Exploring the effect of bioisosteric replacement of carboxamide by a sulfonamide moiety on N-glycosidic torsions and molecular assembly: Synthesis and x-ray crystallographic investigation of n-(β- D -glycosyl)sulfonamides as n-glycoprotein linkage region analogues

Article abstract of DOI:10.1002/chem.201302018

N-Glycoprotein linkage region constituents, 2-acetamido-2-deoxy-β-D- glucopyranose (GlcNAc) and asparagine (Asn) are conserved among all the eukaryotes. To gain a better understanding for nature's choice of GlcNAcβAsn as linkage region constituents and inter- and intramolecular carbohydrate-protein interactions, a detailed systemic structural study of the linkage region conformation is essential. Earlier crystallographic studies of several N-(β-glycopyranosyl)alkanamides showed that N-glycosidic torsion, φ_N, is influenced to a larger extent by structural variation in the sugar part than that of the aglycon moiety. To explore the effect of the bioisosteric replacement of a carboxamide group by a sulfonamide moiety on the N-glycosidic torsions as well as on molecular assembly, several glycosyl methanesulfonamides and glycosyl chloromethanesulfonamides were synthesized as analogues of the N-glycoprotein linkage region, and crystal structures of seven of these compounds have been solved. A comparative analysis of this series of crystal structures as well as with those of the corresponding alkanamido derivatives revealed that N-glycosidic torsion, φ_N, does not alter significantly. Methanesulfonamido and chloromethanesulfonamido derivatives of GlcNAc display a different aglycon conformation compared to other sulfonamido analogues. This may be due to the cumulative effect of the direct hydrogen bonding between N1 and O1′ and C-H×××O interactions of the aglycon chain, revealing the uniqueness of the GlcNAc as the linkage sugar. Unique molecular assembly motif of GlcNAc: The different aglycon conformations of methanesulfonamido and chloromethanesulfonamido derivatives of GlcNAc as compared to other sulfonamido analogues is a unique feature of their molecular assembly. This could be due to the cumulative effect of the direct hydrogen bonding between N1 and O1′ and C-H×××O interactions of the aglycon chain. Copyright

Full text of DOI:10.1002/chem.201302018

DOI: 10.1002/chem.201302018
Exploring the Effect of Bioisosteric Replacement of Carboxamide by a
Sulfonamide Moiety on N-Glycosidic Torsions and Molecular Assembly:
Synthesis and X-ray Crystallographic Investigation of N-(b-d-
Glycosyl)sulfonamides as N-Glycoprotein Linkage Region Analogues
Amrita Srivastava,*[a] Babu Varghese,[b] and Duraikkannu Loganathan[a]
17720
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 17720 – 17732

FULL PAPER
Abstract:
region constituents, 2-acetamido-2-
deoxy-b-d-glucopyranose (GlcNAc)
and asparagine (Asn) are conserved
among all the eukaryotes. To gain
N-Glycoprotein
linkage
in the sugar part than that of the agly-
con moiety. To explore the effect of the
bioisosteric replacement of a carbox-
have been solved. A comparative anal-
ysis of this series of crystal structures
as well as with those of the correspond-
ing alkanamido derivatives revealed
that N-glycosidic torsion, fN, does not
alter significantly. Methanesulfonamido
and chloromethanesulfonamido deriva-
tives of GlcNAc display a different
aglycon conformation compared to
other sulfonamido analogues. This may
be due to the cumulative effect of the
direct hydrogen bonding between N1
ACHTUNGTRNEaNUNG mide group by a sulfonamide moiety
on the N-glycosidic torsions as well as
on molecular assembly, several glycosyl
methanesulfonamides and glycosyl
chloromethanesulfonamides were syn-
thesized as analogues of the N-glyco-
protein linkage region, and crystal
structures of seven of these compounds
a
better understanding for natureꢁs
choice of GlcNAcbAsn as linkage
region constituents and inter- and in-
tramolecular carbohydrate–protein in-
teractions, a detailed systemic structur-
al study of the linkage region confor-
mation is essential. Earlier crystallo-
graphic studies of several N-(b-glyco-
pyranosyl)alkanamides showed that N-
glycosidic torsion, fN, is influenced to
a larger extent by structural variation
À
and O1’ and C H···O interactions of
À
Keywords: C H···O interactions ·
the aglycon chain, revealing the
uniqueness of the GlcNAc as the link-
age sugar.
N-glycoproteins · proteins · sulfon-
AHCTUNGERTGaNNUN mides · X-ray diffraction
Introduction
to their structural complexity, micro-heterogeneity, flexibili-
ty, and non-availability in sufficient amounts. In this regard,
use of N-glycoprotein linkage region models and analogues
is a worthwhile approach which provides the finer details of
atomic architecture and molecular recognition and also
helps in understanding the effect of structural variation on
the conformation of the linkage region.
Glycosylation is the most frequent, highly diverse post-
translational covalent protein modification found in nature,
occurring across all kingdoms of life.[1] Carbohydrate com-
ponents of glycoproteins play important roles in many bio-
logical processes such as protein folding, inflammation, and
bacterial and viral infection.[2,3] The GlcNAcbAsn linkage is
conserved in N-glycoproteins of all eukaryotes (Figure 1).
A major program of our laboratory is focused on the syn-
thesis, crystallography, and ab initio calculations of the N-
glycoprotein linkage region models and analogues.[4–11]
A
systematic investigation pertaining to the effect of structural
variation in the linkage region sugar and its aglycon moiety,
among several N-(b-glycopyranosyl)alkanamido derivatives,
on the N-glycosidic torsion, fN (O5-C1-N1-C1’) revealed
that fN (Figure 1) is influenced to a larger extent by the
structural variation in the sugar part than that of the aglycon
moiety.[4] X-ray crystallographic analysis and ab initio calcu-
lations on the N-(b-d-glycopyranosyl)alkanamides showed
that the N-acetyl group at C2 controls the side chain torsion
angle c2 (N1-C1’-C2’-C3’) at the linkage region and helps in
establishing the extended aglycon conformation.[7] Further
studies on the various glycosyl alkanamides illustrated the
influence of the substituent at C2 and C5 as well as environ-
mental factors particularly inter- and intramolecular interac-
Figure 1. Schematic representation of the linkage region (GlcNAcbAsn)
of the N-glycoproteins with the depiction of the torsion angles, w=O5-
C5-C6-O6, fN =O5-C1-N1-C1’, yN =C1-N1-C1’-C2ꢁ and c2 =N1-C1’-C2’-
C3’.
Elucidation of the conformation of the linkage region is of
fundamental importance as the dynamics of the GlcNAc-
Asn linkage can significantly influence the presentation of
the glycan chains on the cell/protein surface. Understanding
the structure–function correlations of the protein-linked gly-
cans is certainly a challenging problem in glycobiology due
À
tions involving hydrogen bonds and the weak C H···O con-
tacts on the energy preference of the fN torsion angle.[8] The
critical role of C2-NHAc was also confirmed by the study of
C3-NHAc analogues, which showed the gauche conforma-
tion of the amido aglycon moiety.[10] A comprehensive anal-
ysis of both the regular hydrogen bonds and the weak inter-
[a] Dr. A. Srivastava, Dr. D. Loganathan+
Department of Chemistry
Indian Institute of Technology Madras, Chennai - 600036 (India)
Fax : (+91)44-22574202
E-mail: amrisriv9@gmail.com
À
actions involving C H···O hydrogen bonds present in the
crystal structures of N-glycoprotein models and analogues
[b] Dr. B. Varghese
revealed a cooperative antiparallel network of bifurcated
Sophisticated Analytical Instrumentation Facility
Indian Institute of Technology Madras, Chennai - 600036 (India)
[+] Deceased on February 9, 2013.
À
À
hydrogen bonds consisting of N H···O and C H···O interac-
tions seen uniquely for the models, GlcNAcbAsn and
GlcNAcbNHAc, and not for any analogue including the
propionamide derivative, GlcNAcbNHPr. Such bifurcated
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201302018.
Chem. Eur. J. 2013, 19, 17720 – 17732
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
17721

