Recognition properties of an acyclic biphenyl-based receptor toward carbohydrates

Article abstract of DOI:10.1021/jo0610309

(Figure Presented) Biphenyl-based receptor 1, incorporating four heterocyclic recognition units, was synthesized, and its binding properties toward neutral sugars were determined. Receptor 1 is a representative of a new series of acyclic carbohydrate-bind

Full text of DOI:10.1021/jo0610309

Recognition Properties of an Acyclic
Biphenyl-Based Receptor toward Carbohydrates
and molecular modeling calculations. It is worth noting that the
binding motifs found in the crystal structures of the complexes
formed between the acyclic receptors and monosaccharides2c
show remarkable similarity to the motifs observed in the
Monika Mazik* and Alexander K o¨ nig
3
protein-carbohydrate complexes. The molecular structures of
Institut f u¨ r Organische Chemie der Technischen UniVersit a¨ t
Braunschweig, Hagenring 30, 38106 Braunschweig, Germany
the synthetic complexes provide valuable model systems to study
the basic molecular features of carbohydrate recognition. The
acyclic scaffold provides simplicity in the synthetic plan for
many modifications of the receptor structure, supplying a base
for systematic studies toward recognition motifs for carbohy-
drates.
m.mazik@tu-bs.de
ReceiVed May 21, 2006
Molecular modeling calculations indicated that a 3,3′,5,5′-
tetrasubstituted biphenyl scaffold provides a cavity of the correct
shape and size for disaccharide encapsulation. In this paper,
we describe the synthesis and binding properties of a representa-
tive of the new series of acyclic carbohydrate-binding receptors,
which were expected to prefer disaccharides.
In the area of sugar recognition, the biphenyl unit has mostly
been used as a building block for macrocyclic receptors.1
Particularly interesting biphenyl-based macrocyclic architecture
,4,5
4
was designed by Davis and co-workers. The tricyclic octa-
amide receptor system was constructed to provide both apolar
and polar contacts to a monosaccharide, such as glucose. The
recognition properties of a series of tricyclic oligoamides have
4
d
4b,c
been explored in organic solvents, in two-phase systems,
4
a
and in water. A related macrotricyclic receptor featuring two
,1′-biphenyl platforms linked by amide bridges was designed
Biphenyl-based receptor 1, incorporating four heterocyclic
recognition units, was synthesized, and its binding properties
toward neutral sugars were determined. Receptor 1 is a
representative of a new series of acyclic carbohydrate-binding
receptors, which were designed to recognize disaccharides.
The compound 1 has been established as a highly effective
receptor for dodecyl â-D-maltoside, showing successive 1:1
and 2:1 receptor/substrate complexation behavior toward the
disaccharide. Both hydrogen bonding and interactions of the
sugar CH’s with the aromatic units of the receptor contribute
to the stabilization of the receptor-maltoside complexes.
1
5
by molecular modeling by Diederich and co-workers. The
authors described synthetic routes to 3,3′,5,5′-tetraarylbiphenyls,
suitably functionalized for the targeted construction of the
macrocyclic system. Suzuki cross-coupling starting from 3,3′,5,5′-
tetrabromo-1,1′-biphenyl provided access to a series of extended
5,6
aromatic platforms for cleft-type and macrocyclic receptors.
As a starting point for the design of the acyclic biphenyl-
based receptors, we examined the binding properties of the
receptor 1, incorporating four heterocyclic recognition groups
based on the 2-aminopyridine unit (our previous binding studies
toward monosaccharides showed that aminopyridines and ami-
7
The selective recognition of carbohydrates by synthetic
receptors operating through noncovalent interactions still rep-
resents a significant challenge (for reviews on carbohydrate
recognition with artificial receptors, see ref 1). As pointed out
by Davis and Wareham1b “synthetic carbohydrate receptors
could be used as drugs (e.g., anti-infective agents), to target
cell types (acting as synthetic antibodies), to transport saccha-
rides or related pharmaceuticals across cell membranes, or in
carbohydrate sensors”. Recently, we have shown that acyclic
benzene-spaced receptors (for example, amino- and amidopy-
ridine receptors based on a 2,4,6-trimethyl- or 2,4,6-triethyl-
benzene frame and a 1,3,5-benzenetricarbonyl unit) perform
effective recognition of carbohydrates through multiple interac-
(2) (a) Mazik, M.; Cavga, H. J. Org. Chem. 2006, 71, 2957-2963. (b)
Mazik, M.; Kuschel, M.; Sicking, W. Org. Lett. 2006, 8, 855-858. (c)
Mazik, M.; Cavga, H.; Jones, P. G. J. Am. Chem. Soc. 2005, 127, 9045-
9
052. (d) Mazik, M.; Radunz, W.; Boese, R. J. Org. Chem. 2004, 69, 7448-
462. (e) Mazik, M.; Sicking, W. Tetrahedron Lett. 2004, 45, 3117-3121.
7
(f) Mazik, M.; Bandmann, H.; Sicking, W. Angew. Chem., Int. Ed. 2000,
3
6
4
9, 551-554. (g) Mazik, M.; Sicking, W. Chem.sEur. J. 2001, 7, 664-
70. (h) Mazik, M.; Radunz, W.; Sicking, W. Org. Lett. 2002, 4, 4579-
582.
(3) For examples of the crystal structures of protein-carbohydrate
complexes, see: (a) Lis, H.; Sharon, N. Lectins; Kluwer Academic
Publishers: Dordrecht, The Netherlands, 2003. (b) Quiocho, F. A. Pure
Appl. Chem. 1989, 61, 1293-1306. (c) Quiocho, F. A.; Wilson, D. K. Nature
1989, 340, 404-408. (d) Vyas, N. K.; Vyas, M. N.; Quiocho, F. A. Science
1988, 242, 1290-1295. (e) Weiss, W. I.; Drickamer, K. Annu. ReV.
Biochem. 1996, 65, 441-473. (f) Lemieux, R. U. Chem. Soc. ReV. 1989,
18, 347-374. (g) Lis, H.; Sharon, N. Chem. ReV. 1998, 98, 637-674. (h)
Ravishankar, R.; Ravindran, N.; Suguna, A.; Surolia, A.; Vijayan, M. Curr.
Sci. 1997, 72, 855. (i) Spurlino, S. P.; Lu, G.-Y.; Quiocho, F. A. J. Biol.
Chem. 1991, 266, 5202-5219.
2
tions. The binding modes were discussed in detail on the basis
1
of chemical shift changes in H NMR spectra, X-ray analyses,
*
To whom correspondence should be addressed. Phone: +49-531-391-5266.
Fax: +49-531-391-8185.
1) (a) Davis, A. P.; James, T. D. In Functional Synthetic Receptors;
Schrader, T., Hamilton, A. D., Eds.; Wiley-VCH: Weinheim, Germany,
(4) (a) Klein, E.; Crump, M. P.; Davis, A. P. Angew. Chem., Int. Ed.
2005, 44, 298-302. (b) Velasco, T.; Lecollinet, G.; Ryan, T.; Davis, A. P.
Org. Biomol. Chem. 2004, 2, 645-647. (c) Ryan, T. J.; Lecollinet, G.;
Velasco, T.; Davis, A. P. Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 4863-
4866. (d) Davis, A. P.; Wareham, R. S. Angew. Chem., Int. Ed. 1998, 37,
2270-2273.
(
2
005; pp 45-109. (b) Davis, A. P.; Wareham, R. S. Angew. Chem., Int.
Ed. 1999, 38, 2979-2996. (c) For a review on boronic acid based receptors,
using covalent interactions for sugar binding, see: James, T. D.; Shinkai,
S. Top. Curr. Chem. 2002, 218, 159-200.
(5) Welti, R.; Abel, Y.; Gramlich, V.; Diederich, F. HelV. Chim. Acta
2003, 86, 548-562.
10.1021/jo0610309 CCC: $33.50 © 2006 American Chemical Society
7
854
J. Org. Chem. 2006, 71, 7854-7857
Published on Web 09/07/2006

