Chemistry Reference
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carbohydrate conformation is essential both with respect to synthetic
strategy and to stereocontrol.
9
Generally speaking, one of the most important features of a ring is its
dynamic conformational equilibrium. For example, the conformation of
the iduronic acid ring was shown to be essential to the biological activity
of the heparin pentasaccharides.
10
The ability of glycosidase inhibitors to
mimic the conformation of the carbohydrate ring in the transition state
for enzymatic hydrolysis is a key element of drug design in this field.
8a
Finally, the conformational constraints of the ring is the central element
of the transition state models for cyclic stereoinduction such as the
Furst-Plattner model for epoxide opening and related model for the
axial addition to pyranose oxonium ions,
11
models for stereoselective
nucleophilic additions to cyclohexanones,
12
the Woerpel model for
additions to furanose oxonium ions,
13
and the Giese model for radical
substitution reactions at the anomeric center.
14
The understanding of the preferred conformations of furanoses is of
particularly significant interest, in view their presence in nucleoside
structures, in bacterial cell walls of mycobacteria, and in arabinan, for
example.
13,15,16
While the conformational behaviour of saturated six
membered rings can be treated reasonably in terms of two dominant chair
conformations, our understanding of five-membered rings is hampered by
two related factors: a more complex set of ideal, limiting conformations
due to a lower symmetry, requiring 10 envelope and 10 twist conform-
ations, and less well-defined energy barriers between conformers, re-
quiring descriptors of intermediate conformational states.
17
In addition,
while fairly straightforward predictive rules are available for six-membered
rings, no such simple empirical rules allow us to predict the conformation
of a 5-membered ring compound. As a result, our relatively limited
understanding of furanose conformation is compounded by our inability
to adequately describe these conformations once they are known.
The overwhelming majority of work on furanose conformation has
focused on the N-ribofuranoside structure present in nucleosides. The
pioneering work of Altona provided both a useful descriptor of furanose
conformation and a reasonable description of the conformation of
nucleotides based on two dominant conformational
families,
the
''North'' and ''South'' conformations.
18
Somewhat less attention has
been paid to O-furanosides.
19
As part of a general approach to the characterization and rep-
resentation of conformational behaviour of furanoses, we would like
to focus in this article on the conformational behaviour of the tetra-
hydrofuran ring of a small series of voluntarily simple 2,5-anhydro-
heptitols (C-furanosyl compounds). One issue in particular warrants
more study in our opinion, and is a focus of this article: what is the most
appropriate representation of the conformation of a furanose ring?
A DFT quantum mechanical approach is used here to first obtain
potential energy profiles along the pseudo-rotational cycle of these model
structures. To complete these studies so as to take into account
temperature effects (populations), molecular dynamics are investigated in
order to study the conformational equilibria. Uncommonly, full quantum
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