Functionalized calix[4]arene-based receptor for saccharide recognition

Article abstract of DOI:10.1007/s10847-015-0540-9

A novel class of functionalized-calix[4]arene such as 1,4-dihydropyridine-calix[4]arene, acridine-calix[4]arene and pyrimidine-calix[4]arene were synthesized using multicomponent reaction. These compounds have been characterized by ¹H NMR, ¹³C NMR and HRMS. Fluorescent and ¹H NMR titration investigations reveal that these derivatives have the high binding constant towards the monosaccharide and disaccharide in aqueous solution. The formation of complex was also supported by electrospray mass spectrometry.

Full text of DOI:10.1007/s10847-015-0540-9

J Incl Phenom Macrocycl Chem
DOI 10.1007/s10847-015-0540-9
ORIGINAL ARTICLE
Functionalized calix[4]arene-based receptor for saccharide
recognition
1
1
1
•
Maryam Mirza-Aghayan
1
•
Masoud Yarmohammadi
1
•
Narges Mohammadian
Reza Zadmard
•
Fatemeh Asadi
Received: 4 January 2015 / Accepted: 9 June 2015
Ó Springer Science+Business Media Dordrecht 2015
Abstract A novel class of functionalized-calix[4]arene
such as 1,4-dihydropyridine-calix[4]arene, acridine-
calix[4]arene and pyrimidine-calix[4]arene were synthe-
sized using multicomponent reaction. These compounds
S (ARS) in equilibrium with a phenyl boronic acid can be
used for fructose recognition at pH 7.4. Another report
indicates that phenylboronic acid-functionalized tetrathia-
fulvalene (TTFAQ) system to show pronounced electro-
chemical responses selectively toward fructose and ribose
[5]. In recent years the development of supramolecular
macrocyclic architectures has received intensive interest
[6–8]. Supramolecular chemistry examines the weaker and
reversible noncovalent interactions between molecules.
These forces include hydrogen bonding, metal coordina-
tion, hydrophobic forces, van der Waals forces, pi–pi
interactions and electrostatic effects [9–11]. Several water
soluble porphyrines investigated such as the suitable
receptors for the recognition of saccharides in water [12].
1
13
have been characterized by H NMR, C NMR and
1
HRMS. Fluorescent and H NMR titration investigations
reveal that these derivatives have the high binding constant
towards the monosaccharide and disaccharide in aqueous
solution. The formation of complex was also supported by
electrospray mass spectrometry.
Keywords Functionalized-calix[4]arene Á
Multicomponent reaction Á Fluorescent titration Á
Saccharide recognition
1
Fluorescent and H NMR investigations of Chen et al.
reveal that metallocyclophanes can efficiently complex
mono- and disaccharide derivatives in chloroform, with a
binding selectivity for disaccharides, which is driven by
intermolecular hydrogen bonding [13]. Calixarenes are
used in several areas of supramolecular chemistry such as
macrocyclic receptors for anions, amino acids, and small
peptides [14–17]. In 2003 Segura et al. explored the
potential of functionalized calix[4]arenes in carbohydrate
recognition [18].
Introduction
A carbohydrate is a large biological molecule or macro-
molecule and performs numerous roles in living organisms
[
1–3]. The development of biomolecule recognition is one
of the interesting topics of the modern biology, medicine
and chemistry. Several host system have been described for
the recognition of biological important substrate. Schu-
macher and co-workers [4] have reported that Alizarin Red
1,4-Dihydropyridines (DHPs) have attracted immense
attention of synthetic chemists due to their pharmacologi-
cal properties [19, 20] and display prominent biological
activities [21–23]. They are known as neuroprotectants,
antiplatelet treatment of aggregators and are important in
Alzheimer’s disease as antiischemic agents [24–26].
Pyrimidines display also a diverse range of biological
activities such as antibacterial, antiviral, antitumor, anti-
inflammatory and antihypertensive as well as calcium
channel blockers, a-1a-antagonists, and neuropeptide Y
(NPY) antagonists [27]. Many synthetic methods for the
Electronic supplementary material The online version of this
article (doi:10.1007/s10847-015-0540-9) contains supplementary
material, which is available to authorized users.