A. Srivastava et al.
hydrogen bonds between the core glycan and protein could
stabilize the linkage region conformation.[6,9]
were obtained by the displacement of their corresponding
a-chlorides[18] with NaN3 in aqueous acetone at room tem-
perature.[19]
To understand the effect of the bioisosteric replacement
of a carboxamide with a sulfonamide moiety on the N-glyco-
sidic torsion, fN and molecular assembly, several glycosyl
methanesulfonamides and glycosyl chloromethanesulfona-
mides, which are very interesting glycosylasparagine ana-
logues, have been designed and synthesized in the present
work. Owing to its more acidic nature, introduction of a sul-
fonamide group increases the polarity and hydrogen-bond
donor properties of a molecule. Moreover, due to the enor-
mous stability towards enzymatic degradation and the struc-
tural similarity of the sulfonamido bond with the tetrahedral
transition state involved in the enzymatic hydrolysis of an
amide bond, these molecules can be used as enzyme inhibi-
tors. Several glycosyl sulfonamides are known to be good in-
hibitors of carbonic anhydrases[12] and hepatocellular carci-
noma cell lines.[13] Among all the glycosyl sulfonamides syn-
thesized, X-ray crystal structures of seven (Figure 2) of
these compounds have been solved. The molecular confor-
mation and packing of these compounds were compared
with this series as well as with the corresponding alkanami-
do derivatives. Glycosyl chloromethanesulfonamides were
studied to examine the influence of chlorine, an electronega-
tive substituent and potential hydrogen bond acceptor, on
the molecular assembly.
Synthesis and characterization
Synthesis of N-(b-d-glycosyl)methanesulfonamides: Per-O-
acetylated b-d-glycosylamines were prepared by the reduc-
tion of per-O-acetylated b-d-glycosyl azides (1–8) using Pd/
C and hydrogen in dry CH2Cl2. Reaction of these glycosyl
amines with methanesulfonyl chloride in the presence of
triethylamine afforded the per-O-acetylated N-(b-d-glyco-
syl)methanesulfonamides (9–16) in moderate to good yield
with complete b-stereoselectivity (Scheme 1, Table 1). All
Scheme 1. Synthesis of N-(b-d-glycosyl)methanesulfonamides (17–24).
Reagents and conditions: i) Pd/C, H2, dry CH2Cl2, RT; ii) CH3SO2Cl,
Et3N, 0 8C–RT, ca. 8 h; iii) BaACHTUNTRGNENUG(OMe)2, dry MeOH, 08C–RT, 12 h.
the fully acetylated glycosyl methanesulfonamides (9–16)
were taken up for de-O-acetylation using Ba(OMe)2/MeOH
AHCTUNGTRENNUNG
Results and Discussion
at 08C. In all cases, deprotection was achieved in fairly good
yield (Scheme 1, Table 1). All the products were character-
1
Glycosyl sulfonamides can be synthesized from the glycosyl
amines[14,15] or from per-O-acetylated sugars.[16] In the pres-
ent work, acetylated glycosyl azides[17] were chosen as start-
ing material. The fully acetylated b-d-glycosyl azides (1–8)
ized based on physical and spectral data. The H NMR spec-
trum of the products displayed the anomeric proton signal
around d=4.47–4.95 ppm with a coupling constant of J=
8.8–9.6 Hz indicating the b-linkage.
Synthesis of N-(b-d-glycopyra-
nosyl)chloromethanesulfona-
mides: 2,3,4,6-Tetra-O-acetyl-
b-d-glucopyranosylamine was
allowed to react with chloro-
methanesulfonyl
chloride
under the same reaction condi-
tions as used for the synthesis
of fully acetylated glycosyl
methanesulfonamides (9–16),
which resulted in only 30%
yield of the expected product.
To improve the yield, the reac-
tion was performed with differ-
ent bases (N,N-diiosopropyle-
thylamine (DIEA), 4-dimethyl-
AHCTUNGERTGaNNUN minopyridine (DMAP), and
pyridine) and pyridine was
found to be the best among all
the bases chosen for the reac-
tion. The maximum yield was
obtained when pyridine was
Figure 2. Structures of the model GlcNAcbNHAc and the sulfonamido analogues studied.
17722
www.chemeurj.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 17720 – 17732

N-Glycoprotein Linkage Region Analogues
FULL PAPER
1
on physical and spectral methods including H and 13C NMR
Table 1. The N-(b-d-glycosyl)methanesulfonamides synthesized.
spectroscopy. The 1H NMR spectra of the products dis-
played the anomeric proton signal around d=4.50–4.90 ppm
with a coupling constant of J=8.8–9.6 Hz indicating the b-
linkage.
No.
Per-O-acetylated
Per-O-acetylated
De-O-acetylated
glycosyl azide
Product
Yield [%]
Product
Yield [%]
1
2
3
4
5
6
7
8
GlcbN3 (1)
GalbN3 (2)
GlcNAcbN3 (3)
ManbN3 (4)
XylbN3 (5)
CellbN3 (6)
LacbN3 (7)
MaltbN3 (8)
9
70
76
70
80
50
62
53
30
17
18
19
20
21
22
23
24
95
98
93
85
90
97
90
80
10
11
12
13
14
15
16
X-ray crystallographic investigation
Structure description: Among all the thirteen glycosyl sul-
ACHUTNGRENfNUG onACHUTNGTRENaNGUN mides synthesized, crystal structures of seven of them
(17–19, 22, 23, 31, and 32) have been solved. The single crys-
tals of all the free sulfonamides were obtained from aqueous
methanol by using the slow evaporation method. The
ORTEP representations of their solved structures with atom
numbering are shown in Figure 3. All the N-(b-d-glycosyl)-
methanesulfonamides (17, 19, 22, and 23) crystallized in the
monoclinic crystal system with a P21 space group except for
N-(b-d-galactopyranosyl)methanesulfonamide (18), which
crystallized in the C2 space group. GalbNHSO2CH3 (18),
GlcNAcbNHSO2CH3 (19), and LacbNHSO2CH3 (23) crys-
tallized as monohydrates, whereas GlcbNHSO2CH3 (17) and
CellbNHSO2CH3 (22) turned out to be anhydrous crystalline
used as a solvent. Per-O-acetylated b-d-glycosylamines were
dried, dissolved in anhydrous pyridine and treated with
chloromethanesulfonyl chloride at 08C to afford the per-O-
acetylated
N-(b-d-glycopyranosyl)chloromethanesulfona-
mides (25–29) (Scheme 2, Table 2). All the fully acetylated
glycosyl chloromethanesulfonamides (25–29) were de-O-
acetylated by using NaOMe/MeOH at 08C in very good
yield (Scheme 2). All the products were characterized based
solids. The two N-(b-d-glycopyranosyl)chloromethanesul
ACHTUNGTRENNUNGfon-
AHCTUNGTRENNUNG
system with a P212121 space group. GalbNHSO2CH2Cl (31)
crystallized in anhydrous form, whereas GlcNAcbNH-
SO2CH2Cl (32) crystallized as a monohydrate. The b ano
AHCTUNGTREGiNNNU c configuration of compounds 17–19, 22, 23, 31, and 32 was
ACHTUNGTRENNUNGmer-
Scheme 2. Synthesis of N-(b-d-glycopyranosyl)chloromethanesulfona-
mides (30–34). Reagents and conditions: i) Pd/C, H2, dry CH2Cl2, RT; ii)
ClCH2SO2Cl, pyridine, 08C–RT, ca. 3 h; iii) NaOMe, dry MeOH, 08C–
RT, 12 h.
evident from the ORTEP representation (Figure 3). All
atoms of the reducing end residue of the disaccharides are
numbered with a suffix A, whereas those of non-reducing
end residue are numbered with a suffix B. The pyranose
4
ring adopts a C1 conformation in all the seven crystals. Lists
Table 2. The N-(b-d-glycopyranosyl)chloromethanesulfonamides synthe-
of selected bond lengths and bond angles are provided in
Table 3 and Table 4, respectively. Geometrical parameters
for all the crystals are compared with the series as well as
with those already reported for alkanamido derivatives. Two
different conformers were present in the asymmetric unit of
CellbNHSO2CH3 (22) labeled as A and B.
sized.
No.
Per-O-acetylated
glycosyl azide
Per-O-acetylated
De-O-acetylated
Product
Yield [%]
Product
Yield [%]
1
2
3
4
5
GlcbN3 (1)
25
26
27
28
29
75
73
70
76
60
30
31
32
33
34
85
96
90
75
90
GalbN3 (2)
GlcNAcbN3 (3)
ManbN3 (4)
XylbN3 (5)
À
The C C bond lengths in all these compounds are close
to 1.54 ꢂ, which is observed in most sugar derivatives.[20]
Table 3. Selected bond lengths [ꢂ] in compounds 17–19, 22, 23, 31, and 32.
GlcbNH
SO2CH3
(17)
GalbNH
SO2CH3·
H2O (18)
GlcNAcbNH
SO2CH3·
H2O (19)
CellbNH
SO2CH3
(22A)
CellbNH
SO2CH3
ACHTUNGTNER(NUNG 22B)
LacbNH
SO2CH3·
H2O (23)
GalbNH
SO2CH2Cl
(31)
GlcNAcbNH
SO2CH2Cl·
H2O (32)
Parameter
1.426(3)
1.431(3)
1.436(3)
1.440(3)
1.449(3)
1.635(2)
1.439(2)
1.425(2)
1.755(3)
–
1.433(3)
1.425(3)
1.432(3)
1.440(3)
1.438(3)
1.626(2)
1.410(3)
1.439(3)
1.742(3)
–
1.424(3)
1.427(3)
1.435(3)
1.437(3)
1.440(3)
1.620(2)
1.413(2)
1.425(2)
1.738(3)
–
À
C1 O5
1.424(3)
1.431(3)
1.420(2)
1.432(2)
1.421(2)
1.429(3)
1.421(3)
1.434(2)
1.437(4)
1.413(4)
À
C5 O5
À
C1 N1
1.431(3)
1.635(2)
1.428(2)
1.445(2)
1.753(3)
–
1.442(2)
1.621(1)
1.434(1)
1.427(2)
1.752(3)
–
1.428(2)
1.611(2)
1.430(2)
1.424(2)
1.740(3)
–
1.431(3)
1.603(2)
1.425(2)
1.426(2)
1.784(2)
1.751(2)
1.410(5)
1.605(4)
1.397(3)
1.435(4)
1.763(5)
1.747(5)
À
S1 N1
À
S1 O1’
À
S1 O2’
À
S1 C2’
À
C2’ Cl
1.541(3)
1.506(3)
1.530(3)
1.516(3)
1.517(3)
1.512(3)
À
C1 C2
1.529(3)
1.531(2)
1.528(3)
1.521(3)
1.540(5)
Chem. Eur. J. 2013, 19, 17720 – 17732
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
17723