SCHEME 1. Synthesis of Receptor 1a
a
6
10
Key: (a) NaNO2, 20% HCl, KI, yield ) 49%; (b) PdCl2(dppf), KOAc/DMF, 80 °C, 2 h; (c) 2 equiv of 5, PdCl2(dppf), CsF, 80 °C, 12 h, yield ) 82%;
d) 10% NaOH; (e) 50% H2SO4, yield ) 89%; (f) SOCl2, THF; (g) NEt3, THF, yield ) 76%.
(
dopyridines provide an excellent structural motif for binding
groove is heavily populated by polar and aromatic groups many
of which are involved in extensive hydrogen-bonding and van
der Waals interactions with the maltose. Quiocho et al. pointed
carbohydrates, associated with the ability to form cooperative
2
3i
and bidentate hydrogen bonds with the sugar OH groups ). The
biphenyl spacer of 1 provides additional apolar contacts to a
out that “the maltose is wedged between four aromatic side
chains and the resulting stacking of these aromatic residues on
the faces of the glucosyl units provides a majority of the van
der Waals contacts in the complex”.
saccharide, similar to sugar-binding proteins, which commonly
3
place aromatic surfaces against patches of sugar CH groups.
The artificial receptor 1 has been established as a highly
effective receptor for â-D-maltoside 2â. The synthesis of 1 is
shown in Scheme 1 (see also refs 6 and 10). Interactions of
1
this receptor with saccharides were investigated by H NMR
1
1
spectroscopy.
Contrary to â-glucopyranoside 3, the â-maltoside 2â is poorly
soluble in chloroform, but could be solubilized in this solvent
in the presence of receptor 1, indicating favorable interactions
between 1 and 2â. Thus, the receptor in CDCl3 was titrated
with a solution of maltoside dissolved in the same receptor solu-
tion. The shifts of the receptor amide NH, aromatic CH’s, and
CH3 protons were monitored as a function of sugar concentra-
To evaluate the recognition capabilities of receptor 1 in aprotic
8,9
solvents, such as chloroform (or water-containing chloroform),
and compare the binding properties with the properties of the
previously published receptors, the dodecyl â-D-maltoside (2â),
dodecyl R-D-maltoside (2R), and octyl â-D-glucopyranoside (3)
were selected as substrates.
(9) The importance of the model studies in organic media has been
pointed out by Gokel et al. in J. Am. Chem. Soc. 2005, 127, 18281-
8295: “In a recent and excellent review by Kubik and co-workers titled
1
“
Recognition of Anions by Synthetic Receptors in Aqueous Solution,” the
authors state that “the chemistry of life mainly takes place in water...” While
this is true in the broadest sense, relatively little biological chemistry takes
place in bulk water per se. Instead, biological reactions and interactions
occur in or between proteins or membranes or both. Assuredly, cytosolic
proteins interact with numerous species, but most recognition, catalysis,
signaling, and other processes occur in enzyme pockets or in or on
membranes. This contradiction in medium requirements presents the organic
chemist with the challenge of developing a model system that is truly
suitable for the study of biological phenomena.”
The crystal structure of the maltose-binding protein (MBP)
with bound maltose shows one of the best examples of the
extensive use of polar and aromatic residues in binding
3
i
oligosaccharides. The bound maltose is buried in the groove
and is almost completely inaccessible to the bulk solvent. The
(
10) For one-pot biaryl synthesis via in situ boronate formation, see:
(
6) For examples of other tetrafunctionalized biphenyl building blocks,
see: Boomgaarden, W.; V o¨ gtle, F.; Nieger, M.; Hupfer, H. Chem.sEur. J.
999, 5, 345-355.
7) The 2-aminopyridine unit can be regarded as a heterocyclic analogue
Giroux, A.; Han, Y. X.; Prasit, P. Tetrahedron Lett. 1997, 38, 3841-3844.
(11) (a) The binding constants were determined in chloroform at 25 °C
by titration experiments, and the titration data were analyzed by nonlinear
regression analysis, using the program HOSTEST 5.6 (see ref 11e). The
stoichiometry of receptor-sugar complexes was determined by mole ratio
plots and by the curve-fitting analysis of the titration data. Dilution
experiments show that receptor 1 does not self-aggregate in the used
concentration range. For each system at least three titrations were carried
out (for each titration, 12-20 samples were prepared). CDCl3 was
deacidified with Al2O3. (b) Error in a single Ka estimation was <10%. (c)
Ka was estimated on the base of a 2:1 receptor/sugar binding model
incorporated in the Hostest 5.6 program. (d) Ka1 corresponds to the 1:1
association constant. Ka2 corresponds to the 1:2 receptor/sugar association
constant. (e) Wilcox, C. S.; Glagovich, N. M. HOSTEST 5.6; University of
Pittsburgh: Pittsburgh, PA, 1994.
1
(
of the asparagine/glutamine primary amide side chain. See: Huang, C.-Y.;
Cabell, L. A.; Anslyn, E. V. J. Am. Chem. Soc. 1994, 116, 2778-2792.
(8) Although molecular recognition of carbohydrates is relevant in water,
the complexation studies in organic media are also of high importance.
Quiocho et al. have shown that the hydrogen bonds between sugar-binding
proteins and essential recognition determinants on sugars are shielded from
bulk solvent, meaning that they exist in a lower dielectric environment (see
refs 3b,c,d,i). Thus, the recognition of sugars in lipophilic solvents provides
important information about the factors which contribute to the affinity
between receptors and saccharides. Such model studies are very useful in
the development of both effective and selective receptor architectures.
J. Org. Chem, Vol. 71, No. 20, 2006 7855

