The initial computational studies on d-arabinofuranosides were molecular mechanics calculations of methyl ¡-d-arabinofuranoside done by Perez and coworkers . Through a process by which the MM3 force field was used to optimize 360 unique conformations, two energy minima, the 3T2 (N) and 2T3 (S) conformations, were identified. The N conformer is about 1.3 kcal/mol more stable than the S, and the favored conformation about the C4—C5 bond was the gt orientation, which was favored over the gg rotamer by less than 2 kcal/mol. Additionally, the most favorable pathway for pseudorotation was shown to be through the east.
More recently, gas phase ab initio (HF/6-31G*, HF/6-31+G**, MP2/6-31+G**, MP3/6-31+G**) and density functional theory (B3LYP/6-31G*, B3LYP/ 6-31 + G**) calculations have been carried out on methyl a-d-arabinofuranose . A protocol developed by Serianni and coworkers [117,118], was used to construct the 10 possible envelope forms by fixing four atoms in a plane; then, upon minimization, the other parameters (bond lengths, bond angles, etc.) were optimized.
These studies identified 3E and 2E as the N and S minima, respectively, with the latter being the global minima (Fig. 25). B3LYP/6-31+G** calculations indicated that in the gas phase, the N conformer was 1.5 kcal/mol less stable than the S conformer. Additionally, comparison of the relative energies of the conformers showed, as expected, that pseudorotation through the east was preferred. The highest energy conformer along this pathway is °E (3.2 kcal/mol less stable than the global minima), whereas pseudorotation through the west would require proceeding through the E° conformer, which is 7.0 kcal/mol less stable than the global minima. Inter-esting°ly, these studies also showed that the planar species is approximately equivalent in energy to the E° conformer, and thus inversion through the planar ring form is a viable alternative t°o pseudorotation through the west. However, neither pathway is expected to be important because the east pseudorotation pathway is more favorable.
In 9 of the 10 envelopes, the favored rotamer about the C4—C5 bond is the gg orientation; the gt rotamer is favored in the other. In the gg orientation O5 can
Figure 25 N (3E) and S (2E) conformers for 24a as determined by gas phase density fashion theory (B3LYP/6-31G*) calculations.
form an intramolecular H bond with OH2 and this capability appears to be of major importance in stabilization of the conformations in the gas phase. Indeed, in the two most stable ring conformers, 2E and E1, an intramolecular H bond is formed between these two groups (OH2 • • • O5) in addition to another such interaction between OH3 and O1 (OH3 • • • O1). These H bonds undoubtedly stabilize the conformers to a significant degree. This observation is consistent with other recent gas phase calculations on sugars, which revealed that the formation of intramolecular H bonds is critically important in the stabilization of these molecules .
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