Synthesis and characterization of thiourea- and urea-linked glycolipids as low-molecular-weight hydrogelators

Article abstract of DOI:10.1039/c3ra42041h

Novel glycolipids with thiourea- and urea-linkers have been synthesized as low-molecular-weight gelators by reacting glycosyl aminoacetamides with alkyl isothiocyanates and isocyanates. The influence of the linker groups on their self-assembly properties has been studied. A gelation study of the obtained neoglycolipids in various solvents showed that they are good hydrogelators. Urea-linked glycolipids showed better hydrogelating ability as compared to thiourea linked glycolipids. The influence of sugar head group and alkyl chain length on the glycolipid's self-assembly has also been studied. The fibrillar structures of the supramolecular hydrogels have been characterized by scanning electron microscopy (SEM). The thermal properties of the hydrogels formed by urea linked glycolipids have been studied by differential scanning calorimetry (DSC) and VT-NMR. Molecular packing has been studied by small angle (SAXS) and single crystal X-ray diffraction methods. The Royal Society of Chemistry 2013.

Full text of DOI:10.1039/c3ra42041h

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Synthesis and characterization of thiourea- and urea-
linked glycolipids as low-molecular-weight
hydrogelators3
Cite this: RSC Advances, 2013, 3,
14528
Manoharan Mathiselvam,*a Duraikkannu Loganathan{a and Babu Vargheseb
Novel glycolipids with thiourea- and urea-linkers have been synthesized as low-molecular-weight gelators
by reacting glycosyl aminoacetamides with alkyl isothiocyanates and isocyanates. The influence of the
linker groups on their self-assembly properties has been studied. A gelation study of the obtained
neoglycolipids in various solvents showed that they are good hydrogelators. Urea-linked glycolipids
showed better hydrogelating ability as compared to thiourea linked glycolipids. The influence of sugar
head group and alkyl chain length on the glycolipid’s self-assembly has also been studied. The fibrillar
structures of the supramolecular hydrogels have been characterized by scanning electron microscopy
(SEM). The thermal properties of the hydrogels formed by urea linked glycolipids have been studied by
differential scanning calorimetry (DSC) and VT-NMR. Molecular packing has been studied by small angle
(SAXS) and single crystal X-ray diffraction methods.
Received 25th April 2013,
Accepted 29th May 2013
DOI: 10.1039/c3ra42041h
www.rsc.org/advances
tures using non-covalent interactions such as hydrogen bonds
and hydrophobic and van der Waals interactions. The
Introduction
Glycolipids are biocompatible and biodegradable and can be
synthesized from renewable resources.1 These compounds are
widely used as detergents, personal care products, pharma-
ceuticals and agrochemicals.2 They are also used in food and
cosmetic industries due to their relatively low toxicity.
Moreover, non-ionic glycolipid surfactants are employed in
the extraction of biological membrane proteins.3 Glycolipids
produced by fermentation4 have antioxidant, antimicrobial
and antiviral activities and cell-differentiating or fibrinolytic
effects.5 Glycolipids have also been considered as ligands for
targeted drug delivery and are used extensively to modify the
surface properties of colloids such as liposomes and lipid
nanoparticles in order to favor interactions with specific cells
and tissues.6 They are also used as low-molecular-weight
gelators7 which have attracted immense attention due to their
impact in the field of molecular self-assembly, smart materials
and controlled chemical release.8
dimensions and shape of the self-assembled structures formed
by the glycolipids depend on various factors such as the nature
of the head group, lipid chain length, presence of double
bonds and their position in the lipid moiety, and linkage
between sugar and lipid.7,9 Common linkages between the
sugar and lipid chain in most of the literature reports are of
ether, ester, amide, amine and urea type.4b,10 Linkers between
the sugar and lipid were also introduced in order to improve
the self-assembly properties (e.g. aromatic rings and amino
acids).8b,11 These linkers can facilitate the self assembly by
enabling non-covalent interactions such as p–p stacking,
hydrogen bonding and hydrophobic interactions. In the
present work, we report the synthesis and characterization of
glycolipids with thiourea- and urea-linkages (Fig. 1), which
differ in their hydrogen bonding ability. The gelation proper-
ties of the synthesized glycolipids have been studied in various
solvents. The formed hydrogels were characterized by SEM,
DSC, NMR and small angle X-ray diffraction (SAXS).
Glycolipids are amphiphilic molecules that contain a polar
sugar head group and a nonpolar alkyl chain, which are able to
self-assemble into well-defined and stable macroscopic struc-
aDepartment of Chemistry, Indian Institute of Technology Madras, Chennai 600036,
India. E-mail: mathi24@gmail.com; Fax: 091-44-22574202; Tel: 091-44-22575221
bSophisticated Analytical Instrumentation Facility, Indian Institute of Technology
Madras, Chennai 600036, India
Electronic supplementary information (ESI) available: Additional SEM images,
3
DSC graphs, X-ray refinement statistics, 1H and 13C-NMR spectra. CCDC 924326.
For ESI and crystallographic data in CIF or other electronic format see DOI:
10.1039/c3ra42041h
Fig. 1 Structure of the designed thiourea- and urea-linked glycolipids.
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{ Deceased on February 9, 2013.
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Scheme 2 Synthesis of thiourea- and urea-linked glycolipids. a) H2, Pd/C, dry
DCM, rt; b) CH3(CH2)nNCS (n = 8 or 12), DCM, 48 h (or) CH3(CH2)7NCO, DCM, 0.5
h; c) NaOMe, dry MeOH, 0 uC, 4 h.
around 7.5 ppm, and urea protons appeared at around 5.0
ppm as a triplet, along with other sugar protons. In the 13C-
NMR spectrum, per-O-acetylated thiourea linked glycolipids
(21–33) showed broad peaks at around 183.0 ppm correspond-
ing to a thiocarbonyl group (CLS). The methylene carbons
attached to NH groups also showed a broad peak at 48.0–44.5
ppm. In the case of per-O-acetylated urea linked glycolipids
(34–43), a urea carbonyl peak appeared at around 158.5 ppm,
and methylene carbons attached to the urea NH appeared at
44.1–40.5 ppm.
Scheme 1 Synthesis of per-O-acetylated N-(glycosyl)azidoacetamides (11–20).
a) H2, Pd/C, dry DCM, rt; b) (ClCH2CO)2O, DCM, 0 uC, 92–95%; c) NaN3, acetone–
H2O (2 : 1), 70 uC, 94–98%.
Results and discussion
To synthesize the target glycolipids, per-O-acetylated N-(b-D-
glycosyl)azidoacetamides (11–20) were chosen as key inter-
mediates. These azidoacetamides (11–20) were synthesized
from the respective per-O-acetylated glycosyl azides (1–10)12
following the procedure developed in our laboratory
(Scheme 1).13 Hitherto unknown D-arabinopyranosyl (17), L-
arabinopyranosyl (18) and maltosyl (20) azidoacetamides were
fully characterized. The thiourea linked glycolipid was initially
planned to be prepared from an isothiocyanatoacetamido
derivative of the sugar. Accordingly, the per-O-acetylated N-b-D-
(glucopyranosyl)azidoacetamide (11) was reduced to the
corresponding aminoacetamide followed by reaction with
thiophosgene in the presence of calcium carbonate.14 This
reaction, however, did not give the expected isothiocyanato
derivative. Therefore, another methodology was followed
wherein the aminoacetamide obtained from azidoacetamide
(11) was reacted with octyl isothiocyanate to give per-
O-acetylated glucolipid 21 in quantitative yield. The above
methodology was extended to other azidoacetamides (12–20).
The aminoacetamides obtained from the respective azidoace-
tamides (12–20) were reacted with alkyl isothiocyanate (octyl
and dodecyl) or octylisocyanate in dry dichloromethane
(Scheme 2) to give the respective thiourea- (22–33) and urea-
(34–43) linked glycolipids.
All the per-O-acetylated glycolipids (21–43) were de-
O-acetylated using catalytic amounts of sodium methoxide in
dry methanol to give the target glycolipids (44–65) in good to
excellent yield (Table 1). In the case of L-rhamnolipid (26), de-
O-acetylation gave a mixture of products. Complete de-
O-acetylation of urea-linked glycolipids (34–43) led to the
formation of gel in the reaction mixture, which was dissolved
by adding chloroform. De-O-acetylated thiourea (44–55) and
urea (56–65) linked glycolipids were also fully characterized.
The gelation ability of the thiourea-linked glycolipids
GlcTUC8 (44), GlcTUC12 (45) and urea-linked glycolipid
GlcUC8 (56) was examined in ten different solvents (Table 2).
A weighed amount of glycolipid was transferred into a sealed
glass vial in 1 mL of solvent and heated until dissolved
completely. The solution was allowed to cool to room
temperature, and formation of the gel was examined by an
inverse flow method. The thiourea-linked glycolipid GlcTUC8
did not form a gel in any of the solvents whereas GlcTUC12
formed a hydrogel (Fig. 2) after 12 h. The minimum amount of
gelator required for the formation of a stable gel (minimum
gelator concentration) was found to be 5 mg mL21 (0.5% w/v).
In the case of the urea-linked glycolipid GlcUC8, gelation
occurred in various solvents including water (hydrogel, Fig. 2),
dioxane, methanol and isopropanol (organogel) while cooling
to room temperature. The minimum gelator concentration was
found to be 5 mg mL21 (0.5% w/v) for the hydrogel, 10 mg
mL21 (1.0% w/v) for dioxane and 30 mg mL21 (3.0% w/v) for
methanol and isopropanol.
All the compounds were characterized by 1H and 13C NMR,
as well as HR-MS. Per-O-acetylated thiourea- (21–33) and urea-
(34–43) linked glycolipids showed characteristic N–H proton
signals in the 1H-NMR spectra. Thiourea-linked glycolipids
(21–33) showed a doublet at around 7.0 ppm corresponding to
an amide proton, and two broad singlets around 6.5 and 6.2
ppm corresponding to thiourea protons. In the case of urea
linked glycolipids (34–43), an amide proton signal appeared at
Hydrogel formation of other thiourea- (46–55, Fig. 2) and
urea- (57–65, Fig. 3) linked glycolipids was performed at a
concentration of 0.5% w/v (5 mg mL21). Glycolipids XylTUC8
and D-AraTUC8 formed gels after 12 h, whereas in the case of
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Table 1 List of synthesized thiourea and urea-linked glycolipids
Thiourea-linked glycolipid
Urea-linked glycolipid
Product
S. No
Glycosyl azidoacetamide
Product
Yield (%)a
Yield (%)a
1
2
3
4
5
6
7
8
11
11
12
13
14
15
16
17
18
19
19
20
20
44 (GlcTUC8)
45 (GlcTUC12)
46 (GalTUC8)
47 (ManTUC8)
48 (GlcNAcTUC8)
—
49 (XylTUC8)
50 (D-AraTUC8)
51 (L-AraTUC8)
52 (LacTUC8)
53 (LacTUC12)
54 (MaltTUC8)
55 (MaltTUC12)
80
82
90
87
75
—
86
88
87
90
89
92
91
56 (GlcUC8)
—
96
—
95
97
96
70
95
94
98
98
—
97
—
57 (GalUC8)
58 (ManUC8)
59 (GlcNAcUC8)
60 (L-RhaUC8)
61 (XylUC8)
62 (D-AraUC8)
63 (L-AraUC8)
64 (LacUC8)
—
9
10
11
12
13
65 (MaltUC8)
—
a
Starting from azidoacetamides.
maltosyl derivatives MaltTUC8 and MaltTUC12 gels formed
after 5 days of incubation. Glycolipids GalTUC8, ManTUC8
and L-AraTUC8 were completely soluble at room temperature.
The lactosyl glycolipids LacTUC8 and LacTUC12 formed
colloids.
All the monosaccharide-derived urea-linked glycolipids (56–
63) showed hydrogelation ability, which was found to be
thermally reversible in nature, retaining their gelation ability
for several cycles of repeated heating and cooling. Gel–sol
transitions were studied in a temperature controlled water
bath at up to 100 uC. For GlcUC8 and GalUC8, gel–sol
transitions were observed at 64 uC and 68 uC, respectively. For
L-RhaUC8 and XylUC8 transitions were observed at around
The thermal reversibility of the gels was confirmed by
repeated heating and cooling. The gel formed by GlcTUC12
was stable for several weeks and found to be the most stable
among the thiourea linked glycolipids. Gels formed by
XylTUC8, MaltTUC8 and MaltTUC12 were stable for more
than two weeks whereas in the case of D-AraTUC8, the gel
collapsed after four days. The N-acetylglucosamine-derived
glycolipid GlcNAcTUC8 precipitated during the cooling pro-
cess. This could be due to the C2-acetamido group which may
not favor the molecular self assembly. The difference in color
of the thiourea-linked glycolipid hydrogels could be attributed
to the difference in their anion complexation with the thiourea
moiety. Thiourea derivatives are well-known anion receptors
for selective recognition of hydrophilic anions based on their
hydrogen bonding.15
Fig. 2 Gel images of thiourea-linked glycolipids (44–55) in water at a
concentration of 0.5 wt% (5 mg mL21).
Table 2 Gelation studies of glycolipids 44, 45 and 56
S. No Solvent
44 (GlcTUC8) 45 (GlcTUC12) 56 (GlcUC8)
1
2
3
4
5
6
7
8
9
10
Water
S
I
I
P
P
P
S
S
S
S
Ga
I
I
P
P
P
S
S
S
S
Ga
I
I
I
I
Acetonitrile
Ethyl acetate
Chloroform
Toluene
Acetone
Tetrahydrofuran
Dioxane
I
I
Gb
Gc
Gc
Methanol
Isopropanol
a
b
c
0.5 wt% (5 mg mL21). 1 wt% (10 mg mL21). 3 wt% (30 mg
mL21) S = Soluble, I = Insoluble, P = Precipitate, G = Gel.
Fig. 3 Gel images of urea linked-glycolipids (56–65) in water at a concentration
of 0.5 wt% (5 mg mL21).
