Tuning methyl 4,6-O-benzylidene α-D-glucopyranosides' gelation ability by minor group modifications

Article abstract of DOI:10.1016/j.carres.2012.03.021

Ten methyl 4,6-O-benzylidene α-d-glucopyranosides were synthesized for the purpose of studying systematically the effect of small group changes at position 4 of the aromatic ring on the ability to gelate organic solvents. The gelation properties are discussed on the basis of small angle X-ray scattering (SAXS), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) measurements, and scanning electron microscopy (SEM) observations. Sol-gel transition temperatures were determined simultaneously by DSC and temperature-dependent FTIR measurements. The current study emphasizes that carbohydrates furnish not only valuable information about structural requirements for organogelator design, but also for molecular assembly systems in general.

Full text of DOI:10.1016/j.carres.2012.03.021

Carbohydrate Research 353 (2012) 69–78
Contents lists available at SciVerse ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Tuning methyl 4,6-O-benzylidene
minor group modifications
a-D-glucopyranosides’ gelation ability by
Marlon F. Abreu a, Vítor T. Salvador a, Letícia Vitorazi a, Carlos E.N. Gatts b, Denise R. dos Santos b,
Rosana Giacomini b, Sergio L. Cardoso b, Paulo C.M.L. Miranda a,
⇑
a Institute of Chemistry, State University of Campinas, UNICAMP, Cidade Universitária Zeferino Vaz, Barão Geraldo, Campinas, P.O. Box: 6154, SP 13083-970, Brazil
b Northern State University of Rio de Janeiro, UENF, Campos dos Goytacazes, RJ, Brazil
a r t i c l e i n f o
a b s t r a c t
Article history:
Ten methyl 4,6-O-benzylidene a-D-glucopyranosides were synthesized for the purpose of studying sys-
Received 5 February 2012
Received in revised form 14 March 2012
Accepted 19 March 2012
Available online 3 April 2012
tematically the effect of small group changes at position 4 of the aromatic ring on the ability to gelate
organic solvents. The gelation properties are discussed on the basis of small angle X-ray scattering (SAXS),
Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) measurements,
and scanning electron microscopy (SEM) observations. Sol–gel transition temperatures were determined
simultaneously by DSC and temperature-dependent FTIR measurements. The current study emphasizes
that carbohydrates furnish not only valuable information about structural requirements for organogelator
design, but also for molecular assembly systems in general.
Keywords:
LMOG
SAFIN
Organogelators
Self-assembly
Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction
diverse applicability, very little is known about their behavior
and mechanism of gelation.9 So, it is hitherto unclear how to syn-
Low molecular mass organogelators (LMOG) are an important
class of functional compounds formed by small organic molecules
(PM <3000) and are capable of creating a supramolecular structure
with the ability to immobilize organic media, through anisotropic
self-recognition and self-assemblage.1 The interaction among
gelator monomers occurs through some functional groups that di-
rect the initial stacking in the construction of self-assembled fibril-
lar networks. These aggregates can retain solvent molecules in
nanopores of fibrillar networks through capillary effect.2 Gels pro-
duced by organogelators differ from polymeric gels, whose tridi-
mensional fibrous networks are formed by cross-linked covalent
bonds. In organogelators, the aggregation is accomplished by phys-
ical interactions, that is, coulombic, hydrogen bonding, dipole–
thesize a new class of gelator and the most of them are discovered
serendipitously.10 Several families of compounds with ability of
organic media gelation have been reported, and examples include
ureas,11 steroids,12 anthracenes,13 and monosaccharide deriva-
tives.14 However, in order to improve gelation ability, it is impor-
tant to synthesize and study the behavior of organogels to
understand their unique properties more profoundly. To achieve
this objective, intensive research has been focused on manipulat-
ing small changes in organogelator skeleton, focusing a refined
knowledge about optimization of gelation properties, mainly
strength and ability. In the case of 4,6-O-benzylidene-a-D-gluco-
pyranosides,14a anomeric carbon and the aromatic ring are the
main sites for structure modification and study of gelation process.
Insertions of groups such as nitro15 or amine16 at position 4 of the
aromatic ring modify its electronic density and significantly alter
the gelation ability. In this case, the electron withdrawing group
(nitro) demonstrated the best gelation capacity in comparison to
the amine group.17 However, variations both in the contribution
of aromatic ring electronic density and chain size have not yet been
explored simultaneously in order to evaluate van de Waals and
dipole, van der Waals,
p–p stacking, hydrophobic interactions, or
different combinations among them. Such types of non-covalent
interactions guarantee a peculiar property for these systems: the
thermoreversibility.3 Thermoreversible gelation has attracted the
interest of diverse academic as well as industrial groups due to
their potential applications as for example controlled drug deliv-
ery,4 chemical and physical molecular devices,5 synthesis of nano-
structured templates,6 oil recovery,7 and paintings restoration.8
Understanding the supramolecular architecture of these gelators
is an exciting and worthwhile challenge because despite their
p–p stacking contributions together. In this context, this work de-
scribes the synthesis of ten new glucose derivatives: five n-alkoxyl
substituents (electron donating series) and five n-alkoxycarbonyl
(electron withdrawing series) at position 4 of the aromatic ring.
Additionally, gels formed by new organogelators were character-
ized by FTIR, SEM, DSC, and SAXS in order to study the role of these
⇑
Corresponding author. Tel.: +55 19 35213083; fax: +55 19 35213023.
E-mail address: miranda@iqm.unicamp.br (P.C.M.L. Miranda).
0008-6215/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.carres.2012.03.021

70
M. F. Abreu et al. / Carbohydrate Research 353 (2012) 69–78
substituents in the gelation process and to advance our knowledge
of these systems.
4a–e and 7a–e were obtained through a benzylidene acetal forma-
tion with OH groups at positions 4 and 6 of methyl a-D-glucopyran-
oside (1) in DMF.21 All compounds prepared were characterized by
NMR, FTIR, and MS (see Section 4).
2. Results and discussion
2.1. Synthesis of methyl
2.2. Gelation test of compounds 4a–e and 7a–e
4,6-O-benzylidene-a-D-glucopyranoside derivatives
Gelation tests were carried out using 13 organic solvents at
different concentrations (between 10 and 150 mmol Lꢀ1) for the
gelators 4a–e and 7a–e (Table 1). Initially, the mixture was heated
in a vial close to the solvent boiling point in an oil bath. The vial
was kept inside the oil bath and was slowly cooled to room tem-
perature, which took approximately 1 h. Next, the vial was gently
agitated, inverted, and classified according to visual inspection.
When the solution in the vial was immobilized without any flow
after mechanical agitation, it was classified as a gel (G) as shown
in Figure 2. Other classifications included: partial self-supporting
precipitation (Pps), when sample showed immobilization of the sol-
vent similar to a gel, but mechanical agitation caused a visible sep-
aration of solid from the liquid phase; precipitation after cooling
(P); soluble (S) and insoluble at high temperature (I).14a
The glucose based gelators were synthesized by adapting meth-
odologies well described in the literature with very slight modifica-
tions (Fig. 1). Firstly, O-methyl acetal was prepared in acidic medium
to provide methyl a-D-glucopyranoside, 1, where HCl was generated
in situ by addition of few drops of thionyl chloride in anhydrous
methanol. The synthesis of 1 was made selectively under the
adopted conditions, that is, high temperature and long reaction
time, and the desired isomer was easily obtained from the reaction
media by crystallization.18 Alkylations of p-hydroxybenzaldehyde
and p-formylbenzoic acid were carried out using the corresponding
alkylation agents (n-alkyl bromide, n-CnH(2n+1)Br, where n = 2, 3, 4, 8,
or 16 C) and resulted in the formation of products 2a–e and 5a–e.19
The respective dimethylacetals 3a–e and 6a–e were prepared
by transacetalization reactions of 2a–e and 5a–e with trimethyl
orthoformate in acidic medium.20 Finally, the two series of gelators
For all gels, the heating/cooling process could be repeated sev-
eral times, indicating that these gels are completely thermorevers-
OH
OH
MeOH
SOCl2
reflux, 6 days
O
O
HO
HO
HO
HO
OH
OH
OCH3
OH
1
O
H
O
H
MeO
OMe
O
1
NaOEt/EtOH
CH(OMe)3
O
RO
O
Br-R
MeOH/HCl(aq
rt, 2-4days
)
p-TSA/DMF
HO
70ºC, 48h
80ºC, 4-6 h
OH
OH
OR
OR
OMe
2a-e
3a-e
4a-e
O
O
H
O
H
MeO
OMe
O
O
O
CH(OMe)3
1
K2CO3/DMF
O
Br-R
MeOH/HCl
rt, 2-4 days
p-TSA/DMF
HO
RO
70ºC, 12h
80 ºC, 4-6 h
OH
OMe
OH
O
OR
O
OR
5a-e
6a-e
7a-e
R = CnH2n+2
a, n = 2
b, n = 3
c
,
n = 4
d, n = 8
e
, n = 16
Figure 1. Synthesis of the LMOG of both series 4a–e and 7a–e.