&
Maryam Mirza-Aghayan
m.mirzaaghayan@ccerci.ac.ir
1
Chemistry and Chemical Engineering Research Center of
Iran (CCERCI), P. O. Box 14335-186, Tehran, Iran
123

J Incl Phenom Macrocycl Chem
synthesis of 1,4-dihydropyridines [28–34] and pyrimidine
35–38] derivatives have been reported but into the best of
afforded 1,4-dihydropyridine-calix[4]arene derivative 4 in
the cone conformation in 82 % yield after 5 min
(Scheme 2). We also investigated the synthesis of pyrim-
idine-calix[4]arene 5 by multicomponent reaction of
monoaldehyde calix[4]arenes 6 under the optimized reac-
tion conditions in our previously report [41]. The obtained
results shown that the three component reaction of
monoaldehyde calix[4]arene 6 (1 mmol), ethyl cyanoac-
etate (1 mmol) and guanidinium carbonate (1 mmol) in the
presence of amino-functionalized SBA-15 catalyst
(60 mol %) in ethanol afforded 2-amino-pyrimidine-
calix[4]arene building block 5 in the cone conformation in
83 % yield after 2 h (Scheme 2). The 1,4-dihydropyridine-
[
our knowledge there is no report for the synthesis of
functionalized-calix[4]arene derivatives with 1,4-dihy-
dropyridine or pyrimidine compound.
Recently we have synthesized acridine-calix[4]arene
derivatives 1, 2, 3 via multicomponent reaction (MCR) of
aminocalix[4]arene with dimedone and 3-hydroxyben-
zaldehyde or 4-bromobenzaldehyde which selectively bind
Calf Thymus DNA and ds DNA with submicromolar Kf
values in buffered aqueous solution (Scheme 1) [39].
In continuation of our investigations on the synthesis of
1
,4-dihydropyridines (DHPs) [40] and pyrimidines [41] via
a MCR reaction, herein we describe a simple and efficient
method for the preparation of the novel 1,4-dihydropy-
ridine-calix[4]arene 4 and 2-amino-pyrimidine-calix[4]ar-
ene 5. In this work, we introduce an efficient reaction of
monoaldehyde calix[4]arene 6 in the cone conformation
with methyl 3-aminocrotonate using chlorotrimethylsilane
calix[4]arene derivative
4
calix[4]arene 5 were characterized on the basis of its
and 2-amino-pyrimidine-
1
13
spectroscopic data such as H and C NMR, mass spec-
troscopy, and infrared (IR) spectra. It should be noted that
the spectroscopic data confirm the cone conformation for
1,4-dihydropyridine-calix[4]arene derivative 4
2-amino-pyrimidine-calix[4]arene derivative 5 [42].
and
(
TMSCl) or with ethyl cyanoacetate and guanidinium
carbonate in the presence of amino-functionalized SBA-15
catalyst that provides an easy access to 1,4-dihydropy-
ridine-calix[4]arene derivative 4 and 2-amino-pyrimidine-
calix[4]arene derivative 5 blocked in the cone conforma-
tion respectively. Furthermore, we studied the interaction
of the synthesized calix[4]arene derivatives 1–5 with sev-
eral saccharides using fluorescence titration experiments in
aqueous solution (Scheme 2).
It should be noted that for comparison of binding con-
stant of the 1,4-dihydropyridine-calix[4]arene derivative 4
with an ordinary 1,4-dihydropyridine derivative, we have
synthesized the 1,4-dihydropyridine 7 from the reaction of
benzaldehyde with methyl-3-aminocrotonate in the pres-
ence of TMSCl (Scheme 3) [40].
Fluorescence titration is widely used, because of its
sensitivity, and the availability of the spectroscopic tech-
nique [43]. To evaluate the binding ability of the synthe-
sized calix[4]arene derivaitives 1–5, fluorescence titration
experiments were performed with monosaccharides such as
fructose, glucose, sorbitol and mannitol, and disaccharides
such as maltose and sucrose in aqueous solution. So, the
binding constants (Kassociation value) were determined by
using the fluorescence titration experiments by addition of
the functionalized-calix[4]arene 1–5 into the different
guest molecules. The binding ability of the receptors 1–5
towards saccharides were investigated in aqueous solution
Results and discussion
1
,4-Dihydropyridine-calix[4]arene derivative 4 is synthe-
sized from MCR reaction of monoaldehyde calix[4]arenes
under the optimized reaction conditions in our previously
6
report [40]. The results shown that the reaction of
monoaldehyde calix[4]arene 6 (1 mmol) with methyl
3
-aminocrotonate (4 mmol) using TMSCl at 80 °C
Scheme 1 Acridine-
calix[4]arene derivatives 1, 2,
and 3
1
23

J Incl Phenom Macrocycl Chem
Scheme 2 Synthesis of 1,4-
dihydropyridine-calix[4]arene
derivative 4 and 2-amino-
pyrimidine-calix[4]arene
derivative 5
Scheme 3 4-Phenyl-1,4-
dihydropyridine 7
binding constant and [G] is the guest concentration. Plot-
-1
ting [1/(I - Iobs)] versus [G] yields a linear plot with a
0
slope corresponding to 1/(KDImax) and intercept to 1/DImax
.