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85 uC. ManUC8, D-AraUC8 and L-AraUC8 were stable up to
100 uC. The stability of the hydrogel depends on the type of
sugar head group. Gels formed by glycolipids GlcUC8 and
GalUC8 are stable for more than six months, whereas gels
formed by glycolipids ManUC8, D-AraUC8 and L-AraUC8 were
found to be stable for one month. The stability of these
glycolipids increases at higher concentration (1 wt%). Gels
from L-RhaUC8, and XylUC8 collapsed after 24 h. In the case of
the N-acetylglucosamine-derived glycolipid GlcNAcUC8,
a
white opaque hydrogel was formed at around 60–70 uC but
collapsed while cooling to room temperature. Glycolipids with
a disaccharide head group (64 and 65) did not form any gel.
Lactose derived glycolipid LacUC8 precipitated while cooling
to room temperature, whereas maltose-derived glycolipid
MaltUC8 was completely soluble at room temperature.
In general, urea-linked glycolipids (56–65) formed more
stable hydrogels compared to thiourea-linked glycolipids (44–
55). The hydrogen bonds among amide groups as well as
linker groups such as thiourea and urea could facilitate
parallel packing of lipid molecules. The orientation of the
hydroxyl group and conformation of the pyranose ring also
play a significant role in the solubility of the glycolipids and
stability of the gels. Monosaccharide-derived glycolipids may
pack in parallel in their self-assembled structure, and formed
Fig. 4 HR-SEM images of freeze-dried thiourea-linked glycolipids (0.5 wt% in
water) a) 44 (GlcTUC8) b) 45 (GlcTUC12) c) 52 (LacTUC8) d) 53 (LacTUC12).
of deformed fibres (Fig. 4a), and the dodecyl derived
glycolipid, GlcTUC12 formed 3D fibrous networks with widths
of 50 to 200 nm (Fig. 4b). Lactosyl glycolipid LacTUC8 formed
uniform nanofibers with a width of 150 nm and length of
several micrometers (Fig. 4c), but the corresponding dodecyl
derivative LacTUC12 showed a ribbon structure of 930 nm to
1.30 mm width and a few micrometers length as well as
bundles of thin flakes (Fig. 4d). The different morphologies
formed by thiourea-linked glycolipids show the influence of
hydrophilic sugar head groups as well as hydrophobic alkyl
stable gels (Fig. S1a, ESI ). In the case of disaccharide-derived
3
glycolipids, in addition to the above factors, interglycosidic
linkage also influences the molecular self-assembly. In lactose-
derived glycolipids, b(1–4) interglycosidic linkage can facilitate
parallel packing of glycolipids (Fig. S1b, ESI ). This parallel
3
molecular packing was also observed in the crystal structure of
lactosyl acetamide.16 Highly water soluble disaccharide head
group and short lipid chain length led to the formation of
colloids in thiourea-linked lactosyl lipids LacTUC8 and
LacTUC12, and precipitate in urea-linked lactosyl lipid,
LacUC8. In the case of maltose, a(1–4) interglycosidic linkage
is known for its anti-parallel (Fig. S1c, ESI ) packing in the
3
crystal structure,17 which could lead to loose packing as
compared to b(1–4) linkage. This loose packing might be
responsible for slow and less stable gel formation in MaltTUC8
and MaltTUC12 and complete solubility in MaltUC8.
The self-assembled structure of the thiourea and urea-
linked glycolipids was studied by scanning electron micro-
scopy (SEM), which revealed the typical fibrillar network that
characterizes supramolecular gels. In order to understand the
effect of sugar head group size and alkyl chain length on
supramolecular self-assembly, thiourea-linked glycolipids
GlcTUC8, GlcTUC12, LacTUC8 and LacTUC12 were inspected
by SEM. Air-dried specimens of these glycolipids aggregated to
lumps. As a consequence, SEM images of the GlcTUC12
xerogel and the drop casted specimens of GlcTUC8, LacTUC8
and LacTUC12 revealed the formation of a multilayer structure
(Fig. S2, ESI ). In order to avoid aggregation, specimens were
3
prepared by freeze-drying the gels, and colloids were formed
by the above glycolipids. These specimens revealed the
formation of different organizational networks of varying
morphologies. The glycolipid GlcTUC8 showed the formation
Fig. 5 HR-SEM images of the hydrogelator (urea-linked glycolipids, 0.5% wt)
xerogels a) 56 (GlcUC8) b) 57 (GalUC8) c) 58 (ManUC8) d) 62 (D-AraUC8).
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Fig. 6 Differential scanning calorimetry in a nitrogen atmosphere (2 cycles heating scan, 10 uC m21) a) 56 (GlcUC8) b) 57 GalUC8.
chain length. In the case of urea-linked glycolipids, stable
hydrogels (56–58 and 62) were chosen for morphological
studies. A xerogel of glycolipids GlcUC8, GalUC8, ManUC8 and
D-AraUC8 showed that the conformation of the hydroxyl
groups in the sugar influences the self-assembly resulting in
different organizational networks of varying morphologies.
SEM images of the xerogel of GlcUC8 showed a 3-D network of
fibers and ribbons with a width of 500 nm to 1 mm (Fig. 5a).
Glycolipid GalUC8 formed a network of ribbons with a width
of y200 nm to several micrometers (Fig. 5b). The glycolipid
bearing a mannose head group, ManUC8, also showed fiber
formation (Fig. 5c), but it was not well-organized like other
hexoses (glucose and galactose). The morphology of the
glycolipid D-AraUC8 (Fig. 5d) was found to be similar to that
of ManUC8.
The thermal transition of gels formed by glycolipids
GlcUC8, GalUC8, ManUC8, D-AraUC8 and L-AraUC8 at 0.5
wt% was studied by DSC (10 uC min21). Glycolipid GlcUC8
showed an endotherm at 64 uC due to gel–sol transition, and
no thermal peak in the cooling scan, but in the second cycle,
an endotherm was observed in the same region. This showed
the thermal reversibility of the above gel (Fig. 6a). In the case
of glycolipid GalUC8, two endotherms were observed at 68.3 uC
and 71.8 uC (10 uC min21) but they were absent in the second
cycle (Fig. 6b). Reduction of the heating rate to 5 uC min21
gave endotherms at 61.6 and 68.2 uC during heating and
exotherms at 47.6 and 44.3 uC during cooling, but the above
thermal peaks were absent in the second cycle (Fig. S3, ESI ).
3
These thermal peaks reappeared when DSC analysis was
performed after 24 h of incubation at room temperature. The
two endotherms could be due to the formation of two different
phases in their gel state which requires more time to reform.
In the case of ManUC8, D-AraUC8 and L-AraUC8, no
endotherm was observed at up to 100 uC (Fig. S4, ESI ), and
3
a broad peak observed for ManUC8 (85 uC) and D-AraUC8 (95
uC) (first thermal cycle) was due to free water (outside the gel
network) evaporation. They were absent in the second and
third cycle. These glycolipids were thermally more stable as
compared to GlcUC8 and GalUC8.
Fig. 8 Experimental SAXS pattern of 56 (GlcUC8), 57 (GalUC8), 58 (ManUC8),
61 (XylUC8) and 62 (D-AraUC8).
Fig. 7 Temperature-dependent 1H-NMR of 56 (GlcUC8) (0.5 wt% in D2O).
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Fig. 9 Proposed packing model for urea linked glycolipids a) 56 (GlcUC8), b) 57 (GalUC8), c) 58 (ManUC8), d) 61 (XylUC8) and e) 62 (D-AraUC8).
The thermal reversibility of glucolipid GlcUC8 was also
studied by variable temperature NMR (Fig. 7). At room
temperature, the 1H-NMR spectrum showed broad low
intensity peaks, but the intensity of the peaks gradually
double the length of a single molecule (4.26 nm). Thus, the
thickness of this bilayer is affected by the inclination of the
alkyl chain and the packing of the sugar moieties, as shown in
Fig. 9a. The presence of periodic reflection peaks and their
relative peak positions (2h value) q1 : q2 : q3 (1 : 2 : 3) is a
characteristic of the Bragg diffraction pattern from the 1D
lamellar structure. Galactolipid GalUC8 had a diffraction peak
at 3.8 nm. This could be due to the tilted molecular packing in
the self-assembled structure (Fig. 9b). Moreover, the galacto-
lipid did not show any periodicity in peak positions.
Glycolipids ManUC8, XylUC8 and D-AraUC8 had diffraction
peaks at 4.8, 4.6 and 4.0 nm, respectively. These spacings are
longer than double their molecular lengths. Thus, these
molecules packed without inclination in their bilayers
(Fig. 9c–9e). Like glucolipid GlcUC8, ManUC8 and XylUC8
showed the characteristics of a 1D lamellar structure, whereas
arabinolipid D-AraUC8 showed similarity in its diffraction
pattern compared to that of galactolipid GalUC8.
In spite of the difficulties in crystallizing the amphiphilic
systems in general, we have successfully solved the crystal
structure of GlcUC8. It was crystallized from water by a slow
evaporation method, and the structure has been solved in the
space group C2. The asymmetric unit contains two molecules
of glucolipid, designated A and B, along with 4.5 molecules of
water (Fig. 10). Molecules A and B differ in their conformation
and molecular assembly. The pyranose ring adopts a 4C1
conformation. Double pillar hydrogen bonds formed by a urea
group, which facilitates the stacking of the molecule one over
another (Fig. 10). With respect to the urea linked octyl chain,
the amide-linked sugar moiety is tilted by 18.9u and 21.5u in
molecules A and B, respectively, and forms a bent structure.
The bent structure could be stabilized by an intense network of
hydrogen bonds in the sugar head group as well as by an
inclined urea-linked octyl chain in the molecular packing. The
hydrogen bonds between sugar hydroxyl groups and water
molecules are responsible for trapping large quantities of
water in their self-assembled structure. This molecule has a
1-D lamellar structural arrangement with a bilayer thickness of
3.27 nm, which agreed with the SAXS pattern (Fig. 11).
increased with the temperature and
a highly resolved
spectrum with intense peaks was observed at 65 uC. The
maximum intensity observed was due to gel–sol transition and
the transition temperature (65 uC) matches the DSC
endotherm (64 uC). A downfield shift in the chemical shift
values of the sugar as well as the alkyl chain protons was
observed with increasing temperature, which indicates dis-
turbances in their molecular self-assembly. At low tempera-
ture, formation of the gel leads to definite molecular packing
(supramolecular), whereas at higher temperature, molecules
are isolated (sol state). During heating, the steric environment
of protons in supramolecular arrangement gets disturbed by
breaking noncovalent interactions such as hydrogen bonds
and van der Waals interactions, which leads to shifts in NMR
signals. The reverse 1H-NMR patterns observed during the
cooling process also showed the thermal reversibility of the
gel-sol transition.
X-Ray powder diffraction (SAXS) analysis of a xerogel of
urea-linked glycolipids GlcUC8, GalUC8, ManUC8, XylUC8 and
D-AraUC8 also showed that the sugar head group affects the
molecular packing (Fig. 8). The xerogel of glucolipid GlcUC8
had a strong diffraction peak at 3.3 nm which is shorter than
Fig. 10 Molecules in the asymmetric unit and hydrogen bonding.
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Experimental section
Materials and methods
Thin-layer chromatograms were performed on 25 mm E.
Merck silica gel plates (60F-254). Detection was done by
spraying the plates with 10% sulfuric acid in ethanol and
heating on a hot plate. Optical rotations were measured at 30
uC on a JASCO-DIP 200 digital polarimeter using a cell of 10
mm length. NMR spectra were recorded on a Bruker AV400
spectrometer. IR spectra were recorded using a JASCO FT-IR-
4100 spectrometer. ESI-MS spectra were measured on a
Micromass Q-Tof mass spectrometer. The samples for SEM
imaging were coated with Au–Pd (Gatan precision etching
coating system (model no. 682) operating at 5 keV) and
analysed with a FEI Quanta FEG 200 High Resolution Scanning
Electron Microscope operating at 10–30 kV. DSC analyses were
done on a Q 200M DSC (10 uC min21, 25 to 110 uC) under a N2
atmosphere. Powder X-ray diffraction patterns were recorded
on a BRUKER D8-Advance diffractometer using CuKa radia-
tion (l = 1.5418 Å) over the range of 0.5u , 2q , 15u with 0.05u
increments at RT.
Fig. 11 1-D lamellar structural arrangement in 56 (GlcUC8).
Conclusions
Crystal structure solution and refinement
Glycolipids containing various sugar head groups with
thiourea and urea linker groups have been designed and
synthesized in good to excellent yields. The synthetic approach
to thiourea- and urea-linked glycolipids is based on the
reaction of per-O-acetyled N-(glycosyl)aminoacetamides with
alkyl isothiocyanates (octyl and dodecyl) or octyl isocyanate.
The gelation of the synthesized glycolipids was determined in
various solvents with different polarities, and these glycolipids
were found to be excellent hydrogelators. In the case of the
linker group (thiourea and urea), urea-linked glycolipids
formed more stable gels compared to thiourea-linked glycoli-
pids. The different structures observed in the SEM images
showed that apart from the linker group, the conformation of
the hydroxyl group in the sugar, and the length of the lipid
chain also significantly influence the self-assembling nature of
the neoglycolipids. A DSC study of urea-linked glycolipids
showed that the thermal stability of the hydrogel is influenced
by the orientation of hydroxyl groups and the conformation of
the pyranose ring. A variable temperature 1H-NMR study of
urea-linked glucolipids demonstrated the thermal reversibility
of the hydrogel. The SAXS diffraction peak of the xerogel of
urea-linked glycolipids also confirmed the effect of the sugar
on their molecular packing. The crystal structure of the urea-
linked glucolipid was solved, and its molecular packing
analysis showed that the linker urea group is involved in
molecular stacking.
Single crystals of compound 56 (GlcUC8) were obtained from
water at room temperature by the slow evaporation method.