A. Srivastava et al.
Figure 3. ORTEP representations (probability 30%) of the crystal structures of compounds 17–19, 22, 23, 31, and 32.
Table 4. Selected bond angles [8] in compounds 17–19, 22, 23, 31 and 32.
GlcbNH
SO2CH3
(17)
GalbNH
SO2CH3·
H2O (18)
GlcNAcbNH
SO2CH3·
H2O (19)
CellbNH
SO2CH3
(22A)
CellbNH
SO2CH3
(22B)
LacbNH
SO2CH3·
H2O (23)
GalbNH
SO2CH2Cl
(31)
GlcNAcbNH
SO2CH2Cl·
H2O (32)
Parameter
O5-C1-N1
C2-C1-N1
N1-S1-O1’
N1-S1-O2’
O1’-S1-O2’
S1-C2’-Cl
109.1(2)
111.5(2)
108.0(1)
105.0(1)
118.5(1)
–
107.5(1)
109.6(1)
107.74(8)
105.44(8)
118.34(9)
–
108.4(2)
112.2(2)
108.0(1)
107.3(1)
119.5(1)
–
107.8(2)
108.3(2)
105.8(1)
107.2(1)
118.8(1)
–
107.9(2)
110.7(2)
106.6(2)
107.5(1)
117.4(2)
–
109.0(2)
108.9(2)
106.8(1)
105.7(1)
119.0(1)
–
108.6(2)
111.5(2)
106.9(1)
109.1(1)
118.5(1)
109.5(1)
108.1(3)
112.6(3)
111.2(2)
108.8(2)
119.2(2)
113.0(2)
116.1(2)
114.9(2)
109.1(2)
105.8(2)
109.9(2)
113.2(3)
112.3(2)
113.6(2)
120.1(2)
112(2)
113.7(2)
114.6(2)
107.5(2)
106.4(2)
111.6(2)
108.9(2)
110.8(2)
112.1(2)
117.6(2)
115(2)
114.2(2)
113.3(2)
107.7(2)
106.3(2)
110.6(2)
109.5(2)
112.1(2)
113.1(2)
120.8(2)
114(2)
C4-C5-C6
O5-C5-C6
C5-C6-O6
C5-O5-C1
112.6(2)
106.9(2)
111.6(2)
112.1(2)
112.9(1)
106.7(1)
111.2(1)
112.8(1)
114.7(2)
107.5(2)
113.6(2)
112.1(2)
113.8(2)
107.0(2)
111.6(2)
111.8(2)
114.2(3)
107.2(3)
112.8(3)
112.3(3)
C1-N1-S1
C1-N1-H1N
S1-N1-H1N
118.1(2)
116(2)
110(2)
120.0(1)
114(1)
108(1)
121.7(1)
119.1
119.1
121.0(2)
121(2)
116(2)
123.1(3)
107(3)
125(3)
110(2)
110(2)
111(2)
17724
www.chemeurj.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 17720 – 17732

N-Glycoprotein Linkage Region Analogues
FULL PAPER
À
À
Among the C O bond lengths, The C5 O5 bond lengths
quite different from the tetrahedral angle; <O-S-O=117–
1198, giving the sulfonamido group as a distorted tetrahedral
geometry.
À
are found to be longer than the C1 O5 bond lengths for
compounds GlcbNHSO2CH3 (17), GalbNHSO2CH3 (18),
GlcNAcbNHSO2CH3 (19), LacbNHSO2CH3 (23), and
GalbNHSO2CH2Cl (31), as seen in most of the b-1-N-alkan-
ACHTUNGTRENNUNGamido sugar derivatives, whereas the reverse was true for
GlcNAcbNHSO2CH2Cl (32). In the case of conformer A of
Molecular conformation: The molecular conformation of
the compounds 17–19, 22, 23, 31, and 32 is defined by the
torsion angles, w, w’, f0, y0, fN, yN, and c2 (Figure 4,
À
CellbNHSO2CH3 (22), the C5 O5 bond is longer than the
À
C1 O5 bond (in both the non-reducing end residue and re-
À
ducing end residue) but both the bond lengths (C1 O5 and
C5 O5) were equal in the case of the reducing end residue
of conformer B. The C N bond lengths (C1 N1) for all the
compounds 17–19, 22, 23, 31, and 32 were 1.41–1.44 ꢂ in
good agreement with the value of 1.44 ꢂ observed for
À
À
À
GlcNAcbAsn.[21] The S N bond lengths (S1 N1) for all the
compounds 17–19, 22, 23, 31, and 32 were in the range of
1.60–1.64 ꢂ, which is less than the normal length of a single
bond (1.73 ꢂ). This can be explained by the donor–acceptor
interaction of the unshared electron pair in the amido-group
nitrogen atom with the 3d orbitals of the sulfur atom. The
À
À
Figure 4. Depiction of the various torsion angles, w=O5-C5-C6-O6, w’=
C4-C5-C6-O6, fO =C4A-O4A-C1B-O5B, YO =C1B-O4A-C4A-C5A,
fN =O5-C1-N1-S1, yN =C1-N1-S1-C2’ and c2 =N1-S1-C2’-Cl.
À
length of the S O bond agrees with the average value found
Table 5). The hydroxymethyl group adopts a gg conforma-
tion in GlcbNHSO2CH3 (17), GlcNAcbNHSO2CH3 (19),
and GlcNAcbNHSO2CH2Cl (32), as evident from the values
of the torsion angles, O5-C5-C6-O6 (w, ca. À608) and C4-
C5-C6-O6 (w’, ca. 608). For the compounds GalbNHSO2CH3
(18) and GalbNHSO2CH2Cl (31), in which the C4-OH
group is in an axial position, the hydroxymethyl group
adopts a gt conformation with the torsion angles, w, close to
638 and wꢁ around À1758. In the case of CellbNHSO2CH3
(22), however, the two conformers A and B differ in the
conformation of the hydroxymethyl group. The hydroxy-
methyl group in conformer A adopts a gg conformation in
both the reducing end residue as well as the non-reducing
in other sulfonamides reported in the literature. All the
angles involving carbon are close to the tetrahedral value of
109.58 (Table 4). The N-glycosidic valence angle, O5-C1-N1,
is smaller than that of C2-C1-N1 for compounds 17–19, 22,
31, and 32 except for LacbNHSO2CH3 (23). The exocyclic
bond angles, namely C4-C5-C6 and O5-C5-C6 have a mean
value of 114.18 and 107.18, respectively, with the latter being
consistently smaller than the former. Due to the presence of
a lone pair of electrons, the valence angle at the ring oxygen
atom, namely C5-O5-C1 deviates from the tetrahedral by
about 1–58. This variation is seen in all the compounds 17–
19, 22, 23, 31, and 32. The valance angles at the S atom are
Table 5. Selected torsion angles [8] of compounds 17–19, 22, 23, 31, 32, and related compounds.
Compound
O5-C1-
N1-C1’/S1
(fN)
C1-N1-
C1’/S1-C2’
(yN)
N1-C1’/S1
-C2’-Cl
(c2)
O5-C5-
C6-O6
(w)
C4-C5-
C6-O6
(w’)
C4A-O4A -
C1B-O5B
(fO)
C1B-O4A-
C4A-C5A
(yO)
H1-C1-
N1-N1H
GlcNAcbAsn·3H2O[21]
GlcNAcbNHAc·H2O[32]
GlcbNHAc[33]
À98.9
180.0
À172.2
À60.4
59.8
55.4(2)
50.1(4)
–
–
–
–
–
–
–
–
–
–
–
À89.8(1)
À93.8(2)
À105.2(3)
À114.5(2)
174.2(2)
À179.2(3)
178.5(3)
171.3(2)
–
–
–
–
À66.4(2)
À71.8(3)
60.5(3)
À161.9
À154.8
À171.0
177.3
GalbNHAc[4]
À177.1(2)
ManbNHAc[4]
À55.5(2)
À59.3(2)[a]
58.3(3)[b]
61.7(3)
À53.7(7)
À62.0(3)
63.6(2)
À66.7(2)
À70.6(2)[a]
À61.7(3)[b]
À64.3(2)[a]
57.7(3)[b]
À57.0(2)[a]
61.3(2)[b]
63.1(3)
67.0(2)
62.4(3)[a]
179.0(2)[b]
À175.8(2)
67.0(6)
LacbNHAc[24]
À100.9(2)
175.1(2)
–
À89.3(2)
À157.8(2)
À162.5(2)
174.4
GalbNHCOCH2Cl[34]
À111.5(3)
À91.7(6)
À85.5(2)
À83.7(1)
À97.0(2)
À81.7(2)
À76.6(2)
À81.9(2)
176.6(3)
173.6(7)
70.9(2)
69.4(2)
À94.8(2)
77.1(2)
74.7(3)
70.6(2)
153.3(2)
173.0(6)
–
–
–
–
–
–
–
–
–
–
–
–
–
GlcNAcbNHCOCH2Cl[7]
GlcbNHSO2CH3 (17)
164.7
60.7(3)
167(2)
166(1)
À158.5(2)
169(2)
174(2)
175(2)
GalbNHSO2CH3·H2O (18)
GlcNAcbNHSO2CH3·H2O (19)
À176.4(1)
55.5(3)
49.3(3)[a]
58.9(4)[b]
56.2(3)[a]
175.8(2)[b]
63.5(2)[a]
À177.4(2)[b]
À174.9(2)
54.7(4)
CellbNHSO2CH3 (22A)
CellbNHSO2CH3 (22B)
LacbNHSO2CH3·H2O (23)
–
–
–
À80.9(2)
À86.9(2)
À90.0(2)
À124.5(2)
À144.0(2)
À156.8(2)
GalbNHSO2CH2Cl (31)
GlcNAcbNHSO2CH2Cl·H2O (32)
À76.2(2)
68.7(2)
À125.2(4)
À177.9(1)
–
–
–
–
À156(2)
À174(3)
À90.3(4)
67.1(3)
À68.6(4)
[a] Reducing end residue. [b] Non-reducing end residue.
Chem. Eur. J. 2013, 19, 17720 – 17732
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
17725