The results of binding constants are summarized in
Table 1, and calculations and full data are given in sup-
plementary data. The investigations of fluorescence titra-
tions of 1–5 derivatives indicated the high binding constant
value for the monosaccharides, and disaccharides. We
assume that the formation of the multiple hydrogen bonds
between host molecule and sugar are possible and can be
justifying the binding constant. Indeed the hydrogen
bonding forces and WDW interactions could justify the
binding constant. The obtained binding constant values
(
except receptor 3 that was investigated in water/methanol
4:1) solution). The fluorescence titrations of calix[4]arene
(
-
-5 (1 9 10 M) were performed in aqueous solutions at
6
1
room temperature. For each compound, 1700 lL of the
receptors solution (1 9 10 M) was filled into cuvettes
-
6
and fluorescence intensity was measured (F ), then up to
0
-
5
5
0 lL of saccharide solution (1 9 10 M) was added
3
-1
5
-1
were between 7.50 9 10 M
and 9.50 9 10 M
in
stepwise. For each addition, after stirring for 30 s and
standing for 2 min, the change of the emission intensity
was measured (Fobs). The change of the emission intensity
was observed. As an example, the plot of the emission
intensity of 1, 2, 4 and 5 with sucrose in aqueous solution
are provided in Fig. 1. According to the fluorescence
titration chart in Fig. 1, after each addition (sucrose) the
intensity of fluorescence emission is decreased.
aqueous solution (Table 1).
From the results in Table 1, the binding constants
obtained for these molecules indicated that they are
attractive receptors to the range of receptors already known
for saccharides recognition [13]. For example, the associ-
ation constants complex obtained by Chen and co-workers,
between metallocyclophanes and monosaccharides or dis-
accharides in chloroform solution were between
The calculation of the binding constant (K) was carried
out using Benesi–Hildebrand analysis [44]. The Eq. (1) was
used for calculation of binding constants.
2
4
-1
9
.40 9 10 and 4.30 9 10 M . The obtained results
show that acridine-calix[4]arene derivative 2 exhibits a
5
greater binding ability for sorbitol (6.60 9 10 M ),
5
mannitol (8.75 9 10 M ), maltose (7.20 9 10 M
-1
1
=DI ¼ 1=ðK½GŠDImaxÞ þ 1=DImax
ð1Þ
-1
5
-1
)
5
-1
In this equation, DI = I - I and DImax = I - Imax,
and sucrose (9.50 9 10 M ). In the case of the
monosaccharides recognition, 2-amino-pyrimidine-
calix[4]arene derivative 5 exhibits a greater binding ability
0
obs
0
where Imin, Iobs, and Imax are the emission intensities of
receptor considered in the absence of guest, observed
intensity of each point during titration and at a concen-
tration of complete saturation, respectively. K is the
5
-1
for
fructose
(3.60 9 10 M
)
and
glucose
5
-1
(3.13 9 10 M ) in comparison with the other receptors.
123

J Incl Phenom Macrocycl Chem
Fig. 1 Fluorescence titration of 3-hydroxy-calix[4]arene 1 with sucrose (a), 4-bromo-calix[4]arene 2 with sucrose (b), 1,4-dihydropyridine-
calix[4]arene 4 with sucrose (c), and 2-amino-pyrimidine-calix[4]arene 5 with sucrose (d)
Table 1 also shows that the acridine-calix[4]arene deriva-
more details. Remarkably, the CH protons of methyl
group (indicated with number 1 in Fig. 3), CH protons of
tive 3 is good receptor only for the recognition of glucose
-1
4
with a binding constant of 8.00 9 10 M
.
methyl ester (OCOCH , indicated with number 2 in
3
The 1,4-dihydropyridine-calix[4]arene derivative 4 has a
binding selectivity for sorbitol with a binding constant of
Fig. 3), CH proton of dihydropyridine (indicated with
number 3) and CH protons of calixarene ring (in the ortho
position, indicated with number 4) shown a significant
upfield shift *0.14, 0.14, 0.15 and 0.12 ppm respectively
upon sorbitol addition. This can be explained by possible
complexation through an intermolecular hydrogen bond-
ing between host 1,4-dihydropyridine-calix[4]arene 4 and
sorbitol.
