30
1
General Principles
the same methods except that only idealized envelope conformers were considered [286]. In
most cases, the change in the regions of the pseudorotational itineraries that were populated
on moving to the solution were calculated to be small. Agreement with results from detailed
analyses of 3 J H,H and 3 J COCH data [287] was good as was agreement with the conformations present in the crystal [288]. For individual compounds, the conformational situations
varied widely; methyl α-D-xylofuranoside appears to exist as close to a single E 1 conformer
in solution with most conformers > 12 kJ mol −1 higher in energy while the conformers of
methyl β-D-xylofuranoside lie on a fairly flat potential energy surface. β-Ribofuranose has
also been studied using an ab initio molecular dynamics method that concluded that the ring
conformer and the hydroxymethyl group rotamer populated were linked as well as emphasizing the importance of solvation [289,290]. The former observation had been made earlier [291,292]. β-D-Galactofuranose derivatives exist preferentially in the southwestern part of
the pseudorotational cycle, in the 4 E, 4 T O , E O , and 1 T O range, as shown by analysis of coupling constants and molecular mechanics calculations using the PIMM91 force field [229].
Methyl α-D-mannofuranoside is present in an E 3 conformation in the crystal [293].
Anomeric effects were first demonstrated in furanosides by means of X-ray diffraction [61,68,
294]. The importance of the anomeric effect for furanosides in solution was shown by studies
of fused ring systems [295,296], from studies of nucleosides [297,298], and by comparing
C-, N-, and O-furanosyl glycosides in the solid state and solution [299]. Interestingly, the
magnitude of the anomeric effect for nucleosides is pH dependent with the largest effect being
observed under the most acidic conditions [300].
1.3.4 Conformations of Septanoses
There have been recent indications that septanose sugars can have biological activity [301,302,
303]. Stoddard outlined clearly how the conformational properties of cycloheptanes [304,305]
can be applied to oxepanes and septanoses [2] and recent studies [306,307] have used
the nomenclature scheme introduced by Stoddart that is analogous to those used for conformations of furanoses and pyranoses [124]. For cycloheptane, the C 2 -symmetric twistchair (TC) (35) is the most stable conformation as indicated by molecular mechanics calculations [304,308,309] and high level ab initio studies [310,311], and confirmed by spectroscopic
information [310,312,313], electron diffraction [314], and inelastic neutron scattering [315].
The TC conformer pseudorotates through a C s -symmetric barrier, the chair (C) conformation
(36), calculated to be about 4 to 6 kJ mol −1 above the TC [310,311] at room temperature.
Another family of pseudorotating conformations includes the boat (B) and twist-boat (TB)
where the B is minimum, about 12 kJ mol −1 above the TC [311]. Virtually all conformational
information on septanoses has been interpreted in terms of TC conformers. In the TC conformation, the C 2 axis runs through one carbon atom and the center of the opposing bond giving
four different types of carbon positions, numbered 1 to 4 starting with the atom on the axis
(35). Positions 2–4 have axial and equatorial substituent positions. Hendricksen calculated
with an early forcefield that it is much more unfavorable to have methyl groups on axial positions at positions 2 and 3 than in cyclohexane [305]. Position 1 has two identical substituent
positions, termed isoclinal that were calculated to be similar to equatorial positions [305].
1
General Principles
the same methods except that only idealized envelope conformers were considered [286]. In
most cases, the change in the regions of the pseudorotational itineraries that were populated
on moving to the solution were calculated to be small. Agreement with results from detailed
analyses of 3 J H,H and 3 J COCH data [287] was good as was agreement with the conformations present in the crystal [288]. For individual compounds, the conformational situations
varied widely; methyl α-D-xylofuranoside appears to exist as close to a single E 1 conformer
in solution with most conformers > 12 kJ mol −1 higher in energy while the conformers of
methyl β-D-xylofuranoside lie on a fairly flat potential energy surface. β-Ribofuranose has
also been studied using an ab initio molecular dynamics method that concluded that the ring
conformer and the hydroxymethyl group rotamer populated were linked as well as emphasizing the importance of solvation [289,290]. The former observation had been made earlier [291,292]. β-D-Galactofuranose derivatives exist preferentially in the southwestern part of
the pseudorotational cycle, in the 4 E, 4 T O , E O , and 1 T O range, as shown by analysis of coupling constants and molecular mechanics calculations using the PIMM91 force field [229].
Methyl α-D-mannofuranoside is present in an E 3 conformation in the crystal [293].
Anomeric effects were first demonstrated in furanosides by means of X-ray diffraction [61,68,
294]. The importance of the anomeric effect for furanosides in solution was shown by studies
of fused ring systems [295,296], from studies of nucleosides [297,298], and by comparing
C-, N-, and O-furanosyl glycosides in the solid state and solution [299]. Interestingly, the
magnitude of the anomeric effect for nucleosides is pH dependent with the largest effect being
observed under the most acidic conditions [300].
1.3.4 Conformations of Septanoses
There have been recent indications that septanose sugars can have biological activity [301,302,
303]. Stoddard outlined clearly how the conformational properties of cycloheptanes [304,305]
can be applied to oxepanes and septanoses [2] and recent studies [306,307] have used
the nomenclature scheme introduced by Stoddart that is analogous to those used for conformations of furanoses and pyranoses [124]. For cycloheptane, the C 2 -symmetric twistchair (TC) (35) is the most stable conformation as indicated by molecular mechanics calculations [304,308,309] and high level ab initio studies [310,311], and confirmed by spectroscopic
information [310,312,313], electron diffraction [314], and inelastic neutron scattering [315].
The TC conformer pseudorotates through a C s -symmetric barrier, the chair (C) conformation
(36), calculated to be about 4 to 6 kJ mol −1 above the TC [310,311] at room temperature.
Another family of pseudorotating conformations includes the boat (B) and twist-boat (TB)
where the B is minimum, about 12 kJ mol −1 above the TC [311]. Virtually all conformational
information on septanoses has been interpreted in terms of TC conformers. In the TC conformation, the C 2 axis runs through one carbon atom and the center of the opposing bond giving
four different types of carbon positions, numbered 1 to 4 starting with the atom on the axis
(35). Positions 2–4 have axial and equatorial substituent positions. Hendricksen calculated
with an early forcefield that it is much more unfavorable to have methyl groups on axial positions at positions 2 and 3 than in cyclohexane [305]. Position 1 has two identical substituent
positions, termed isoclinal that were calculated to be similar to equatorial positions [305].