A. Srivastava et al.
end residue as evident from the values of the torsion angles,
w (À708) and wꢁ (498) for the reducing end residue and w
(À628) and wꢁ (598) for the non-reducing end residue. The
torsion angle values of À648 and 568 of conformer B for the
reducing end residue and 578 and 1768 for the non-reducing
end residue reveal the gg conformation of the former and gt
conformation of the later. The hydroxymethyl group in
LacbNHSO2CH3 (23) adopts the gg conformation (w, À578
and w’, 638) in the reducing end residue and the gt confor-
mation (w, 618 and w’, À1778) in the non-reducing end resi-
due. The gt conformation is also noted in many of the cello-
biose derivatives.[22]
The inter glycosidic torsions angles f0 and y0 of analogue
22A are À80.9(2)8 and À124.5(2)8, respectively, whereas for
analogue 22B, the values are À86.9(2)8 and À144.0(2)8, re-
spectively. These angles compare well with those reported
for cellobiose related structures.[23] Torsion angle f0 and y0
values for LacbNHSO2CH3 (23) are À90.0(2) and
À156.8(2)8, respectively, which are comparable to the values
of À89.3(2)8 and À157.8(2)8 observed for LacbNHAc.[24] For
most of the compounds (17, 18, 22, 23 and 31), values of tor-
sion angle yN were close to about 758 except for methane-
sulfonamido (19) and chloromethanesulfonamido (32) deriv-
atives of GlcNAc. The values of torsion angle yN for com-
pounds 19 and 32 were À94.8(2)8 and À125.2(4)8, respec-
tively. The aglycon chain of methanesulfonamido (19) and
chloromethanesulfonamido (32) derivatives of GlcNAc
adopts a different aglycon conformation as evident from
their torsion angle (yN) values. The conformation about the
Figure 5. Graphical representation of the variation of fN values of N-(b-
d-glycosyl)sulfonamides relative to that of GlcNAcbNHAc.
À
ing, C H···O interactions and crystal packing forces might
strongly influence the conformations adopted.[25]
Molecular packing: The various hydrogen bonds present in
the crystal structures of compounds 17–19, 22, 23, 31, and 32
were analyzed and their parameters are listed in Table 6 and
À
8. The molecular packing is stabilized by several N H···O,
À
À
À
C1 N1 bond is anti in all the compounds as evident from
O H···O as well as C H···O interactions occurring through
finite and infinite chains of hydrogen bonds (Table 7).
the values of the torsion angle H1-C1-N1-N1H, which is
greater than 1508.
The N-glycosidic linkage torsion angle fN (O5-C1-N1-S1)
values for GlcbNHSO2CH3 (17), GalbNHSO2CH3 (18),
GlcNAcbNHSO2CH3 (19), conformer A of CellbNHSO2CH3
(22), LacbNHSO2CH3 (23), and GlcNAcbNHSO2CH2Cl
(32) are close to the values reported for the model
GlcNAcbNHAc (Table 5, Figure 5). In the case of confor-
mer B of CellbNHSO2CH3 (22) and GalbNHSO2CH2Cl
(31), the fN values are À76.6(2)8 and À76.2(2)8, respectively,
which deviates by a maximum of approximately 158 from
the model compound, GlcNAcbNHAc. This indicates that
N-glycosidic torsion, fN does not vary significantly by chang-
ing the linkage from a carboxamido group to a sulfonamido
moiety. Variation in the torsion angle c2 (N1-S1-C2’-Cl)
among GalbNHSO2CH2Cl (31) and GlcNAcbNHSO2CH2Cl
(32) was also examined and the values are found to be
À177.9(1)8 and 67.1(3)8, respectively, in contrast to the
value of 153.3(2)8 reported for GalbNHCOCH2Cl and of
173.0(6)8 reported for GlcNAcbNHCOCH2Cl. The near anti
Finite and infinite chain: In all the compounds (17–19, 22,
23, 31, and 32), N1 is connected to O1’ or O2’ through
a finite chain of hydrogen bonds except for CellbNH-
SO2CH3 (22). In GlcbNHSO2CH3 (17), the finite chain
begins with N1, passes through O4, O2, O6, O3 of symme-
try-related molecules and ends at O2’. The Gal derivative
GalbNHSO2CH3 (18) differs from Glc (17) in terms of the
altered sequence of oxygen atoms of symmetry-related mol-
ecules. In GalbNHSO2CH3 (18), the finite chain starts with
N1, passes through O3 and bifurcates at O1W into two
finite chains. One chain ends at O1’ and another chain runs
through O6, O2, and O4 and finally ends at O2’ (see Fig-
ure S1 in the Supporting Information). The characteristic
feature of GlcNAc derivatives is the direct hydrogen bond-
ing between N1 and O1’ accompanied by a similar one in-
volving N2 and O1’’ leading to double-pillared molecular
packing along the crystallographic a axis. This feature is also
found in GlcNAcbNHSO2CH3 (19) (Figure 6) and
GlcNAcbNHSO2CH2Cl (32) (see Figure S2 in the Support-
ing Information). Similar to the packing in GlcNAcbNHAc,
that in GlcNAcbNHSO2CH3 (19) is stabilized by two infinite
chains of hydrogen bonds. The first one involves the water
molecule (O1W), O3, and O6 atoms, and propagates along
the b axis (Figure 7). In the second one, the water molecule
acts as a donor as well as an acceptor to its neighboring O4
À
conformation about S1 C2’ bond exhibited by compound
31, gets altered to a gauche conformation in the compound
32. Such a large difference in c2 value is noteworthy. Earlier
conformational calculations on sulfonamide-containing
small molecules showed the energy difference among the
two forms (gauche and anti) to be much less (ca.
0.7 KJmolÀ1). However, in the solid state, hydrogen bond-
17726
www.chemeurj.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 17720 – 17732