X-ray data collection was performed with a Bruker AXS Kappa
Apex II CCD diffractometer equipped with graphite mono-
chromated Mo (Ka) (l = 0.7107 Å) radiation. The crystal fixed at
the tip of the glass fibre was mounted on the goniometer head
with the aid of a video microscope. The automatic cell
determination routine, with 32 frames at three different
orientations of the detector was employed to collect reflec-
tions, and the program APEX2-SAINT18 was used for finding
the unit cell parameters. Four-fold redundancy per reflection
was utilized for achieving a good absorption correction using a
multi-scan procedure. Besides absorption correction, Lorentz
polarization and decay correction were applied during data
reduction. The program SADABS19 was used for absorption
correction using a multi-scan procedure. The structures were
solved by direct methods using SIR92 (WinGX) and refined by
full-matrix least squares techniques using SHELXL-9720
computer programs. All hydrogen atoms except the nitrogen
hydrogen were fixed at chemically meaningful positions and a
riding model refinement was applied. The nitrogen hydrogen
was located through the difference Fourier map and refined
with isotropic thermal parameters. Molecular graphics were
drawn using the Mercury programs (3.0).21 The relevant details
of data collection and refinement are given in Table S1 in the
ESI, and the complete structural data of 56 (CCDC 924326) are
The present study showed that the nature of the linker
group is the major driving force for the molecular self-
assembly of glycolipids. The nature of the sugar head group
and alkyl chain length also significantly influence the
structure and stability of the hydrogels. The neoglycolipids
synthesized could be used as templates for preparing
nanoparticles. These neoglycolipids are also attractive candi-
dates for controlled drug delivery.
also available.
3
General procedure for the synthesis of per-O-acetylated N-
(glycosyl)azidoacetamides (11–20)
Glycosyl azidoacetamides (11–20) were synthesized by follow-
ing the literature procedure.12 Hitherto unknown D-arabino-
pyranosyl (17), L-arabinopyranosyl (18) and maltosyl (20)
azidoacetamides synthesized in the present study were fully
characterized using physical and spectral methods.
14534 | RSC Adv., 2013, 3, 14528–14542
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isothiocyanate/octyl isocyanate to afford the thiourea (21–33)
and urea-linked (34–43) glycolipids in quantitative yield.
1-N-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-N99-(n-octyl)-
thioureidoacetamide (21). White solid; m.p.: 129–131 uC; [a]3D0:
4.8u (c = 1.0, CHCl3); IR (KBr, cm21): 3436, 3073, 2927, 2859,
1756, 1752, 1748, 1671, 1551, 1425, 1373, 1228, 1043, 912, 608;
1H-NMR (400 MHz, CDCl3) d (ppm): 7.08 (d, 1H, J = 8.4 Hz,
NH), 6.48, (br s, 1H, NH), 6.30 (br s, 1H, NH), 5.33 (t, 1H, J = 9.6
Hz, H-3), 5.26 (t, 1H, J = 9.2 Hz, H-1), 5.09 (t, 1H, J = 9.6 Hz,
H-4), 4.97 (t, 1H, J = 9.6 Hz, H-2), 4.35–4.20 (m, 3H), 4.11 (dd,
1H, J = 2.0 & 12.4 Hz, H-6b), 3.89–3.82 (m,1H, H-5), 3.35 (br s,
2H), 2.09, 2.08, 2.03, 2.02 (4s, 12H, 4 6 –OCOCH3), 1.65–1.54
(m, 2H), 1.44–1.22 (m, 10 H), 0.88 (t, 3H, 6.8 Hz, –CH3); 13C-
NMR (100 MHz, CDCl3) d (ppm): 182.8 (CS), 171.1, 170.8,
170.0, 169.6 (5 6 CO), 78.4 (C-1), 73.7 (C-5), 73.0 (C-3), 70.4 (C-
2), 68.3 (C-4), 61.8 (C-6), 48.1 (–COCH2NH–), 44.6, 31.9, 29.3,
29.3, 29.0, 27.0, 22.7, 22.7, 20.9, 20.8, 20.6, 14.1 (–CH3); ESI-MS
(m/z): calcd for C25H42N3O10S: 576.2591 ([M + H]+), found:
576.2599.
N-(2,3,4-Tri-O-acetyl-a-D-arabinopyranosyl)azidoacetamide
(17). Yield = 95%; white solid; m.p.: 161–162 uC; [a]3D0 265.1 (c
1.0, CHCl3); IR (KBr, cm21): 3439, 3332, 3296, 3071, 2956,
2927, 2856, 1751, 1732, 1666, 1555, 1521, 1443, 1417, 1370,
1245, 1226, 1174, 1143, 1091, 1046, 987, 971, 912, 687, 676,
1
607, 551; H-NMR (400 MHz, CDCl3) d (ppm): 7.23 (d, 1H, J =
8.4 Hz, NH), 5.36–5.32 (m, 1H, H-4), 5.22–5.09 (m, 3H), 4.04–
3.92 (m, 3H), 3.79 (dd, 1H, J = 1.2 & 13.2 Hz, H-5b), 2.16, 2.08,
2.04 (3s, 9H, 3 6 –OCOCH3); 13C-NMR (100 MHz, CDCl3) d
(ppm): 171.3, 170.2, 169.9, 167.6 (4 6 CO), 78.9 (C-1), 70.5,
68.5, 68.1, 65.9, 52.7, 21.0, 20.8, 20.7 (3 6 –OCOCH3); ESI-MS
(m/z): calcd for C13H19N4O8: 359.1203 ([M + H]+), found:
359.1219.
N-(2,3,4-Tri-O-acetyl-a-L-arabinopyranosyl)azidoacetamide
(18). Yield = 98%; white solid; m.p.: 161–163 uC; [a]3D0: 55.1u (c =
1.0, CHCl3); IR (KBr, cm21): 3439, 3332, 3296, 3071, 2956,
2927, 2856, 1751, 1732, 1666, 1555, 1521, 1443, 1417, 1370,
1245, 1226, 1174, 1143, 1091, 1046, 987, 971, 912, 687, 676,
1
607, 551; H-NMR (400 MHz, CDCl3) d (ppm): 7.23 (d, 1H, J =
1-N-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-N99-(n-dode-
cyl)-thioureidoacetamide (22). White solid; m.p.: 84–86 uC;
[a]3D0: 14.1u (c = 1.0, CHCl3); IR (KBr, cm21): 3439, 3332, 3073,
2926, 2855, 1752, 1731, 1666, 1557, 1521, 1446, 1418, 1371,
1341, 1247, 1226, 1113, 1089, 1045, 986, 969, 913, 722, 686,
669, 665, 618, 585; 1H-NMR (400 MHz, CDCl3) d (ppm): 7.16 (d,
1H, NH), 6.59, (br s, 1H, NH), 6.39 (br s, 1H, NH), 5.33 (t, 1H, J
= 9.6 Hz, H-3), 5.28 (t, 1H, J = 9.2 Hz, H-1), 5.09 (t, 1H, H-4),
4.98 (t, 1H, H-2), 4.35–4.17 (m, 3H), 4.12 (dd, 1H, J = 2.0 & 12.4
Hz, H-6b), 3.92–3.82 (m, 1H, H-5), 3.37 (br s, 2H), 2.08, 2.08,
2.03, 2.02 (4s, 12H, 4 6 –OCOCH3), 1.63–1.54 (m, 2H), 1.44–
1.22 (m, 18 H), 0.88 (t, 3H, –CH3); 13C-NMR (100 MHz, CDCl3) d
(ppm): 182.8 (CS), 170.9, 170.7, 170.0, 169.52 (5 6 CO), 78.1 (C-
1), 73.5, 72.0, 70.3, 68.2, 61.7 (C-6), 47.9(–COCH2NH–), 44.6,
31.9, 29.6, 29.6, 29.3, 28.9, 27.0, 22.6, 20.9, 20.7, 20.5, 14.1
(–CH3); ESI-MS (m/z): calcd for C29H50N3O10S: 632.3217 ([M +
H]+), found: 632.3211.
1-N-(2,3,4,6-Tetra-O-acetyl-b-D-galactopyranosyl)-N99-(n-
octyl)-thioureidoacetamide (23). White solid; m.p.: 44–46 uC;
[a]3D0: 13.6u (c = 1.0, CHCl3); IR (KBr, cm21): 3469, 3463, 3352,
3068, 2953, 2927, 2857, 2362, 2340, 1751, 1700, 1549, 1459,
1436, 1371, 1227, 1168, 1121, 1083, 1052, 955, 909, 714, 675,
653, 600, 549; 1H-NMR (400 MHz, CDCl3) d (ppm): 6.89 (d, 1H,
J = 8.8 Hz, NH), 6.43 (br s, 1H, NH), 6.27 (br s, 1H, NH), 5.45 (d,
1H, J = 2.4 Hz, H-4), 5.24 (t, 1H, J = 8.8 Hz, H-1), 5.21–5.11 (m,
2H, H-2 & H-3), 4.33 (dd, 1H, J = 5.0 & 17.6 Hz, H-6a), 4.29–4.19
(m, 1H, H-6b), 4.17–4.04 (m, 3H, H-5, –COCH2NH–), 3.35 (br s,
2H, –CONHCH2–), 2.16, 2.09, 2.05, 2.00 (4s, 12H, 4 6
–OCOCH3), 1.63–1.55 (m, 2H), 1.43–1.20 (m, 10 H), 0.88 (t,
3H, J = 6.8 Hz, –CH3); 13C-NMR (100 MHz, CDCl3) d (ppm):
182.8 (CS), 171.2, 170.5, 170.2, 170.1 (4 6 CO), 78.5 (C-1), 72.3,
70.9, 67.9, 67.2, 61.1, 47.8, 44.9, 31.7, 29.3, 29.2, 28.9, 26.9,
22.6, 21.0, 20.7, 20.6, 20.6, 14.1 (–CH3); ESI-MS (m/z): calcd for
C25H42N3O10S: 576.2591 ([M + H]+), found: 576.2590.
8.4 Hz, NH), 5.36–5.32 (m, 1H, H-4), 5.22–5.09 (m, 3H), 4.04–
3.92 (m, 3H), 3.79 (dd, 1H, J = 1.2 & 13.2 Hz, H-5b), 2.16, 2.08,
2.04 (3s, 9H, 3 6–OCOCH3); 13C-NMR (100 MHz, CDCl3) d
(ppm): 171.3, 170.2, 169.9, 167.6 (4 6 CO), 78.9 (C-1), 70.5,
68.5, 68.1, 65.9, 52.7, 21.0, 20.8, 20.7 (3 6 –OCOCH3); ESI-MS
(m/z): calcd for C13H19N4O8: 359.1203 ([M + H]+), found:
359.1204.
N-[4-O-(29,39,49,69-Tetra-O-acetyl-a-D-glucopyranosyl)-2,3,6-
tri-O-acetyl-b-D-glucopyranosyl]azidoacetamide (20). Yield =
94%; white solid; m.p.: 154–156 uC; [a]3D0: 65.7u (c = 1.0,
CHCl3); IR (KBr, cm21): 3468, 3354, 2956, 2116, 1749, 1695,
1528, 1524, 1433, 1373, 1369, 1237, 1132, 1042, 939, 904, 645,
605, 554, 487; 1H-NMR (400 MHz, CDCl3) d (ppm): 6.97 (d, 1H,
J = 9.2 Hz, NH), 5.49–5.32 (m, 3H), 5.25 (t, 1H, J = 9.6 Hz, H-1),
5.06 (t, 1H, H-4), 4.93–4.77 (m, 2H), 4.45 (d, 1H, J = 10.4 Hz),
4.29–4.18 (m 2H), 4.09–3.90 (m, 5H), 3.86–3.77 (m, 1H), 2.18,
2.14, 2.10, 2.07, 2.03, 2.03, 2.0 (6 6 s, 21H, 7 6 –OCOCH3);
13C-NMR (100 MHz, CDCl3) d (ppm): 171.7, 170.7, 170.6, 170.5,
169.9, 169.7, 169.5, 167.4 (8 6 CO), 95.7 (C-19), 77.7 (C-1), 76.8,
74.9, 74.2, 72.7, 71.2, 70.1, 69.4, 68.7, 62.7, 61.5, 52.6, 20.9,
20.9, 20.7, 20.7; ESI-MS (m/z): calcd for C28H39N4O18: 719.2252
([M + H]+), found: 719.2252.
General procedure for the synthesis of fully acetylated 1-N-
(glycopyranosyl)-N99-(n-alkyl)-thioureido/ureidoacetamide (21–
43)
In a 100 mL RB flask, per-O-acetylated N-(glycosyl)azidoaceta-
mide (11–20) (0.5 mmol) was dissolved in dry dichloromethane
(2 mL). To this solution, palladium on activated carbon (25
mg) was added, and the reaction mixture was stirred
vigorously under a hydrogen atmosphere. After complete
disappearance of the azide based on TLC, the alkyl isothio-
cyanate/octyl isocyanate (0.55 mmol) was added. The resulting
solution was vigorously stirred, and the progress of the
reaction was monitored by TLC. After completion of the
reaction (y48 h for thiourea and 30 min for urea), the
resulting mixture was filtered through a celite bed and
concentrated to dryness. The crude solid obtained was
triturated with hexane (5 6 5 mL) to remove the excess alkyl
1-N-(2,3,4,6-Tetra-O-acetyl-b-D-mannopyranosyl)-N99-(n-
octyl)-thioureidoacetamide (24). White solid; m.p.: 61–63 uC;
[a]3D0: 243.9u (c = 1.0, CHCl3); IR (KBr, cm21): 3558, 3482, 3356,
3055, 2929, 2856, 1752, 1693, 1540, 1435, 1371, 1229, 1105,
1055, 966, 907, 674, 656, 645, 599, 560, 515; 1H-NMR (400
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MHz, CDCl3) d (ppm): 7.65 (d, 1H, J = 9.2 Hz, NH), 6.54, (br s,
1H, NH), 6.23 (br s, 1H, NH), 5.55 (d, 1H, J = 9.2 Hz, H-1), 5.38–
5.35 (m, 1H, H-2), 5.24 (t, 1H, H-4), 5.15 (dd, 1H, J = 3.2, 10.4
Hz, H-3), 4.40 (dd, 1H, –COCH2NH–), 4.28 (dd, J = 5.2 & 12.4
Hz, H-6a), 4.20 (dd, 1H, –COCH2NH–), 4.07 (dd, J = 2.0 & 12.4
Hz, H-6b), 3.84–3.77 (m, 1H, H-5), 3.34 (br s, 2H, –CONHCH2–),
2.25, 2.10, 2.05, 1.98 (4s, 12H, 4 6 –OCOCH3), 1.63–1.54 (m,
2H), 1.40–1.22 (m, 10 H), 0.88 (t, 3H, J = 7.2 Hz, –CH3); 13C-NMR
(100 MHz, CDCl3) d (ppm): 182.4 (CS), 171.3, 171.0, 170.8, 170.6,
170.0 (5 6 CO), 76.1 (C-1), 73.8, 71.7, 69.4, 65.3, 62.3 (C-6), 48.1,
45.1, 31.8, 29.3, 29.2, 29.1, 27.0, 22.7, 21.2, 20.9, 20.8, 14.2
(–CH3); ESI-MS (m/z): calcd for C25H42N3O10S: 576.2591 ([M +
H]+), found: 576.2595.
