Bis-triazologlycolipid mimetics - Low molecular weight organogelators

Article abstract of DOI:10.1039/c3nj01591b

A facile regioselective synthesis of bis-triazologlycolipids, a class of organogelators, has been accomplished by "Click reaction". The morphology and self-assembly of the gelators were examined by FESEM and HRTEM analysis. the Partner Organisations 2014.

Full text of DOI:10.1039/c3nj01591b

NJC
View Article Online
View Journal | View Issue
PAPER
Bis-triazologlycolipid mimetics – low molecular
weight organogelators†
Arasappan Hemamalinia and Thangamuthu Mohan Das*ab
Cite this: New J. Chem., 2014,
38, 3015
Received (in Montpellier, France)
17th December 2013,
Accepted 7th April 2014
A facile regioselective synthesis of bis-triazologlycolipids, a class of organogelators, has been accomplished
by ‘‘Click reaction’’. The morphology and self-assembly of the gelators were examined by FESEM and
HRTEM analysis.
DOI: 10.1039/c3nj01591b
www.rsc.org/njc
Low-molecular-weight organogelators (LMOG) are an impor-
tant class of soft matter and have received increasing attention in
Introduction
Glycolipids are membrane components composed of lipids that recent years due to their easy fabrication into soft materials and
are covalently bonded to monosaccharides or polysaccharides wide applications in the field of sensing, catalysis, oil recovery,
and they serve as markers for cellular recognition. They are template synthesis of nanoporous materials, etc.20 It is very
universally distributed in nature constituting the cell membranes important to design suitable gelator molecules involving H-bond
of almost all living organisms. Owing to their intrinsic amphi- forming sites, long alkyl chains and p–p stacking units which are
philic feature as well as their low toxicity and high biocompat- necessary for the gelation. Baddeley et al.21 emphasized the delicate
ibility, they have broad applications in numerous biochemical balance between both the molecular structure and electronic
and especially physicochemical studies.1–11 However, the properties of LMWGs as well as the solvent polarity in the medium
majority of natural glycolipids have unsatisfactory limitations to achieve gelation and to control the morphology of the assembled
such as their structural instability towards acidic and enzymatic fibers. In this paper we report a systematic investigation of gel
cleavage due to the presence of an O-glycosidic linkage between forming chalcone based glycolipid mimetics.
the lipid aglycons and the glycons.
Copper catalyzed azide–alkyne 1,2,3-triazole forming
click reaction is useful for efficient coupling of two entities.12
Results and discussion
Synthesis and characterization of sugar-based long-chain bis-
‘‘Click reaction’’ has a wide range of applications including
drug discovery,13 materials science14 and biology15 and it is
triazole derivatives
used for preparing a large number of new compounds which
include glycodendrimers, glycopolymers and glycopeptides.16 4,6-O-Butylidene-D-glucopyranose was synthesized from D-glucose
However, there are few reports17 on the preparation and by adopting the literature procedure.22 b-C-Glycosidic ketone was
potential functions of triazole-linked glycolipids. Loganathan synthesized by the Knoevenagel condensation of 2,4-pentanedione
and co-workers first described the synthesis of a series of with 4,6-O-butylidene-D-glucopyranose in the presence of sodium
triazologlycolipid mimetics in which the triazole ring acts as bicarbonate using THF–H2O as solvent.23,24 Aldol condensation of
a linker between various carbohydrates and lipid chains.18 two different b-C-glycosidic ketones 1 and 2 with bis-propargylated
Krausz and co-workers subsequently showed the potential aromatic aldehydes, 3 and 4, resulted in the formation of the
utility of this unique non-ionic lipid class for the development corresponding a-,b-unsaturated-b-C-glycosidic ketones, 5a, 5b, 6a
of green surfactants.19
and 6b, in 70–90% yield. The newly synthesized bis-propargylated
compounds, 3, 4, 5a, 5b, 6a and 6b, were well characterized using
NMR (1H and 13C) and elemental analysis.
Triazole chemistry is implied to link the bis-propargylated
glycoside to the known azide. The preparation of the azide was
accomplished from the corresponding bromide in a single step
with an excellent yield. Cycloaddition reaction of bis-alkyne
compounds, 5a, 5b, 6a and 6b, with two equivalents of dodecyl-
azide, 7, using copper sulphate and sodium ascorbate in catalytic
a Department of Organic Chemistry, University of Madras, Guindy Campus,
Chennai-600 025, India
b Department of Chemistry, School of Basic and Applied Sciences, Central University
of Tamil Nadu, Thiruvarur-610 004, India. E-mail: tmohandas@cutn.ac.in;
Fax: +91 4366-225312; Tel: +91 9489054264
† Electronic supplementary information (ESI) available: Experimental details. See
DOI: 10.1039/c3nj01591b
This journal is ©The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2014
New J. Chem., 2014, 38, 3015--3021 | 3015

View Article Online
Paper
NJC
Scheme 2 Structures of bis-(triazole-sugar) compounds.
