted in our laboratories during the last few years are surveyed, and some of our more recent results in each of these areas are introduced. For each aspect the sugar derivatives were examined in solution by proton magnetic resonance (PMR) spectroscopy, and the data obtained were used to provide conformational information. Acyclic systems will be treated first. 

First, the anomeric equilibria of the aldopentopyranose tetraacetates were examined by NMR spectroscopy and by optical rotation (25). Each of the acetylated anomeric forms of the aldopentopyranose tetraacetates was allowed to attain equilibrium in a 1 1 mixture of acetic anhydride and acetic acid containing perchloric acid as a catalyst (Table II). The... 

Table II. Anomeric Equilibria of D-Aldopentopyranose Tetraacetates at 27°C in 1 1 Acetic Anhydride—Acetic Acid, 0.1M in Perchloric Acid...

Study of the eight stereoisomeric aldopentopyranose tetraacetates showed that significant population of both chair conformers is the rule... 

Table VII. Conformational Equilibria of D-Aldopentopyranose Tetraacetates in Acetone- at 31°C...

Table XII. Comparison of Equilibrium Positions for the Peracetylated and Perbenzoylated Aldopentopyranoses...

Solvent polarity has a negligible effect on conformational equilibrium in the aldopentopyranose tetrabenzoates, but a regular effect is observed for methyl glycoside derivatives. 

The aldopentopyranoses are not constrained to the Ci conformation by the presence of a hydroxymethyl group. As a result, the equitibria between the Ci and conformers are more closely balanced, with the D-xylopyranoses present in aqueous solution mainly as " Ci conformers (25), the D-arabinopyranoses mainly as 4 conformers (26), and the others as mixtures [136,137,138]. 

The susceptibility of the atoms of sugar molecules to attack by acid and base catalysts may be associated with electronic density, as well as with stereomeric factors. Zhdanov and coworkers259 have calculated the electronic charges of the atoms of various types of carbohydrate molecules by an adaptation of the molecular-orbital method. The charge distributions calculated for aldopentopyranose and aldopento-furanose molecules are as follows ... 

Durette and Horton295(c) studied, by nuclear magnetic resonance spectroscopy, the anomeric equilibria at 27° of the aldopentopyranose tetraacetates in 1 1 acetic anhydride-acetic acid that was 0.1 M in perchloric acid. They found the following values for the ratios of the anomeric tetraacetates (/3la) at equilibrium, with the free energy A G° values for the J3 equilibrium (in parentheses) D-ribopyra-nose, 3.4 (—0.73 0.03) D-arabinopyranose, 5.4 (—1.01 0.03) D-xylopyranose, 0.23 (+0.89 0.03) and D-lyxopyranose, 0.20 (+ 0.98 0.05). 

The introduction of substituents and the effects of solvation profoundly influence the conformational equilibria of monocyclic pyranoid sugars and their derivatives, because of the changes in steric and electronic interactions that result. The conformations of numerous polysubstituted pyranoid sugars in various solvents have been investigated, mostly by application of the n.m.r. spectroscopic method. Six aldopentopyranose tetraacetates were examined in chloroform solution near room temperature they were considered to exist almost entirely in the CJ(d) conformation, except for the jS-D-ribo derivative, which appeared to contain substantial proportions of each chair form, and the -L.-arahino derivative which was estimated to contain mostly the CJ(l) conformation. 2-Deoxy-j8-D-e/T/thro-pentopyranose triacetate was considered to exist mainly in the 1C conformation. 

The only aldopentopyranose tetraacetates for which conformational freeze-outs were observed at temperatures down to —100° were the p-D-ribo and the (3-D-lyxo derivatives. ... 

Conformational Equilibria of Aldopentopyranose Derivatives in Acetone-d Solution at 31°... 

D-Aldopentopyranose derivative % Cl Equilibrium data %1C K = C1I1C ACgio, kcal.mole forlC(D) JSCI(D) Refer- ences... 

From a consideration of detailed results on the conformational equilibria of aldopentopyranose derivatives, it has been pointed out92- 9 that a more sophisticated model is required before conformational populations can be reliably predicted, at least with acylated derivatives. Even with adjustment of the original parameters in order to take revised values for the anomeric equilibrium of D-lyxopyranose tetraacetate and the conformational equilibrium of /3-D-arabinopyranose tetraacetate into account, the observed data cannot be accommodated within the framework of this model, except on a very broad, qualitative basis. Other possible factors that should be considered " include polar contributions from substituents other than that on C-1, attractive interactions between syn-diaxial acyloxy groups, non-bonded interactions between atoms that have unshared pairs of electrons,repulsive interactions between gauche-vicinal groups, the effect of solvent pressure, and differences between the molar volume of conformers. 

Estimates of the magnitude of the anomeric effect of other polar groups have been reported (a) OMe 1.2 kcal.mole in the methyl aldopentopyranosides and 1.4 kcal.mole" in the methyl aldohexo-pyranosides in 1% methanolic hydrogen chloride, 1.3 kcal.mole in 2-methoxy-4-methyltetrahydropyran in p-dioxane and 0.9 kcal. mole in aqueous methanoP (b) OAc 1.3 kcal.mole in peracetyl-ated aldopentopyranoses and 1.5 kcal.mole in the peracetylated aldohexopyranoses in 1 1 acetic acid-acetic anhydride, - 1.35 kcal.mole" in 2-acetoxy-4-methyltetrahydropyran in acetic acid (c) Cl 2 kcal.mole in tetra-O-acetyl-D-glucopyranosyl chloride in acetonitrile and 2.7 kcal.mole" in neat 2-chlorotetrahydropyran ... 

Surprisingly, the equilibration studies consistently show a substantial proportion of the -D-arabino ion (75), as indicated by a corresponding proportion of tetra-0-acetyl-/3-D-arabinopyranose obtained after hydrolysis and subsequent analysis of the product mixture. The /3-D ion (75) cannot be formed through acetoxonium rearrangement of 72, but must arise through subsequent anomerization of the a-D ion (74) formed initially, because the acetoxonium salt functions as an effective catalyst for anomerization If solutions of anomerically pure aldopentopyranose tetraacetates in nitromethane are treated with 2-metiiyl-l,3-dioxolan-2-ylium hexachloroantimonate (2,R=Me), a rapid onset of anomeric equilibration is observed. Under these conditions, tetra-O-acetyl-D-arabinopyranose gives an a /3 ratio of 9 91, and tetra-O-acetyl-D-xylopyranose, an a /3 ratio of 96 4. 

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