1-N-(2-Deoxy-2-acetamido-3,4,6-tri-O-acetyl-b-D-glucopyrano-
syl)-N99-(n-dodecyl)thioureidoacetamide (25). White solid;
m.p.: 134–136 uC; [a]D30: 24u (c = 1.0, CHCl3); IR (KBr , cm21):
3444, 3394, 3322, 3067, 2927, 2856, 1748, 1664, 1547, 1436,
1375, 1242, 1114, 1046, 963, 907, 680, 669, 665, 647, 680, 669,
665, 647, 602, 558, 546, 509; 1H-NMR (400 MHz, CDCl3) d
(ppm): 7.73 (d, 1H, J = 8.0 Hz, NH), 6.75, (br s, 3H, NH), 5.28
(br s, 1H, H-1), 5.25 (t, 1H, J = 9.6 Hz, H-3), 5.10 (t, 1H, H-4),
4.50–4.05 (m, 5 H, H-2, H-6a, H-6b & –COCH2NH–), 3.91–3.80
(m, H-5), 3.43 (br s, 2H, –CONHCH2–), 2.09, 2.07, 2.04, 1.97 (4s,
12H, 3 6 –OCOCH3 & –NHCOCH3), 1.65–1.54 (m, 2H), 1.44–
1.22 (m, 10 H), 0.88 (t, 3H, –CH3); 13C-NMR (100 MHz, CDCl3) d
(ppm): 183.3 (CS), 172.3, 171.6, 171.1, 170.8, 169.4 (5 6 CO),
79.8 (C-1), 73.7, 73.4, 68.7, 62.2 (C-6), 53.4, 48.1, 44.8, 31.9,
29.4, 29.3, 29.2, 27.1, 23.3, 22.7, 20.8, 20.6, 14.1 (–CH3); ESI-MS
(m/z): calcd for C25H43N4O9S: 575.2751 ([M + H]+), found:
575.2752.
1-N-(2,3,4-Tri-O-acetyl-a-L-rhamnopyranosyl)-N99-(n-octyl)-
thioureidoacetamide (26). White solid; m.p.: 41–43 uC; [a]3D0:
10.9u (c = 1.0, CHCl3); IR (KBr, cm21): 3470, 3339, 3069, 2927,
2857, 1748, 1691, 1550, 1439, 1371, 1250, 127, 1167, 1088,
1054, 1025, 961, 944, 910, 875, 743, 722, 672, 655, 602, 540,
502; 1H-NMR (400 MHz, CDCl3) d (ppm): 7.72 (d, 1H, J = 9.2 Hz,
NH), 6.76, (br s, 1H, NH), 6.38 (br s, 1H, NH), 5.52 (d, 1H, J =
9.2 Hz, H-1), 5.36 (d, J = 3.2 Hz, H-2), 5.13 (d, 1H, J = 10 Hz,
H-3), 5.03 (t, 1H, J = 10 Hz, H-4), 4.45–4.17 (m, 2H, –CH2NH),
3.68 (m, 1H, H-5), 3.37 (br s, 2H, –NHCH2), 2.25, 2.06, 2.00, (3s,
9H, 3 6 –OCOCH3), 1.63–1.55 (m, 2H), 1.40–1.20 (m, 13 H),
0.88 (t, 3H, J = 6.8 Hz, –CH3); 13C-NMR (100 MHz, CDCl3) d
(ppm): 182.6 (CS), 170.7, 169.9 (3 6 CO), 75.9 (C-1), 72.1, 71.6,
70.2, 69.7, 48.1, 44.7, 31.8, 29.6, 29.2, 28.9, 26.9, 22.6, 21.1,
20.7, 17.5, 14.0 (–CH3); ESI-MS (m/z): calcd for C23H40N3O8S:
518.2536 ([M + H]+), found: 518.2531.
1-N-(2,3,4-Tri-O-acetyl-b-D-xylopyranosyl)-N99-(n-octyl)-thiour-
eidoacetamide (27). White solid; m.p.: 57–59 uC; [a]3D0: 2.5u (c =
1.0, CHCl3); IR (KBr, cm21): 3463, 3408, 3347, 3062, 2954,
2925, 2855, 1747, 1697, 1546, 1532, 1464, 1420, 1371, 1312,
1249, 1227, 1152, 1104, 1071, 1036, 984, 938, 904, 872, 767,
729, 701, 657, 604, 549, 530; 1H-NMR (400 MHz, CDCl3) d
(ppm): 7.14 (d, 1H, J = 8.8 Hz, NH), 6.54, (br s, 1H, NH), 6.34
(br s, 1H, NH), 5.32 (t, 1H, J = 9.2 Hz, H-3), 5.17 (t, 1H, J = 9.2
Hz, H-1), 5.05–4.95 (m, 1H, H-4), 4.92 (t, 1H, J = 9.2 Hz, H-2),
4.35–4.18 (m, 2H, –COCH2NH–), 4.09 (dd, J = 6.0 & 11.2 Hz,
H-5a), 3.46 (t, 1H, J = 11.2 Hz, H-5b), 3.36 (br s, 2H, –
CONHCH2–), 2.08, 2.05, 2.04, (3s, 9H, 3 6 –OCOCH3), 1.63–
1.55 (m, 2H), 1.40–1.20 (m, 10 H), 0.88 (t, 3H, J = 6.8, –CH3);
13C-NMR (100 MHz, CDCl3) d (ppm): 182.9 (CS), 1.71.4, 170.9,
169.9, 169.9 (4 6 CO), 78.6 (C-1), 72.5, 70.3, 68.9, 64.3 (C-5),
47.8, 44.7, 31.7, 29.6, 29.2, 28.9, 26.9, 22.5, 20.8, 20.6, 20.5, 14.0
(–CH3); ESI-MS (m/z): calcd for C22H37N3O8SNa: 526.2199 ([M +
Na]+). found: 576.2187.
1-N-(2,3,4-Tri-O-acetyl-a-D-arabinopyranosyl)-N99-(n-octyl)-
thioureidoacetamide (28). White solid; m.p.: 51–53 uC; [a]3D0:
252.4u (c = 1.0, CHCl3); IR (KBr, cm21): 3344, 3070, 2928, 2857,
2179, 2111, 1748, 1688, 1550, 1436, 1372, 1250, 1227, 1168,
1087, 1053, 1025, 944, 909, 875, 741, 721, 675, 656, 601, 540,
501; 1H-NMR (400 MHz, CDCl3) d (ppm): 7.08 (d, 1H, J = 8.8 Hz,
NH), 6.64, (br s, 1H, NH), 6.45 (br s, 1H, NH), 5.34 (s, 1H, H-4),
5.31–5.19 (m, 3H), 4.35–4.15 (m, 2H, –COCH2NH–), 3.99 (d,
1H, H-5a), 3.83 (d, 1H, H-5b), 3.38 (br s, 2H, –CONHCH2–),
2.16, 2.10, 2.03, (3s, 9H, 3 6 –OCOCH3), 1.64–1.54 (m, 2H),
1.42–1.22 (m, 10 H), 0.88 (t, 3H, –CH3); 13C-NMR (100 MHz,
CDCl3) d (ppm): 182.7 (CS), 171.0, 170.2, 170.1 (4 6 CO), 78.8
(C-1), 76.8, 70.6, 68.2, 68.1, 65.8 (C-5), 47.8, 45.0, 31.7, 29.2,
29.1, 28.9, 26.9, 22.5, 20.9, 20.7, 20.5, 14.0 (–CH3); ESI-MS (m/
z): calcd for C22H37N3O8SNa: 526.2199 ([M + Na]+). found:
526.2197.
1-N-(2,3,4-Tri-O-acetyl-a-L-arabinopyranosyl)-N99-(n-octyl)-
thioureidoacetamide (29). White solid; m.p.: 51–53 uC; [a]3D0:
33.4u (c = 1.1, CHCl3); IR (KBr, cm21): 3460, 3343, 3071, 2928,
2857, 1748, 1689, 1549, 1436, 1372, 1249, 1227, 1168, 1088,
1053, 1025, 944, 910, 875, 742, 721, 673, 656, 601, 502; 1H-NMR
(400 MHz, CDCl3) d (ppm): 7.03 (d, 1H, NH), 6.50 (br s, 1H,
NH), 6.33 (br s, 1H, NH), 5.34 (s, 1H, H-4), 5.29–5.11 (m, 3H),
4.37–4.18 (m, 2H, Hz, –COCH2NH–), 3.99 (dd, 1H, J = 2.0 & 13.2
Hz, H-5a), 3.83 (d, 1H, J = 13.2 Hz, H-5b), 3.36 (br s, 2H,
–CONHCH2–), 2.16, 2.10, 2.03, (3s, 9H, 3 6 –OCOCH3), 1.64–
1.54 (m, 2H), 1.42–1.22 (m, 10 H), 0.88 (t, 3H, J = 6.4 Hz, –CH3);
13C-NMR (100 MHz, CDCl3) d (ppm): 182.5 (CS), 171.3, 170.3,
170.2, 170.0 (4 6 CO), 78.9 (C-1), 70.7, 68.3, 68.1, 65.9 (C-5),
47.9, 45.1, 31.8, 29.3, 29.2, 28.9, 27.0, 22.6, 21.0, 21.0, 20.7, 14.1
(–CH3); ESI-MS (m/z): calcd for C22H37N3O8SNa: 526.2199 ([M +
Na]+), found: 576.2198.
1-N-[4-O-(29,39,49,69-Tetra-O-acetyl-b-D-galactopyranosyl)-
2,3,6-tri-O-acetyl-b-D-glucopyranosyl]-N99-(n-octyl)-thioureidoa-
cetamide (30). White solid; m.p.: 146–148 uC; [a]3D0: 21.7u (c =
1.0, CHCl3); IR (KBr, cm21): 3465, 3366, 3068, 2928, 2857,
1752, 1548, 1436, 1372, 1231, 1172, 1132, 1051, 985, 954, 906,
717, 646, 603, 548, 505; 1H-NMR (400 MHz, CDCl3) d (ppm):
6.99 (br s, 1H, NH), 6.43 (br s, 1H, NH), 6.25 (br s, 1H, NH),
5.36 (d, 1H, J = 2.8 Hz, H-4), 5.30 (t, 1H, J = 9.2 Hz, H-3), 5.20 (t,
1H, J = 9.2 Hz, H-1), 5.10 (m, 1H, H-29), 4.96 (dd, 1H, H-39), 4.86
(t, 1H, H-2), 4.55–4.40 (m, 2H, H-19 & H-6a), 4.39–4.04 (m, 5H,
–COCH2NH–, H-5, H-6b & H-69a), 3.94–3.70 (m, 3H, H-4, H-5 &
H-69b), 3.34 (br s, 2H, –CONHCH2–), 2.16, 2.13, 2.07, 2.06, 2.05,
2.04, 1.97 (7s, 21H, 7 6 OCOCH3), 1.67–1.55 (m, 2H), 1.43–
1.22 (m, 10 H), 0.88 (t, 3H, –CH3); 13C-NMR (100 MHz, CDCl3) d
(ppm): 182.4 (CS), 170.8, 170.4, 170.3, 170.1, 170.0, 169.5, 169.1
(8 6 CO), 100.7 (C-19), 77.7 (C-1), 75.7, 74.4, 72.8, 70.9, 70.5,
69.0, 66.7, 61.9 60.7, 47.7, 44.6, 31.6, 29.5, 29.1, 29.1, 26.8, 22.5,
20.8, 20.7, 20.6, 20.5, 20.4, 13.9 (–CH3); ESI-MS (m/z): calcd for
C
37H57N3O18SNa: 886.3256 ([M + Na]+), found: 886.3254.
14536 | RSC Adv., 2013, 3, 14528–14542
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1-N-[4-O-(29,39,49,69-Tetra-O-acetyl-b-D-galactopyranosyl)-
2,3,6-tri-O-acetyl-b-D-glucopyranosyl]-N99-(n-dodecyl)-thiourei-
doacetamide (31). White solid; m.p.: 71–73 uC; [a]3D0: 0.8u (c =
1.0, CHCl3); IR (KBr, cm21): 3469, 3367, 2926, 2855, 1751,
1549, 1435, 1372, 1232, 1171, 1135, 1052, 946, 907, 603; 1H-
NMR (400 MHz, CDCl3) d (ppm): 7.15 (d, 1H, J = 8.8 Hz, NH),
6.59, (br s, 1H, NH), 6.37 (br s, 1H, NH), 5.36 (d, 1H, J = 2.8 Hz,
H-49), 5.30 (t, 1H, J = 9.2 Hz, H-3), 5.21 (t, 1H, J = 9.2 Hz, H-1),
5.10 (dd, 1H, H-29), 4.91 (dd, 1H, J = 3.6 & 10.4 Hz, H-39), 4.88
(t, 1H, H-2), 4.55–4.40 (m, 2H, H-19 & H-69a), 4.37–4.20 (m, 2H,
–COCH2NH), 4.20–4.02 (m, 3H, H-6a, H-59, H-69b), 4.00–3.70
(m, 3H, H-5, H-6b, H-4), 3.36 (br s, 2H, –CONHCH2), 2.16, 2.13,
2.07, 2.06, 2.05, 1.97, 1.94 (7s, 21H, 7 6 –OCOCH3), 1.65–1.55
(m, 2H), 1.41–1.20 (m, 18 H), 0.88 (t, 3H, J = 6.8 Hz, –CH3); 13C-
NMR (100 MHz, CDCl3) d (ppm): 181.3 (CS), 171.1, 170.6,
170.4, 170.2, 170.2, 169.9, 169.2 (7 6 CO), 100.9 (C-19), 77.9 (C-
1), 75.8, 74.6, 72.7, 71.0, 70.6, 70.6, 69.1, 66.7, 61.9, 60.8, 47.9,
44.7, 31.9, 29.6, 29.3, 28.9, 27.0, 22.7, 21.0, 20.9, 20.8, 20.7,
20.5, 14.1; ESI-MS (m/z): calcd for C41H66N3O18S: 920.4062 ([M
+ H]+), found: 920.4070.