N-Glycoprotein Linkage Region Analogues
FULL PAPER
Table 6. Hydrogen bond parameters for compounds 17–19, 22, 23, 31, and 32.
atoms facilitating the forma-
tion of a homodromic hydro-
À
À
À
À
À
D H···A
D H [ꢂ]
H A [ꢂ]
D A [ꢂ]
D H···A [8]
Symmetry
gen-bonded
network
GlcbNHSO2CH3 (17)
À
(Figure 8). Thus, the water
molecule is tetra-coordinated
donating both the hydrogens
to O3 and O4, while acting as
an acceptor for O4 and O6
leading to the formation of
claw-shaped hydrogen bonds
(Figure 7).
In CellbNHSO2CH3 (22),
one finite chain starts from
N1A, passes through O2A,
O2D, O6A, and O3C of sym-
metry-related molecules and
ends at O5D. Another finite
chain starts from O2C, running
through O4D, O6B, O4B and
finally ends at O1’A (see Fig-
ure S3 in the Supporting Infor-
mation). O1’A acts as a double
acceptor for O3D and O4B
N1 H1N···O4
0.84(3)
0.82
0.82
0.82
0.82
1.98(3)
1.89
1.95
2.04
1.99
2.802(3)
2.664(3)
2.759(3)
2.856(3)
2.801(2)
165(2)
156.6
170.4
172.4
170.5
xÀ1, y, z
À
O4 H4O···O2
Àx+1, y+1/2, Àz+1
Àx+1, y+1/2, Àz+1
Àx, y+1/2, Àz+1
Àx, yÀ1/2, Àz+1
À
O6 H6O···O3
À
O3 3O···O2’
À
O2 H2O···O6
GalbNHSO2CH3·H2O (18)
À
N1 H1N···O3
0.86(2)
0.82
0.83(2)
0.82
0.82
0.80(2)
0.82
2.05(2)
1.96
2.10(2)
1.98
1.96
1.98(2)
1.88
2.881(2)
2.758(2)
2.899(2)
2.787(2)
2.780(1)
2.772(2)
2.689(2)
162(2)
164.7
162(3)
168.2
174.7
171(3)
170.8
Àx+3/2, yÀ1/2, Àz
x, y, z+1
x, y, z+1
À
O4 H4O···O2’
À
O1W H2W···O1’
À
O6 H6O···O2
x, yÀ1, z
À
O2 H2O···O4
Àx+3/2, y+1/2, Àz
Àx+2, y+1, Àz+1
–
À
O1W H1W···O6
À
O3 H3O···O1W
GlcNAcbNHSO2CH3·H2O (19)
À
N1 H1N···O1’
0.86
0.86
0.82(2)
0.82
0.82
2.13
2.04
1.96(2)
1.96
1.95
2.929(2)
2.807(2)
2.737(2)
2.758(2)
2.745(3)
2.767(3)
2.721(3)
154.0
148.3
159(3)
163.3
163.3
159.6
170(3)
x+1, y, z
À
N2 H2N···O1’’
xÀ1, y, z
À
O1W H2W···O3
xÀ1, y, z
À
O3 H3O···O6
x, y+1, z
Àx+1, yÀ1/2, Àz
Àx+1, yÀ1/2, Àz
–
À
O4 H4O···O1W
À
O6 H6O···O1W
0.82
0.83(2)
1.98
1.90(2)
À
O1W H1W···O4
CellbNHSO2CH3 (22)
N1A H1NA···O2A
À
0.85(1)
0.85(1)
0.82
0.82
0.82
0.82
0.82
0.82
0.82
0.82
0.82
0.82
0.82
2.20(1)
2.23(1)
1.92
1.98
1.93
2.08
2.41
1.95
2.01
2.04
2.12
2.17
1.89
3.033(3)
3.065(4)
2.705(2)
2.798(2)
2.739(3)
2.899(3)
3.166(3)
2.739(2)
2.833(2)
2.818(2)
2.893(3)
2.934(3)
2.712(3)
2.735(3)
168(3)
173(3)
160.4
171.6
169.2
173.8
153.3
160.2
175.0
157.1
157.9
154.8
179.1
156.6
Àx+1, y+1/2, Àz+2
Àx+2, yÀ1/2, Àz+1
Àx+1, y+1/2, Àz+1
Àx+2, y+1/2, Àz
x, yÀ1, zÀ1
À
N1C H1NC···O3B
À
atoms (O3D H3OD···O1’A···-
À
O2A H2OA···O2D
À
H4OB O4B). O6C acts as
À
O2C H2OC···O4D
O2D H2OD···O6A
O3D H3OD···O1’A
O4B H4OB···O1’A
O4D H4OD···O6B
O6A H6OA···O3C
O3C H3OC···O5D
O3A H3OA···O5B
O6B H6OB···O4B
O6C H6OC···O1’C
O6D H6OD···O6C
LacbNHSO2CH3·H2O (23)
À
À
a donor (O6C H6OC···O1’C)
as well as an acceptor atom
À
Àx+1, yÀ1/2, Àz+1
x, y, zÀ1
À
À
(O6D H6OD···O6C).
direct hydrogen bonds are also
present which lend further sta-
Two
À
Àx+1, yÀ1/2, Àz
Àx+2, y+1/2, Àz+1
x, y, z
À
À
À
bilization (N1C H1NC···O3B
À
x, y, z
À
À
Àx+1, yÀ1/2, Àz+1
Àx+2, yÀ1/2, Àz+1
Àx+2, y+1/2, Àz
and
O3A H3OA···O5B).
À
LacbNHSO2CH3 (23) exhibits
direct hydrogen bonding be-
tween N1 and O1’. Molecular
packing of 23 is stabilized by
one infinite and one finite
chain of hydrogen bonds. The
finite chain starts from O4B,
passes through O1W, O6A,
O2A, O2B, and O3A of sym-
metry-related molecules and
ends at O5B. O3A acts as a bi-
À
À
0.82
1.96
À
N1 H1N···O1’
0.81(2)
0.82
0.82
0.82
0.82
0.82
0.82
0.82
2.05(2)
2.03
2.44
1.97
1.95
1.93
2.01
1.95
2.837(3)
2.763(2)
3.079(3)
2.769(2)
2.757(3)
2.749(2)
2.823(2)
2.727(2)
2.812(4)
3.016(3)
2.802(3)
162(3)
148.0
135.6
163.1
166.1
176.9
171.4
157.6
166(4)
123(5)
171.2
x+1, y, z
–
–
x, y, z+1
x, y, z+1
xÀ1, y, zÀ1
x+1, y, z+1
À
O3A H3OA···O5B
À
O3A H3OA···O6B
O2B H2OB···O3A
O3B H3OB···O6B
O6B H6OB···O3B
O6A H6OA···O2A
O2A H2OA···O2B
O1W H1W···O2’
O1W H2W···O6A
À
À
À
À
À
À
x 1, y, zÀ1
À
À
z
0.84(2)
0.81(2)
0.82
1.99(2)
2.50(5)
1.99
Àx+1, yÀ1/2,
À
Àx+2, yÀ1/2, Àz+1
x, y, z
À
O4B H4OB···O1W
GalbNHSO2CH2Cl (31)
furcated
H3OA···O5B
donor
and
(O3A
À
O3A
À
N1 H1N···O3
0.82(1)
0.82
0.82
0.82
0.82
2.06(1)
2.33
2.34
2.29
1.92
2.857(2)
2.864(2)
3.077(2)
2.993(2)
2.745(2)
2.845(2)
165(3)
122.8
150.8
144.8
178.6
170.6
Àx, yÀ1/2, Àz+1/2
Àx, y+1/2, Àz+1/2
Àx+1, y+1/2, Àz+1/2
x, y+1, z
H3OA···O6B). The infinite
chain involves O3B and O6B
acting as donor and acceptor
and runs along the a axis. This
pattern is similar to that in
LacbNHAc.2H2O.[24] In addi-
tion, one direct hydrogen bond
À
À
O2 H2O···O1’
À
O2 H2O···O2’
À
O4 H4O···O1’
À
O3 H3O···O2
Àx+1, y+1/2, Àz+1/2
À
O6 H6O···O6
0.82
2.03
xÀ1/2, Ày+1/2,Àz+1
GlcNAcbNHSO2CH2Cl·H2O (32)
À
N1 H1N···O1’
0.87(2)
0.85(2)
0.82
2.11(3)
2.06(3)
1.94
2.898(5)
2.821(4)
2.737(4)
2.760(4)
2.713(4)
2.706(4)
2.750(4)
150(4)
149(4)
163.5
x+1, y, z
xÀ1, y, z
À
N2 H2N···O1’’
is
also
present
(O1W
À
O4 H4O···O1W
Àx+1, yÀ1/2, Àz+1/2
Àx+1, yÀ1/2, Àz+1/2
x, y+1, z
À
O6 H6O···O1W
0.82
1.98
158.4
H1W···O2’). In the crystal of
GalbNHSO2CH2Cl (31), there
is no direct hydrogen bonding
between N1 and O1’. A finite
À
O1W H2W···O3
0.82(2)
0.83(2)
0.82
1.92(2)
1.88(2)
1.94
166(5)
175(5)
168.8
À
O1W H1W···O4
x+1, y+1, z
x, yÀ1, z
À
O3 H3O···O6
Chem. Eur. J. 2013, 19, 17720 – 17732
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
17727

A. Srivastava et al.
Table 7. Finite and infinite chain of hydrogen bonding in compounds 17–19, 22, 23, 31, and 32.
Compound
Finite chain of hydrogen bonding
Infinite chain of hydrogen bonding
À
À
À
À
À
GlcbNHSO2CH3 (17)
GalbNHSO2CH3·H2O (18)
N1 H1N···O4 H4O···O2 H2O···O6 H6O···O3 H3O···O2’
no infinite chain
no infinite chain
À
À
À
À
À
N1 H1N···O3 H3O···O1W H1W···O6 H6O···O2 H2O···
À
···O4 H4O···O2’
O1W H2W···O1’
À
À
À
À
À
À
GlcNAcbNHSO2CH3·H2O (19) N1 H1N···O1’ N2 H2N···O1’’
···O3 H3O···O6 H6O ···O1W
H2W···O3···
À
À
···O4 H4O···O1W H1W···O4···
no infinite chain
À
À
À
À
À
CellbNHSO2CH3 (22)
N1A H1NA···O2A H2OA···O2D H2OD···O6A H6OA···O3C
H3OA···O5D
À
À
À
À
O2C H2OC···O4D H4OD···O6B H6OB···O4B H4OB···O1’A
À
À
N1C H1NC···O3B, O3D H3OD···O1’A
À
À
O6C H6OC···O1’C, O6D H6OD···O6C
À
À
À
LacbNHSO2CH3·H2O (23)
GalbNHSO2CH2Cl (31)
N1 H1N···O1’
···O3B H3OB···O6B H6OB···O3B···
À
À
À
À
O4B H4OB···O1W H2W···O6A H6OA···O2A H2OA···
À
À
···O2B H2OB···O3A H3OA···O5B
À
À
O3A H3OA···O6B, O1W H1W···O2’
À
À
À
À
À
N1 H1N···O3 H3O···O2 H2O···O1’, O2 H2O···O2’,
O6 H6O···O6
À
O4 H4O···O1’
À
À
À
À
GlcNAcbNHSO2CH2Cl·H2O
(32)
N1 H1N···O1’
···O3 H3O···O6 H6O···O1W
H2W···O3···
À
À
À
N2 H2N···O1’’
···O4 H4O···O1W H1W···O4···
Figure 8. Formation of the homodromic cycle in GlcNAcbNH-
SO2CH3·H2O (19).
chain starts from N1, passes through O3 and O2 of symme-
try-related molecules and ends at O1’. The infinite chain in-
volves O6 as a donor as well as acceptor (see Figure S4 in
the Supporting Information). A direct hydrogen bond be-
À
tween O2 H and O2’ of another molecule is also present.
Figure 6. Representation of the double-pillared packing in GlcNAcbNH-
SO2CH3·H2O (19).
À
O2 H2O acts as a bifurcated hydrogen donor for O1’ and
O2’, whereas O1’ acts as a double acceptor for O2 and O4
À
À
atoms (O2 H2O···O1’···H4O O4). The molecular packing
of GlcNAcbNHSO2CH2Cl (32) is similar to that in
GlcNAcbNHSO2CH3 (19) and the model GlcNAcbNHAc.
N1 and O1’ and N2 and O1’’ are connected through a finite
chain of hydrogen bonds. The water molecule is tetra-coor-
dinated, acting as donor for O3 and O4 and an acceptor for
the atoms O4 and O6. The O6 atom also serves as an ac-
À
ceptor for O3 H3O.
À
À
C H···X interactions: C H···X (X=O/N/Cl) contacts were
determined by using three geometrical parameters namely,
the distance C···X representing the donor–acceptor distance
(D–A); the distance H···X (H–A), the hydrogen bond
À
length; and the C H···X angle (q). Only those interactions
for which the D–A values are shorter than 3.6 ꢂ and the q
values are greater than 1108 are considered as significant
(see Table 8). In GlcbNHSO2CH3 (17), two methyl hydro-
Figure 7. Finite and infinite chains of hydrogen bonds in GlcNAcbNH-
SO2CH3·H2O (19).
À
gens of the aglycon chain are involved in the C H···O inter-
17728
www.chemeurj.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 17720 – 17732

