Structure and Conformation of Carbohydrates
1.1
21
conformers that have the side chain and the carboxyl group equatorial (31). Solutions of
free KDO show a much more complex tautomeric mixture than NANA, containing 60–65%
α-pyranose, 2–11% β-pyranose, 20–25% α-furanose, and 8–9% β-furanose [178,179]. The
ammonium salts of the α- and β-pyranose methyl glycosides are also present in solution as
5 C 2 conformers but these compounds differ in their C-7-C-8 rotameric populations [174].
Non-chair conformations are often populated for anhydro sugars. Depending on the type of
substitution, these sugars can exist entirely in boat conformations as in 2,6-anhydro [180] or
3,6-anhydro derivatives or to a small extent as for 1,6-anhydro-β-D-glucopyranose ( > Fig. 13).
1,6-Anhydro-β-D-hexopyranoses are in equilibrium with the D-hexopyranoses and water
when the latter compounds are heated in aqueous acid [181]. On formation of a 1,6-anhydro ring, the normal 4 C 1 conformer is forced into a 1 C 4 conformation. The amount of the
1,6-anhydro-β-D-hexopyranose present at equilibrium at 100 °C in aqueous acid can be predicted quite successfully from Angyal’s interaction energies with a value of G° for anhydro
ring formation of −11.7 kJ mol −1 [181]. The 3 J H2,H3 and 3 J H3,H4 values observed for most
1,6-anhydro-β-D-glucopyranose derivatives are small, 1–2 Hz, consistent with a 1 C 4 conformation and all of the derivatives that have been studied by X-ray diffraction adopt this
conformer [182,183]. It was therefore surprising that the 3 J H2,H3 and 3 J H3,H4 values for
3-amino-3-deoxy-1,6-anhydro-β-D-glucopyranose were both 5.5 Hz in dimethyl sulfoxided 6 [184], even though this compound adopted the 1 C 4 conformation in the solid state [185],
and 3 J H2,H3 and 3 J H3,H4 values for 3-amino-2-O-benzyl-3-deoxy-1,6-anhydro-β-D-glucopyranose were both < 2.0 Hz in chloroform-d [183]. It was concluded that the all axial substituent
orientations in 1,6-anhydro-β-D-glucopyranose derivatives bring the energy of the 1 C 4 conformation (32) close to a boat conformation, the B O,3 (33). The more polar B O,3 conformer is
favored by more polar solvents and even the parent compound is present in this conformer to
an extent of about 20% in water or dimethyl sulfoxide [183]. Two large or very polar groups
on C-2 and C-4 also move the equilibrium toward the boat [186,187,188,189] as can unusual
hydrogen bonding situations [190].
Exocyclic Groups The conformations adopted by the exocyclic groups will be considered in
three sections: the hydroxymethyl group and longer side chains, the hydroxyl groups, and the
anomeric group.
1.1
21
conformers that have the side chain and the carboxyl group equatorial (31). Solutions of
free KDO show a much more complex tautomeric mixture than NANA, containing 60–65%
α-pyranose, 2–11% β-pyranose, 20–25% α-furanose, and 8–9% β-furanose [178,179]. The
ammonium salts of the α- and β-pyranose methyl glycosides are also present in solution as
5 C 2 conformers but these compounds differ in their C-7-C-8 rotameric populations [174].
Non-chair conformations are often populated for anhydro sugars. Depending on the type of
substitution, these sugars can exist entirely in boat conformations as in 2,6-anhydro [180] or
3,6-anhydro derivatives or to a small extent as for 1,6-anhydro-β-D-glucopyranose ( > Fig. 13).
1,6-Anhydro-β-D-hexopyranoses are in equilibrium with the D-hexopyranoses and water
when the latter compounds are heated in aqueous acid [181]. On formation of a 1,6-anhydro ring, the normal 4 C 1 conformer is forced into a 1 C 4 conformation. The amount of the
1,6-anhydro-β-D-hexopyranose present at equilibrium at 100 °C in aqueous acid can be predicted quite successfully from Angyal’s interaction energies with a value of G° for anhydro
ring formation of −11.7 kJ mol −1 [181]. The 3 J H2,H3 and 3 J H3,H4 values observed for most
1,6-anhydro-β-D-glucopyranose derivatives are small, 1–2 Hz, consistent with a 1 C 4 conformation and all of the derivatives that have been studied by X-ray diffraction adopt this
conformer [182,183]. It was therefore surprising that the 3 J H2,H3 and 3 J H3,H4 values for
3-amino-3-deoxy-1,6-anhydro-β-D-glucopyranose were both 5.5 Hz in dimethyl sulfoxided 6 [184], even though this compound adopted the 1 C 4 conformation in the solid state [185],
and 3 J H2,H3 and 3 J H3,H4 values for 3-amino-2-O-benzyl-3-deoxy-1,6-anhydro-β-D-glucopyranose were both < 2.0 Hz in chloroform-d [183]. It was concluded that the all axial substituent
orientations in 1,6-anhydro-β-D-glucopyranose derivatives bring the energy of the 1 C 4 conformation (32) close to a boat conformation, the B O,3 (33). The more polar B O,3 conformer is
favored by more polar solvents and even the parent compound is present in this conformer to
an extent of about 20% in water or dimethyl sulfoxide [183]. Two large or very polar groups
on C-2 and C-4 also move the equilibrium toward the boat [186,187,188,189] as can unusual
hydrogen bonding situations [190].
Exocyclic Groups The conformations adopted by the exocyclic groups will be considered in
three sections: the hydroxymethyl group and longer side chains, the hydroxyl groups, and the
anomeric group.