1-N-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-N99-(n-octyl)-
ureidoacetamide (34). White solid; m.p.: 92–93 uC; [a]3D0: 10.1u
(c = 1.1, CHCl3); IR (KBr, cm21): 3369, 3133, 3057, 3020, 2927,
2856, 1752, 1687, 1641, 1570, 1521, 1461, 1435, 1373, 1232,
1
1143, 1042, 984, 909, 644, 603, 562, 527; H-NMR (400 MHz,
CDCl3) d (ppm): 7.18 (d, 1H, J = 8.8 Hz, NH), 5.31 (t, 1H, J = 9.6
Hz, H-3), 5.24 (t, 1H, J = 9.2 Hz, H-1), 5.07 (t, 1H, J = 9.6 Hz,
H-4), 5.00–4.90 (m, 2H, H-2 & –CH2NH–), 4.61 (t, 1H, J = 5.4 Hz,
–NHCH2–), 4.30 (dd, 1H, J = 4.2 & 12.6 Hz, H-6a), 4.09 (dd, 1H, J
= 1.8 & 12.6 Hz, H-6b), 3.93–3.76 (m, 2H, H-5, –COCH2NH–),
3.17 (q, 2H, –CONHCH2–), 2.08, 2.06, 2.03, 2.02 (4s, 12H, 4 6
–OCOCH3), 1.57–1.44 (m, 2H), 1.44–1.22 (m, 10 H), 0.88 (t, 3H,
J = 6.8 Hz, –CH3); 13C-NMR (100 MHz, CDCl3) d (ppm): 171.9,
170.7, 170.6, 170.0, 169.5 (5 6 CO), 158.6 (–NHCONH–), 77.8
(C-1), 73.4, 73.1, 70.3, 68.2, 61.7 (C-6), 44.1 (–COCH2NH–), 40.4,
31.8, 30.2, 29.4, 29.3, 27.0, 22.6, 20.7, 20.6, 14.0 (–CH3); ESI-MS
(m/z): calcd for C25H41N3O11ONa: 582.2639 ([M + Na]+), found:
582.2618.
1-N-(2,3,4,6-Tetra-O-acetyl-b-D-galactopyranosyl)-N99-(n-
octyl)-ureidoacetamide (35). White solid; m.p.: 64–66 uC; [a]3D0:
21.3u (c = 1.0, CHCl3); IR (KBr, cm21): 3395, 2934, 2864, 2805,
2728, 1756, 1599, 1351, 1228, 1085, 767; 1H-NMR (400 MHz,
CDCl3) d (ppm): 7.25 (d, 1H, J = 9.2 Hz, NH), 5.44 (d, 1H, J = 1.6
Hz, H-4), 5.31–5.09 (m, 4H, H-1, H-2, H-3 & –COCH2NH–), 4.78
(t, 1H, J = 5.6 Hz, –CONHCH2–), 4.23–4.03 (m, 3H, H-5, H-6a &
H-6b), 3.87 (d, 2H, J = 5.6 Hz, –COCH2NH–), 3.26–3.11 (m, 2H,
–CONHCH2–), 2.16, 2.07, 2.04, 2.00 (4s, 12H, 4 6 –OCOCH3),
1.60–1.46 (m, 2H), 1.40–1.20 (m, 10 H), 0.88 (t, 3H, J = 6.8 Hz, –
CH3); 13C-NMR (100 MHz, CDCl3) d (ppm): 171.8, 170.9, 170.5,
170.2, 170.1 (5 6 CO), 158.6 (–NHCONH–), 78.3 (C-1), 72.2,
71.1, 68.0, 67.3, 61.1 (C-6), 44.1(–COCH2NH–), 40.5, 31.8, 30.2,
29.4, 29.3, 27.0, 22.6, 20.7, 20.6, 14.1(–CH3); ESI-MS (m/z):
calcd for C25H42N3O11: 560.2819 ([M + H]+), found: 560.2815.
1-N-(2,3,4,6-Tetra-O-acetyl-b-D-mannopyranosyl)-N99-(n-
octyl)-ureidoacetamide (36). White solid; m.p.: 134–136 uC;
[a]3D0: 241.4u (c = 1.0, CHCl3); IR (KBr, cm21): 3406, 2934, 2857,
2812, 2717, 1749, 1599, 1354, 1228, 1057, 764, 599; 1H-NMR
(400 MHz, CDCl3) d (ppm): 8.12 (d, 1H, J = 9.2 Hz, NH), 5.87 (br
s, 1H, –COCH2NH–), 5.53 (d, 1H, J = 9.2 Hz, H-1), 5.42–5.16 (m,
3H, H-2, H-3 & H-4), 5.01 (br s, 1H, NH), 4.29 (dd, 1H, J = 4.8 &
12.4 Hz, H-6a), 4.10 (dd, 1H, J = 2.0 & 12.4 Hz, H-6b), 3.93 (dd,
1H, J = 5.6 & 16.0 Hz, –COCH2NH), 3.89–3.82 (m, 1H, H-5), 3.93
(dd, 1H, J = 5.6 & 16.0 Hz, –COCH2NH), 3.23–3.12 (m, 2H,
–CONHCH2–), 2.24, 2.10, 2.05, 1.98 (4s, 12H, 4 6 –OCOCH3),
1.35–1.42 (m, 2H), 1.38–1.20 (m, 10 H), 0.88 (t, 3H, J = 6.8 Hz,
–CH3); 13C-NMR (100 MHz, CDCl3) d (ppm): 171.0, 170.8,
170.5, 169.7, (5 6 CO), 159.0 (–NHCONH–), 76.0 (C-1), 73.6,
71.8, 69.4, 65.5, 62.5 (C-6), 44.5, 40.4, 31.8, 30.2, 29.4, 29.3,
27.0, 22.7, 20.9, 20.8, 20.7, 14.1 (–CH3); ESI-MS (m/z): calcd for
C25H42N3O11: 560.2819 ([M + H]+), found: 560.2816.
1-N-[4-O-(29,39,49,69-Tetra-O-acetyl-a-D-glucopyranosyl)-2,3,6-
tri-O-acetyl-b-D-glucopyranosyl]-N99-(n-octyl)-thioureidoaceta-
mide (32). White solid; m.p.: 74–76 uC; [a]3D0: 39.9u (c = 1.0,
CHCl3); IR (KBr, cm21): 3363, 2929, 2858, 1752, 1545, 1434,
1
1372, 1234, 1165, 1132, 1043, 940, 902, 647, 605, 552, 517; H-
NMR (400 MHz, CDCl3) d (ppm): 6.92 (d, 1H, J = 8.8 Hz, NH),
6.35, (br s, 1H, NH), 6.17 (br s, 1H, NH), 5.44–5.32 (m, 3H, H-3,
H-19 & H-39), 5.26 (t, 1H, J = 9.2 Hz, H-1), 5.06 (t, 1H, H-49), 4.86
(dd, 1H, J = 3.8, 10.6 Hz, H-29), 4.81 (t, 1H, H-2), 4.47 (d, 1H, J =
11.6 Hz, H-6a), 4.33–4.16 (m, 4H, H-6b, H-69a & –COCH2NH–),
4.12–3.90 (m, 3H, H-4, H-59 & H-69b), 3.85–3.76 (m, 1H, H-5),
3.33 (br s, 2H, –CONHCH2–), 2.14, 2.10, 2.06, 2.04, 2.03, 2.01
(6s, 21H, 7 6 –OCOCH3), 1.66–1.56 (m, 2H), 1.40–1.22 (m, 10
H), 0.88 (t, 3H, –CH3); 13C-NMR (100 MHz, CDCl3) d (ppm):
181.3 (CS), 171.1, 171.0, 170.7, 170.6, 170.2, 169.9, 169.5 (8 6
CO), 95.6 (C-19), 77.7(C-1), 75.3, 74.0, 72.5, 71.0, 70.1, 69.3,
68.5, 68.0, 62.6, 61.4, 48.0, 44.7, 31.8, 29.2, 29.2, 26.9, 22.6,
20.9, 20.8, 20.7, 20.6, 14.1 (–CH3); ESI-MS (m/z): calcd for
C37H57N3O18SNa: 886.3256 ([M + Na]+), found: 886.3226.
1-N-[4-O-(29,39,49,69-Tetra-O-acetyl-a-D-glucopyranosyl)-2,3,6-
tri-O-acetyl-b-D-glucopyranosyl]-N99-(n-dodecyl)-thioureidoace-
tamide (33). White solid; m.p.: 69–71 uC; [a]3D0: 52.8u (c = 1.0,
CHCl3); IR (KBr, cm21): 3480, 3358, 3065, 2927, 2855, 1752,
1700, 1547, 1436, 1371, 1233, 1168, 1132, 1042, 938, 901, 647,
1
604, 553; H-NMR (400 MHz, CDCl3) d (ppm): 6.99 (d, 1H, J =
9.2 Hz, NH), 6.46, (br s, 1H, NH), 6.24 (br s, 1H, NH), 5.44–5.32
(m, 3H, H-3, H-19 & H-39), 5.27 (t, 1H, J = 9.2 Hz, H-1), 5.07 (t,
1H, H-49), 4.86 (dd, 1H, J = 4.0 & 10.8 Hz, H-29), 4.81 (t, 1H,
H-2), 4.48 (dd, 1H, J = 2.0 & 12.4 Hz, H-6a), 4.33–4.16 (m, 4H,
H-69a, H-69b & –COCH2NH), 4.12–3.90 (m, 3H, H-4, H-59 &
H-69b), 3.85–3.76 (m, 1H, H-5), 3.34 (br s, 2H, –CONHCH2–),
2.17, 2.14, 2.10, 2.06, 2.04, 2.03, 2.01 (7s, 21H, 7 6 –OCOCH3),
1.66–1.56 (m, 2H), 1.40–1.22 (m, 18 H), 0.88 (t, 3H, –CH3); 13C-
NMR (100 MHz, CDCl3) d (ppm): 182.5 (CS), 170.8, 170.5,
169.9, 169.8, 169.4 (7 6 CO), 95.5 (C-19), 75.3 (C-1), 72.6, 70.9,
70.0, 69.2, 68.4, 67.9, 62.6, 61.4, 47.8, 44.4, 31.8, 29.5, 29.2,
28.8, 26.8, 22.5, 20.7, 20.5, 20.4, 14.0 (–CH3); ESI-MS (m/z):
calcd for C41H66N3O18S: 920.4062 ([M + H]+), found: 920.4055.
1-N-(2-Deoxy-2-acetamido-3,4,6-tri-O-acetyl-b-D-glucopyrano-
syl)-N99-(n-octyl)-ureidoacetamide (37). White solid; m.p.: 202–
203 uC; [a]3D0: 7.1u (c = 1.1, MeOH); IR (KBr, cm21): 3324, 2931,
1749, 1658, 1592, 1374, 1238, 1048, 607; 1H-NMR (400 MHz,
CD3OD + CDCl3) d (ppm): 7.86 (d, 1H, J = 8.4 Hz, NH), 7.62 (d,
1H, J = 9.2 Hz, NH), 5.15 (t, 1H, J = 9.8 Hz, H-3), 5.08–5.03 (m,
2H, H-1 & H-4), 4.27 (dd, 1H, J = 4.4 & 12.4 Hz, H-6a), 4.17–4.05
(m, 2H, H-2 & H-6b), 3.88 & 3.71 (ABq, 2H, –COCH2NH), 3.86–
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3.78 (m, 1H, H-5), 3.19–3.00 (m, 2H, –CONHCH2–), 2.08, 2.04,
2.03, 1.92 (4s, 12H, 4 6 –OCOCH3), 1.53–1.44 (m, 2H), 1.36–
1.22 (m, 10 H), 0.88 (t, 3H, J = 6.8 Hz, –CH3); 13C-NMR (100
MHz, CD3OD) d (ppm): 172.5, 172.4, 171.0, 171.0, 169.7 (5 6
CO), 158.6 (–NHCONH–), 78.9 (C-1), 73.3, 73.1, 68.4, 62.0 (C-6),
52.5, 43.6, 40.2, 31.8, 30.0, 29.3, 29.2, 26.9, 22.6, 22.6, 20.6,
20.6, 20.5, 14.0 (–CH3); ESI-MS (m/z): calcd for C25H43N4O10O:
559.2979 ([M + H]+), found: 559.2978.
1-N-(2,3,4-Tri-O-acetyl-a-L-rhamnopyranosyl)-N99-(n-octyl)-
ureidoacetamide (38). White solid; m.p.: 92–94 uC; [a]3D0: 4.6u (c
= 1.0, CHCl3); IR (KBr, cm21): 3406, 2934, 2809, 2724, 2025,
1753, 1599, 1379, 1351, 1228, 1057, 764, 607; 1H-NMR (400
MHz, CDCl3) d (ppm): 7.98 (d, 1H, J = 9.2 Hz, NH), 5.74 (br s,
1H, –COCH2NH–), 5.47 (d, 1H, J = 9.2 Hz, H-1), 5.35 (br s, 1H,
H-3), 5.12 (dd, 1H, J = 3.2 & 10.4 Hz, H-2), 5.09–4.96 (m, 2H,
NH, H-4), 3.89 (dd, 1H, J = 5.2 &, 16.4 Hz, –COCH2NH–), 3.80–
3.62 (m, 2H, H-5 & –COCH2NH–), 3.25–3.22 (m, –CONHCH2–),
2.23, 2.06, 1.98 (3s, 9H, 3 6 –OCOCH3), 1.55–1.41 (m, 2H),
1.38–1.20 (m, 13 H), 0.88 (t, 3H, J = 6.4 Hz, –CH3); 13C-NMR
(100 MHz, CDCl3) d (ppm): 171.1, 170.9, 170.5, 170.1 (4 6 CO),
159.0 (–NHCONH–), 75.9 (C-1), 72.1, 71.7, 70.4, 69.8, 44.5, 40.6,
31.9, 30.2, 29.4, 29.3, 27.0, 22.7, 20.9, 20.9, 20.8, 17.6,
14.1(–CH3); ESI-MS (m/z): calcd for C23H40N3O9: 502.2765
([M + H]+), found: 502.2762.