N-Glycoprotein Linkage Region Analogues
FULL PAPER
À
Table 8. C H···O hydrogen bond parameters for compounds 17–19, 22, 23, 31, and 32.
as compared to other methane-
sulfonamido derivatives. All
three methyl hydrogens of the
aglycon chain are involved in
À
À
À
À
À
D H···A
D H [ꢂ]
H A [ꢂ]
D A [ꢂ]
D H···A [8]
Symmetry
GlcbNHSO2CH3 (17)
C2’ H2’B···O1’
C2’ H2’A···O2
C3 H3···O2’
GalbNHSO2CH3·H2O (18)
C2 H2···O5
C5 H5···O1’
C6 H6B···O3
GlcNAcbNHSO2CH3·H2O (19)
C2’ H2’A···O1’’
C2’ H2’B···O2’
C2’ H2’C···O2’
C1 H1···O1’’
C2’’ H’’B···O5
C2’’ H’’C···O1’
CellbNHSO2CH3 (22)
Molecule A (22A)
À
0.96
0.96
0.98
2.57
2.65
2.66
3.190
3.492
3.567
122.4
147.3
154.6
Àx, 1/2+y, 2Àz
x, y, 1+z
1+x, y, z
À
À
À
the C H···O interactions (C2’
À
À
H2’B···O2’, C2’ H2’C···O2’ and
C2’-H2’A···O1’’)
(Figure 9),
À
0.98
0.98
0.97
2.70
2.71
2.72
3.424
3.619
3.327
131.1
154.8
121.4
1.5Àx, 1/2+y, Àz
2Àx, y, Àz
which may also contribute to
the altered aglycon conforma-
tion. O1’ and O2’ act as double
acceptors. The molecular pack-
ing is also stabilized by one bi-
À
À
x, À1+y, z
À
0.96
0.96
0.96
0.98
0.96
0.96
2.62
2.40
2.62
2.53
2.55
2.61
3.537
3.340
3.294
3.263
3.307
3.403
159.2
166.8
127.9
131.3
136.1
139.9
À1+x, y, z
À
2Àx, 1/2+y, 1Àz
1Àx, 1/2+y, 1Àz
À1+x, y, z
À
À
À
furcated hydrogen bond (N1
À
x, 1+y, z
À
H1N···O1’···H’’C C2’’) and one
À
1+x, 1+y, z
À
À
C H···O interaction (C2’’
H’’B···O5) (Table 8).
The molecular packing of
CellbNHSO2CH3 (22) is stabi-
À
C2’A H’AA···O6C
0.96
0.98
0.98
0.98
2.59
2.54
2.60
2.66
3.118
3.434
3.500
3.556
114.9
152.5
152.8
151.3
x, 1+y, 1+z
x, y, 1+z
x, 1+y, 1+z
x, 1+y, 1+z
À
C5A H5A···O5D
À
C1B H1B···O3D
À
lized by various C H···O inter-
À
C5B H5B···O3D
actions leading to several bifur-
cated hydrogen bonds. O2A,
O4D, O6A, O3D, O2’A, O6C,
O5D, and O2B act as double
À
Molecule B (22B)
À
C2’C H’BC···O4D
0.96
0.98
0.98
0.98
0.97
0.97
0.98
0.98
0.97
2.34
2.49
2.56
2.47
2.70
2.55
2.56
2.37
2.66
3.254
3.414
3.469
3.285
3.409
3.497
3.207
3.129
3.563
159.6
156.7
154.4
140.9
130.4
164.4
123.1
134.2
155.8
x, y, 1+z
À
C1C H1C···O2’A
x, y, À1+z
À
C5C H5C···O2’A
x, y, À1+z
À
C2C H2C···O2B
2Àx, À1/2+y, 1Àz
x, y, À1+z
acceptor
atoms
(N1A
À
C6D H6D2···O2B
À
H1NA···O2A···H6C2 C6C,
À
C6D H6D2···O4A
x, y, À1+z
À
À
O2C H2OC···O4D···H’BC
C2’C, O2D
H2OD···O6A···H3D C3D,
À
C5D H5D···O2C
2Àx, À1/2+ y, Àz
x, À1+y, À1+z
1Àx, À1/2+ y, 1Àz
À
C3D H3D···O6A
À
À
C6C H6C2···O2A
LacbNHSO2CH3·H2O (23)
À
À
À
C1B H1B···O3D···H5B C5B,
À
C2’ H2’B···O3B
C2’-H2’A···O1W
C2’ H2’C···O1W
0.96
0.96
0.96
0.98
0.97
0.97
0.98
2.43
2.64
2.64
2.44
2.68
2.67
2.59
3.251
3.257
3.365
3.277
3.443
3.575
3.342
144.0
122.4
132.6
142.8
135.5
155.6
133.5
2Àx, 1/2+y, 1Àz
2Àx, 1/2+y, 1Àz
1Àx, 1/2+y, 1Àz
À1+x, y, z
À
À
C1C H1C···O2’A···H5C C5C,
O6D H6OD···O6C···H’AA
À
À
À
À
C5A H5A···O6A
À
C2’A,
C5A H5A···O5D···
À
C6A H6A2···O2A
x, y, 1+z
À
À
H3OC O3C
and
C2C
À
C6B H6B1···O2’
2Àx, À1/2+y, Àz
À
H2C···O2B ···H6D2 C6D). In
À
C3B H3B···O4B
1+x, y, z
addition to bifurcated hydro-
GalbNHSO2CH2Cl (31)
À
C2’ H2’B···O2’
0.97
0.98
0.98
2.30
2.66
2.51
3.151
3.198
3.353
145.5
114.9
143.8
À1+x, y, z
À
gen bonds, two C H···O inter-
À
C2 H2···O1’
Àx, 1/2+y, 1/2Àz
1+x, y, z
À
actions are also seen (C6D
À
C3 H3···O4
À
H6D2···O4A
and
C5D
GlcNAcbNHSO2CH2Cl·H2O (32)
H5D···O2C). The molecular
packing of LacbNHSO2CH3
(23) is also stabilized by vari-
ous bifurcated hydrogen bonds
involving O1W, O3B, O2A,
O6A and O2’ atoms as double
À
C2’ H2’A···O2’
0.97
0.96
0.98
0.98
2.38
2.42
2.44
2.61
3.237
3.294
3.181
3.324
146.5
152.1
132.1
130.0
À1/2+x, 1/2Ày, Àz
x, À1+y, z
À
C2’’ H’’B···O5
À
C1 H1···O1’’
À1+x, y, z
À
C3 H3···O1’’
À1+x, y, z
À
À
À
À
actions (C2’–H2’B···O1’ and C2’ H2’A···O2). O2 and O2’
acceptors
H2’B···O3B···H6OB O6B,
O6A,
(C2’ H2’A···O1W···H2’C C2’,
C2’
À
À
À
À
À
À
act as double acceptors (C2’ H2’A···O2···H4O O4 and C3
C6A H6A2···O2A···H6OA
À
À
À
À
À
C6B
H3···O2’···H3O O3). There are only three C H···O interac-
C5A H5A···O6A···H2W O1W
H6B1···O2’···H1W O1W). The molecular packing is further
stabilized by one more C H···O interaction (C3B H3B···
O4B) (Table 8).
and
À
À
À
À
tions (C2 H2···O5, C5 H5···O1’ and C6 H6B···O3) in
GalbNHSO2CH3 (18). As O1’ and O3 atoms are already ac-
cepting heteroatom-held (O/N) hydrogens, these serve as
À
À
À
double acceptors. Examination of the C H···O interactions
in the crystal structure of GlcNAcbNHSO2CH3 (19) reveals
In GalbNHSO2CH2Cl (31), the molecular packing is
mainly stabilized by one trifurcated and one bifurcated hy-
drogen bond, where O1’ acts as a triple acceptor and O2 as
the presence of a trifurcated hydrogen-bond pattern involv-
À
À
À
À
À
À
ing C1 H1···O1’’···H2N N2 and C2’ H2’A···O1’’ (Figure 9).
This trifurcated hydrogen bonding along with the direct hy-
drogen bond between N1 and O1’ may be the cause of the
different aglycon conformation of GlcNAcbNHSO2CH3 (19)
a double acceptor (O2 H2O···O1’···H4O O4 and C2
À
À
À
H2···O1’, O2 H2O···O2’···H2’B C2’). One more C H···O in-
À
teraction (C3 H3···O4) is also noted. Examination of the
C H···O/N interactions in the crystal structure of
À
Chem. Eur. J. 2013, 19, 17720 – 17732
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
17729