M. F. Abreu et al. / Carbohydrate Research 353 (2012) 69–78
71
Table 1
Gelation test for compounds 4a–e (n-alkoxyl substituents, the electron donating series) and 7a–e (n-alkoxycarbonyl, the electron withdrawing series) in
different organic solvents
Concentration ranges are expressed in mmol Lꢀ1 below descriptors, which are (G) for gel formation after cooling without any flow after gentle
mechanical perturbation; (Pps) for solution immobilization after cooling, but with partial liquid flow after gentle mechanical perturbation; (P) for
precipitation after cooling; (I) for insolubility at high temperature; and (S) for solubility at low temperatures.
ible. By analyzing Table 1, various inferences could be made for the
characterization of gelation behavior of organogelators. In general,
comparing the two series, n-alkoxycarbonyl derivatives (electron
withdrawing series, 7a–e) presented better gelation properties by
immobilizing two more solvents than the other series: acetone
and dimethylsulfoxide. Among 10 different compounds of both
series, only 7a was unable to form gel under the conditions stud-
ied. Another notable difference between these two groups was
observed in the aforementioned concentration range. The other
n-alkoxycarbonyl derivatives (electron withdrawing series, 7b–e)
formed gels in various solvents and at a wider range of concentra-
tions than the electron rich series (4a–e). Interestingly, certain
compounds of the electron deficient series (7d–e) gelated within
the whole concentration range studied (10-150 mmol Lꢀ1). In
aprotic solvents with intermediate dielectric constant, that is,
dichloromethane and acetone, all compounds but 7e were soluble
at room temperature. On the other side, protic polar solvents such
as n-butanol and n-propanol were gelated by 4b–e and 7b–e, even
methanol was gelated by compounds 4d–e and 7d–e. In the case of
these solvents gelation took longer than 1 h, sometimes overnight
(methanol), and therefore suggestive of hydrogen bonding compe-
tition between gelator and solvent during the gelation process.
Interestingly, compounds 4e and 7e revealed excellent gelation
ability in comparison to the others, gelling from nonpolar to polar
solvents. Between these two compounds, gelator 7e was found to
be the most efficient as it was capable of forming gel in a wider
range of solvents and concentrations, even immobilizing acetone
and dimethylsulfoxide as well. This characteristic is less common
in most of gelators found in the literature, which gelate only a
narrow range of solvents and concentration.14a,22 These results
allowed to conclude that the presence of long alkyl chains in both
series enhanced the ability to gelate various organic solvents.
This may be possibly due to the contribution of van der
Waals interaction and has been previously described for gelator
methyl 4,6-O-benzylidene-a-D-glucopyranoside in the litera-
ture.14a However, it should be noted that even gelators with short-
er alkyl chains formed gels, although in a restricted range, and
could be classified as good gelators. Finally, n-alkoxycarbonyl
derivative series exhibited better gelation properties in compari-
son to the n-alkoxyl.

72
M. F. Abreu et al. / Carbohydrate Research 353 (2012) 69–78
be found, principally for the molecules that can make hydrogen
bonds.23 However relatively few studies have investigated thermal
evolution of samples during sol–gel transition.24 In this work,
experiments were conducted varying temperature from 50 °C to
30 °C for the purpose of being in close proximity to the sol–gel tran-
sition temperature in the chosen solvent (p-xylene). Initially, gels
were prepared in p-xylene at a concentration of 30 mmol Lꢀ1 for
both series. Next, all samples were analyzed using FTIR coupled
with a thermal system and the spectra in 3160–4000 cmꢀ1 region
were acquired (Fig. 3). At the highest temperature (50 °C) all sam-
ples were found in sol phase and exhibited a peak at 3576 cmꢀ1
,
referring to the stretching vibration of the free OH group. Upon
cooling the system to 30 °C, it is clearly observed that the OH peak
broadens and substantially shifted toward a lower wavenumber
(red-shift), indicating that organogelators aggregated and assem-
bled themselves through hydrogen bonding. The 1640–1780 cmꢀ1
region (C@O stretching region) was also examined for compounds
7b–e, but they had not revealed any significant difference among
solutions and gels spectra. This behavior is the result of initial
self-assembly of primary structure driven by the formation of a fi-
brous network. It is common to encounter these types of interac-
tions in various derivatives of monosaccharide,14d but in this
work it was evidently predominant even with the increasing of
the alkyl chain, which could favor van der Waals interactions in
both these series. Nevertheless, we believe that the interaction
among alkyl groups also contributed in the self-assembly of the
secondary structure of fibrils as can be inferred from Table 1, where
increase of the van der Waals force contribution augmented scope
and rigidity of the gels.
Figure 2. Photography of the organogel produced by compound 4e in p-xylene at
30 mmol Lꢀ1
.
2.3. FTIR analyses
2.4. Morphological study with SEM
The FTIR spectroscopy with temperature variation was used to
probe the intermolecular interactions among gelator molecules in
both series (4b–e and 7b–e) during gel formation. Several examples
reported in the literature that use FTIR to characterize the primary
interactions of the supramolecular structure of organogelators can
The scanning electron microscopy (SEM)25 was used for morpho-
logic characterization of the supramolecular aggregate formed by
gelators of the series 4b–e and 7b–e obtained from the xerogel in
p-xylene. All these organogelators are aggregated in self-assembled
fibrillar networks, which are responsible for the immobilization
Figure 3. FTIR transmittance spectra of the gels 4b–e (up) and 7b–e (bottom) in p-xylene (30 mmol Lꢀ1) at 50 °C (sol, at left) and 30 °C (gel, at right).

M. F. Abreu et al. / Carbohydrate Research 353 (2012) 69–78
73
Figure 4. SEM images of the xerogel prepared from 4b–e (up) and 7b–e (bottom) in p-xylene.
of the solvent as can be observed from Figure 4. The morphology
adopted is preferentially the cylindrical or tape-like organized
aggregates. They have approximately 500 nm width for 4b and 7b,
results also confirm the thermoreversibility of the organogelators.
Although large alkyl chain LMOG derivatives present a broader
capability of solvent immobilization, as seen in gelation tests, small
alkyl chain LMOG derivatives present higher Tgel. Both results, and
also FTIR analyses, indicate that though van der Waals interaction
plays an important role in gel formation, the hydrogen bonding is
the driving force in self assembling and fibril structural mainte-
nance. Alkyl chain lengthening obstructs or limits hydrogen bond
interactions in the fibrils, reducing Tgel, but the raise of van der
Waals interactions among distinct fibrils during the building of
the secondary structure helps to immobilize a greater number of
solvent molecules, even polar protic ones. In other words, the gela-
tors with short alkyl chain undergo a more ordered molecular
stacking during self-organization process than the gelators with
long alkyl chains do. These results are in agreement with the
microscopic observations (7b, Fig. 4, expanded view), where the
short alkyl chain gelator built visually more compact network, that
is, the adopted morphology of the fibers appears more regularly
arranged.
and 1 lm for 4c–e and 7c–e. They are also hundreds of micrometers
in length, which is characteristic of one-dimensional stacking and
anisotropic self-assembly. It is worth noting that fibers forming
the tangled network are composed of various fibrils.26 This type of
secondary self-assembly among fibers justifies the large diameter
of microfibers observed for the organogelators with long chain alkyl
group, for example, 16 C in 4e and 7e. No significant difference was
observed among the two series, just the increasing in the fiber diam-
eter with the growth of the alkyl chain.
2.5. DSC analyses
The thermal behavior of the organogels formed by 4b–e and
7b–e in p-xylene was investigated using differential scanning cal-
orimetry (DSC)27 and results are presented in Figure 5 as plots of
Tgel versus gelator concentration. In general it was observed that
sol–gel transition temperature increases with the molar concentra-
tion and decreases with alkyl chain size in both series of the gela-
tors. Curiously, this last behavior is in accordance with the melting
point found for the solid compounds. The gelators with shorter al-
kyl chain showed the higher melting points (mp 4b 146 °C, 4c
141 °C, 4d 137 °C, 4e 130 °C, and 7b 148 °C, 7c 146 °C, 7d 138 °C,
7e 132 °C). Finally, cycles of cooling/heating could be carried out
without any loss in gelation ability or modification on Tgel, proving
the process thermoreversibility and that any thermal history can
be easily erased by heating above Tgel. The effect of thermal hyster-
esis presented in Figure 6 is common in gels and the obtained
2.6. SAXS analyses
Results obtained by SEM analyses supported the use Guinier’s
(Eq. 1), appropriate for cylindrical-shaped systems.28
2
f
uð
p
ꢁ r ꢁ
D
q
Þ g
ꢀq2r2
I ¼
ꢁ expð
Þ
ð1Þ
q
4
where,
u
is the concentration of gelator, r is radius of gyration, Dq
is the electronic density contrast between the aggregates and the
surrounding medium. Thus, angular coefficient (ꢀr2/4) obtained in
Figure 5. DSC curves of the Tgel for gels of4c–e (left) and 7c–e in (right) p-xylene at different concentrations (mmol Lꢀ1).