1-N-(2,3,4-Tri-O-acetyl-b-D-xylopyranosyl)-N99-(n-octyl)-urei-
doacetamide (39). White solid; m.p.: 119–121 uC; [a]3D0: 213.6u
(c = 1.0, CHCl3); IR (KBr, cm21): 3395, 2930, 2861, 2812, 2724,
1753, 1596, 1379, 1351, 1232, 1071, 1039, 764, 596; 1H-NMR
(400 MHz, CDCl3) d (ppm): 7.53 (d, 1H, J = 9.2 Hz, NH), 5.43 (br
s, 1H, –COCH2NH–), 5.31 (t, 1H, J = 9.6 Hz, H-3), 5.18 (t, 1H, J =
9.6 Hz, H-1), 5.08 (br s, 1H, –CONHCH2–), 5.03–4.90 (m, 2H,
H-2 & H-4), 4.09 & 4.07 (ABq, 1H, H-5a), 3.94–3.78 (m, 1H,
–COCH2NH–), 3.47 (t, 1H, J = 11 Hz, H-5b), 3.22–3.11 (m, 2H),
2.06, 2.05, 2.04 (3s, 3H, 3 6 –OCOCH3), 1.54–1.44 (m, 2H),
1.39–1.22 (m, 10 H), 0.88 (t, 3H, J = 6.4 Hz, –CH3); 13C-NMR
(100 MHz, CDCl3) d (ppm): 172.5, 170.8, 170.0, 169.9 (4 6 CO),
158.8 (–NHCONH–), 78.5 (C-1), 72.6, 70.4, 69.0, 64.4 (C-5), 44.2,
40.5, 31.8, 30.3, 29.4, 29.3, 27.0, 22.7, 20.7, 14.1 (–CH3); ESI-MS
(m/z): calcd for C22H38N3O9: 488.2608 ([M + H]+), found:
488.2629.
1-N-(2,3,4-Tri-O-acetyl-a-D-arabinopyranosyl)-N99-(n-octyl)-
ureidoacetamide (40). White solid; m.p.: 52–53 uC; [a]3D0: 259.5
(c = 1.1, CHCl3); IR (KBr, cm21): 3416, 2934, 2808, 2724, 1745,
1596, 1351, 1228, 1050, 764; 1H-NMR (400 MHz, CDCl3) d
(ppm): 7.32 (d, 1H, J = 7.6 Hz, NH), 5.33 (s, 1H), 5.40–5.12 (m,
4H, H-1, H-2, H-4 & –COCH2NH–), 4.86 (t, 1H, J = 5.2 Hz,
–CONHCH2–), 3.98 (dd, 1H, J = 2.4 & 13.6 Hz, H-5a), 3.94–3.77
(m, 3H, H-5b & –COCH2NH–), 3.25–3.13 (m, 2H, –CONHCH2–),
2.15, 2.07, 2.02 (3s, 9H, 3 6 –OCOCH3), 1.55–1.45 (m, 2H),
1.39–1.23 (m, 10 H), 0.88 (t, 3H, J = 6.8 Hz, –CH3); 13C-NMR
(100 MHz, CDCl3) d (ppm): 171.0, 170.8, 170.5, 169.4, (4 6
CO), 158.6 (–NHCONH–), 78.6 (C-1), 70.8, 68.3, 68.2, 65.8 (C-5),
44.0, 40.4, 31.7, 31.6, 30.2, 29.3, 26.9, 22.6, 20.8, 20.6, 20.5, 14.0
(–CH3); ESI-MS (m/z): calcd for C22H38N3O9: 488.2608 ([M +
H]+), found: 488.2608.
1749, 1596, 1375, 1351, 1225, 1092, 1054, 764, 606; 1H-NMR
(400 MHz, CDCl3) d (ppm): 7.12 (d, 1H, J = 7.6 Hz, NH), 5.33 (s,
1H), 5.20–5.10 (m, 3H, H-1, H-2 & H-4), 4.98 (t, 1H, J = 5.2 Hz,
–COCH2NH–), 4.64 (t, 1H, J = 5.2 Hz, –CONHCH2–), 3.98 (dd,
1H, J = 2.4 & 13.2 Hz, H-5a), 3.93–3.92 (m, 3H, H-5b &
–COCH2NH–), 3.22–3.14 (m, 2H, –CONHCH2–), 2.15, 2.07, 2.02
(3s, 9H, 3 6 –OCOCH3), 1.55–1.45 (m, 2H), 1.38–1.22 (m, 10
H), 0.88 (t, 3H, J = 6.8 Hz, –CH3); 13C-NMR (100 MHz, CDCl3) d
(ppm): 172.1, 171.0, 170.3, 170.1, (4 6 CO), 158.5 (–NHCONH–),
78.7 (C-1), 70.8, 68.4, 68.2, 65.9 (C-5), 44.1, 40.5, 31.8, 30.2, 29.4,
29.3, 24.0, 22.7, 20.9, 20.7, 20.7, 14.1 (–CH3); ESI-MS (m/z): calcd
for C22H38N3O9: 488.2608 ([M + H]+), found: 488.2591.
N-[4-O-(29,39,49,69-Tetra-O-acetyl-b-D-galactopyranosyl)-2,3,6-
tri-O-acetyl-b-D-glucopyranosyl]-N99-(n-octyl)-ureidoacetamide
(42). White solid; m.p.: 131–133 uC; [a]3D0: 225.7u (c = 1.0,
CHCl3); IR (KBr, cm21): 3403, 2934, 2808, 2721, 2025, 1749,
1595, 1351, 1235, 1057, 764; 1H-NMR (400 MHz, CDCl3) d
(ppm): 7.25 (d, 1H, J = 9.2 Hz, NH), 5.36 (d, J = 3.2 Hz, H-49),
5.29 (t, 1H, J = 9.2 Hz, H-3), 5.12 (t, 1H, J = 9.6 Hz, H-1), 5.14–
5.04 (m, 2H, H-29 & –COCH2NH–), 4.95 (dd, 1H, J = 3.6 & 10.4
Hz, H-39), 4.87 (t, 1H, J = 9.6 Hz, H-2), 4.77 (br s, 1H, –
CONHCH2–), 4.50–4.40 (m, 2H, H-19 & H-6a), 4.18–4.04 (m, 3H,
H-5, H-6b & H-69a), 3.91–3.72 (m, 5H, H-59, H-69b, H-4 &
–CONHCH2–), 3.20–3.12 (m, 2H, –CONHCH2–), 2.16, 2.14,
2.07, 2.05, 2.04, 1.97, (6s, 21H, 7 6 –OCOCH3), 1.55–1.45 (m,
2H), 1.38–1.22 (m, 10 H), 0.88 (t, 3H, J = 6.8 Hz, –CH3); 13C-
NMR (100 MHz, CDCl3) d (ppm): 171.9, 170.7, 170.5, 170.4,
170.2, 170.2, 169.7, 169.1 (8 6 CO), 158.6 (–NHCONH–), 100.8
(C-19), 77.7 (C-1), 75.9, 74.5, 72.8, 71.0, 70.6, 69.0, 66.7, 62.0,
60.8, 44.0, 40.5, 31.8, 30.1, 29.3, 29.2, 26.9, 22.6. 20.8, 20.7,
20.6, 20.5, 14.0 (–CH3); ESI-MS (m/z): calcd for C37H58N3O19:
848.3665 ([M + H]+), found: 848.3657.
N-[4-O-(29,39,49,69-Tetra-O-acetyl-a-D-glucopyranosyl)-2,3,6-
tri-O-acetyl-b-D-glucopyranosyl]-N99-(n-octyl)-ureidoacetamide
(43). White solid; m.p.: 93–94 uC; [a]3D0: 25.1u (c = 1.0, CHCl3); IR
(KBr, cm21): 3392, 3065, 2928, 2857, 1752, 1680, 1648, 1554,
1436, 1372, 1235, 1170, 1132, 1043, 939, 901, 643, 604; 1H-NMR
(400 MHz, CDCl3) d (ppm): 7.12 (d, 1H, J = 8.8 Hz, NH), 5.47–
5.33 (m, 3H, H-3, H-19 & H-29), 5.29 (t, 1H, J = 9.6 Hz, H-1), 5.10
(t, 1H, J = 9.6 Hz, H-4), 4.96–4.87 (m, –COCH2NH– & H-39), 4.84
(t, J = 9.6 Hz, H-2), 4.57 (t, 1H, –CONHCH2–), 4.48 (d, 1H, J =
10.8, H-69a), 4.33–4.22 (m 2H, H-59 & H-6a), 4.13–3.92 (m, 3H,
H-5, H-6b, H-69b), 3.91–3.80 (m, 3H, H-49 & –COCH2NH–), 3.20
(q, 2H, –CONHCH2–), 2.18, 2.14, 2.10, 2.07, 2.06, 2.04 (6s, 21H,
7 6 –OCOCH3), 1.59–1.48 (m, 2H), 1.40–1.26 (m, 10H), 0.91 (t,
3H, J = 7.2 Hz, –CH3); 13C-NMR (100 MHz, CDCl3) d (ppm):
171.7, 170.8, 170.7, 170.0, 169.9, 169.6 (8 6 CO), 158.6
(–NHCONH–), 95.6 (C-19), 77.5 (C-1), 76.8, 75.5, 72.7, 71.1, 70.0,
69.3, 68.5, 68.0, 62.8, 61.5, 44.2, 40.6, 31.8, 30.2, 29.4, 29.3,
27.0, 22.7, 20.9, 20.9, 20.7, 20.6, 20.6, 14.1 (–CH3); ESI-MS (m/
z): calcd for C37H57N3O19Na: 870.3484 ([M + H]+), found:
870.3486.
General procedure for the synthesis of N-(b-glycopyranosyl)-
N99-(n-alkyl)-thioureido/ureidoacetamides (44–65)
1-N-(2,3,4-Tri-O-acetyl-a-L-arabinopyranosyl)-N99-(n-octyl)-
ureidoacetamide (41). White solid; m.p.: 52–53 uC; [a]3D0: 16.2u
(c = 1.0, CHCl3); IR (KBr, cm21): 3395, 2930, 2861, 32 812, 2721,
The per-O-acetylated 1-N-(glycopyranosyl)-N99-(n-alkyl)-thiour-
eido/ureidoacetamides (21–43, 0.5 mmol) were dissolved in dry
MeOH (5 mL) and cooled to 0 uC. To this solution, freshly
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prepared NaOMe (1 M, 0.5 mL) was added, and the mixture
was stirred for 2 h. The reaction mixture was then treated with
IR-120 cation-exchange resin. After filtration of the resin, the
filtrate was concentrated to give the product in good to
excellent yield.
3H, –CH3); 13C-NMR (100 MHz, CD3OD) d (ppm): 174.9, 173.3
(2 6 CO), 80.7 (C-1), 79.6, 75.9, 71.8, 62.6, 55.9, 48.4
(–COCH2NH–), 45.3, 32.9, 30.4, 30.3, 30.0, 23.7, 23.1, 14.4
(–CH3); ESI-MS (m/z): calcd for C19H36N4O6SNa: 471.2253 ([M +
Na]+), found: 471.2253.
1-N-(b-D-Glucopyranosyl)-N99-(n-octyl)-thioureidoacetamide
(44). Yellow solid; m.p.: 168 uC; [a]3D0: 14.1u (c = 1.2, DMF); IR
(KBr, cm21): 3409, 2924, 2855, 1668, 1558, 1461, 1417, 1361,
1315, 1261, 1080, 1042, 892, 616, 582; 1H-NMR (400 MHz, D2O)
d (ppm): 4.98 (d, 1H, J = 8.8 Hz, H-1), 4.30 (s, 2H, –COCH2NH–),
3.87 (d, 1H, J = 11.8 Hz, H-6a), 3.71 (dd, 1H, J = 4.8 & 11.8 Hz,
H6b), 3.64–3.25 (m, 6H), 1.60 (br s, 2H), 1.45–1.22 (m, 10 H),
0.88 (t, 3H, J = 6.8 Hz, –CH3); 13C-NMR (100 MHz, D2O +
CD3OD) d (ppm): 173.3 (CO), 80.7 (C1), 79.0, 78.0, 73.3, 70.7,
62.0 (C6), 48.0 (–COCH2NH–), 32.5, 29.9, 29.8, 27.5, 23.3, 14.3
(–CH3); ESI-MS (m/z): calcd for C17H34N3O6S: 408.2168 ([M +
H]+), found: 408.2176.
1-N-(b-D-Xylopyranosyl)-N99-(n-octyl)-thioureidoacetamide
(49). Yellow solid; m.p.: 130 uC; [a]3D0: 4.2u (c = 0.9, DMF); IR
(KBr, cm21): 3334, 3070, 2956, 2924, 2853, 2474, 2404, 1741,
1665, 1563, 1462, 1410, 1361, 1308, 1236, 1187, 1097, 1060,
974, 894, 722, 651, 581, 543, 516; 1H-NMR (400 MHz, CD3OD) d
(ppm): 4.84 (d, 1H), 4.34–4.19 (m, 2H, –COCH2NH), 3.83 (dd,
1H, J = 5.2 & 11.2 Hz, H-5a), 3.56–3.22 (m, 6H), 1.64–1.52 (m,
2H), 1.40–1.24 m, 10H), 0.90 (t, 3H, J = 6.8 Hz, –CH3); 13C-NMR
(100 MHz, CD3OD) d (ppm): 172.8 (CO), 81.8 (C-1), 78.6, 73.8,
71.1, 68.6 (C-5), 48.3, 45.7, 33.0, 30.4, 30.4, 30.0, 23.7, 14.4
(–CH3); ESI-MS (m/z): calcd for C16H32N3O5S: 378.2063
([M+H]+), found: 378.2051.