A. Srivastava et al.
hydrogen in this case comes
À
from C3 H rather than from
À
C2’ H as in the case of com-
À
(C1
pound
19
À
À
H1···O1’’···H2N N2 and C2’
H2’A···O1’’). Only one hydro-
gen atom of the aglycon chain
À
is involved in the C H···O in-
À
teraction
(C2’ H2’A···O2’)
leading to the formation of
a helical assembly (Figure 11).
Like
(19), GlcNAcbNHSO2CH2Cl
(32) also shows different
GlcNAcbNHSO2CH3
a
aglycon conformation than
GalbNHSO2CH2Cl (31), which
may be due to the direct hy-
À
Figure 9. Presence of trifurcated hydrogen bonds and C H···O interactions (green) of the aglycon chain in
GlcNAcbNHSO2CH3·H2O (19).
drogen
bonding
between
À
N1···O1’ and the C H···O in-
teraction of the aglycon chain. The molecular packing is fur-
GlcNAcbNHSO2CH2Cl (32) reveals the presence of a trifur-
À
À
À
cated hydrogen bond pattern involving C1 H1···O1’’···H2N
ther stabilized by one C H···O hydrogen bond formed by
À
À
N2 and C3 H3···O1’’ (Figure 10). This pattern is different
the methyl carbon of the C-2 acetamido moiety (C2’’
À
from that of GlcNAcbNHSO2CH3 (19), as the third donor
H’’B···O5). No C H···N interaction is noted in any of the
seven compounds studied. The chloromethanesulfonamido
À
derivatives 31 and 32 did not display any C H···Cl hydrogen
bond in the crystal.
Conclusion
A series of novel glycosyl sulfonamides have been designed
as analogues of the N-glycoprotein linkage region and syn-
thesized successfully in moderate to good yields. An im-
proved procedure was developed for the preparation of N-
(b-d-glycosyl)methanesulfonamides (17–24) from the corre-
sponding glycosyl azides. A series of N-(b-d-glycopyranosyl)
chloromethanesulfonamides (30–34) were also designed and
synthesized as analogues of the N-glycoprotein linkage
region. These compounds may have potential as glycogen
phosphorylase inhibitors. Among all the compounds synthe-
sized (17–24 and 30–34), crystal structures of seven of them
have been solved as part of the present work. The influence
of the structural variation of the glycan as well as the agly-
con part on the key torsion angles (w, f0, y0, fN, yN, and c2)
was examined. A comparative analysis of the fN values
showed that the torsion angle fN does not alter significantly
by changing the carboxamido group to the sulfonamido
moiety as compared to that of the model compound
GlcNAcbNHAc. For most of the compounds (17, 18, 22, 23,
and 31), the value of the torsion angle yN was close to 758
except for methanesulfonamido (19) and chloromethanesul-
fonamido (32) derivatives of GlcNAc. Lastly, the side chain
torsion angle c2 of GalbNHSO2CH2Cl (31) and
GlcNAcbNHSO2CH2Cl (32) differ substantially, resulting in
À
À
Figure 10. Presence of trifurcated hydrogen bonds, N H···O and O H···O
À
(red) and C H···O (green) interactions in GlcNAcbNHSO2CH2Cl·1H2O
(32).
À
a turnaround of the conformation about S1 C2’ from close
to anti in 31 to syn in 32. This large variance may be due to
Figure 11. Presence of the hydrogen-bonded helical network (green) of
the aglycon moiety in GlcNAcbNHSO2CH2Cl·1H2O (32).
differences in the molecular packing.
17730
www.chemeurj.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 17720 – 17732

N-Glycoprotein Linkage Region Analogues
FULL PAPER
A comprehensive analysis of the molecular packing stabi-
the interaction with the other sulfonamido oxygen atom,
À
À
lized by hydrogen bonds and C H···O interactions in the
namely, O2’ (C2’ H2’···O2’). The characteristic feature of
crystal structures of all the sulfonamides was also carried
out. The molecular packing of GlcNAcbNHSO2CH3 (19),
LacbNHSO2CH3 (23), GalbNHSO2CH2Cl (31), and
GlcNAcbNHSO2CH2Cl (32) is stabilized by finite as well as
infinite chains of hydrogen bonds. Bioisosteric replacement
of the carboxamide with sulfonamide causes a few changes
in the molecular packing. The most significant of these
the molecular packing of GlcNAcbNHSO2CH3 (19) and
GlcNAcbNHSO2CH2Cl (32) is the presence of a trifurcated
hydrogen bond involving O1’’ as a triple acceptor atom,
which was also seen in the case of GlcNAcbNHAc. The
direct hydrogen bonding between N1 and O1’ seems to be
a distinctive molecular recognition motif that controls the
aglycon conformation in compounds 19 and 32. Besides this,
À
À
changes is the absence of a C2’ H2’···O1’ interaction in the
the weaker C H···O contacts also play a co-operative role
À
sulfonamido derivatives 19 and 32. This characteristic C
in controlling the conformation of the aglycon moiety. The
above structural analysis shows that glycosyl sulfonamides
due to insignificant deviation in the fN value may serve as
linkage region analogues. This study illustrated for the first
time the effect of the bioisosteric replacement of a carboxa-
mide group by a sulfonamide group on the N-glycosidic tor-
sion fN as well as on the molecular assembly.
H···O interaction plays an important role in the formation
of the anti-parallel bifurcated double-pillared hydrogen
bond network, a hallmark feature of the molecular packing
of the models (GlcNAcbNHAc and GlcNAcbAsn) of the
conserved N-glycoprotein linkage region. In both these com-
pounds (19 and 32), C2’ of the aglycon chain is involved in
Table 9. Data collection and refinement statistics for compounds 17–19, 22, 23, 31, and 32.
Parameter
17
18
19
22
23
31
32
empirical
formula
formula
weight
C7H15N O7S
C7H17NO8S
C9H20N2O8S
C13H25NO12S
C13H27O13S
C7H14ClNO7S
C9H19ClN2O8S
257.26
275.28
316.33
419.40
437.42
291.70
350.77
temp [K]
l [ꢂ]
crystal system monoclinic
space group
a [ꢂ]
298(2)
0.71073
298 (2)
0.71073
monoclinic
C2
19.1916(15)
7.5767(5)
9.4859(8)
90
297(2)
0.71073
monoclinic
P21
4.9905(2)
7.8973(2)
18.6950(7)
90
293(2)
298(2)
293(2)
298(2)
0.71073
orthorhombic
P212121
5.0424(6)
7.8402(10)
38.401(5)
90
0.71073
monoclinic
P21
12.8879(2)
10.0481(2)
14.6387(4)
90
0.71073
monoclinic
P21
4.8289(2)
26.0236(8)
7.5513(2)
90
0.71073
orthorhombic
P212121
4.9221(2)
9.6824(5)
24.2790(11)
90
P21
6.8460(3)
9.7882(4)
8.6000(4)
90
b
c [ꢂ]
a [8]
b [8]
g [8]
107.059(2)
90
550.93(4)
2
1.551
0.315
117.126(4)
90
1227.62(16)
4
1.489
0.294
96.455(2)
90
732.13(4)
2
1.435
0.259
107.7850(10)
90
1805.10(7)
4
1.543
0.245
101.805(2)
90
928.87(5)
2
1.564
0.246
90
90
90
90
volume [ꢂ3]
Z
1157.08(9)
4
1.674
1518.1(3)
4
1.535
1calcd [MgmÀ3
]
m [mmÀ1
]
0.535
0.428
F
(000)
272
584
336
888
464
608
736
crystal size
[mm]
0.55ꢃ0.25ꢃ0.20 0.38ꢃ0.25ꢃ0.22
0.38ꢃ0.22ꢃ0.18
0.35ꢃ0.22ꢃ0.18
0.32ꢃ0.28ꢃ0.20
0.30ꢃ0.20ꢃ0.20
0.38ꢃ0.25ꢃ0.22
theta range
[8]
2.48 to 25.00
2.94 to 24.97
3.39 to 25.00
2.50 to 25.00
2.76 to 25.00
2.26 to 25.00
2.65 to 24.99
index ranges À8hꢀ7,
À22ꢀhꢀ22,
À8ꢀkꢀ8,
À11ꢀlꢀ8
3716/2074
À5ꢀhꢀ5,
À9ꢀkꢀ6,
À18ꢀlꢀ22
4498/2381
À13ꢀhꢀ15,
À11ꢀkꢀ11,
À17ꢀlꢀ17
11245/6030
À5ꢀhꢀ4,
À30ꢀkꢀ30,
À8ꢀlꢀ8
À5ꢀhꢀ3,
À11ꢀkꢀ10,
À28ꢀlꢀ28
6048/1961
À5ꢀhꢀ5,
À9ꢀkꢀ7,
À45ꢀlꢀ31
6162/2626
À11ꢀkꢀ10,
À10ꢀlꢀ10
reflections
collected/
unique
3438/1594
5795/3014
[RN
(int)=0.0135]
[R
A
(int)=0.0214]
[R
A
(int)=0.0164]
[RACHTNGUTERN(UNG int)=0.0225]
completeness 97.0
to theta [%]
98.9
99.7
99.9
94.7
98.0
99.8
refinement
method
full-matrix
full-matrix
least-squares
on F2
full-matrix
least-squares
on F2
full-matrix
least-squares
on F2
full-matrix
least-squares
on F2
full-matrix
least-squares on
F2
full-matrix
least-squares
on F2
least-squares
on F2
data restraint 1594/1/154
parameters
2074/4/172
2381/4/194
6030/3/526
3014/5/273
1961/1/162
2626/5/207
goodness-of
fit on F2
final R
1.082
1.094
1.048
1.027
1.092
1.061
1.071
R1=0.0277,
wR2=0.0706
R1=0.0212,
wR2=0.0558
R1=0.0282,
wR2=0.0726
R1=0.0317,
wR2=0.0731
R1=0.0281,
wR2=0.0675
R1=0.0259,
wR2=0.0652
R1=0.0501,
wR2=0.1209
indices
ACHTUNGTRENNUNG
R1=0.0224,
wR2=0.0573
R1=0.0292,
wR2=0.0732
R1=0.0361,
wR2=0.0757
R1=0.0301,
wR2=0.0687
R1=0.0270,
wR2=0.0661
R1=0.0555,
wR2=0.1245
Chem. Eur. J. 2013, 19, 17720 – 17732
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
17731