further confirmed by DEPT-135 and 2D spectrum [see ESI† for
more details]. The methylene carbons in the product, 8a, were
1
identified by DEPT-135 experiment. Moreover, the H–13C[COSY]
spectrum reveals the correlation of characteristic protons with
their corresponding carbons. In addition, the mass spectrum of
compound 8a shows the exact mass value of the product, 8a, which
Scheme 1 Structures of sugar–chalcone based bis-propargylated derivatives.
amounts led to the formation of sugar chalcone-based bis-triazole matches with the experimental results ultimately confirming the
having long alkyl derivatives. However, since compound 5a was formation of the bis-triazole derivative.
poorly soluble in tertiary butanol and acetonitrile, the tetrahydro-
Absorption and emission spectra were recorded in aceto-
furan and water mixture in 1 : 1 ratio was used to improve nitrile for all the synthesized sugar derivatives, 8a, 8b, 9a
the solubility of the reaction. The cycloadduct was obtained in and 9b. The profile of both the absorption and emission
82% yield in this case (Scheme 1). The reaction condition was spectra is presented in Fig. 1.
optimized using different solvents [see ESI† for more details].
All the four triazole compounds, 8a, 8b, 9a and 9b, gave
Thus the reaction of a-,b-unsaturated-b-C-glycosidic ketones, three consecutive bands, a weak band around 250 nm and two
5a, 5b, 6a and 6b, with dodecyl azide, 7, using the THF : water strong bands around 300 and 350 nm. From the emission
mixture in 1 : 1 ratio as solvent resulted in 78–90% yield of the spectra, it was found that compounds 8a and 9a gave peaks
corresponding sugar-based long-chain bis-triazole derivatives around 650 nm whereas compounds 8b and 9b gave bands
8a, 8b, 9a and 9b (Scheme 2).
around 500 nm [Fig. 1]. Thus, it is concluded from the result
The structures of the resulting chalcone based triazologlyco- that irrespective of the position of the triazole moiety, the
lipid analogues were characterized by FT-IR and (1H, 13C) NMR change in the protecting group of the sugar moiety has led to
spectral techniques, mass analysis and elemental analysis. The a shift in the wavelength on emission.
FT-IR spectrum of compound 8a shows bands around 1596,
All the four bis-triazole sugar derivatives 8a, 8b, 9a and 9b
1512, and 1226 cmꢀ1 which correspond to the frequency of form gel in organic solvents [Table 2]. The gelation property of
CQO, CQC (alkene) and C–N respectively. The presence of the dendritic bis-triazole sugar derivatives in other dielectric
sugar–chalcone in compound 8a was further confirmed from media was examined in a wide range of solvents and mixture of
1H NMR spectroscopy by the appearance of doublets at d 7.51 solvents. The instant gel formed from the hexane–ethyl acetate
and 6.69 ppm with a coupling constant of B16 Hz which mixture was dried under vacuum and then dissolved in a
correspond to the trans alkene double bond whereas the selected solvent or solvent mixture by heating. The homo-
presence of the sugar-triazole core was confirmed from the geneous solution was then cooled to room temperature to obtain
appearance of two sharp singlets at d 7.69 ppm and d 7.68 ppm the gel [Fig. 2]. The critical gelation concentration (CGC) of
which correspond to methine protons (trz-H) of the triazole compounds 8a, 8b, 9a and 9b was determined using the hexane–
ring [Table 1]. The triazole carbons resonate around d 151 and ethyl acetate solvent mixture [Table 2]. The long-chain bis-
148 ppm. Furthermore, from the 13C NMR spectrum the 1,4 triazole sugar derivatives, 8a and 9a, which have butylidene
regioisomeric product formation of bis-triazole is confirmed as the protecting group with two free hydroxyl groups form gel
from Rodios calculation where the compound 8a found to have at very low CGC (1%) whereas compounds 8b and 9b which
(d C4–C5) as 29.1 and 29.2 ppm. The product formation was have a similar core structure as that of 8a and 9a were found to
3016 | New J. Chem., 2014, 38, 3015--3021
This journal is ©The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2014

View Article Online
NJC
Paper
Table 1 Spectral data and optimization of triazole based lipid appended a-,b-unsaturated-b-C-glycosidic ketones, 8a, 8b, 9a and 9b
NMR data
3
3
Compound No.