5 -1
.35 9 10 M . It can be found that 1,4-dihydropyridine-
2
calix[4]arene derivative 4 has 31 times greater binding
5
ability for sorbitol (2.35 9 10 M ) than for mannitol
-1
3
-1
7.50 9 10 M ) as sugar alcohol. It should be noted that
(
the formation of complex between sorbitol and 1,4-dihy-
dropyridine-calix[4]arene derivative 4 was also supported
by electrospray ionization time of flight mass spectrometry
The binding constants obtained for 1,4-dihydropyridine
7 with the monosaccharides indicated that this compound is
(
ESI-TOF-MS). The spectrum of an equimolar solution of
5
not selective towards the sorbitol (1.58 9 10 M ) or
-1
sorbitol and 4 in CH OH shows the charged signal of the
3
5
-1
complex as the base peak at m/z 1053.5244 (calcd for
?
sorbitol@4] : 1053.5814) (Fig. 2).
mannitol (2.23 9 10 M ). We assume that in the solu-
tion, the aggregation process take place between sorbitol
and 1,4-dihydropyridine 7. The aggregation between sor-
bitol and 1,4-dihydropyridine 7 in ratio 2:1 was also
[
1
Moreover, the H NMR titration spectra of 1,4-dihy-
dropyridine-calix[4]arene 4 and sorbitol were analyzed in
1
23

J Incl Phenom Macrocycl Chem
supported by ESI-TOF-MS in Fig. 4. The comparison of
binding constant of 1,4-dihydropyridine-calix[4]arene
derivative 4 with 1,4-dihydropyridine 7 indicated that the
binding takes place probably in the cavity of the
calix[4]arene.
In summary, we have synthesized a new family of 1,4-
dihydropyridine-calix[4]arene and 2-amino-pyrimidine-
calix[4]arene receptor for saccharide recognition in water
solution. Fluorescent titration investigations reveal that
these derivatives have the high binding constant towards
the monosaccharides and disaccharides in aqueous solu-
tion. The results show that acridine-calix[4]arene deriva-
tive 2 exhibits a greater binding ability for sorbitol,
mannitol and disaccharides and 2-amino-pyrimidine-
calix[4]arene derivative 5 for fructose and glucose
respectively in comparison with the other receptors. 1,4-
Dihydropyridine-calix[4]arene derivative 4 has 31 times
greater binding ability for sorbitol than for mannitol as
sugar alcohol.
Experimental
Materials
All reagents were purchased at highest commercial grade
from Merck Company and used as supplied. Reactions
were monitored by thin layer chromatography (TLC) with
Merck silica gel 60 F254 plates. Silica gel 60 for flash
chromatography (particle size 230–400 mesh) was sup-
plied by Merck Company. D-(-)-fructose was purchased
from Sigma-Aldrich Company. D-(?)-glucose monohy-
drate, D-(-)-sorbitol, D-(-)-mannitol, maltose monohy-
drate and sucrose were purchased from Merck Company.
All commercially available materials were used as
received. The acridine-calix[4]arene derivatives 1, 2 and 3
were synthesized according to our previously reported
methods [39].
Instrumentation
Melting points were determined in evacuated capillaries
with a Buchi B-545 apparatus. Mass spectra were obtained
1
on a FISONS GC 8000/TRIO 1000 under 70 eV. H or
13
C
NMR spectra were recorded on a Bruker 80, 250 and 500
or 125 MHz, respectively in CDCl using tetramethylsi-
3
lane as internal standard. High resolution mass spectrom-
etry (HRMS) was recorded with a Qstar ESI-q-TOF mass
spectrometer (Applied Biosystems, Germany). The fluo-
rescence spectra were recorded using a Jasco FP-6500
device.
123

J Incl Phenom Macrocycl Chem
Fig. 2 ESI-TOF-MS spectrum
for complex of sorbitol and 1,4-
dihydropyridine-calix[4]arene
derivative 4
1
Fig. 3 a H NMR spectra of pure 1,4-dihydropyridine calix[4]arene 4 in CDCl
calix[4]arene 4 and sorbitol solution in 3.63 equivalents point
1
solution, b H NMR spectra of mixture 1,4-dihydropyridine
3
Monoaldehyde calix[4]arenes 6
2CH ), 4.48 (d, J = 13.5 Hz, 2H, 2CH ), 6.35 (s, 3H, 3CH
2 2
Arom), 6.63 (m, 6H, 6CH Arom), 6.93 (s, 2H, 2CH Arom),
9.49 (s, 1H, CHO); MS (E. I) (70 eV): m/z (%) 676 (1)
Tin(IV) chloride (20 equiv.) was added rapidly to the
?