1-N-(b-D-Glucopyranosyl)-N99-(n-dodecyl)-thioureidoaceta-
mide (45). Yellow solid; m.p.: 175 uC; [a]3D0: 14.8u (c = 1.2, DMF);
IR (KBr, cm21): 3417, 2922, 2852, 2361, 2338, 2113, 1675, 1638,
1565, 1462, 1312, 1256, 1083, 1046, 720, 618, 586, 523, 418; 1H-
NMR (400 MHz, CD3OD) d (ppm): 4.87 (d, 1H, J = 8.8 Hz, H-1),
4.22 (s, 2H, –COCH2NH–), 3.84–3.17 (m, 8H), 1.62–1.47 (m,
2H), 1.38–1.15 (m, 18H), 0.84 (t, 3H, J = 6.8 Hz, CH3); 13C-NMR
(100 MHz, CD3OD) d (ppm): 172.9 (CO), 81.2 (C1), 79.7, 78.8,
74.1, 71.4, 62.7 (C6), 48.4, 33.1, 30.9, 30.8, 30.5, 30.2, 28.1, 23.7,
14.5 (–CH3); ESI-MS (m/z): calcd for C21H41N3O6NaS: 486.2614
([M + Na]+), found: 486.2617.
1-N-(a-D-Arabinopyranosyl)-N99-(n-octyl)-thioureidoaceta-
mide (50). Yellow solid; m.p.: 125 uC; [a]3D0: 21.3u (c = 1.0,
DMF); IR (KBr, cm21): 3395, 3081, 2955, 2926, 2856, 1685,
1555, 1457, 1376, 1249, 1146, 1088, 1012, 945, 917, 864, 779,
722, 705, 634, 620, 601, 584, 566, 544, 510; 1H-NMR (400 MHz,
CD3OD) d (ppm): 4.79 (H-1 hidden under HOD peak), 4.17 (s,
2H, –COCH2NH–), 3.84–3.26 (m, 7H), 1.55–1.43 (m, 2H), 1.30–
1.16 (m, 10 H), 0.80 (t, 3H, –CH3); 13C-NMR (100 MHz, CD3OD)
d (ppm): 172.9 (CO), 81.4 (C1), 74.6, 71.2, 69.6, 68.3, 57.1, 46.2,
32.9, 30.4, 30.3, 27.9, 23.6, 14.4 (–CH3); ESI-MS (m/z): calcd for
C16H31N3O5SNa: 400.1882 ([M + Na]+), found: 400.1882.
1-N-(a-L-Arabinopyranosyl)-N99-(n-octyl)-thioureidoaceta-
mide (51). Yellow solid; m.p.: 123 uC; [a]3D0: 18.0u (c = 1.0, DMF);
IR (KBr, cm21): 3337, 3078, 2956, 2925, 2855, 2461, 2416, 1670,
1558, 1456, 1414, 1360, 1250, 1147, 1088, 1012, 944, 862, 778,
1-N-(b-D-Galactopyranosyl)-N99-(n-octyl)-thioureidoaceta-
mide (46). Yellow solid; m.p.: 98 uC; [a]3D0: 15.2u (c = 1.2, DMF);
IR (KBr, cm21): 3354, 3083, 2956, 2926, 2856, 1677, 1560, 1459,
1440, 1415, 1375, 1246, 1084, 892, 871, 783, 760, 703, 675, 660,
1
1
617, 538; H-NMR (400 MHz, CD3OD) d (ppm): 4.90 (d, 1H, J =
719, 640, 618, 588, 538; H-NMR (400 MHz, CD3OD) d (ppm):
8.8 Hz, H-1), 4.39–4.20 (m, 2H, –COCH2NH–), 3.98–3.34 (m,
8H), 1.70–1.53 (m, 2H), 1.42–1.24 (m, 10 H), 0.73 (t, 3H, J = 7.2
Hz, –CH3); 13C-NMR (100 MHz, CD3OD) d (ppm): 173.0 (CO),
81.6 (C1), 78.3, 75.5, 71.3, 70.4, 62.6 (C6), 45.9, 43.4, 33.0, 30.4,
30.3, 30.2, 28.0, 23.7, 14.4 (–CH3); ESI-MS (m/z): calcd for
C17H34N3O6SNa: 430.1988 ([M + Na]+), found: 430.1971.
4.79 (H-1 hidden under HOD peak), 4.17 (s, 2H, –COCH2NH–),
3.82–3.24 (m, 7H), 1.54–1.42 (m, 2H), 1.30–1.15 (m, 10 H), 0.80
(t, 3H, –CH3); 13C-NMR (100 MHz, CD3OD) d (ppm): 172.9 (CO),
81.4 (C1), 74.6, 71.2, 69.6, 68.3 (C-5), 45.8, 32.9, 30.4, 30.3, 27.9,
23.6, 14.4 (–CH3); ESI-MS (m/z): calcd for C16H31N3O5SNa:
400.1882 ([M + Na]+), found: 400.1878.
1-N-(b-D-Mannopyranosyl)-N99-(n-octyl)-thioureidoacetamide
(47). Yellow solid; m.p.: 118 uC; [a]3D0: 5.2u (c = 0.9, DMF); IR
(KBr, cm21): 3359, 2955, 2926, 2855, 2472, 2423, 1734, 1670,
1557, 1456, 1363, 1307, 1236, 1147, 1115, 1080, 961, 904, 862,
790, 675, 663, 601, 581, 517; 1H-NMR (400 MHz, CD3OD) d
(ppm): 5.19 (s, 1H, H-1), 4.27 (s, 2H, –CH2NH), 3.90–2.37 (m,
8H), 1.64–1.53 (m, 2H), 1.42–1.24 (m, 10 H), 0.90 (t, 3H, J = 7.2
Hz, CH3); 13C-NMR (100 MHz, CD3OD) d (ppm): 172.3 (CO),
79.8 (C1), 79.1, 75.5, 72.1, 68.0. 62.6, 45.7, 41.8, 32.9, 30.4, 30.3,
30.2, 27.9, 23.7, 14.4 (–CH3); ESI-MS (m/z): calcd for
C17H34N3O6SNa: m/z 430.1988 ([M + Na]+), found: 430.1985.
1-N-(2-Deoxy-2-acetamido-b-D-glucopyranosyl)-N99-(n-dode-
cyl)-thioureidoacetamide (48). Yellow solid; m.p.: 140 uC; [a]3D0:
9.6u (c = 1.0, DMF); IR (KBr, cm21): 3323, 3079, 2954, 2926,
2855, 2411, 1738, 1670, 1637, 1554, 1456, 1369, 1313, 1237,
1158, 1114, 1085, 1039, 946, 890, 718, 670, 617, 595, 570, 558;
1H-NMR (400 MHz, CD3OD) d (ppm): 4.90 (d, 1H, J = 9.6 Hz,
H-1), 4.12 (s, 2H, –COCH2NH), 3.91–3.27 (m, 8H), 1.94 (s, 3H,
–NHCOCH3) 1.65–1.47 (m, 2H), 1.40–1.35 (m, 10 H), 0.83 (t,
1-N-[4-O-(b-D-Galactopyranosyl)-b-D-glucopyranosyl]-N99-(n-
octyl)-thioureidoacetamide (52). Yellow solid; m.p.: 152 uC;
[a]3D0: 9.3u (c = 1.0, DMF); IR (KBr, cm21): 3403, 2926, 2855,
2363, 2339, 1674, 1561, 1461, 1377, 1315, 1253, 1115, 1082,
1024, 896, 779, 698, 618; 1H-NMR (400 MHz, D2O) d (ppm):
4.97 (d, 1H, J = 8.9 Hz, H-1), 4.41 (d, 1H, J = 6.4, H-19), 4.26 (s,
2H, –COCH2NH–), 3.96–3.36 (m, 14H), 1.64–1.52 (m, 2H), 1.41–
1.15 (m, 10H), 0.87 (s, 3H, –CH3); 13C-NMR (100 MHz, CD3OD)
d (ppm): 172.3 (CO), 104.6 (C-19), 80.6 (C-1), 80.4, 77.7, 76.7,
76.5, 74.5, 73.3, 72.1, 69.9, 62.2, 61.8, 45.3, 32.5, 30.2, 29.9,
29.8, 29.7, 27.6, 23.2, 14.2 (–CH3); ESI-MS (m/z): calcd for
C23H43N3O11NaS: 592.2516 ([M + Na]+), found: 592.2523.
1-N-[4-O-(b-D-Galactopyranosyl)-b-D-glucopyranosyl]-N99-(n-
dodecyl)-thioureidoacetamide (53). Yellow solid; m.p.: 162 uC;
[a]3D0: 17.8u (c = 1.0, DMF); IR (KBr, cm21): 3431, 2923, 2853,
2360, 2337, 2079, 1640, 1563, 1461, 1415, 1375, 1115, 1085,
1
1046, 777, 618; H-NMR (400 MHz, CD3OD) d (ppm): 5.30 (d,
1H, J = 8.9 Hz, H-1), 4.74 (d, 1H, J = 7.6, H-19), 4.63 (s, 2H,
–COCH2NH), 4.26–3.68 (m, 14H), 1.99–1.89 (m, 2H), 1.78–1.60
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(m, 18H), 1.24 (t, 3H, J = 7.2 Hz, CH3); 13C-NMR (100 MHz,
CD3OD) d (ppm): 172.8 (CO), 105.1 (C-19), 80.1 (C-1), 80.7, 78.2,
77.2, 77.1, 75.0, 73.8, 72.6, 70.4, 62.5, 62.1, 45.4, 32.9, 30.6,
30.3, 30.3, 30.0, 27.9, 23.5, 14.2 (–CH3); ESI-MS (m/z): calcd for
C27H51N3O11NaS: 648.3142 ([M + Na]+), found: 648.3158.
1-N-[4-O-(a-D-Glucopyranosyl)-b-D-glucopyranosyl]-N99-(n-
octyl)-thioureidoacetamide (54). Yellow solid; m.p.: 143 uC;
[a]3D0: 44.5u (c = 1.1, DMF); IR (KBr, cm21): 3348, 2924, 2853,
2470, 1676, 1555, 1460, 1416, 1365, 1259, 1147, 1075, 1038,
913, 777, 716, 606, 586, 553; 1H-NMR (400 MHz, CD3OD) d
(ppm): 5.18 (d, 1H, J = 3.6 Hz, H-19), 4.94 (d, 1H, J = 8.8 Hz,
H-1), 4.32–4.24 (m, 2H, –COCH2NH–), 3.90–3.22 (m, 14H),
1.65–1.53 (m, 2H), 1.41–1.26 (m, 10 H), 0.90 (t, 3H, –CH3); 13C-
NMR (100 MHz, CD3OD) d (ppm): 172.9 (CO), 102.7 (C-19), 81.0
(C-1), 80.8, 78.5, 78.2, 75.0, 74.7, 74.7, 74.1, 73.5, 71.4, 62.6,
62.0, 45.9, 32.9, 30.4, 30.3, 28.0, 23.6, 14.4 (–CH3); ESI-MS (m/
z): calcd for C23H43N3O11NaS: 592.2484 ([M + K]+), found:
592.2471.
1-N-(b-D-Mannopyranosyl)-N99-(n-octyl)-ureidoacetamide
(58). White solid; m.p.: 176–178 uC; [a]3D0: 1.1u (c = 1.1, DMF); IR
(KBr, cm21): 3319, 2954, 2925, 2854, 1673, 1627, 1578, 1546,
1464, 1444, 1372, 1324, 1291, 1238, 1148, 1081, 1027, 957, 938,
910, 891, 859, 799, 707, 663, 629, 575, 520; 1H-NMR (400 MHz,
CDCl3 + CD3OD) d (ppm): 5.19 (s, 1H, H-1), 3.92–3.70 (m, 5H),
3.62 (t, 1H, J =.9.6 Hz), 3.55 (dd, J =.3.2 & 9.6 Hz), 3.36–3.29 (m,
1H, H-5), 3.13 (t, 2H, J = 7.2 Hz, –CONHCH2–), 1.56–1.42 (m,
2H, –CH2), 1.38–1.22 (m, 10H), 0.81 (t, 3H, J = 6.8 Hz, –CH3);
13C-NMR (100 MHz, CDCl3+ CD3OD) d (ppm): 172.1 (CO), 159.4
(–NHCONH–), 77.9 (C-1), 77.5, 73.8, 70.5, 66.3, 61.0 (C-6), 43.3,
40.1, 31.7, 29.9, 29.6, 29.3, 26.8, 22.5, 13.9 (–CH3); ESI-MS (m/
z): calcd for C17H34N3O7: 392.2397 ([M + H]+), found: 392.2404.
1-N-(2-Deoxy-2-acetamido-b-D-glucopyranosyl)-N99-(n-octyl)-
ureidoacetamide (59). White solid; m.p.: 214–215 uC; [a]3D0:
12.6u (c = 1.0, DMF); IR (KBr, cm21): 3317, 3254, 3092, 2925,
2855, 1682, 1633, 1553, 1503, 1445, 1420, 1376, 1341, 1321,
1242, 1189, 1112, 1085, 1038, 971, 953, 891, 757, 724, 656, 614,
580, 542; 1H-NMR (400 MHz, CD3OD) d (ppm): 4.83 (d, 1H, J =
9.6 Hz, H-1), 3.77–3.53 (m, 5H), 3.43–3.36 (m, 1H), 3.26–3.23
(m, 2H), 3.07–2.08 (m, 2H), 4.14–1.34 (m, 2H), 1.29–1.15 (m,
10H), 0.78 (t, 3H, J = 6.8 Hz, –CH3); 13C-NMR (100 MHz, DMSO-
D6) d (ppm): 170.8, 170.4 (2 6 CO), 157.9 (–NHCONH–), 79.3
(C-1), 78.7, 74.2, 70.5, 60.8, 54.4, 43.0, 39.4, 31.3, 29.9, 28.8,
28.7, 26.4, 22.7, 22.1, 14.0 (–CH3); ESI-MS (m/z): calcd for
C19H37N4O7: 433.2662 ([M + H]+), found: 433.2657.