Time (h)
24
Yield (%)
85
d Ano-H/ppm JH1H2 Hz
d Alk-H/ppm JH1H2 Hz
d Trz-H/ppm
8a
4.15, 9.9
5.25, 9.5
4.12, 9.9
5.07, 9.6
7.51, 6.69
16.2, 15.9
7.48, 6.63
15.9, 16.2
7.88, 6.73
16.2, 16.2
7.83, 6.72–6.62a
16.2
7.69, 7.68
8b
9a
9b
20
24
20
90
78
83
7.70, 7.68
7.67, 7.66
7.71, 7.67
a
Trans alkene protons are merged with aromatic protons.
have higher CGC (1.5%). This difference in the CGC may pre- It is well known that for gelation the participation of both
sumably be due to hydrogen bond formation of the two hydroxyl hydrophilic and hydrophobic groups is necessary. Here in this
groups which lowers the CGC and improves the gelation.
paper, the precursors, 5a and 6a, utilized for the synthesis of
Gelation ability refers to the ability of the compound bis-triazolyl derivatives, 8a and 9a, formed a partial gel with
(glycosidic ketone) to gelate the solvent used for gelation.24 hexane–ethyl acetate whereas gel formation was not observed
with the precursors 5b and 6b. This is because in the former,
the presence of two hydroxyl groups which are responsible for
the hydrogen bonding may result in partial gelation whereas in
the latter since there is no site of hydrophilic groups in the
molecules 5b and 6b, self-assembly was not observed and hence
they acted as non-gelators.
The xerogel of the organogelator was subjected to morpho-
logical studies using FESEM and HRTEM analysis. SEM images
of the organogelators 8a and 8b are shown in Fig. 3. From
FESEM, the morphology of compound 8a is observed to be a
fibrous network. The size of the fibril is found to be around
58 nm. A crystal clear picture of the interior morphology of
the gelator which exhibits a fibrous network was obtained
from HRTEM.
Two types of aggregation modes, fibrous and lamellar, are
proposed for the observed morphology. Compound 8a, the
long-chain bis-triazole derivative bearing partially protected
sugar, exhibits fibrous aggregated morphology with nanopores
[Fig. 3a], whereas the corresponding completely protected
sugar, 8b, exhibits a lamellar structure with less voids [Fig. 3b].
In addition, compound 8b does not show any branched struc-
ture; instead it has an aggregated mode of each individual
layer. Generally, fibrous structures can incorporate more
solvent than lamellar structures because of their greater void
volume as documented from FESEM and HRTEM analysis.
In the SEM image of gelator 8a, the larger flat tubules are
composed of a fibrous network as shown in Fig. 3a. The bulk
structure of the organogelator 8b is lamellar. Except the differ-
ence in the protecting group of the sugar moiety, the core
architecture of molecules 8a and 8b was found to be similar
and hence it was assumed that for compound 8b, the fibrils
aggregate together to form a lamellar-like structure [Fig. 3b].
The interior morphology of compound 8a was determined
using HRTEM and the representative HRTEM image of com-
pound 8a is shown in Fig. 4. The aggregation mode is identified
based on fibrils joined together to form an interlinked network
structure. The repeated interlinks which gave an aggregated
form confirmed the formation of an organogelator.
Fig. 1 (a) Absorption spectra of compounds 8a, 8b, 9a, and 9b in
acetonitrile (1 ꢁ 10ꢀ5 M) and (b) emission spectra of compounds 8a, 8b,
9a, and 9b in acetonitrile (1 ꢁ 10ꢀ5 M).
This journal is ©The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2014
New J. Chem., 2014, 38, 3015--3021 | 3017

View Article Online
Paper
NJC
Table 2 Gelation studies of compounds 8a, 8b, 9a and 9ba
Solvent
8a
8b
9a
9b
Water
Methanol
I
S
I
S
I
S
I
S
Ethanol
S
P
P
S
S
P
P
S
S
P
P
S
S
P
P
S
DMSO + water (3 : 1)
DMF + water (3 : 1)
Acetonitrile
Dichloroethane
Hex + EtOAc (1 : 10)
Hex + CHCl3 (1 : 10)
Ethyl acetate
Chloroform
S
S
S
S
G (CGC = 1)
G (CGC = 1.2)
G (CGC = 1.8)
G (CGC = 1.5)
G (CGC = 1.5)
G (CGC = 1)
G (CGC = 1.2)
G (CGC = 1.6)
G (CGC = 1.4)
G (CGC = 1.5)
PG
PG
PG
PG
PG
PG
a
Note: G – gelator, PG – partial gelator, S – solution, I – insoluble, P – precipitation; CGC represented in % (g mLꢀ1).
Fig. 2 Gel picture of compound 8a: (a) heating followed by cooling and
(b) upon inversion.
Fig. 4 HR-TEM images of compound 8a in CHCl3 under different
magnifications: (a) 1 mm, (b) 0.5 mm and (c) 200 nm.
Fig. 5 Powder XRD of organogelators: (a) 8a and (b) 8b.