74
M. F. Abreu et al. / Carbohydrate Research 353 (2012) 69–78
Figure 6. Heating and cooling cycles in a DSC thermogram of gel 4e in p-xylene at 20 mmol Lꢀ1
.
the linear region by plotting a graph of lnꢁ(Iꢁq) vs q2, gives the radius
of the fiber for cylindrical aggregates.29 Once the images obtained
by SEM show the presence of cylindrical aggregates, the radius of
gyration can be determined by using Guinier equation. As can be
observed from Figures 7 and 8 for gels 4c–e and 7c–e in p-xylene,
agreement with the SEM, which also showed different diameters for
microfibers. When gelators of both series were compared, no signif-
icant change in relation to size of alkyl chain was observed, except
the fiber of the gel 7e/p-xylene that showed a slight increase in its
radius, that is, 4.8–9.9 nm. Likewise, the increase in concentration
did not result in any prominent change. Therefore, only the estima-
tion of radius of the fiber in gel phase was possible under the
adopted conditions.
the profile showed
a
range of linear and angular
coefficients in that region indicating the existence of a polydisperse
system possessing nanofibers with different radii. These data are in
Figure 7. Photography SAXS data plots for gels of 4c–e and 7c–e, in p-xylene at 30 mmol Lꢀ1
.
Figure 8. Photography SAXS data plots for gels of 4e and 7e in p-xylene at 15, 30 and 40 mmol Lꢀ1
.

M. F. Abreu et al. / Carbohydrate Research 353 (2012) 69–78
75
distillation. Compound 2e was fussily purified by flash chromatog-
raphy in silica gel (hexane/ethyl acetate; 95:05, Rf 0.4).
3. Conclusion
Compound 2a (73% yield); IR (NaCl, cmꢀ1):
m 2985, 2935, 2738,
This study has demonstrated that among several methyl 4,
6-O-benzylidene
1692, 1260, 1163, 1040, 836; 1H NMR (250 MHz, CDCl3, TMS) d
(ppm): 9.87 (s, 1H), 7.82 (d, 2H, J = 8.9 Hz), 6.98 (d, 2H,
J = 8.6 Hz), 4.12 (q, 2H, J = 7.0 Hz), 1.45 (t, 3H, J = 7.0 Hz); EI-MS,
m/z 150 [M]+Å, 121 [HO–C6H4–C„O]+, 93 [HO–C6H4]+. Compound
a-D-glucopyranosides (4b–e and 7b–e) acting as
efficient gelators for diverse organic solvents, the hydrogen-bond
remains to be the main driving force for self-assembly despite alkyl
chain size lengthening or electron density at the aromatic ring.
Nevertheless, van der Waals interaction plays an important role
in broadening the scope of solvent immobilization as long chain
derivatives were capable of gelling even polar protic ones. Calorim-
etry showed Tgel increases with the molar concentration but de-
creases with alkyl chain size in both series of the gelators, which
was interpreted as being a hurdled self assemblage with alkyl chain
lengthening. DSC analyses also showed well defined peaks during
sol–gel transition that is coherent with hydrogen bond driven
assembling. FTIR spectroscopy positively confirmed that the chief
intermolecular interaction among gelator molecules in both series
(4b–e and 7b–e) during gel formation is the hydrogen bond, despite
the implemented structural modifications. SAXS study showed a
polydisperse system possessing nanofibers with different radii.
There was no significant change in radii among gelators of both ser-
ies, although LMOG with larger alkyl chains presented larger radii
suggesting a higher tendency for fibril merging in larger alkyl chain
derivatives. As described elsewhere, a one-dimensional intermolec-
ular hydrogen bonding network to both hydroxyl groups must
occur for efficient formation of a gel.14a In addition of such require-
ment the presence of junction nodes and the enhancement of fiber
thickness are also important to improve the organogelator effi-
2b (75% yield); IR (NaCl, cmꢀ1):
m 2967, 2876, 2734, 1692, 1602,
1261, 1160, 834; 1H NMR (250 MHz, CDCl3, TMS) d (ppm): 9.88
(s, 1H), 7.82 (d, 2H, J = 8.8 Hz), 6.99 (d, 2H, J = 8.8 Hz), 4.00 (t, 2H,
J = 6.5 Hz), 1.85 (h, 2H, J = 7.3 Hz), 1.05 (t, 3H, J = 7.5 Hz);EI-MS,
m/z 164 [M]+Å, 121 [HO–C6H4–C„O]+, 93 [HO–C6H4]+. Compound
2c (73% yield); IR (NaCl, cmꢀ1):
m 2964, 2872, 2733, 1692, 1600,
1260, 1158, 828; 1H NMR (250 MHz, CDCl3, TMS) d (ppm): 9.87
(s, 1H), 7.82 (d, 2H, J = 8.8 Hz), 6.99 (d, 2H, J = 8.7 Hz), 4.04 (t, 2H,
J = 6.5 Hz), 1.80 (p, 2H, J = 6.9 Hz), 1.50 (h, 2H, J = 7.5 Hz), 0.99 (t,
3H, J = 7.3 Hz); EI-HRMS, calculated for C11H14O2 m/z 178.0994,
found: m/z 178.0898 [M]+Å, 121.0211 [HO–C6H4–C„O]+ (calcd
121.0290), 93.0286 [HO–C6H4]+ (calcd 93.0340). Compound 2d
(66% yield); IR (NaCl, cmꢀ1):
m 2931, 2856, 2741, 1697, 1600,
1254, 1156, 832; 1H NMR (250 MHz, CDCl3, TMS) d (ppm): 9.87
(s, 1H), 7.83 (d, 2H, J = 8.8 Hz), 6.99 (d, 2H, J = 8.7 Hz), 4.03 (t, 2H,
J = 6.5 Hz), 1.81 (p, 2H), 1.29–152 (m, 10H), 0.89 (t, 3H,
J = 6.6 Hz); EI-MS, m/z 234 [M]+Å, 121 [HO–C6H4–C„O]+, 93 [HO–
C6H4]+. Compound 2e (isolated as a white solid, mp 44 °C, in 73%
yield); IR (KBr, cmꢀ1):
m 2913, 2852, 2730, 1691, 1603, 1255,
1174, 837; 1H NMR (250 MHz, CDCl3, TMS) d (ppm): 9.88 (s, 1H),
7.82 (d, 2H, J = 8.8 Hz), 6.99 (d, 2H, J = 8.8 Hz), 4.03 (t, 2H,
J = 6.5 Hz), 1.81 (p, 2H, J = 6.7 Hz), 1.26–1.49 (m, 26H), 0.88
ciency. The occurrence of these characteristics permits
or -galactose 4,6-O-benzylidene derivatives to be better gelators
than
-glucose derivatives.14a Nevertheless, the attachment of large
D-mannose
(t, 3H, J = 6.9 Hz); EI-HRMS, calculated for
C23H38O2 m/z
D
346.2872, found: m/z 346.2749 [M]+Å, 121.0077 [HO–C6H4–C„O]+
D
(calcd 121.0290).
alkyl groups promoted merging among different fibrils creating a
van der Waals based three-dimensional fiber network with hydro-
gen bonded based fibers, helping to immobilize a greater number of
solvents. Despite this secondary interaction, the supramolecular
core stands fibrillar and undergoes self-assemblage by hydrogen
bonds, following the model described elsewhere.14a–d We believe
that the abovementioned findings may be useful for discovery, de-
sign, or improvement of new gelators. This opens up the possibility
that the carbohydrate library provided by nature can be modified
even further, in particular to the rational design of molecular
assemblies with a very defined function.
4.1.1.2. Compounds 5a–e.20 To a mixture of 4-formylbenzoic acid
(1.5 g, 0.01 mol) and potassium carbonate (2.76 g, 0.02 mol) in dry
N,N-dimethylformamide (30 mL), the corresponding n-alkyl bro-
mide was added. The solution was maintained at 70 °C under mag-
netic stirring for 12 h. The solvent was evaporated under reduced
pressure and the product was separated by solvent extraction
(dichloromethane/water, 50:10 mL). The organic phase was dried
with anhydrous sodium sulfate and evaporated under reduced
pressure furnishing yellowish liquids for compounds 5a–d and a
white solid for 5e. Compounds 5a–d were purified by distillation
leading to the formation of colorless products and compound 5e
was purified flash chromatography in silica gel (hexane/ethyl ace-
tate; 95:05, Rf 0.3).
