MM3(92) was used to minimize energies in exhaustive searches of the ri
ng shapes and orientations of exocyclic groups for four fructose tauto
mers (alpha-furanose, beta-furanose, alpha-pyranose and alpha-pyranose
). A dielectric constant of 4.0 was used to emulate a ''general conden
sed phase'' environment. Calculated energies of the three major tautom
ers were within a range of 0.86 kcal after the correction by -5.5 kcal
as done by MM3 for heats of formation for five-membered rings. The en
ergy of the minor alpha-pyranose form was 2.5 kcal above the minimum.
Tautomeric ratios from crystal structures and from DMSO as well as aqu
eous solutions differ depending on the environment. However, no experi
ment has found quite as much alpha-furanose as we predict, unlike our
results on other monosaccharides where the extents of beta-anomers are
slightly over-estimated, In all cases, however, the apparent error of
the MM3 calculations has been less than 1.0 kcal/mol. Energy surfaces
for ring puckering depict the degree of pseudorotation and rationaliz
e the distribution of conformers of each tautomer. Numerous beta-furan
ose rings in crystals fit well as do the beta-pyranose rings, and our
interpretation of literature NMR data requires a north-south equilibri
um for alpha-furanose. Model bond lengths were compared with averaged
data from precise X-ray studies of crystals containing beta-D-fructopy
ranose. Bonds between heavy atoms based on r(alpha) (an optional compu
tation corresponding to distances between thermally averaged centers)
ft about 25% better than the normal MM3 values that correspond to r (g
as-phase electron diffraction results). The C2-O2 (anomeric) bond leng
th was over-estimated by 0.024 Angstrom, but the mean absolute deviati
on of the other bonds was only 0.006 Angstrom. Intramolecular hydrogen
bonds were weak in most preferred fructose models, shown by a plot of
energy vs, lengths and angles of hydrogen bonds. The stabilization of
sugar models with peripheral intramolecular hydrogen bonds is augment
ed by the lack of destabilizing dipole-dipole forces. MM3(92) (with a
dielectric constant of 4.0) accommodated hydrogen bond geometries foun
d in crystals. (C) 1997 Elsevier Science B.V.