Fig. 3 FESEM images of organogels formed from CHCl3: (a) 8a [5 mm],
(b) 8b [5 mm] and (c) 8b [500 nm].
at 2y = 2.281 with an interlayer distance of 38.6 nm which arises
from the packing of long alkyl chains due to van der Waals
X-ray powder diffraction analysis was carried out for the interaction. The diffraction pattern in the wide angle gave two
organogelators 8a and 8b. The xerogel of compounds 8a and 8b broad peaks at 2y = 11.961 and 20.391 with an interlayer
was subjected to X-ray diffraction pattern. In general, the X-ray distance of 7.3 nm and 4.3 nm respectively. This may be due
diffraction pattern gives an idea about the molecular packing in to the p–p interaction of aromatic rings as well as two triazole
the gel. The X-ray diffractograms of compounds 8a and 8b rings. As shown in Fig. 5b, compound 8b has the same pattern
are shown in Fig. 5. In Fig. 5a one can recognize a sharp peak as that of 8a, where one can observe a peak at a low angle of
3018 | New J. Chem., 2014, 38, 3015--3021
This journal is ©The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2014

View Article Online
NJC
Paper
2.871 with an interlayer distance of 30.6 nm followed by a broad Spectral characterization of organogelators
peak at a higher angle around 11.171 and 19.861 with an
Abbreviations such as Trz, Sac, Alk and Ar correspond to
triazole, saccharide, alkene and aromatic, respectively.
General procedure for the synthesis of sugar-bis-triazole
derivatives (8a, 8b, 9a and 9b). To a solution of sugar–chalcone
(1 equiv.) the tetrahydrofuran and water mixture in 1 : 1 ratio
was added. To the reaction mixture, 2.2 equiv. of dodecylazide,
7, was added. CuSO4ꢂ5H2O (0.2 equiv.) and sodium ascorbate
(0.4 equiv.) were added in catalytic amounts. The reaction
mixture was then stirred at room temperature for 24 h. After
completion of the reaction, the solvent was evaporated and the
product was extracted with CHCl3 (200 ml) and water (200 ml).
The organic layer was then evaporated, slurried and purified by
column chromatography.
interlayer distance of 7.1 and 4.4 nm respectively. The only
difference observed is the variation in the intensity of the peaks
at the low angle. The intensity of the peak was found to be
around 255 for compound 8a whereas it was only 70 in the case
of compound 8b. This shows that compound 8a is more
crystalline than compound 8b.
Thus the XRD studies confirm that both the gels obtained
from the organogelators 8a and 8b are one-dimensional aggre-
gates. Thus, XRD analysis gives additional information about
the morphology that has been determined using FESEM.
Conclusion
Synthesis, physicochemical properties and spectral data
of (E)-1-(4,6-O-butylidene-b-D-glucopyranosyl)-4-{3,4-bis[10-(dode-
cyl)-40-hydroxy-methylene-triazolo]phenyl}but-3-ene-2-one (8a).
Compound 8a was obtained by the ‘‘Click reaction’’ of
propargylated-sugar derivative 5a (0.47 g, 1 mmol) and dodecyl-
azide 7 (0.46 g, 2.2 mmol) as a dark yellow solid.
We have designed and synthesized several chalcone based
glycolipid derivatives, which are prone to form organogels,
and characterized them using different spectral techniques.
The existence of the 1,4-regioisomer of triazole and the b-
anomeric form of the sugar derivatives was identified using
NMR studies. A CGC value of 1.5 was observed for almost all
Mp: 172–174 1C; yield 0.76 g (85%); 1H NMR (300 MHz, CDCl3):
sugar triazole derivatives. The morphology of the gel forming d 7.69 (s, 1H, Trz-H), 7.68 (s, 1H, Trz-H), 7.51 (d, J = 16.2 Hz, 1H,
compounds was studied using FESEM and HRTEM. Both Alk-H), 7.34 (s, 1H, Ar-H), 7.17–7.05 (m, 2H, Ar-H), 6.69 (d, J =
fibrous and lamellar structures were obtained for the bis-
triazole derivatives. In addition to the morphological structure,
the molecular packing in the gel was identified from powder
XRD studies. Further manipulation of a-,b-unsaturated-b-C-
glycosidic ketones for the synthesis of several gelator molecules
is under progress in our laboratory.