4. Experimental section
Compound 5a (73% yield); IR (NaCl, cmꢀ1):
m 2975, 2837, 2732,
4.1. Synthesis of compounds
1721, 1709, 1275, 1102, 764; 1H NMR (250 MHz, CDCl3, TMS) d
(ppm): 10.10 (s, 1H), 8.20 (d, 2H, J = 8.2 Hz), 7.95 (d, 2H,
J = 8.5 Hz), 4.42 (q, 2H, J = 7.0 Hz), 1.42 (t, 2H, J = 7.2 Hz); EI-MS,
m/z 178 [M]+Å, 149 [HO2C–C6H4–C„O]+, 133 [O„C–C6H4–CHO]+.
4.1.1. Methyl
Prepared as described elsewhere and isolated as white solid:
3600–3050,
a-
D-glucopyranoside (1)
mp 165-166 °C (lit.164–165 °C).18IR (KBr, cmꢀ1):
m
3547, 2915, 1036; 1H NMR (400 MHz, D2O) d (ppm): 4.73 (d, 1H,
J1-2 = 3.6 Hz, H-1), 3.77–3.81 (m, 1H), 3.65–3.69 (m, 1H), 3.54–
3.60 (m, 2H), 3.46–3.49 (m, 1H), 3.33 (s, 3H, OCH3), 3.29–3.31
(m, 1H); 13C NMR (100 MHz, D2O) d (ppm) 99.3, 73.1, 71.6, 71.2,
69.5, 60.5, 55.0. TOF-MS, m/z calculated for C6H11O5+[MꢀOCH3]+
163.0607, found: m/z 163.0636.
Compound 5b (75% yield); IR (NaCl, cmꢀ1):
m 2976, 2879, 2734,
1721, 1708, 1272, 1104, 762; 1H NMR (250 MHz, CDCl3, TMS) d
(ppm): 10.07 (s, 1H), 8.20 (d, 2H, J = 8.5 Hz), 7.95 (d, 2H,
J = 8.2 Hz), 4.32 (t, 2H, J = 6.7 Hz), 1.82 (h, 2H, J = 7.2 Hz), 1.04 (t,
3H, J = 7.5 Hz); EI-MS, m/z 192 [M]+Å, 151 [H2O2C–C6H4–CHO]+,
133 [O„C–C6H4–CHO]+. Compound 5c (82% yield); IR (NaCl,
cmꢀ1):
m
2957, 2879, 2734, 1722, 1709, 1282, 1106, 759; 1H NMR
4.1.1.1. Compounds 2a–e.19
4-Hydroxybenzaldehyde (244 mg,
(250 MHz, CDCl3, TMS) d (ppm): 10.10 (s, 1H), 8.20 (d, 2H,
J = 8.3 Hz), 7.95 (d, 2H, J = 8.4 Hz), 4.36 (t, 2H, J = 6.7 Hz), 1.78 (p,
2H, J = 7.2 Hz), 1.50 (h, 2H, J = 7.3 Hz), 0.98 (t, 3H, J = 7.3 Hz);
EI-MS, m/z 205 [MꢀH]+, 151 [H2O2C–C6H4–CHO]+, 133 [O„C–
2 mmol) was added to a solution of 46 mg (2 mmol) of sodium eth-
oxide in 12 mL of ethanol and stirred until completely consumed.
Solution was kept under reflux (70 °C) with magnetic stirring for
20 min. The corresponding alkylation agent (n-alkyl bromide,
2 mmol) was added to the system and the temperature was main-
tained at 70 °C with stirring for 48 h. Compounds 2a-d were isolated
by solvent extraction (ethyl acetate/water, 3:1) and then purified by
C6H4–CHO]+. Compound 5d (80% yield); IR (NaCl, cmꢀ1):
m 2963,
2852, 1721, 1279, 1110, 726; 1H NMR (250 MHz, CDCl3, TMS) d
(ppm): 10.10 (s, 1H), 8.20 (d, 2H, J = 8.3 Hz), 7.95 (d, 2H,
J = 8.5 Hz), 4.36 (t, 2H, J = 6.7 Hz), 1.79 (p, 2H, J = 6.7 Hz),

76
M. F. Abreu et al. / Carbohydrate Research 353 (2012) 69–78
1.29–1.48 (m, 12H), 0.88 (t, 3H, J = 6.5 Hz); EI-MS, m/z 262[M]+Å,
151 [H2O2C–C6H4–CHO]+, 133 [O„C–C6H4–CHO]+. Compound 5e
(isolated as a white solid, mp 52 °C, in 61% yield); IR (KBr, cmꢀ1):
C6H4–C„O]+. Compound 6b (85% yield); IR (NaCl, cmꢀ1):
m 2974,
2828, 1719, 1279, 1106, 1056, 762; 1H NMR (250 MHz, CDCl3,
TMS) d (ppm): 8.05 (d, 2H, J = 8.3 Hz), 7.50 (d, 2H, J = 8.3 Hz),
5.44 (s, 1H), 4.28 (t, 2H, J = 6.7 Hz), 3.33 (s, 6H), 1.80 (h, 2H,
J = 7.2 Hz), 1.03 (t, 3H, J = 7.4 Hz); EI-MS, m/z 207[CH3O@CH–
C6H4–CO2C3H7]+, 179 [H(CH3O)2C–C6H4–C„O]+. Compound 6c
m
2960, 2916, 2854, 1724, 1282, 1124, 753; 1H NMR (250 MHz,
CDCl3, TMS) d (ppm): 10.10 (s, 1H), 8.20 (d, 2H, J = 8.3 Hz), 7.95
(d, 2H, J = 8.4 Hz), 4.35 (t, 2H, J = 6.7 Hz), 1.78 (p, 2H, J = 6.9 Hz),
1.25–1.47 (m, 26H), 0.88 (t, 3H, J = 6.3 Hz); EI-HRMS, calculated
for C24H38O3 m/z 374.2821, found: m/z 374.2845 [M]+Å, 151.0409
[H2O2C–C6H4–CHO]+ (calcd 151.0395), 133.0285 [O„C–C6H4–
CHO]+ (calcd 133.0290).
(77% yield); IR (NaCl, cmꢀ1):
m 2990, 2832, 1724, 1280, 1105,
1056, 761; 1H NMR (250 MHz, CDCl3, TMS) d (ppm): 8.04 (d, 2H,
J = 8.4 Hz), 7.52 (d, 2H, J = 8.1 Hz), 5.44 (s, 1H), 4.32 (t, 2H,
J = 6.5 Hz), 3.33 (s, 6H), 1.76 (p, 2H, J = 7.0 Hz), 1.48 (h, 2H,
J = 7.8 Hz), 0.98 (t, 3H, J = 7.3 Hz); EI-MS, m/z 251 [MꢀH]+, 221
[CH3O@CH–C6H4–CO2C4H9]+, 179 [H(CH3O)2C–C6H4–C„O]+. Com-
4.1.1.3. Compounds 3a–e and 6a–e21 Starting material (0.01 mol
of 2a–e or 5a–e) and trimethyl orthoformate (1.59 g, 0.015 mol) in
1.5 mL of methanol were stirred at room temperature. Two drops
of concentrated hydrochloric acid were added to this solution.
Procedures for compounds 2a–d were left under stirring for two
days at room temperature, and reactions with compounds 5a–d
were kept for only 6 h under agitation at room temperature. Never-
theless, compounds 2e and 5e were prepared similarly to their ana-
logues, but under somewhat higher temperature (50 °C) and longer
reaction times (four days). After these periods, all products were iso-
lated by neutralization with KOH dissolved in methanol followed by
evaporation of volatiles under reducedpressure, and extraction with
ethyl ether and water (8 mL, 3:1). Organic phases were dried over
anhydrous Na2SO4 followed by volatile removing on rotary evapora-
tor. The compounds 3a–d and 6a–d were purified by distillation at
reduced pressure resulting in colorless liquids. Compounds 3e and
6e were purified by flash chromatography in silica gel (hexane/ethyl
acetate, 95:05, Rf 0.5 and 0.4, respectively).
pound 6d (75% yield); IR (NaCl, cmꢀ1):
m 2956, 2860, 1722, 1267,
1106, 1060, 759;1H NMR (250 MHz, CDCl3, TMS) d (ppm): 8.05
(d, 2H, J = 8.4 Hz), 7.53 (d, 2H, J = 8.3 Hz), 5.44 (s, 1H), 4.31 (t, 2H,
J = 6.7 Hz), 3.33 (s, 6H), 1.77 (p, 2H, J = 7.2 Hz), 1.28–1.46 (m,
10H), 0.88 (t, 3H, J = 7.0 Hz); EI-MS, m/z 277.1[CH3O@CH–C6H4–
CO2C8H17]+, 179 [H(CH3O)2C–C6H4–C„O]+. Compound 6e (isolated
as a white solid, mp 48 °C, in 73% yield); IR (KBr, cmꢀ1):
m 2955,
2854, 1719, 1273, 1105, 1050, 759; 1H NMR (250 MHz, CDCl3,
TMS) d (ppm): 8.04 (d, 2H, J = 8.3 Hz), 7.53 (d, 2H, J = 8.1 Hz),
5.44 (s, 1H), 4.31 (t, 2H, J = 6.6 Hz), 3.33 (s, 6H), 1.76 (p, 2H, J = 7.
