Conformation instability factors

Table VIII lists the instability factors for the various aldohexopyranosides and aldopentopyranosides (D-series) in the two chair conformations. The Symbols Cl and 1C refer to Figure 3.

Reeves has suggested that the spontaneous formation of 1,6-anhydro derivatives of idopyianose and altropyranose may be due to the conformational behavior of the aldoses his instability factors show that /3-Didose and /3-D-altrose will exist partly in the conformations favorable for closure of the 1,6-anhydro ring. This reasoning could lead to the further conclusions that D-talose, but probably not n-gulose, should fairly readily afford a 1,6-arihydro derivative of the pyranose form. 

In Table I, the differences in the rates of oxidation of anomeric aldoses have been compared with the instability factors of the two possible chair conformations these include the axial substituents and the presence of the A2 arrangement (see page 28). 

Tables IV and V provide a comparison between the rates of hydrolysis of the above methyl glycopyranosides and the degree of instability or strain in the chair conformations of their pyranose rings. Using the Reeves method, the instability factors are denoted by the position of the axial substituents and by that arrangement in which an axial hydroxyl group on C2 bisects the oxygen valences of Cl (XXII), denoted by A2.

An example of the power of these instability factors is their prediction that epimerisation of p-o-mannopyranose at C5 to give a-L-gulose will change the conformational preference of the ring from Ci to 4. A closely analogous epimerisation occurs during biosynthesis of alginate (Chapter 4), whose... 

Figure 2.18 Use of instability factors to predict the conformation of P-o-mannopyra-nose and a-L-gulopyranose.

Another conformationally unstable, anomeric pair of glycosides, the methyl pyranosides of a- and -D-lyxose, have calculated, composite rate-constants of 14.5 and 46.4, respectively, relative to the rate constant for methyl o-n-glucopyranoside (1.0). In this case, it is the /3-n glycoside which is hydrolyzed three times faster than the a-n glycoside, and the /3-d glycoside which possesses both an equatorial methoxyl group and a A2 instability factor. 

Less ambiguous results have been obtained by examination of the electrophoretic behavior of cyclitols. With these, the possibility of complex-formation with open-chain and with five-membered ring structures, as in the case of aldoses and ketoses, does not arise. The complex-forming compounds of this group all possess a m-m-1,2,3-triol system. Their rates of migration have been related to the instability factors of their conformations possessing this triol system as in (13). 

In an attempt to correlate conformational stability and the physical properties of some methyl O-methylaldopyranosides, Kelly modified Reeves s arbitrary instability factors as follows (i) axial hydroxyl group, 1 unit (2) A2 factor, 2.5 units (3) the Hassel-Ottar effect, 2.5 units and (4) an axial hydroxymethyl group, 2.0 units. With these values, improved agreement between the predicted and the experimentally determined conformations was obtained. 

The instability of the eclipsed form of ethane was originally postulated to result from repulsion of filled hydrogen orbitals. However, state-of-the-art quantum chemical calculations now indicate that two main factors contribute to the preference for the staggered conformation of ethane. First, the eclipsed form is selectively destabilized by unfavorable four-electron interactions between the filled C-H bonding orbitals of... 

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