15.9 Hz, 1H, Alk-H), 5.32 (s, 2H, –OCH2), 5.31 (s, 2H, –OCH2), 4.55
(t, J = 5.1 Hz, 1H, Sac-H), 4.35 (t, J = 7.2 Hz, 4H, –CH2), 4.15 (dd,
J = 4.2 Hz, J = 9.9 Hz, 1H, Sac-H), 3.97–3.91 (m, 1H, Sac-H), 3.75
(t, J = 8.7 Hz, 1H, Sac-H), 3.45 (t, J = 9.3 Hz, 1H, Sac-H), 3.26
(t, J = 9.0 Hz, 1H, Sac-H), 3.10 (dd, J = 4.2 Hz, J = 15.9 Hz, 1H, –CH2),
2.98 (dd, J = 6.9 Hz, J = 15.9 Hz, 1H, –CH2), 1.33–1.27 (m, 43H, –CH2,
–CH3), 0.96–0.87 (m, 7H, –CH2, –CH3); 13C NMR (75 MHz, CDCl3): d
197.9, 150.8, 148.4, 143.7, 143.5, 143.1, 128.3, 124.9, 123.9, 123.0
(2C), 114.6, 114.3, 102.4, 80.5, 77.2, 76.3, 75.4, 74.6, 70.6, 68.3, 63.4,
63.2, 50.5, 43.7, 36.3, 31.9, 30.2, 29.6, 29.5, 29.4, 29.3, 29.0, 26.5, 22.7,
17.5, 14.1, 13.9; ESI-MS: calc. for C50H80N6O8, 892.60; m/z found,
893.61 [M + H]+; elemental analysis: anal. calc. for C50H80N6O8: C,
67.23; H, 9.03; N, 9.41%. Found: C, 67.28; H, 9.07; N, 9.46.
Synthesis, physicochemical properties and spectral data
of (E)-1-(2,3,4,6-tetra-O-acetyl-b-D-glucopyranosyl)-4-{3,4-bis[10-
(dodecyl)-40-hydroxy-methylene-triazolo]phenyl}but-3-ene-2-one (8b).
Compound 8b was obtained by the ‘‘Click reaction’’ of sugar-
propargylated derivative 5b (0.58 g, 1 mmol) and dodecylazide 7
(0.46 g, 2.2 mmol) as a pale yellow solid.
Experimental
Materials and methods
D-Glucose, dodecylbromide, propargyl bromide, 3,4-dihydroxybenz-
aldehyde and 2,4-dihydroxybenzaldehyde were purchased from
Sigma-Aldrich Chemicals Pvt. Ltd, USA, and were of high purity.
Butyraldehyde and organic catalyst (pyrrolidine) were obtained from
SRL, India. Other reagents, such as hydrochloric acid, sodium
hydrogen carbonate, and solvents (AR Grade), were obtained from
Sd-fine, India, in high purity and were used without any further
purification. Acetylacetone, copper sulphate and sodium ascorbate
were purchased from Loba-chemie, India. Acetic anhydride was
obtained from Fischer Chemicals Pvt. Ltd, India. The solvents were
purified according to the standard methods. Column chromatogra-
phy was performed on silica gel (100–200 mesh). NMR spectra were
recorded on a Bruker DRX 300 MHz instrument in either CDCl3 or
DMSO-d6. Chemical shifts were referenced to internal TMS. SEM
images were recorded using Hitachi-S-3400W and HRTEM was
recorded using a JEOL, JEM 3010 model (LaB6 filament). Absorption
studies were carried out on a 1800 Shimadzu UV spectrophotometer
in the range of 190–800 nm. Emission studies were recorded using a
Perkin Elmer LS 45 fluorescence spectrometer. The electro-spray
ionization mass spectrum was recorded using a WATERS-Q-TOF
Premier-HAB213 spectrometer. Elemental analysis was performed
using a Perkin-Elmer 2400 series CHNS/O analyzer.
Mp: 128–131 1C; yield: 0.91 g (90%); 1H NMR (300 MHz, CDCl3):
d 7.70 (s, 1H, Trz-H), 7.68 (s, 1H, Trz-H), 7.48 (d, J = 15.9 Hz, 1H,
Alk-H), 7.32 (s, 1H, Ar-H), 7.18–7.08 (m, 2H, Ar-H), 6.63 (d, J =
16.2 Hz, 1H, Alk-H), 5.32 (s, 2H, –OCH2), 5.30 (s, 2H, –OCH2),
5.25 (t, J = 9.5 Hz, 1H, Sac-H), 5.10 (t, J = 9.6 Hz, 1H, Sac-H), 5.00
(t, J = 9.6 Hz, 1H, Sac-H), 4.36 (t, J = 7.2 Hz, 4H, –CH2), 4.28
(dd, J = 5.1 Hz, J = 12.5 Hz, 1H, Sac-H), 4.15 (t, J = 7.7 Hz, 1H, Sac-H),
4.06–4.02 (m, 1H, Sac-H), 3.76–3.72 (m, 1H, Sac-H), 3.02
(dd, J = 8.4 Hz, J = 16.1 Hz, 1H, –CH2), 2.68 (dd, J = 2.7 Hz,
J = 16.2 Hz, 1H, –CH2), 2.04–2.03 (m, 12H, –COCH3), 1.33–1.27
(m, 43H, –CH2, –CH3), 0.91–0.87 (m, 7H, –CH2, –CH3); 13C NMR
(75 MHz, CDCl3): d 195.9, 170.6, 170.2, 170.0, 169.5, 151.0, 148.5,
143.6, 143.5, 143.2, 128.2, 124.8, 123.9, 122.9, 114.6, 114.5, 75.7,
This journal is ©The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2014
New J. Chem., 2014, 38, 3015--3021 | 3019

View Article Online
Paper
NJC
74.3, 74.2, 71.7, 68.6, 63.6, 63.3, 62.1, 50.5, 42.7, 31.9, 30.3, 29.6, 300 MHz NMR facility under the DST-FIST programme to the
Department of Organic Chemistry, University of Madras,
Guindy Campus, Chennai, India. T.M. also thanks the Central
University of Tamil Nadu (CUTN), Thiruvarur, Tamil Nadu, for
infrastructure facilities. A.H. thanks CSIR, New Delhi, for SRF.