(M ), 148 (1), 147 (1), 131 (10), 118 (5), 105 (20), 102
2
2
5,26,27,28-tetraboutoxycalix[4]arene [45] (1 equiv.) in
mL of dry chloroform at -30 °C in the presence of
(18), 91 (5), 77 (40), 55 (8), 43 (65), 41 (75), 29 (100); IR
dichloro(methoxy)methane (1 equiv.). The reaction mix-
ture was then stirred for 1 min and quenched with crushed
ice. The organic layer was separated, washed three times
with water, and dried over Na SO , and the solvent was
(KBr): m = 3013, 2957, 2930, 2870, 2728, 1693,
-
1
1586,1477, 1378 cm
.
2
4
1,4-Dihydropyridine-calix[4]arene 4
removed under reduced pressure. Fine purification was
achieved by column chromatography using hexane/ethy-
1
lacetate (20:1) as eluent. The yield is 76 %. H NMR
A mixture of monoaldehyde calix[4]arene 6 (1 mmol),
methyl 3-aminocrotonate (4 mmol) and chlorotrimethylsi-
lane (1 mmol) were stirred at 80 °C for 5 min. After
completion of the reaction as indicated by TLC, the mix-
ture was poured into ice cold water and extracted with ethyl
acetate. The organic layer was dried and concentrated in
(
CDCl , 80 MHz): d = 0.93 (t, J = 13.6 Hz, 12H, 4CH ),
3
3
1
.42 (m, 8H, 4CH ), 1.88 (m, 8H, 4CH ), 3.03 (d,
2 2
J = 13.3 Hz, 2H, 2CH ), 3.20 (d, J = 13.5 Hz, 2H,
2
2
CH ), 3.81 (m, 8H, 4OCH ), 4.31 (d, J = 13.3 Hz, 2H,
2
2
1
23

J Incl Phenom Macrocycl Chem
Fig. 4 Aggregation process
between sorbitol and 1,4-
dihydropyridine 7 supported by
ESI-TOF-MS spectrum
vacuum. The crude products were purified by recrystal-
1
lization in hexane/ethyl acetate (4:1). The yield is 82 %. H
(m, 4H, 2CH ), 1.91 (m, 8H, 4CH ), 3.19 (d, J = 13.3 Hz,
2 2
2H, 2CH ), 3.28 (d, J = 13.3 Hz, 2H, 2CH ), 3.86 (m, 4H,
2 2
NMR: (CDCl , 250 MHz): d = 0.95–1.02 (m, 12H, 4CH ),
2OCH ), 3.99 (m, 4H, 2OCH ), 4.48 (d, J = 13.5 Hz, 2H,
2 2
3
3
1
.26–1.37 (m, 4H, 2CH ), 1.48–1.62 (m, 4H, 2CH ),
2
2CH ), 4.52 (d, J = 13.3 Hz, 2H, 2CH ), 6.51 (m, 6H,
2 2
2
1
.80–1.97 (m, 8H, 4CH ), 2.34 (s, 6H, 2CH ), 3.02–3.15
2
6CH Arom), 6.64 (s, 2H, NH ), 6.80 (m, 3H, 3CH Arom),
2
3
1
3
7.58 (s, 2H, 2CH Arom), 12.01 (br. s, 1H, OH); C NMR
(
dd, J = 13.25, J = 18.75 Hz, 4H, 2CH ), 3.65 (s, 6H,
2
2
OCH ), 3.71–3.76 (t, J = 6.7 Hz, 4H, 2OCH ), 3.90–4.02
3
(CDCl , 125 MHz): d = 14.01, 19.19, 19.25, 19.44, 29.67,
2
3
(
m, 4H, 2OCH ), 4.35–4.45 (t, J = 25.2 Hz, 4H, 2CH ),
2
30.98, 31.08, 32.20, 32.26, 32.36, 74.77, 74.90, 77.18,
121.83, 122.26, 127.97, 128.20, 128.50, 128.85, 129.23,
133.57, 134.52, 135.71, 136.26, 155.29, 155.99, 156.98,
161.01, 165.12, 171.80; MS (E. I) (70 eV): m/z (%) 783
2
4
.87 (s, 1H, CH), 5.51 (s, 1H, NH), 6.14–6.30 (m, 6H, 6CH
1
3
Arom), 6.79–6.85 (t, J = 7.5 Hz, 3H, 3CH Arom);
C
NMR (CDCl , 75 MHz): d = 14.02, 14.16, 14.20, 19.12,
3
?