Hz), 1.23 (m, 26H), 0.88 (t, 3H, J = 6.7 Hz); EI-HRMS, m/z calculated
for
C
25H41O3 [MꢀOCH3]+ 389.3056, found: m/z 389.3313
[CH3O@CH–C6H4–CO2C16H33]+, 374.3141 [O@CH–C6H4–CO2C16
+Å
H33
]
(calcd 374.2821).
4.1.1.4. Compounds 4a–e and 7a–e.22 Methyl
a-D-glucopyrano-
side (1, 0.97 g, 5 mmol), dimethylacetal derivatives 3a–e or 6a–e
(5 mmol), dry N,N-dimethylformanide (4 mL), and p-toluenesul-
fonic acid monohydrate (p-TSA, 2.5 mg) were mixed and heated
at 80 °C for 4–6 h. Then, DMF was evaporated under reduced pres-
sure, and a solution of 2% NH4OH (5 mL) was added to the residue.
The resulting suspension was stirred and heated at 80 °C for 1 h,
and after that cooled in an ice bath. The final product was filtered
off and washed with distilled water (3 ꢂ 10 mL), resulting in a
white solid which was dried in a high vacuum pump at room tem-
perature. Compounds 4a and 7a were purified by recrystallization
from ethyl acetate, and the other ones were purified by column
chromatography in silica gel with dichloromethane/ethyl acetate
3:1 (4b and 7b), or alumina with dichloromethane/methanol
95:05 (4c–e and 7c–e).
Compound 3a (81% yield); IR (NaCl, cmꢀ1):
m 2983, 2821, 1610,
1512, 1242, 1052, 830; 1H NMR (250 MHz, CDCl3, TMS) d (ppm):
7.35 (d, 2H, J = 8.5 Hz), 6.88 (d, 2H, J = 8.8 Hz), 5.34 (s, 1H), 4.03
(q, 2H, J = 7.0 Hz), 3.30 (s, 6H), 1.41 (t, 3H, J = 7.0 Hz); EI-MS, m/z
196 [M]+Å, 165 [CH3O@CH–C6H4–OC2H5]+, 150 [O@CH–C6H4–
OC2H5]+Å. Compound 3b (70% yield);IR (NaCl, cmꢀ1):
m 2964,
2825, 1611, 1513, 1246, 1055, 831; 1H NMR (250 MHz, CDCl3,
TMS) d (ppm): 7.36 (d, 2H, J = 8.6 Hz), 6.88 (d, 2H, J = 8.7 Hz),
5.34 (s, 1H), 3.92 (t, 3H, J = 6.5 Hz), 3.30 (s, 6H), 1.80 (h, 2H,
J = 7.3 Hz), 1.03 (t, 3H, J = 7.4 Hz); EI-MS, m/z 210.1[M]+Å, 179.1
[CH3O@CH–C6H4–OC3H7]+, 164.1 [O@CH–C6H4–OC3H7]+Å. Com-
pound 3c (62% yield); IR (NaCl, cmꢀ1):
m 2957, 2820, 1610, 1507,
1242, 1055, 818; 1H NMR (250 MHz, CDCl3, TMS) d (ppm): 7.34
(d, 2H, J = 8.7 Hz), 6.88 (d, 2H, J = 8.8 Hz), 5.34 (s, 1H), 3.96 (t, 2H,
J = 6.5 Hz), 3.31 (s, 6H), 1.76 (p, 2H, J = 6.6 Hz), 1.49 (h, 2H,
J = 7.5 Hz), 0.97 (t, 3H, J = 7.3 Hz); EI-HRMS, m/z calculated for
Compound 4a (isolated as white needle-like crystals in 66%
yield, mp 188–190 °C,½a D20
ꢃ
+85 (c 0.5 g/100 mL, MeOH); IR (KBr, cmꢀ1):
m 3180–3616,
C
12H17O2 [MꢀOCH3]+ = [CH3O@CH–C6H4–OC4H9]+ m/z 193.1229,
2997, 2848, 1617, 1513, 1376, 1255, 1076, 1039, 820; 1H NMR
(250 MHz, DMSO-d6, TMS) d (ppm): 7.34 (d, 2H, J9-10 = 8.7 Hz,
H-9), 6.89 (d, 2H, J10-9 = 8.7 Hz, H-10), 5.49 (s, 1H, H-7), 5.16 (d,
1H, JOH-3 = 5.0 Hz, OH), 4.98 (d, 1H, JOH-2 = 6.5 Hz, OH), 4.63 (d,
1H, J1-2 = 3.7 Hz, H-1), 4.13 (dd, 1H, J6B-5 = 4.1 Hz, J6B-6A = 9.5 Hz,
H-6B), 4.01 (q, 2H, J12-13 = 7.5 Hz, H-12), 3.62–3.70 (m, 1H, H-6A),
5.52–3.62 (m, 2H, H-3, H-5), 3.34–3.37 (m, 2H, H-2, H-4), 3.33 (s,
3H, OCH3), 1.31 (t, 3H, H-13); 13C NMR (62.5 MHz, DMSO-d6,
TMS) d (ppm): 158.7, 129.9, 127.6, 113.6, 100.7, 100.4, 81.2, 72.3,
69.8, 68.0, 62.9, 62.3, 54.6, 14.5; TOF-MS, m/z calculated for
found: m/z 193.1203, 178.0967 [O@CH–C6H4–OC4H9]+Å (calcd
178.0994). Compound 3d (73% yield); IR (NaCl, cmꢀ1):
m 2928,
2828, 1617, 1512, 1242, 1057, 826; 1H NMR (250 MHz, CDCl3,
TMS) d (ppm): 7.35 (d, 2H, J = 8.6 Hz), 6.88 (d, 2H, J = 8.6 Hz),
5.34 (s, 1H), 3.94 (t, 2H, J = 6.5 Hz), 3.31 (s, 6H), 1.77 (p, 2H,
J = 6.6 Hz), 1.28–1.47 (m, 10H), 0.88 (t, 3H, J = 6.3 Hz); EI-HRMS:
calculated for C17H28O3 m/z 280.2038, found: m/z280.2093 [M]+Å,
+
249.1814[CH3O@CH–C6H4–OC8H17
]
(calcd 249.1855), 234.1648
+Å
[O@CH–C6H4–OC8H17
]
(calcd 234.1620). Compound 3e (isolated
2916,
as a white solid, mp 42 °C, in 71% yield); IR (KBr, cmꢀ1):
m
C16H22O7 326.1366, found: m/z 326.1366. Compound 4b (isolated
2846, 1620, 1517, 1246, 1049, 808; 1H NMR (250 MHz, CDCl3,
TMS) d (ppm): 7.34 (d, 2H, J = 8.6 Hz), 6.87 (d, 2H, J = 8.7 Hz),
5.41 (s, 1H), 3.97 (t, 2H, J = 6.6 Hz), 3.31 (s, 6H), 1.77 (p, 2H,
J = 6.5 Hz), 1.26–1.47 (m, 26H), 0.88 (t, 3H, J = 6.2 Hz); EI-MS, m/z
361.3 [CH3O@CH–C6H4–OC16H33]+, 346.3 [O@CH–C6H4–OC16H33]+Å.