A. Srivastava et al.
[2] A. Varki, Glycobiology 1993, 3, 97–130.
[3] R. A. Dwek, Chem. Rev. 1996, 96, 683–720.
Experimental Section
[4] T. Lakshmanan, D. Sriram, K. Priya, D. Loganathan, Biochem. Bio-
phys. Res. Commun. 2003, 312, 405–413.
[5] D. Loganathan, U. Aich, T. Lakshmanan, Proc. Indian Natl. Sci.
Acad. 2005, 71, 213–235.
[6] D. Loganathan, U. Aich, Glycobiology 2005, 16, 343–348.
[7] M. M. N. Ali, U. Aich, B. Varghese, S. Pꢄrez, A. Imberty, D. Logana-
than, J. Am. Chem. Soc. 2008, 130, 8317–8325.
[8] M. M. N. Ali, U. Aich, S. Pꢄrez, A. Imberty, D. Loganathan, Carbo-
hydr. Res. 2009, 344, 355–361.
[9] G. Cioci, A. Srivastava, D. Loganathan, S. A. Mason, S. Pꢄrez, A.
Imberty, J. Am. Chem. Soc. 2011, 133, 10042–10045.
[10] M. Mathiselvam, B. Varghese, D. Loganathan, Glycoconjugate J.
2011, 28, 573–580.
[11] A. Srivastava, B. Varghese, D. Loganathan, J. Carbohydr. Chem.
2012, 31, 31–47.
[12] P. A. Colinas, R. D. Bravo, Carbohydr. Res. 2007, 342, 2297–2302.
[13] P. A. Colinas, R. D. Bravo, Org. Lett. 2003, 5, 4509–4511.
[14] T. Y. Shen, J. P. Li, C. P. Dorn, D. Ebel, R. Bugianesi, R. Fecher,
Carbohydr. Res. 1972, 23, 87–102.
Preparation of single crystals and X-ray crystallographic analysis: Single
crystals of the compounds 17–19, 22, 23, 31, and 32 were obtained from
aqueous methanol by slow evaporation at room temperature. X-ray data
collection was performed by using a Bruker AXS Kappa Apex II CCD
diffractometer equipped with graphite-monochromated Mo (Ka) (l=
0.7107 ꢂ) radiation. A crystal fixed at the tip of the glass fiber was
mounted on the goniometer head with the aid of a video microscope.
The automatic cell determination routine, with 36 frames at three differ-
ent orientations of the detector was employed to collect reflections for
unit cell determination. Thereafter, intensity data for the structure deter-
mination were collected through an optimized strategy which gave an
average fourfold redundancy. The program APEX2-SAINT[26] was used
for integrating the frames. The fourfold redundancy per reflection was
utilized for achieving good multi-scan absorption correction using the
program SADABS.[27] Besides absorption, Lorentz, polarization, and
decay corrections were applied during data reduction. The structures
were solved by direct methods using SIR92[28] and refined by full-matrix
least squares techniques using the SHELXL-97[29] computer program.
All hydrogen atoms attached to carbon were fixed at chemically mean-
ingful positions and a riding model refinement was applied. The nitrogen
hydrogen atoms were located by using a difference Fourier map and re-
fined with isotropic thermal parameters. All the hydrogen atoms of the
hydroxyl groups could be located in the difference Fourier map. The free
[15] A. P. Butera, J. D. S. Filho, D. T. Carvalho, R. C. Figueiredo, L. C. A.
Faria, M. A. Nunes, M. A. F. Prado, R. J. Alves, M. H. Andrade,
A. T. Silva, Quim. Nova 2007, 30, 1267–1274.
[16] P. A. Colinas, C. A. Tꢄmpera, O. M. Rodrꢅguez, R. D. Bravo, Synthe-
sis 2009, 24, 4143–4148.
[17] Z. Gyorgydeak, J. Theim, Adv. Carbohydr. Chem. Biochem. 2005,
60, 103–182.
[18] R. Ghosh, A. Chakraborty, S. Maiti, Tetrahedron Lett. 2004, 45,
9631–9634.
[19] F. M. Ibatullin, K. A. Shabalin, Synth. Commun. 2000, 30, 2819–
2823.
[20] G. A. Jeffrey, Acta Crystallogr. Sect. B 1990, 46, 89–103.
[21] J. Ohanessian, D. Avenel, A. Neuman, H. Gillier-Pandraud, Carbo-
hydr. Res. 1980, 80, 1–13.
[22] A. D. French, Adv. Carbohydr. Chem. Biochem. 2012, 67, 19–92.
[23] Z. Peralta-Inga, G. P. Johnson, M. K. Dowd, A. J. Rendleman, E. D.
Stevens, A. D. French, Carbohydr. Res. 2002, 337, 851–861.
[24] T. Lakshmanan, D. Sriram, D. Loganathan, Acta Crystallogr. Sect C:
Struct. Commun. 2001, 57, 825–826.
À
refinement of these hydrogens did not yield satisfactory O H distances
in all the cases. Hence, these atoms were fixed at geometrically meaning-
ful positions and were allowed to ride over the respective oxygen atoms
during the refinement. The starting coordinates of the hydrogen atoms
were chosen from Fourier peak positions. The thermal parameters of
these hydrogen atoms were fixed at 1.5 times the equivalent thermal pa-
À
rameters of the parent oxygen. The O H distances were judiciously fixed
after the inspection of distances in the difference map. The details of the
À
O H hydrogen fixing in individual structures are described in the respec-
tive cif files. The water hydrogen atoms were located in the difference
À
Fourier map and refined with O H distances restrained to 0.82 ꢂ. The
H-O-H angles were also restrained to near tetrahedral values. Molecular
graphics were drawn using ORTEP32[30] and Mercury programs.[31] The
relevant details for the data collection and refinement are given in
Table 9.
[25] A. Parkin, A. Collins, C. J. Gilmore, C. C. Wilson, Acta Crystallogr.-
Sect. B 2008, 64, 66–71.
[26] Bruker, APEX2, SAINT-Plus and XPREP, Bruker Axs Inc., Madi-
son, Wisconsin, USA, 2004.
[27] Bruker SADABS, Bruker AXS Inc., Madison, Wisconsin, USA,
1999.
CCDC-932532 (17), CCDC-932533 (18), CCDC-932534 (19), CCDC-
932535 (22), CCDC-932536 (23), CCDC-932537 (31), and CCDC-932538
(32) contain the supplementary crystallographic data for this paper.
These data can be obtained free of charge from The Cambridge Crystal-
lographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
[28] A. Atarmare, G. Gascarano, C. Giacovazzo, A. Guagliardi, J. Appl.
Crystallogr. 1993, 26, 343–350.
[29] G. M. Sheldrick, SHELXL97, Program for Crystal Structure Refine-
ment; University of Gçttingen, Gçttingen (Germany), 1997.
[30] ORTEP-3 for Windows-a version of ORTEP-III with a Graphical
User Interface (GUI): L. J. Farrugia, J. Appl. Crystallogr. 1997, 30,
565.
[31] I. J. Bruno, J. C. Cole, P. R. Edgington, M. Kessler, C. F. Macrae, P.
McCabe, J. Pearson, R. Taylor, Acta Crystallogr.Sect. B 2002, 58,
389–397.
[32] D. Sriram, T. Lakshmanan, D. Loganathan, S. Srinivasan, Carbohydr.
Res. 1998, 309, 227–236.
[33] D. Sriram, H. Sreenivasan, S. Srinivasan, K. Priya, M. Vishnu Thir-
tha, D. Loganathan, Acta Crystallogr.Sect. C 1997, 53, 1075–1077.
[34] U. Aich, T. Lakshmanan, B. Varghese, D. Loganathan, J. Carbohydr.
Chem. 2003, 22, 883–893.
Acknowledgements
This work was supported by Indo-French Centre for Promotion of Ad-
vanced Research (IFCPAR), New Delhi. The funding provided by the
Department of Science and Technology, New Delhi, for the purchase of
a 400 MHz NMR under IRHPA Scheme and ESI-MS under the FIST
program is gratefully acknowledged. The authors thank the single crystal
X-ray facility, Chemistry Department, IIT Madras for the X-ray data col-
lection. We are thankful to Mr. V. Ram Kumar for X-ray data collection
and cooperation. One of us (A.S.) is thankful to the Council of Scientific
and Industrial Research (CSIR), New Delhi, for the award of a Senior
Research Fellowship. We also thank Cambridge Crystallographic Data
Centre (CCDC), UK, for making the program Mercury 3.1 available for
use.
Please note: Minor changes have been made to this manuscript since its
publication in Chemistry – A European Journal Early View. The Editor.
[1] A. Varki, R. D. Cumming, J. D. Esko, H. H. Freeze, P. Stanley, C. R.
Bertozzi, G. W. Hart, M. E. Etzler, Essential of Glycobiology, 2nd
ed, Cold Spring Harbor Laboratory, 2009.
Received: May 25, 2013
17732
www.chemeurj.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 17720 – 17732