1
1
1
1
9.55, 30.93, 32.05, 32.24, 32.44, 38.74, 50.86, 74.76,
04.44, 121.70, 121.84, 127.30, 127.41, 128.23, 128.58,
33.70, 133.89, 135.32, 136.51, 140.96, 143.38, 155.49,
(10) (M ), 703 (8), 635 (5), 608 (10), 566 (10), 488 (10),
387 (10), 281 (15), 265 (15), 239 (15), 221 (25), 149 (30),
129 (30), 105 (100), 77 (100), 57 (100); IR (KBr):
m = 3432, 2959, 2930, 2870, 2244, 2215, 1655, 1622,
?
55.90, 157.46, 168.29; HRMS (ESI): m/z [M] Calcd. for
-
1
C H NO : 872.14; Found: 871.4983; IR (KBr):
69
1457, 1382 cm .
5
5
8
m = 3337, 2957, 2869, 1699, 1650, 14.58, 1433, 1382,
1
-
304, 1215, 1119, 1091, 1021, 760 cm .
1
Acknowledgments The authors would like to thank the Chemistry
Chemical Engineering Research Center of Iran for financial
support.
&
2
-Amino-pyrimidine-calix[4]arene 5
A solution of monoaldehyde calix[4]arene (1 mmol), ethyl
References
cyanoacetate (1 mmol) and NH -SBA-15 (0.3 g,
2
6
0 mol %) in 2 mL ethanol was stirred mechanically for at
1
2
. Bertozzi, C.R., Kiessling, L.K.: Chemical glycobiology. Science
91, 2357–2364 (2001)
. Mammen, M., Choi, S.-K., Whitesides, G.M.: Polyvalent inter-
actions in biological systems: implications for design and use of
multivalent ligands and inhibitors. Angew. Chem. Int. Ed. Engl.
least 10 min, then guanidinium carbonate (1 mmol) was
added to the above reaction mixture and refluxed for 2 h.
After the completion of reaction, the reaction mixture was
poured into ice-cooled water and neutralized by 0.1 N HCl
aqueous solutions. The mixture was filtered and washed
with water. Fine purification was achieved by column
2
37, 2754–2794 (1998)
. Lundquist, J.J., Toone, E.J.: The cluster glycoside effect. Chem.
Rev. 102, 555–578 (2002)
3
chromatography using hexane/ethyl acetate (10:1) as elu-
1
ent. The yield is 83 %. H NMR (CDCl , 500 MHz):
4. Schumacher, S., Nagel, T., Scheller, F.W., Gajovic-Eichelmann,
N.: Alizarin Red S as an electrochemical indicator for saccharide
recognition. Electrochim. Acta 56, 6607–6611 (2011)
3
d = 1.04 (m, 12H, Hz, 4CH ), 1.44 (m, 4H, 2CH ), 1.52
3
2
123

J Incl Phenom Macrocycl Chem
5
6
7
8
. Shao, M., Zhao, Y.: Phenylboronic acid-functionalized TTFAQ:
modular synthesis and electrochemical recognition for saccha-
rides. Tetrahedron Lett. 51, 2508–2511 (2010)
. Dietrich, B., Viout, P., Lehn, J.M.: Macrocyclic Chemistry:
Aspects of Organic and Inorganic Supra Molecular Chemistry,
p. 384. VCH, Weinheim (1993)
synthesis of 1,4-dihydropyridines. J. Org. Chem. 61, 924–928
(1996)
24. Klusa, V.: Cerebrocrast. Neuroprotectant, cognition enhancer.
Drugs Future 20, 135–138 (1995)
25. Bretzel, R.G., Bollen, C.C., Maeser, E., Federlin, K.F.: Nephro-
protective effects of nitrendipine in hypertensive type I and type
II diabetic patients. Am. J. Kidney Dis. 21, 53–64 (1993)
26. Boer, R., Gekker, V.: Chemosensitizers in tumor therapy: new
compounds promise better efficacy. Drugs Future 20, 499–509
(1995)
27. McDaniel, M.P., Collins, K.S., Benham, E.A.: Activation of
Phillips Cr/silica catalysts, IV. Mobility of Cr(VI). J. Catal. 252,
281–295 (2007)
. Geng, X., Zhu, S., Guo, H., Yang, F.: Calix[4]benzocrown-
[60]fullerene dyads: synthesis and complexation properties for
dyes. J. Incl. Phenom. Macrocycl. Chem. 82, 93–99 (2015)
. Yang, F., Liu, W., Xie, J., Bai, X., Guo, H.: Novel deep-cavity
calix[4]arene derivatives with large s-triazine conjugate systems:
synthesis and complexation for dyes. J. Incl. Phenom. Macrocycl.
