Aldopyranoses anomerization

Scheme 1.—Occurrence of Ring Protons Expected to Have a Major Influence on the Relaxation Rates (R,) of the Anomeric Protons (H-1) of Aldopyranoses and Derivatives (4-25, Table I) in the C, or C4, Conformation.

Since 2-deoxy-2-fluoro derivatives of aldopyranoses and furanoses are far more stable towards hydrolytic conditions than their 2-deoxy counterparts, the synthesis of the former entails primary preparation of the anomeric phosphotriesters 31, which are chromatographically separated into individual diastereomers and subsequently deprotected on phosphorus... 

In studies on the anomerization of acetylated aldopyranoses in acetic anhydride-acetic acid-sulfuric acid at 25°, it was found34 that the peracetates of 6-deoxy-D-glucopyranose anomerize about ten times as fast as those of D-glucopyranose. 

Fig. 6. Limited stereoselectivity in NeuA-catalyzed aldol additions, observed with aldopyranose substrates (including known anomeric ratios)...

Isbell was also ahead of his time in grasping the concept of reaction mechanisms. In collaboration with the late Ward Pigman, he proposed two important mechanisms one for the anomerization of aldopyranoses by ring opening (see Fig. 3), and the other for the anomerization of their esters via a cyclic carbocation (see Fig. 4). 

Fig. 4.—Mechanism of anomerization of aldopyranose acetates, by formation of carbocations.

Proton Magnetic-resonance Spectra of the Anomeric Hydrogen Atom of Acetylated Aldopyranoses ... 

Equilibrium Constants and Individual Rate Constants for the Anomerization of Acetylated Aldopyranoses in 1 1 Acetic Acid-Acetic Anhydride which is 0.5 M in Sulfuric Acid, at US ... 

Effects of Ring Substituents on the Anomeric Equilibrium of Aldopyranoses and Derivatives... 

The electron-withdrawing effect of the anomeric center, which inhibits displacements of primary sulfonyloxy groups at C-l of fructose and sorbose, strongly hinders displacements at C-2 of aldopyranose derivatives. An alternative or additional effect, proposed by Hough and Richardson,347 may well consist in unfavorable dipolar interactions which would arise in the formation of the SN2 transition state. 

A notable exception has been the application of i.r. spectroscopy by Isbell and Tipson to the analysis of the conformations of methyl aldopyranosides," acetylated methyl aldopyranosides," " and fully acetylated aldopyranoses in the solid state. Their approach was based on (J) the assumption that the pyranoid sugar derivatives predicted by Reeves to exist in only one of the chair conformations in solution would adopt that same conformation in the crystalline state, and (2) the observation that axially and equatorially attached groups at the anomeric carbon atom give rise to different vibrations. 

The conformations of the aldopyranoses in aqueous solution have been investigated by n.m.r. spectroscopy " (see Table IV). The chair form favored by the various aldohexopyranoses appears to be controlled by the tendency of the 5-(hydroxymethyl) group to assume the equatorial orientation. Hence, all the /3-D anomers exist preponderantly in the CJ(d) conformation, as the alternative, 1C(d) conformation appears to be highly destabilized by the si/n-diaxial interaction between the 1-hydroxyl and 5-(hydroxymethyl) groups. Although this interaction is not found in the 1C(d) conformation of the a-D anomers, most of the a-D anomers nevertheless adopt the C1(d) conformation, presumably because of a favorable anomeric effect (see p. 103). Solutions of a-D-idopyranose and a-D-altropy-ranose appear to contain appreciable proportions of each chair con-former at equilibrium. 

The estimated free-energies for both chair conformations of the free aldopyranoses were then calculated by summation of the various steric interactions and the anomeric effect of the anomeric hydroxyl group. The energies calculated are given in Table IV (see p. 85), together with the conformations predicted and those indicated by experiment. When the free-energy difference between the two ehair forms was less than 0.7 kcal.mole", both conformers were considered to be present in comparable amounts at equilibrium. 

In a further quantitative check of the validity of the calculated free-energy values, the predicted a,p anomeric equilibria of the aldopyranoses in aqueous solution were found to be in reasonable agreement with those determined experimentally by studies of their mutarotation, oxidation by bromine, and n.m.r. spectra. In addition, the position of the equilibria between aldohexopyranoses (and 3-deoxy-aIdohexopyranoses) and their 1,6-anhydrides, and between heptuloses and their 2,7-anhydrides, as determined by gas-liquid chromatography, were in good agreement with data estimated from conformational interaction-energies. 

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