as a white solid in 75% yield, mp 146–148 °C, ½a D20
ꢃ
+83 (c 0.6 g/
m 3196–3608, 2987, 2864, 1619,
100 mL, MeOH); IR (KBr, cmꢀ1):
1516, 1373, 1247, 1071, 1037, 802; 1H NMR (400 MHz, DMSO-d6,
TMS) d (ppm): 7.34 (d, 2H, J9-10 = 8.8 Hz, H-9), 6.90 (d, 2H, J10-9
=
8.8 Hz, H-10), 5.49 (s, 1H, H-7), 5.16 (d, 1H, JOH-3 = 5.2 Hz, OH),
4.98 (d, 1H, JOH-2 = 6.8 Hz, OH), 4.62 (d, 1H, J1-2 = 3.6 Hz, H-1),
4.13 (dd, 1H, J6B-5 = 4.4 Hz, J6B-6A = 9.8 Hz, H-6B), 3.91 (t, 2H, J12-13 =
6.8 Hz, H-12), 3.66 (t, 1H, J6A-6B,6A-5 = 10.0 Hz), 3.53–3.59 (m, 2H,
H-3, H-5), 3.31–3.36 (m, 2H, H-2, H-4), 3.33 (s, 3H, OCH3), 1.73
(h, 2H, J13 = 7,2 Hz, H-13), 0.96 (t, 3H, J14 = 7,4 Hz, 8.3 Hz, H-14);
Compound 6a (86% yield); IR (NaCl, cmꢀ1):
m 2982, 2827, 1714,
1277, 1105, 1062, 761; 1H NMR (250 MHz, CDCl3, TMS) d (ppm):
8.00 (d, 2H, J = 8.4 Hz), 7.50 (d, 2H, J = 8.0 Hz), 5.44 (s, 1H), 4.38
(q, 2H, J = 7.2 Hz), 3.33 (s, 6H), 1.40 (t, 3H, J = 7.1 Hz); EI-MS, m/z
223 [MꢀH]+, 193 [CH3O@CH–C6H4–CO2C2H5]+, 179 [H(CH3O)2C–

M. F. Abreu et al. / Carbohydrate Research 353 (2012) 69–78
77
13C NMR (100 MHz, DMSO-d6, TMS) d (ppm): 158.9, 130.1, 127.7,
113.8, 100.8, 100.5, 81.3, 72.4, 69.9, 68.9, 68.1, 62.4, 54.7, 22.0,
10.3; TOF-MS, m/z calculated for C17H24O7 340.1522, found: m/z
340.1518. Compound 4c (isolated as a white solid in 69% yield,
H-6A), 3.58–3.66 (m, 1H, H-2), 3.48–3.53 (m, 1H, H-4), 3.46
(s, 3H, OCH3), 2.86, (s, 1H, OH), 2.36 (d, 1H, JOH-2 = 9.5 Hz, OH),
1.80 (h, 2H, J14-15 = 7.2 Hz, H-14), 1.02 (t, 3H, J15-14 = 7.4 Hz, H-
15); 13C NMR (100 MHz, CDCl3, TMS) d (ppm): 166.3, 141.4,
131.2, 129.6, 126.4, 101.1, 99.7, 80.9, 72.9, 71.8, 68.9, 66.7, 62.3,
55.6, 22.1, 10.5; TOF-MS, m/z calculated for C18H24O8 368.1471,
found: m/z 368.1478. Compound 7c (isolated as a white solid in
mp 141–142 °C, ½a D20
ꢃ
+84 (c 0.6 g/100 mL, MeOH);IR (KBr, cmꢀ1):
m
= 3134–3606, 2962, 2869, 1616, 1516, 1373, 1245, 1079, 1030,
827; 1H NMR (400 MHz, CDCl3, TMS) d (ppm): 7.41 (d, 2H,
9-10 = 8.8 Hz, H-9), 6.89 (d, 2H, J10-9 = 8.8 Hz, H-10), 5.49 (s, 1H,
J
65% yield, mp 146–147 °C, ½a D20
ꢃ
+72 (c 0.5 g/100 mL, MeOH); IR
H-7), 4.78 (d, 1H, J1-2 = 3.9 Hz, H-1), 4.28 (dd, 1H, J6B-5 = 4.3 Hz,
J6B-6A = 9.7 Hz, H-6B), 3.96 (t, 2H, J12-13 = 6.5 Hz, H-12), 3.89–3.94
(m, 1H, H-3), 3.70–3.83 (m, 2H, H-5, H-6A), 3.58–3.64 (m, 1H,
H-2), 3.45–3.49 (m, 1H, H-4), 3.46 (s, 3H, OCH3), 3.05 (s, 1H, OH),
2.53 (d, 1H, JOH-2 = 9.2 Hz, OH), 1.77 (p, 2H, J13-14 = 6.6 Hz, H-13),
1.49 (h, 2H, J14-15 = 7.5 Hz, H-15), 0.98 (t, 3H, J15-14 = 7.4 Hz, H-
15); 13C NMR (100 MHz, CDCl3, TMS) d (ppm): 159.8, 129.3,
127.6, 114.3, 101.9, 99.8, 80.9, 72.8, 71.7, 68.9, 67.7, 62.4, 55.5,
31.2, 19.2, 13.8; TOF-MS, m/z calculated for C18H26O7 354.1578,
found: m/z 354.1663. Compound 4d (isolated as a white solid in
(KBr, cmꢀ1):
m 3133–3006, 2957, 2868, 1723, 1376, 1277, 1088,
1031, 769; 1H NMR (400 MHz, CDCl3, TMS) d (ppm): 8.03 (d, 2H,
J9-10 = 8.3 Hz, H-9), 7.56 (d, 2H, J10-9 = 8.3 Hz, H-10), 5.56 (d, 1H,
J1-2 = 4.0 Hz, H-1), 4.28–4.33 (m, 3H, H-13, H-6B), 3.92 (t, 1H,
J3-4 = 9.4 Hz, H-3), 3.71–3.83 (m, 2H, H-5, H-6A), 3.57–3.65 (m,
1H, H-2), 3.47–3.52 (m, 1H, H-4), 3.45 (s, 3H, OCH3), 2.96 (s, 1H,
OH), 2.44 (d, 1H, JOH-2 = 9.5 Hz), 1.75 (p, 2H, J14-15 = 6.7 Hz, H-14),
1.46 (h, 2H, J15-16 = 6.7 Hz, H-15), 0.97 (t, 3H, J16-15 = 7.4 Hz, H-
16); 13C NMR (100 MHz, CDCl3, TMS) d (ppm): 166.3, 141.4,
131.2, 129.6, 126.4, 101.1, 99.8, 72.9, 71.7, 68.9, 65.0, 62.3, 55.6,
30.7, 19.2, 13.7; TOF-MS, m/z calculated for C19H26O8 382.1628,
found: m/z 382.1628. Compound 7d (isolated as a white solid in
66% yield, mp 137–138 °C, ½a D20
ꢃ
+63 (c 0.6 g/100 mL, MeOH); IR
m 3154–3615, 2926, 2852, 1622, 1513, 1380, 1251,
(KBr, cmꢀ1):
1079, 1031, 823; 1H NMR (400 MHz, CDCl3, TMS) d (ppm): 7.39
(d, 2H, J9-10 = 8.7 Hz, H-9), 6,86 (d, 2H, J10-9 = 8.7 Hz, H-10), 5.46
67% yield, mp 138–140 °C, ½a D20
ꢃ
+58 (c 0.58 g/100 mL, MeOH);IR
m 3119–3600, 2924, 2854, 1717, 1372, 1269, 1084,
(KBr, cmꢀ1):
(s, 1H, H-7), 4.75 (d, 1H, J1-2 = 3.9 Hz, H-1), 4.25 (dd, 1H, J6B-5
=
1039, 746; 1H NMR (250 MHz, CDCl3, TMS) d (ppm): 8.03 (d, 2H,
J9-10 = 8.2 Hz, H-9), 7.56 (d, 2H, J10-9 = 8.1 Hz, H-10), 5.56 (s, 1H,
H-7), 4.80 (d, 1H, J1-2 = 3.8 Hz, H-1), 3.28–4.33 (m, 3H, H-13,
H-6B), 3.85–3.96 (m, 1H, H-3), 3.70–3.81 (m, 2H, H-5, H-6A),
3.58–3.66 (m, 1H, H-2), 3.50–3.53 (m, 1H, H-4), 3.45 (s, 3H,
OCH3), 2.89 (s, 1H, OH), 2.39 (d, 1H, JOH-2 = 9.5 Hz, OH), 1.76 (p,
2H, J18-19 = 6.9 Hz, H-18), 1.28–1.45 (m, 10H, H-14–17), 0.88 (t, 3H,
J20-19 = 6.8 Hz, H-20); 13C NMR (62.5 MHz, CDCl3, TMS) d (ppm):
165.9, 142.8, 130.7, 129.4, 127.2, 101.1, 100.4, 81.8, 72.9, 70.3,
68.6, 65.2, 62.7, 55.2, 31.6, 29.04, 29.01, 28.5, 25.8, 22.5, 14.4;
4.3 Hz, J6B-6A = 9.7 Hz, H-6B), 3.93 (t, 2H, J12-13 = 6.6 Hz, H-12),
3.86–3.89 (m, 1H, H-3), 3.67–3.80 (m, 2H, H-5, H-6A), 3.56–3.61
(m, 1H, H-2), 3.41–3.46 (m, 1H, H-4), 3.43 (s, 3H, OCH3), 3.15 (s,
1H, OH), 2.60 (d, 1H,
JOH-2 = 9.6 Hz, OH), 1.75 (p, 2H,
J13-14 = 7.3 Hz, H-13), 1.28–1.47 (m, 10H, H-14–18), 0.88 (t, 3H,