1-N-(a-L-Rhamnopyranosyl)-N99-(n-octyl)-ureidoacetamide
(60). White solid; m.p.: 150 uC; [a]3D0: 10.1u (c = 1.0, DMF); IR
(KBr, cm21): 3523, 3410, 3358, 3334, 2954, 2927, 2855, 1668,
1633, 1580, 1558, 1514, 1453, 1415, 1381, 1362, 1341, 1322,
1246, 1153, 1094, 1078, 1067, 1019, 972, 902, 859, 791, 774,
719, 631, 602, 576, 557, 516; 1H-NMR (400 MHz, CD3OD) d
(ppm): 5.05 (s, 1H, H-1), 3.75–3.67 (m, 3H), 3.44–3.35 (m, 1H),
3.31–3.19 (m, 2H), 3.02 (t, 2H, –COCH2NH–), 1.44–1.34 (m,
2H), 1.28–1.14 (m, 13H), 0.80 (t, 3H, J = 7.2 Hz, –CH3); 13C-
NMR (100 MHz, DMSO-D6) d (ppm): 170.0 (CO), 157.9
(–NHCONH–), 77.0 (C-1), 73.7, 73.4, 71.6, 70.7, 43.0, 39.3,
31.2, 29.9, 28.8, 28.7, 26.4, 22.1, 17.9 (–CH3), 14.0 (–CH2CH3);
ESI-MS (m/z): calcd for C17H34N3O6: 376.2448 ([M + H]+),
found: 376.2441.
1-N-[4-O-(a-D-Glucopyranosyl)-b-D-glucopyranosyl]-N99-(n-
dodecyl)-thioureidoacetamide (55). Yellow solid; m.p.: 172 uC;
[a]3D0: 52.5u (c = 1, DMF); IR (KBr, cm21): 3353, 2926, 2856, 1677,
1554, 1457, 1411, 1364, 1262, 1147, 1074, 1038, 912, 778, 605,
1
554; H-NMR (400 MHz, CD3OD) d (ppm): 5.08 (d, 1H, J = 3.6
Hz, H-19), 4.84 (d, 1H, J = 8.8 Hz, H-1), 4.18 (s, 2H, –COCH2NH–),
3.78–3.13 (m, 14H), 1.55–1.43 (m, 2H), 1.30–1.16 (m, 18H), 0.80
(t, 3H, –CH3); 13C-NMR (100 MHz, CD3OD) d (ppm): 173.1 (CO),
102.8 (C19), 81.1 (C-1), 80.9, 78.6, 78.3, 75.1, 74.8, 74.2, 73.6,
71.5, 62.7, 62.1, 48.3, 45.7, 33.1, 30.8, 30.5, 30.2, 28.1, 23.8, 14.6
(–CH3); ESI-MS (m/z): calcd for C27H51N3O12KS: 648.3110 ([M +
K]+), found: 648.3124.
1-N-(b-D-Glucopyranosyl)-N99-(n-octyl)-ureidoacetamide (56).
White solid; m.p.: 188–191 uC; [a]3D0: 11.6u (c = 1.0, DMF); IR
(KBr, cm21): 3487, 3442, 3367, 3327, 2955, 2929, 2855, 1662,
1627, 1577, 1554, 1501, 1470, 1406, 1343, 1269, 1131, 1098,
988, 887, 775, 755, 724, 697, 641, 633, 615, 586, 566, 528, 505;
1H-NMR (400 MHz, D2O + DMSO-D6) d (ppm): 5.14 (d, 1H, J =
8.8 Hz, H-1), 4.18–4.02 (m, 3H, H-6a & –COCH2NH–), 3.88 (dd,
1H, J = 3.9 & 12.0 Hz, H-6b) 3.74–3.53 (m, 4H), 3.36 (t, 2H, J
=.6.4 Hz, –CONHCH2–), 1.80–1.70 (m, 2H), 1.68–1.55 (m, 10H),
0.88 (t, 3H, J = 6.8 Hz, –CH3); 13C-NMR (100 MHz, DMSO-D6) d
(ppm): 170.5 (CO), 157.9 (–NHCONH–), 79.5 (C-1), 78.6, 77.4,
72.5, 69.9, 60.9 (C-6), 42.8 (–COCH2NH–), 39.3, 31.3, 30.0, 28.8,
28.7, 26.4, 22.1, 14.0 (–CH3); ESI-MS (m/z): calcd for
C17H34N3O7: 392.2397 ([M + H]+), found: 392.2391.
1-N-(b-D-Xylopyranosyl)-N99-(n-octyl)-ureidoacetamide (61).
White solid; m.p.: 181 uC; [a]3D0: 1.4u (c = 1.0, DMF); IR (KBr,
cm21): 3325, 3088, 2956, 2925, 2854, 1674, 1631, 1584, 1560,
1465, 1410, 1376, 1345, 1263, 1239, 1189, 1145, 1097, 1084,
1061, 1015, 1006, 996, 942, 900, 722, 673, 632, 601, 533, 519;
1H-NMR (400 MHz, CDCl3+ CD3OD) d (ppm): 4.88 (d, 1H, J =
8.8 Hz, H-1), 3.92–3.77 (m, 3H), 3.58–3.48 (m, 1H), 3.42 (t, 1H, J
= 8.8 Hz), 3.33–3.24 (m, 2H), 3.13 (t, 2H, J = 6.8 Hz,
–CONHCH2–), 1.54–1.44 (m, 2H), 1.39–1.22 (m, 10H), 0.89 (t,
3H, J = 6.8 Hz, –CH3); 13C-NMR (100 MHz, DMSO-D6) d (ppm):
170.7 (CO), 157.9 (–NHCONH–), 80.3 (C-1), 77.4, 72.3, 69.6,
67.3 (C-5), 42.8, 39.3, 31.3, 30.0, 28.8, 28.7, 26.4, 22.1, 13.9
(–CH3); ESI-MS (m/z): calcd for C16H32N3O6: 362.2291 ([M +
H]+), found: 362.2291.
1-N-(b-D-Galactopyronosyl)-N99-(n-octyl)-ureidoacetamide
(57). White solid; m.p.: 180–181 uC; [a]3D0: 33.3u (c = 1.0, DMF);
IR (KBr, cm21): 3671, 3509, 3336, 2957, 2926, 2854, 2597, 2477,
2360, 1682, 1605, 1587, 1535, 1464, 1418, 1381, 1341, 1301,
1273, 1237, 1185, 1154, 1083, 1054, 1016, 937, 893, 856, 776,
1
720, 668, 588, 544, 516; H-NMR (400 MHz, CD3OD) d (ppm):
4.87 (d, 1H, J = 8.4 Hz, H-1), 3.89 (d, 1H, J = 2.8 Hz, H-4), 3.81
(br s, 1H, –COCH2NH–), 3.20–3.55 (m, 5H), 3.05 (t, 2H, J =.7.2
Hz, –CONHCH2–), 1.47–1.35 (m, 2H, CH2), 1.30–1.14 (m, 10H),
0.81 (t, 3H, J = 6.8 Hz, –CH3); 13C-NMR (100 MHz, DMSO-D6) d
(ppm): 170.4 (CO), 157.9 (–NHCONH–), 80.0 (C-1), 76.7, 74.1,
69.8, 68.3, 60.5, 42.8, 39.3, 31.2, 29.9, 29.0, 28.8, 28.7, 26.4,
22.1, 13.9 (–CH3); ESI-MS (m/z): calcd for C17H34N3O7: 392.2397
([M + H]+), found: 392.2397.
1-N-(a-L-Arbinopyranosyl)-N99-(n-octyl)-ureidoacetamide
(62). White solid; m.p.: 168–170 uC; [a]3D0: 221.0u (c = 1.1, DMF);
IR (KBr, cm21): 3366, 2924, 2854, 1658, 1627, 1582, 1557, 1462,
1427, 1376, 1346, 1249, 1148, 1091, 1026, 944, 914, 860, 778,
14540 | RSC Adv., 2013, 3, 14528–14542
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1
723, 697, 632, 540, 508; H-NMR (400 MHz, CD3OD) d (ppm):
4.70 (H-1 hidden under HOD), 3.90 (s, 1H), 3.85–3.78 (m, 3H),
3.70–3.56 (m, 3H), 3.04 (t, 2H, J = 6.8 Hz, –CONHCH2–), 1.46–
1.35 (m, 2H), 1.28–1.58 (m, 10H), 0.80 (t, 3H, J = 6.8 Hz, –CH3);
13C-NMR (100 MHz, CD3OD) d (ppm): 173.3 (CO), 160.4
(–NHCONH–), 80.9 (C-1), 74.1, 70.9, 69.1, 67.9 (C-5), 44.1, 40.9,
32.6, 30.8, 30.3, 30.1, 30.0, 27.6, 23.3, 14.3 (–CH3); ESI-MS (m/z):
calcd for C16H32N3O6: 362.2291 ([M + H]+), found: 362.2297.
1-N-(a-L-Arbinopyranosyl)-N99-(n-octyl)-ureidoacetamide
(63). White solid; m.p.: 175–177 uC; [a]3D0: 2.4u (c = 1, DMF); IR
(KBr; cm21): 3372, 3327, 3086, 2956, 2925, 2854, 1641, 1572,
1463, 1417, 1377, 1344, 1281, 1247, 1148, 1092, 1019, 944, 915,
863, 780, 722, 647, 614, 574, 541, 501; 1H-NMR (400 MHz,
CD3OD) d (ppm): 4.83 (d, 1H, J = 8.2 Hz, H-1), 3.91 (s, 1H),
3.85–3.78 (m, 3H), 3.70–3.58 (m, 3H), 3.04 (t, 2H, J = 7.2 Hz,
–CONHCH2), 1.46–1.36 (m, 2H), 1.28–1.58 (m, 10H), 0.80 (t, 3H,
J = 6.8 Hz, –CH3); 13C-NMR (100 MHz, CD3OD) d (ppm): 173.4
(CO), 160.6 (NHCONH), 81.0 (C-1), 74.3, 70.9, 69.2, 68.0 (C-5),
44.2, 40.9, 32.7, 30.9, 30.1, 27.7, 23.4, 14.4 (–CH3); ESI-MS (m/z):
calcd for C16H32N3O6: 362.2297 ([M + H]+), found: 362.2283.
1-N-[4-O-(b-D-Galactopyranosyl)-b-D-glucopyranosyl]-N99-(n-
octyl)-ureidoacetamide (64). White solid; m.p.: 203–205 uC;
[a]3D0: 22.6u (c = 1.1, DMF); IR (KBr, cm21): 3370, 2926, 2856,
1637, 1565, 1463, 1439, 1414, 1380, 1261, 1167, 1119, 1084,
1047, 944, 893, 782, 702, 624, 599, 572; 1H-NMR (400 MHz,
D2O) d (ppm): 5.18 (d, 1H, J = 9.2 Hz, H-1), 4.62 (d, 1H, J = 7.6
Hz, H-19), 4.13–4.80 (m, 12 H), 3.75–3.67 (m, 1H), 3.65 (t, 1H, J
= 8.8 Hz), (t, 2H, J = 6.8 Hz, –CONHCH2–), 1.69–1.59 (m, 2H),
1.51–1.38 (m, 10H), 1.02 (t, 3H, J = 7.2 Hz, –CH3); 13C-NMR (100
MHz, CD3OD) d (ppm): 170.5 (CO), 157.9 (–NHCONH–), 103.7
(C-19), 80.4 (C-1), 79.3, 76.5, 75.5, 73.2, 72.2, 70.6, 68.1, 60.4,
60.3, 42.7, 39.2, 31.1, 29.9, 28.7, 28.6, 26.3, 22.0, 13.8 (–CH3);
ESI-MS (m/z): calcd for C23H44N3O12: 554.2925 ([M + H]+),
found: 554.2931.
X-ray data collection and DSC analysis. SAIF IIT Madras for
SEM facility. We are thankful to Mr. V. Ram Kumar for X-ray
data collection. M.M thanks the Council of Scientific and
Industrial Research (CSIR), New Delhi, for the award of a
Senior Research Fellowship. We also thank the Cambridge
Crystallographic Data Centre (CCDC), United Kingdom, for
making the program Mercury 3.0 available for use.
Notes and references
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1-N-[4-O-(a-D-Glucopyranosyl)-b-D-glucopyranosyl]-N9-(n-
octyl)-ureidoacetamide (65). White solid; m.p.: 172–173 uC;
[a]3D0: 55.7u (c = 1, MeOH); IR (KBr, cm21): 3357, 2954, 2926,
2856, 1648, 1564, 1462, 1415, 1377, 1267, 1149, 1111, 1075,
1039, 956, 914, 776, 717, 700, 640, 610, 585, 542; 1H-NMR (400
MHz, D2O) d (ppm): 5.62 (d, 1H, J = 4.0 Hz, H-19), 5.23 (d, 1H, J
= 9.2 Hz, H-1), 4.16–3.85 (m, 11 H), 3.80 (dd, 1H, J = 4.0 & 10.0
Hz), 3.73–3.60 (m, 2H), 3.33 (t, 2H, J = 6.8 Hz, –CONHCH2–),
1.75–1.65 (m, 2H), 1.57–1.44 (m, 10H), 1.08 (t, 3H, J = 6.8 Hz,
(–CH3); 13C-NMR (100 MHz, CD3OD) d (ppm): 170.5 (CO), 157.9
(–NHCONH–), 100.7 (C-19), 79.5 (C-1), 79.4, 77.1, 76.8, 73.4,
73.3, 72.5, 72.1, 70.0, 60.8, 60.4, 42.8, 39.2, 31.1, 29.9, 28.7,
28.6, 26.3, 22.0, 13.8 (–CH3); ESI-MS (m/z): calcd for
C23H43N3O12Na: 4576.2744 ([M + H]+), found: 576.2742.
´
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Acknowledgements
The funding provided by the Department of Science and
Technology (DST), New Delhi for the purchase of the 400 MHz
NMR under the IRHPA Scheme and the ESI-MS under the FIST
program to the Department of Chemistry, IIT Madras, is
gratefully acknowledged. The authors thank the single crystal
XRD facility, Department of Chemistry, IIT Madras for the
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