Chem. 76, 311–316 (2013)
9
. Steed, J.W., Atwood, J.L.: Supramolecular Chemistry. Wiley,
Chichester (2009)
28. Breitenbucher, J.G., Figliozzi, G.: Solid-phase synthesis of
4-aryl-1,4-dihydropyridines via the Hantzsch three component
condensation. Tetrahedron Lett. 41, 4311–4315 (2000)
29. Ohberg, L., Westman, J.: An efficient and fast procedure for the
Hantzsch dihydropyridine synthesis under microwave conditions.
Synlett 2001(8), 1296–1298 (2001)
30. Yadav, J.S., Reddy, B.V.S., Basak, A.K., Narasaiah, A.V.: Three-
component coupling reactions in ionic liquids: an improved
protocol for the synthesis of 1,4-dihydropyridines. Green Chem.
5, 60–63 (2003)
1
0. Steed, J.W., Turner, D.R., Wallace, K.: Core Concepts in
Supramolecular Chemistry and Nanochemistry. Wiley, Chich-
ester (2007)
1. Gittins, P.J., Twyman, L.J.: Dendrimers and supramolecular
chemistry. Supramol. Chem. 15, 5–23 (2003)
2. Charvatova, J., Rusin, O., Kral, V., Volka, K., Matejka, P.: Novel
porphyrin based receptors for saccharide recognition in water.
Sensors Actuat. B 76, 366–372 (2001)
1
1
1
3. Chen, Y.-Q., Wang, X.-Z., Shao, X.-B., Hou, J.-L., Chen, X.-Z.,
Jiang, X.-K., Lib, Z.-T.: Hydrogen bonding-mediated self-
assembly of rigid and planar metallocyclophanes and their
recognition for mono- and disaccharides. Tetrahedron 60,
31. Kidawai, M., Saxena, S., Mohan, R., Venkatramanan, R.: A novel
one pot synthesis of nitrogen containing heterocycles: an alter-
nate methodology to the Biginelli and Hantzsch reactions.
J. Chem. Soc. Perkin Trans. 1, 1845–1846 (2002)
1
0253–10260 (2004)
32. Sharma, G.V.M., Reddy, K.L., Lakshmi, P.S., Krishna, P.R.: ‘In
situ’ generated ‘HCl’—an efficient catalyst for solvent-free
Hantzsch reaction at room temperature: Synthesis of new dihy-
dropyridine glycoconjugates. Synthesis 1, 55–58 (2006)
33. Tewari, N., Dwivedi, N., Tripathi, R.P.: Tetrabutylammonium
hydrogen sulfate catalyzed eco-friendly and efficient synthesis of
glycosyl 1,4-dihydropyridines. Tetrahedron Lett. 45, 9011–9014
(2004)
34. Zolfigol, M.A., Mokhlesi, M.J.: The first report on the synthesis
of new hantzsch N-ethyldimetyl acetal-1,4-dihydropyridines with
aldehyde synthon under microwave irradiation. Iran. Chem. Soc.
5, S91–S96 (2008)
35. Kappe, C.O., Falsone, S.F.: Polyphosphate ester-mediated syn-
thesis of dihydropyrimidines. Improved conditions for the Big-
inelli reaction. Synlett 7, 718–720 (1998)
36. Lu, J., Bai, Y., Wang, Z., Yang, B., Ma, H.: One-pot synthesis of
3,4-dihydropyrimidin-2(1H)-ones using lanthanum chloride as a
catalyst. Tetrahedron Lett. 41, 9075–9078 (2000)
37. Fu, N.Y., Yuan, Y.F., Cao, Z., Wang, S.W., Wang, J.T., Pepple,
C.: Indium(III) bromide-catalyzed preparation of dihydropyrim-
idinones: improved protocol conditions for the Biginelli reaction.
Tetrahedron 58, 4801–4807 (2002)
38. Lin, H., Ding, J., Chen, X., Zhang, Z.: An efficient synthesis of
5-alkoxycarbonyl-4-aryl-3,4-dihydro-pyrimidin- 2(1H)-ones cat-
alyzed by KSF montmorillonite. Molecules 5, 1240–1243 (2000)
39. Mirza-Aghayan, M., Yarmohammadi, M., Zadmard, R.,
Boukherroub, R.: A convenient and efficient one-pot method for
the synthesis of novel acridine-calix[4]arene derivatives as new
DNA binding agents via multicomponent reaction. Supramol.
Chem. 26, 442–449 (2013)
1
1
1
1
1
4. Sansone, F., Baldini, L., Casnati, A., Lazzarotto, M., Ugozzoli,
F., Ungaro, R.: Biomimetic macrocyclic receptors for carboxylate
anion recognition based on C-linked peptidocalix[4]arenes. Proc.