J19-18 = 7.4 Hz, H-19); 13C NMR (62.5 MHz, CDCl3, TMS) d (ppm):
160.0, 129.5, 127.7, 114.4, 102.1, 99.9, 81.1, 73.0, 71.8, 69.0, 68.2,
62.5, 55.6, 31.9, 29.5, 29.3, 26.1, 22.7, 14.2; TOF-MS, m/z calculated
for C22H34O7 410.2305, found: m/z 410.2305. Compound 4e (iso-
lated as a white solid in 75% yield, mp 130–132 °C, ½a D20
ꢃ
+56
TOF-MS, m/z calculated for C23H34O8 438.2254, found: m/z
(c 0.6 g/100 mL, MeOH); IR (KBr, cmꢀ1):
m
3145–3605, 2925,
438.2284. Compound 7e (isolated as a white solid in 45% yield,
2851, 1620, 1523, 1379, 1252, 1083, 1037, 827; 1H NMR
(400 MHz, DMSO-d6, TMS) d (ppm): 7.33 (d, 2H, J9-10 = 8.6 Hz,
H-9), 6.88 (d, 2H, J10-9 = 8.6 Hz, H-10), 5.48 (s, 1H, H-7), 4.90 (d,
1H, J1-2 = 4.9 Hz, H-1), 4.71 (d, 1H, JOH-3 = 6.6 Hz, OH), 4.62 (d, 1H,
mp 132–134 °C, ½a D20
ꢃ
+58 (c 0.37 g/100 mL, MeOH); IR (KBr,
m 3141–3631, 2926, 2852, 1722, 1373, 1272, 1084, 1037,
cmꢀ1):
756; 1H NMR (400 MHz, DMSO-d6, TMS) d (ppm): 7.94 (d, J10-9
=
8.3 Hz, H-10), 7.60 (d, J9-10 = 8.3 Hz, H-10), 5.62 (s, 1H, H-7), 4.81
(s, 1H, OH), 4.64, (d, 1H, J1-2 = 3.6 Hz, H-1), 4.58 (s, 1H, OH), 4.27,
J
OH-2 = 3.6 Hz, OH), 4.12 (dd, 1H, J6B-5 = 4.4 Hz, J6B-6A = 9.8 Hz,
H-6B), 3.95 (t, 2H, J12-13 = 6.5 Hz, H-12), 3.59–3.68 (m, 1H, H-6A),
3.54–3.61 (m, 2H, H-3, H-5), 3.32–3.40 (m, 1H, H-4), 3.33 (s, 3H,
OCH3), 3.15 (H2O), 1.68 (p, 2H, J13-14 = 6.7 Hz, H-13), 0.85 (t, 3H,
J27-26 = 6.2 Hz, H-27); 13C NMR (62.5 MHz, DMSO-d6, TMS) d
(ppm): 158.9, 130.0, 127.6, 113.7, 100.8, 100.5, 81.3, 72.4, 69.9,
68.1, 67.4, 62.3, 54.7, 31.2, 28.9, 28.7, 28.6, 25.4, 22.0, 13.8; TOF-
MS, m/z calculated for C30H50O7 522.3557, found: m/z 522.3553.
Compound 7a (isolated as white needle-like crystals in 60%
(t, 2H, J13-14 = 6.6 Hz, H-13), 4.17 (dd, 1H, J6B-5 = 4.7 Hz, J6B-6A =
10 Hz, H-6B), 3.71 (t, 1H, J6A-6B,6A-5 = 10.0 Hz), 3.58–3.65 (m, 2H,
H-5, H-3), 3.35–3.43 (m, 2H, H-4, H-2), 3.33 (s, 3H, OCH3), 1.71
(p, 2H, J14-15 = 7.0 Hz, H-14), 1.24–1.39 (m, 27H, H-15-H-27), 0.85
(t, 3H, J28-27 = 6.7 Hz, H-28); 13C NMR (100 MHz, DMSO-d6, TMS)
d (ppm): 165.5, 142.5, 130.5, 128.8, 126.6, 100.7, 100.1, 81.6,
72.8, 70.1, 68.4, 64.7, 62.5, 54.9, 31.2, 28.5–28.9, 28.2, 25.4, 21.9,
13.7; TOF-MS, m/z calculated for C31H50O8 550.3506, found: m/z
550.3677.
yield, mp 190–192 °C, ½a D20
ꢃ
+61 (c 0.48 g/100 mL, MeOH); IR (KBr,
cmꢀ1):
m 3137–3633, 2997, 2868, 1716, 1375, 1279, 1069, 1034,
762; 1H NMR (400 MHz, DMSO-d6, TMS) d (ppm): 7.97 (d, 2H,
J9-10 = 8.5 Hz, H-9), 7.59 (d, 2H, J10-9 = 8.3 Hz, H-10), 5.66 (s, 1H,
H-7), 5.22 (d, 1H, JOH-3 = 4.8 Hz, OH), 5.01 (d, 1H, JOH-2 = 6.8 Hz,
0H), 4.64 (d, 1H, J1-2 = 3.6 Hz, H-1), 4.32 (q, 2H, J13-14 = 6.8 Hz,
H-13), 4.18 (dd, 1H, J6B-5 = 4.7 Hz, J6B-6A = 10.0 Hz, H-6B), 3.72 (t,
1H, J6A-6B,6A-5 = 10 Hz, H-6A), 3.56–3.62 (m, 2H, H-3, H-5), 3.33–
3.43 (m, 2H, H-2, H-4), 3.33 (H2O), 3.31 (s, 3H, OCH3), 1.32 (t, 3H,
J = 7.2 Hz, H-14); 13C NMR (100 MHz, DMSO-d6, TMS) d (ppm):
165.4, 142.4, 130.2, 128.9, 126.7, 100.5, 99.9, 81.3, 72.4, 69.8,
68.2, 62.3, 60.8, 54.7, 14.1; TOF-MS, m/z calculated for C17H22O8
354.1315, found: m/z 354.1330. Compound 7b (isolated as a white
4.2. Gelation test for compounds
The gelation test was carried out in various organic solvents at
10–150 mmol Lꢀ1 concentration range in a 2 mL vial. Mixtures
were heated near to the solvent boiling point in an oil bath and al-
lowed to cool slowly at room temperature for approximately 1 h.
Next, vials were gently agitated, inverted, and classified (Table 1).
All solvents used were previously distilled and dried with molecu-
lar sieves 4 Å.
4.3. FTIR analyses
solid in 72% yield, mp 148–150 °C, ½a D20
ꢃ
+82 (c 0.48 g/100 mL, MeO-
H);IR (KBr, cmꢀ1):
m
3179–3633, 2977, 2858, 1728, 1369, 1273,
FT-IR spectra were acquired in a BOMEM NB spectrophotometer,
model 100-E coupled to a WATLON, model 988, thermal system. An
amount of 0.5 mL of the solution previously heated was carefully
inserted in ZnSe cells, and temperature range was set within 50
and 30 °C. Spectra were acquired with eight scan in the 4000–
1071, 1031, 760; 1H NMR (400 MHz, CDCl3, TMS) d (ppm): 8.04
(d, 2H, J9-10 = 8.4 Hz, H-9), 7.56 (d, 2H, J10-9 = 8.4 Hz, H-10), 5.57
(s, 1H, H-7), 4.80 (d, 1H, J1-2 = 4.0 Hz, H-1), 4.26–4.32 (m, 3H, H-
6B, H-13), 3.93 (t, 1H, J3-4 = 9.1 Hz, H-3), 3.72–3.84 (m, 2H, H-5,

78
M. F. Abreu et al. / Carbohydrate Research 353 (2012) 69–78
600 cmꢀ1 range with a resolution of 4 cmꢀ1. Finally, the spectra
were plotted using Origin 8.0 software.
References
1. (a) Estroff, L. A.; Hamilton, A. D. Chem. Rev. 2004, 104, 1201–1218; (b) Terech,
P.; Weiss, R. G. Chem. Rev. 1997, 97, 3133–3159.
2. Zweep, N.; Hopkinson, A.; Meetsma, A.; Browne, W. R.; Feringa, B. L.; van Esch,
J. H. Langmuir 2009, 25, 8802–8809.
4.4. Morphological study with SEM
3. Weiss, R. G.; Terech, P. Molecular Gels: Materials with Self-Assembled Fibrillar
Networks; Springer: Dordrecht, The Netherlands, 2005.
4. (a) Vemula, P. K.; Li, J.; John, G. J. Am. Chem. Soc. 2006, 128, 8932–8938; (b) van
Bommel, K. J. C.; Stuart, M. C. A.; Feringa, B. L.; van Esch, J. Org. Biomol. Chem.