29.5, 29.4, 29.3, 29.0, 26.5, 22.7, 20.7 (2C), 20.6, 14.1; elemental
analysis: anal. calc. for C54H82N6O12: C, 64.39; H, 8.21; N, 8.34%.
Found: C, 64.43; H, 8.25; N, 8.36.
Synthesis, physicochemical properties and spectral data of
(E)-1-(4,6-O-butylidene-b-D-glucopyranosyl)-4-{2,4-bis[10-(dodecyl)-
40-hydroxy-methylene-triazolo]phenyl}but-3-ene-2-one (9a).
Compound 9a was obtained by the ‘‘Click reaction’’ of sugar-
propargylated derivative 6a (0.47 g, 1 mmol) and dodecylazide 7
(0.46 g, 2.2 mmol) as a dark yellow solid.
Notes and references
1 M. Tsuji, Cell. Mol. Life Sci., 2006, 63, 1889–1898.
2 D. Wu, M. Fujio and C.-H. Wong, Bioorg. Med. Chem., 2008,
16, 1073–1083.
3 W. Worakitkanchanakul, T. Imura, T. Fukuoka, T. Morita,
H. Sakai, M. Abe, R. Rujiravanit, S. Chavadej, H. Minamikawae
and D. Kitamoto, Colloids Surf., 2008, 65, 106–112.
4 T. Morita, T. Fukuoka, M. Konishi, T. Imura, S. Yamamoto,
M. Kitagawa, A. Sogabe and D. Kitamoto, Appl. Microbiol.
Biotechnol., 2009, 83, 1017–1025.
5 M. Piazza, C. Rossini, S. D. Fiorentina, C. Pozzi, F. Comelli,
I. Bettoni, P. Fusi, B. Costa and F. Peri, J. Med. Chem., 2009,
52, 1209–1213.
6 K. Ii, S. Ichikawa, B. Al-Dabbagh, A. Bouhss and A. Matsuda,
J. Med. Chem., 2010, 53, 3793–3813.
7 Z. Zhang, C. Zong, G. Song, G. Lv, Y. Chun, P. Wang, N. Ding
and Y. Li, Carbohydr. Res., 2010, 345, 750–760.
8 J. Vogel, G. Bendas, U. Bakowsky, G. Hummel,
R. R. Schimidt, U. Ketmann and U. Rothe, Biochim. Biophys.
Acta, 1998, 1372, 205–215.
9 R. A. Falconer and I. Toth, Bioorg. Med. Chem., 2007, 15,
7012–7020.
10 M. V. de Almeida and M. L. Hyaric, Mini-Rev. Org. Chem.,
2005, 2, 283–297.
Mp: 132–134 1C; yield: 0.69 g (78%); 1H NMR (300 MHz,
CDCl3): d 7.88 (d, J = 16.2 Hz, 1H, Alk-H), 7.67 (s, 1H, Trz-H), 7.66
(s, 1H, Trz-H), 7.48 (d, J = 8.7 Hz, 1H, Ar-H), 6.80 (s, 1H, Ar-H),
6.73 (d, J = 16.2 Hz, 1H, Alk-H), 6.64 (d, J = 8.4 Hz, 1H, Ar-H), 5.26
(s, 2H, –OCH2), 5.24 (s, 2H, –OCH2), 4.53 (t, J = 5.0 Hz, 1H,
Sac-H), 4.39–4.34 (m, 4H, –CH2), 4.12 (dd, J = 3.9 Hz, J = 9.9 Hz,
1H, Sac-H), 3.93–3.88 (m, 1H, Sac-H), 3.75 (q, J = 7.5 Hz, 1H,
Sac-H), 3.43–3.40 (m, 1H, Sac-H), 3.28–3.22 (m, 1H, Sac-H), 3.17
(dd, J = 4.2 Hz, J = 15.5 Hz, 1H, –CH2), 2.86 (dd, J = 7.2 Hz, J = 15.6
Hz, 1H, –CH2), 1.32–1.25 (m, 43H, –CH2, –CH3), 0.94–0.86
(m, 7H, –CH2, –CH3); 13C NMR (75 MHz, CDCl3): d 197.0, 159.9,
156.8, 141.6, 141.4, 137.1, 128.4, 123.1, 121.2, 121.1, 115.7, 106.2,
100.7, 99.1, 78.8, 73.6, 73.2, 68.9, 66.7, 60.8, 60.4, 48.9, 48.8, 41.8,
34.6, 30.2, 28.6, 28.0, 27.9, 27.8, 27.7, 27.6, 27.3, 24.8, 21.0, 15.8,
12.4, 12.2; elemental analysis: anal. calc. for C50H80N6O8: C, 67.23;
H, 9.03; N, 9.41%. Found: C, 67.28; H, 9.07; N, 9.46.