Natl. Acad. Sci. USA 99, 4842–4847 (2002)
5. Sansone, F., Barboso, S., Casnati, A., Fabbi, M., Pochini, A.,
Ugozzoli, F., Ungaro, R.: Synthesis and structure of chiral cone
calix[4]arenes unctionalized at the upper rim with L-alanine units.
Eur. J. Org. Chem. 1998(5), 897–905 (1998)
6. Sansone, F., Barboso, S., Casnati, A., Sciotto, D., Ungaro, R.: A
new chiral rigid cone water soluble peptidocalix[4]arene and its
inclusion complexes with a-amino acids and aromatic ammonium
cations. Tetrahedron Lett. 40, 4741–4744 (1999)
7. Frish, L., Sansone, F., Casnati, A., Ungaro, R., Cohen, Y.:
Complexation of a peptidocalix[4]arene, a vancomycin mimic,
with alanine-containing guests by NMR diffusion measurements.
J. Org. Chem. 65, 5026–5030 (2000)
8. Segura, M., Bricoli, B., Casnati, A., Munoz, E.M., Sansone, F.,
Ungaro, R., Vicent, C.: A prototype calix[4]arene-based receptor
for carbohydrate recognition containing peptide and phosphate
binding groups. J. Org. Chem. 68, 6296–6303 (2003)
9. Kappe, C.O.: Biologically active dihydropyrimidones of the
Biginelli-type—a literature survey. Eur. J. Med. Chem. 35,
1
1
043–1052 (2000)
2
0. Atwal, K.S., Swanson, B.N., Unger, S.E., Floyd, D.M., Moreland,
S., Hedberg, A., O’Reilly, B.C.: Dihydropyrimidine calcium
channel blockers, 3. 3-Carbamoyl-4-aryl-1,2,3,4-tetrahydro-6-
methyl-5-pyrimidinecarboxylic acid esters as orally effective
antihypertensive agents. J. Med. Chem. 34, 806–811 (1991)
1. Gaudio, A.C., Korolkovas, A., Takahata, Y.: Quantitative struc-
ture-activity relationships for 1,4-dihydropyridine calcium chan-
2
40. Mirza-Aghayan, M., Khoshkameh Langrodi, M., Rahimifard, M.,
nel
antagonists
(nifedipine
analogues):
a
quantum
3 3
Boukherroub, R.: Document Me SiCl and Et SiI-promoted one-
chemical/classical approach. J. Pharm. Sci. 83, 1110–1115 (1994)
2. Bossert, F., Meyer, H., Wehinger, E.: 4-Aryldihydropyridines, a
new class of highly active calcium antagonists. Angew. Chem.
Int. Ed. Engl. 20, 762–769 (1981)
3. Gordeev, M.F., Patel, D.V., Gordon, E.M.: Document Approa-
ches to combinatorial synthesis of heterocycles: a solid-phase
pot synthesis of 1,4-dihydropyridine derivatives. Appl. Organo-
metal. Chem. 23, 267–271 (2009)
41. Mirza-Aghayan, M., Mohammadian, N., Abolghasemi Malak-
shah, M., Boukherroub, R., Tarlani, A.A.: Amino-functionalized
SBA-15 catalyzed one-step synthesis of 2-amino-5-cyano-4-hy-
droxy-6-aryl pyrimidines. J. Iran. Chem. Soc. 3, 559–563 (2013)
2
2
1
23

J Incl Phenom Macrocycl Chem
4
2. Jaime, C., De Mendoza, J., Prados, P., Nieto, P.M., Sanchez, C.:
Carbon-13 NMR chemical shifts. A single rule to determine the
conformation of calix [4] arenes. J. Org. Chem. 56, 3372–3376
44. Goswami, S., Aich, K., Das, S., Das, A.K., Manna, A., Halder, S.:
A highly selective and sensitive probe for colorimetric and flu-
2?
orogenic detection of Cd
1903–1907 (2013)
in aqueous media. Analyst 138,
(1991)
4
3. Marti, A.A., Jockusch, S., Stevens, N., Ju, J.Y., Turro, N.J.:
Fluorescent hybridization probes for sensitive and selective DNA
and RNA detection. Acc. Chem. Res. 40, 402–409 (2007)
45. Verboom, W., Durie, A., Egberink, J.M.R., Asfari, Z., Reinhoudt,
D.N.: Ipso nitration of p-tert-butylcalix[4]arenes. J. Org. Chem.
57, 1313–1318 (1992)
123