2005, 3, 2917–2920; (c) Lim, P. F. C.; Liu, X. Y.; Kang, L.; Ho, P. C. L.; Chan, Y. W.;
Chan, S. Y. Int. J. Pharm. 2006, 311, 157–164.
SEM images of xerogels were obtained on a JEOL SEM 6360-LV.
Samples were micropulverized and a thin layer of graphite was
applied prior to imaging. Xerogels were prepared by spontaneous
evaporation of gels formed by compounds 4b–e or 7b–e in
p-xylene at room temperature.
5. Maeda, H. Chem. Eur. J. 2008, 14, 11274–11282.
6. (a) Jung, J. H.; Amaike, M.; Shinkai, S. Chem. Commun. 2000, 2343–2344; (b) van
Bommel, K. J. C. V.; Friggeri, A.; Shinkai, S. Angew. Chem., Int. Ed. 2003, 42, 980–
999; (c) Jung, J. H.; Shinkai, S.; Shimizu, T. Nano Lett. 2002, 2, 17–20.
7. (a) Jadhav, S. R.; Vemula, P. K.; Kumar, R.; Raghavan, S. R.; John, G. Angew.
Chem., Int. Ed. 2010, 49, 7695–7698; (b) Bhattacharya, S.; Krishnan-Ghosh, Y.
Chem. Commun. 2001, 185–186.
8. Carretti, E.; Dei, L.; Weiss, R. G. Soft Matter 2005, 1, 17–22.
9. van Esch, J. H. Langmuir 2009, 25, 8392–8394.
10. Dastidar, P. Chem. Soc. Rev. 2008, 37, 2699–2715.
4.5. DSC analyses
DSC experiments were performed in a TA instrument, model
Q100 V9.9. Samples were placed in sealed aluminum can and the
thermograms were recorded during the cooling step (80–30 °C)
at 2 °C minꢀ1 rate.
11. (a) Jeong, Y.; Hanabusa, K.; Masunaga, H.; Akiba, I.; Miyoshi, K.; Sakurai, S.;
Sakurai, K. Langmuir 2005, 21, 586–594; (b) Estroff, L. A.; Hamilton, A. D.
Angew. Chem., Int. Ed. 2000, 39, 3447–3450.
4.6. SAXS analyses
12. (a) Murata, K.; Aoki, M.; Suzuki, T.; Harada, T.; Kawabata, H.; Komori, T.;
Ohseto, F.; Ueda, K.; Shinkai, S. J. Am. Chem. Soc. 1994, 116, 6664–6676; (b)
George, M.; Weiss, R. G. Acc. Chem. Res. 2006, 39, 489–497; (c) Hou, Q.; Wang,
S.; Zang, L.; Wang, X.; Jiang, J. J. Colloid Interface Sci. 2009, 338, 463–467.
13. (a) Lescanne, M.; Colin, A.; Mondain-Monval, O.; Fages, F.; Pozzo, J.-L. Langmuir
2003, 19, 2013–2020; (b) Galindo, F.; Burguete, M. I.; Gavara, R.; Luis, S. V. J.
Photochem. Photobiol. A. 2006, 178, 57–61.
14. (a) Gronwald, O.; Sakurai, K.; Luboradzki, R.; Kimura, T.; Shinkai, S. Carbohydr.
Res. 2001, 331, 307–318; (b) Gronwald, O.; Snip, E.; Shinkai, S. Curr. Opin.
Colloid Interface Sci. 2002, 7, 148–156; (c) Cui, J.; Zheng, J.; Qiao, W.; Wan, X. J.
Colloid Interface Sci. 2008, 326, 267–274; (d) Gronwald, O.; Shinkai, S. Chem.
Eur. J. 2001, 7, 4328–4334.
Small angle X-ray scattering experiments were performed using
SAXS1 beam line of Brazilian Synchrotron Light Laboratory (LNLS,
Campinas, Brazil). The wavelength used was 1.488 Å and sample-
detector distance 1.5 m. ACCD type two dimensional position-sen-
sitive gas detector was used in these measurements.
4.7. Polarimetry
Optical rotations were determined in a Perkin–Elmer polarime-
ter, 9585 model, using 589 nm wavelength, and methanol as sol-
vent at 20 °C.
15. Gronwald, O.; Shinkai, S. J. Chem. Soc., Perkin Trans. 2 2001, 1933–1937.
16. Friggeri, A.; Gronwald, O.; van Bommel, K. J. C.; Shinkai, S.; Reinhoudt, D. N. J.
Am. Chem. Soc. 2002, 124, 10754–10758.
17. (a) Amanokura, N.; Kanekiyo, Y.; Shinkai, S.; Reinhoudt, D. N. J. Chem. Soc.,
Perkin Trans. 2 1999, 1995–2000; (b) Jung, J. H.; John, G.; Masuda, M.; Yoshida,
K.; Shinkai, S.; Shimizu, T. Langmuir 2001, 17, 7229–7232; (c) John, G.; Jung, J.
H.; Masuda, M.; Shimizu, T. Langmuir 2004, 20, 2060–2065; (d) Bao, C.; Lu, R.;
Jin, M.; Xue, P.; Tan, C.; Zhao, Y.; Liu, G. Carbohydr. Res. 2004, 339, 1311–1316;
(e) Jung, J. H.; Rim, J. A.; Han, W. S.; Lee, S. J.; Lee, Y. J.; Cho, E. J.; Kim, J. S.;
Shimizu, Q. J. T. Org. Biomol. Chem. 2006, 4, 2033–2038; (f) Cui, J.; Liu, A.; Guan,
Y.; Zheng, J.; Shen, Z.; Wan, X. Langmuir 2010, 26, 3615–3622.
18. Helferich, B.; Schäfer, W. Org. Synth. 1941, 1, 364.
4.8. Melting point
Melting points were determined in a Fisatom apparatus, 430 D
model, using capillary tubes. The measurements were performed
in duplicate.
19. Shao, X. B.; Jiang, X. K.; Wang, X. Z.; Li, Z. T.; Zhu, S. Z. Tetrahedron 2003, 59,
4881–4889.
20. Davis, T. S.; Feil, P. D.; Kubler, D. G.; Wells, D. J. J. Org. Chem. 1975, 40, 1478–
1482.
Acknowledgments
This work was supported by CNPq (INOMAT/CNPq/MCT) and
FAPESP. Authors are indebted to Jason G. Taylor for insightful dis-
cussion and for reviewing the manuscript for its English usage.
P.C.M.L.M. gratefully acknowledges Institute of Chemistry/UNI-
CAMP for analytical facilities. M.F.A., V.T.S., and L.V. are grateful
to CNPq for fellowships. We also acknowledge the Brazilian Syn-
chrotron Light Laboratory (LNLS, Campinas, Brazil) for the use of
SAXS1 beam line.
21. Evans, M. E. Carbohydr. Res. 1972, 21, 473–475.
22. Cheuk, S.; Stevens, E. D.; Wang, G. Carbohydr. Res. 2009, 344, 417–425.
23. (a) Bielejewski, M.; Lapinski, A.; Luboradzki, R.; Tritt-Goc, J. Langmuir 2009, 25,
8274–8279; (b) Roy, S.; Chakraborty, A.; Ghosh, R. Carbohydr. Res. 2008, 343,
2523–2529; (c) Yoza, K.; Amanokura, N.; Ono, Y.; Akao, T.; Shinmori, H.;
Takeuchi, M.; Shinkai, S.; Reinhoudt, D. N. Chem. Eur. J. 1999, 5, 2722–2729.
24. Palui, G.; Simon, F.-X.; Schmutz, M.; Mesini, P. J.; Banerjee, A. Tetrahedron 2008,
64, 175–185.
25. (a) Bhattacharya, S.; Acharya, S. N. G. Chem. Mater. 1999, 11, 3121–3132; (b)
Hirst, A. R.; Smith, D. K.; Feiters, M. C.; Geurts, H. P. M. Chem. Eur. J. 2004, 10,
5901–5910.
26. Zhang, Z.; Yang, M.; Hu, C.; Liu, B.; Hu, M.; Zhang, X.; Wang, W.; Zhoub, Y.;
Wangb, H. New J. Chem. 2011, 35, 103–110.
Supplementary data
27. Watase, M.; Nakatani, Y.; Itagaki, H. J. Phys. Chem. B. 1999, 103, 2366–2373.
28. (a) Jeong, Y.; Friggeri, A.; Akiba, I.; Masunaga, H.; Sakurai, K.; Sakurai, S.;
Okamoto, S.; Inoue, K.; Shinkai, S. J. Colloid Interface Sci. 2005, 283, 113–122; (b)
Terech, P.; Allegraud, J. J.; Garner, C. M. Langmuir 1998, 14, 3991–3998.
29. Terech, P.; Ostuni, E.; Weiss, R. G. J. Phys. Chem. 1996, 100, 3759–3766.
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.carres.2012.03.
021.