Synthesis, physicochemical properties and spectral data
of (E)-1-(2,3,4,6-tetra-O-acetyl-b-D-glucopyranosyl)-4-{2,4-bis-
[10-(dodecyl)-40-hydroxy-methylene-triazolo]phenyl}but-3-ene-
2-one (9b). Compound 9b was obtained by the ‘‘Click reaction’’
of sugar-propargylated derivative 6b (0.58 g, 1 mmol) and
dodecylazide 7 (0.46 g, 2.2 mmol) as a pale yellow solid.
Mp: 81–84 1C; yield: 0.84 g (83%); 1H NMR (300 MHz,
CDCl3): d 7.83 (d, J = 16.2 Hz, 1H, Alk-H), 7.71 (s, 1H, Trz-H),
7.67 (s, 1H, Trz-H), 7.49 (d, J = 8.7 Hz, 1H, Ar-H), 6.81 (s, 1H,
Ar-H), 6.72–6.62 (m, 2H, Ar-H, Alk-H), 5.29 (s, 2H, –OCH2), 5.24
(s, 2H, –OCH2), 5.07 (t, J = 9.6 Hz, 1H, Sac-H), 4.97 (t, J = 9.8 Hz,
1H, Sac-H), 4.38 (q, J = 7.5 Hz, 4H, –CH2), 4.27 (dd, J = 4.5 Hz,
J = 12.5 Hz, 1H, Sac-H), 4.17–4.10 (m, 1H, Sac-H), 4.03–3.99
(m, 1H, Sac-H), 3.75–3.70 (m, 1H, Sac-H), 2.97 (dd, J = 8.1 Hz,
J = 16.5 Hz, 1H, –CH2), 2.65 (dd, J = 3.6 Hz, J = 16.4 Hz, 1H,
–CH2), 2.04–2.01 (m, 12H, –COCH3), 1.94–1.93 (m, 4H, –CH2),
1.25 (m, 36H, –CH2), 0.90–0.85 (m, 6H, –CH2); 13C NMR
(75 MHz, CDCl3): d 196.3, 170.6, 170.2, 170.0, 169.6, 161.8,
158.7, 143.4, 138.7, 130.0, 124.5, 122.7, 116.9, 107.6, 100.5, 75.7,
74.3, 71.8, 68.6, 62.7, 62.2, 62.1, 50.6, 42.5, 31.9, 30.3, 29.6, 29.5,
29.4 (2C), 29.3, 29.0, 26.5, 22.7, 20.7 (2C), 20.6, 14.1; ESI-MS:
calc. for C54H82N6O12, 1006.60; m/z found, 1007.61 [M + H]+;
elemental analysis: anal. calc. for C54H82N6O12: C, 64.39;
H, 8.21; N, 8.34%. Found: C, 64.43; H, 8.25; N, 8.36.
11 P. H. Thiesen, H. Rosenfeld, P. Konidala, V. M. Garamus,
L. He, A. Prange and B. Niemeyer, J. Biotechnol., 2006, 124,
284–301.
12 (a) C. W. Tornoe, C. Christensen and M. Meldal, J. Org.
Chem., 2002, 67, 3057–3064; (b) V. V. Rostovtsev, L. G. Green,
V. V. Fokin and K. B. Sharpless, Angew. Chem., Int. Ed., 2002,
41, 2596–2599.
13 H. C. Kolb and K. B. Sharpless, Drug Discovery Today, 2003,
8, 1128–1137.
