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A. Singhamahapatra et al. / Tetrahedron Letters 54 (2013) 6121–6124
OH
Ac2O/Pyridine
OAc
BiOCl (20 mol %)
40.5° pointing out near the gauche orientation of hydroxyl hydro-
gen with respect to the anomeric hydrogen atom.
Me
HO
Me
AcO
O
O
0 oC-RT, 24 h
SOCl2 (2 equiv.)
dry CH2Cl2, RT, 6 h
The profound significance of this conformation became evident
while analyzing the hydrogen bonding network in the molecule. As
shown in Table 1, only a single regular hydrogen bond involving
anomeric oxygen as the donor and carbonyl oxygen atom (O7) of
the C3 acetoxy moiety is observed (Fig. 2).
In addition to conventional hydrogen bonds, weak interactions
like C–HꢀꢀꢀO interactions have gained enormous importance in the
recent literature for their involvement in deciding the structure
and activity of biomolecules which is useful in the area of medici-
nal chemistry.13 Meticulous analysis of the molecular packing
unraveled five distinct and fairly strong C-HꢀꢀꢀO interactions, listed
in Table 1 and depicted in Figure 1.
The regular hydrogen bond (O1–H1 ꢀꢀꢀO7) interconnects four
molecules of compound 4 related through four fold rotation
symmetry forming a crystallographic synthon, which is further
stabilized by two C–HꢀꢀꢀO interactions (C1–H10ꢀꢀꢀO6 and
C10–H10AꢀꢀꢀO5) as depicted in Figure 3.
HO
AcO
OH
1
OAc
2
Cl
OH
Acetone : H2O (2: 1)
60 oC, 3 h
Me
AcO
O
Me
O
AcO
AcO
AcO
OAc
OAc
3
4
Scheme 1. Synthesis of 2,3,4-tri-O-acetyl-a-L-rhamnopyranose.
2,3,4-tri-O-acetyl-
the
-anomer.10, 22
The stereoselective formation of compound 4 only as
can be explained due to anchimeric assistance of the neighboring
axial C-2 acetate group during hydrolysis of the -chloride. To
L-rhamnopyranose that exists predominantly as
a
a
-anomer
a
explore the generality of this methodology for the synthesis of
per-O-acetylated C-1-hydroxyglycopyranoses with the C-2 axial
As each molecule of 4 is endowed with a valency of twelve, two
of which are of the regular hydrogen bonding type and the rest ten
owing to C–HꢀꢀꢀO interactions, the crystallographic synthon consist-
ing of four molecules derives a gigantic valency of 48, half of which
are satisfied by mutual interactions among these while the remain-
ing valency of 24 are available to expand the network in three
dimension (Fig. 4).
These large valencies of 24 through C–HꢀꢀꢀO interactions enable
the tetramer crystallographic synthon to expand the network indef-
initely in three dimensions. The result of this expansion is the
exquisite molecular assembly (Fig. 5) consisting of channels of
7 Å diameter with a polar interior, formed by criss-crossing of
molecular backbone in which the nonpolar acetyl groups are
grouped together leading to hydrophobic patches.
To the best of our knowledge, the unique molecular packing ob-
served in the present work is hitherto unknown in the area of car-
bohydrate crystallography.
acetate group 2,3,4,6-tetra-O-acetyl-a-D-mannopyranosyl chlo-
ride9 was reacted under identical condition (Scheme 2). This also
resulted in the complete conversion of the chloride (7) to 2,3,4,6-
tetra-O-acetyl-a-D
-mannopyranose (8)11 as the only product in
91% yield.22
Efforts to use the same methodology for other sugars like
cose, 2-deoxy-2-acetamido- -glucopyranose, -arabinose, and
arabinose resulted in a mixture of and b isomers of the per-O-
acetylated C-1-hydroxyglycopyranoses with slower rate of hydro-
lysis of the -chlorides. This observation supported the importance
of the C-2 axial acetate group for the rapid hydrolysis of -chloride
and formation of single isomer as the product. In case of -man-
nose and -rhamnose the neighboring group participation involv-
ing the axial C2 acetate group during hydrolysis of the anomeric
-chloride facilitate the formation of a more stable (due to ano-
meric effect) isomer of the C1 hydroxyl derivative (Scheme 3).
Similar neighboring group participation is not possible in -glucose
D-glu-
D
D
L-
a
a
a
D
L
a
a
Elucidation of the correlation between the complex structures
of cell surface glyconjugates and their myriad biological functions
is a challenging problem in glycobiology. X-ray crystallographic
investigation undertaken during the present study has unraveled
a unique molecular assembly driven by a combination of one reg-
ular hydrogen bond and five C–HꢀꢀꢀO interactions in the crystal
D
and other glycopyranoses, where a mixture of isomers is formed as
the product with a relatively slow rate of hydrolysis.
Interestingly, a survey of the literature revealed no report on
the crystal structure of any per-O-acetylated C-1 hydroxy sugars.
Single crystals of compound 4 suitable for an X-ray study were
obtained by recrystallizing from a mixture of ethyl acetate and
hexane at about 10 °C by the slow evaporation method. The
structure of 4 was solved in the tetragonal space group I4, a rare
phenomenon in carbohydrate literature (Fig. 1). All the C–C bond
lengths are close to 1.54 Å, in good agreement with the observed
sugar derivatives.12 The ring C1–O5 bond length (1.418 Å) in
compound 4 is shorter than that of C5–O5 (1.437 Å). The shorten-
ing may be attributed to the delocalization of oxygen lone pair of
electrons into the anti bonding orbital of the C1–O5 bond. The
structure of 2,3,4-tri-O-acetyl-a-L-rhamnopyranose (4). The occur-
rence of channels of 7 Å diameters in the crystal of compound 4 is a
rather rare phenomenon in the realm of small organic molecules.
Unlike conventional inorganic porous materials for example zeo-
lite,14 porous organic–inorganic hybrid materials such as metal or-
ganic frameworks (MOFs)15 and covalent organic frameworks
(COFs);16,17 stabilized by non-covalent interactions have scope
for targeted application because their constituent building blocks
can be readily diversified using simple organic transformation.18
Such compounds have scope for application in the area of
O-glycosidic torsion angle (
U
), H1–C1–O1–H(O1), is found to be
OAc
OAc
OH
OH
O
Ac2O/Pyridine
O
BiOCl (20 mol %)
AcO
AcO
HO
HO
0 oC-RT, 24 h
SOCl2 (2 equiv.)
dry CH2Cl2, RT, 6 h
OAc
6
5
OH
OAc
OAc
OAc
O
OAc
O
Acetone/ H2O (2: 1)
60 oC, 3 h
AcO
AcO
AcO
AcO
8
7
Cl
OH
Scheme 2. Synthesis of 2,3,4,6-tetra-O-acetyl-
a-D-mannopyranose.