14 C. J. Hawker and K. L. Wooley, Science, 2005, 309, 1200–1205.
15 N. J. Agard, J. M. Baskin, J. A. Prescher, A. Lo and
C. R. Bertozzi, ACS Chem. Biol., 2006, 1, 644–648.
16 (a) M. C. Bryan, F. Fazio, H. K. Lee, C. Y. Huang, A. Chang,
M. D. Best, D. A. Calarese, O. Blixt, J. C. Paulson, D. Burton,
I. A. Wilson and C. H. Wong, J. Am. Chem. Soc., 2004, 126,
8640–8641; (b) S. S. Gupta, K. S. Raja, E. Kaltgrad, E. Strable
and M. G. Finn, Chem. Commun., 2005, 4315–4317;
(c) M. A. Bruckman, G. Kaur, L. A. Lee, F. Xie,
J. Sepulveda, R. Breitenkamp, X. Zhang, M. Joralemon,
T. P. Russel, T. Emrick and Q. Wang, ChemBioChem, 2008,
9, 519–523.
Acknowledgements
17 (a) X. Nie and G. Wang, J. Org. Chem., 2006, 71, 4734–4741;
(b) S. Cheuk and E. D. Stevens, Carbohydr. Res., 2009, 344,
417–425; (c) D. D. Diaz, K. Rajagopal, E. Strable, J. Schneider
The authors acknowledge SERC-DST, New Delhi, India,
for financial support. T.M. thanks DST, New Delhi, for the
3020 | New J. Chem., 2014, 38, 3015--3021
This journal is ©The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2014

View Article Online
NJC
Paper
and M. G. Finn, J. Am. Chem. Soc., 2006, 128, 6056–6057; 19 V. Neto, R. Granet and P. Krausz, Tetrahedron, 2010, 66,
(d) V. Bhalla and H. Singh, Langmuir, 2011, 27, 4633–4646.
15275–15281; (e) S.-X. Song, H.-L. Zhang, C.-G. Kim, 20 (a) P. Terech and R. G. Weiss, Chem. Rev., 1997, 97,
L. Sheng, X.-P. He, Y.-T. Long, J. Li and G.-R. Chen, Tetra-
hedron, 2010, 66, 9974–9980; ( f ) H.-L. Zhang, X.-P. He,
L. Sheng, Y. Yao, W. Zhang, X.-X. Shi, J. Li and G.-R.
Chen, Mol. Diversity, 2011, 15, 889–900; (g) X.-P. He,
X. Xu, H.-L. Zhang, G.-R. Chen, S. Xu and H. Liu, Carbohydr.
Res., 2011, 346, 1320–1326; (h) H.-L. Zhang, X.-P. He,
Q. Deng, Y.-T. Long, G.-R. Chen and K. Chen, Carbohydr.
Res., 2012, 354, 32–39; (i) M. J. Clemente, J. Fitremann,
3133–3159; (b) L. A. Estroff and A. D. Hamilton, Chem.
Rev., 2004, 104, 1201–1217; (c) C. Sanchez, H. Arribart and
M. G. Guille, Nat. Mater., 2005, 4, 277–287; (d) N. M.
Sangeetha and U. Maitra, Chem. Soc. Rev., 2005, 34,
821–836; (e) M. de Loos, B. L. Feringa and J. H. van Esch,
Eur. J. Org. Chem., 2005, 3615–3631; ( f ) M. George and
R. G. Weiss, Acc. Chem. Res., 2006, 39, 489–497; (g) Z. Yang,
G. Liang and B. Xu, Acc. Chem. Res., 2008, 41, 315–326.
M. Mauzac, J. L. Serrano and L. Oriol, Langmuir, 2011, 27, 21 C. Baddeley, Z. Yan, G. King, P. M. Woodward and
15236–15247; ( j) M. P. Leal, M. Assali, I. Fernandez and J. D. Badjic, J. Org. Chem., 2007, 72, 7270–7278.
N. Khiar, Chem. Eur. J., 2011, 17, 1828–1836; 22 (a) R. L. Mellies, C. L. Mehltretter and C. E. Rist, J. Am.
–
(k) M. J. Clemente, P. Romero, J. L. Serrano, J. Fitremann
and L. Oriol, Chem. Mater., 2012, 24, 3847–3858;
Chem. Soc., 1951, 73, 294–296; (b) T. G. Bonner, E. J. Bourne
and D. Lewis, J. Chem. Soc., 1965, 7453–7458.
(l) M. Assali, J.-J. Cid, I. Fernandez and N. Khiar, Chem. 23 N. Bragnier and M.-C. Scherrmann, Synthesis, 2005,
Mater., 2013, 25, 4250–4261. 814–818.
18 K. J. V. Paul and D. Loganathan, Tetrahedron Lett., 2008, 49, 24 S. Nagarajan, T. Mohan Das, P. Arjun and N. Raaman,
6356–6359. J. Mater. Chem., 2009, 19, 4587–4596.
This journal is ©The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2014
New J. Chem., 2014, 38, 3015--3021 | 3021