FIGURE 2. Energy-minimized structure of the 2:1 and 1:1 complexes
formed between receptor 1 and â-D-maltoside 2â (MacroModel V.6.5,
Amber* force field, Monte Carlo conformational searches, 50 000
steps): (a) 2:1 Receptor/sugar complex. (b) Space-filling representation
of the 1:1 complex. Color code: receptor C, blue; O, red; N, green;
the sugar molecule is highlighted in yellow.
FIGURE 1. Plot of the observed chemical shifts of the NH (a), pyridine
CH (b), and CH (c, d) resonances of 1 as a function of added
3
â-maltoside 2â. The [receptor]:[sugar] ratio is marked.
tion. Interestingly, all of the CH and CH3 signals first shifted
upfield until the maltoside/receptor ratio reached 0.5, and then
they moved in the opposite direction (Figures 1b-d and Figure
12
S1). The amide NH signal shifted downfield with broadening,
as shown in Figure S1a. The plot of the observed chemical shifts
of the NH resonances as a function of added â-maltoside (see
Figure 1a) clearly shows two complexation steps.
Analysis of the first part of the titration curve1 (see also
1e
Figure S13a) indicated the formation of a very strong 2:1
13
receptor/maltoside complex. The binding constant was esti-
6
-1 11c
mated to be Ka > 10 M . The titration results clearly
indicate that the addition of maltoside to the solution of receptor
1
leads to the predominant formation of a 2:1 receptor/maltoside
complex at the initial stages of titration up to a maltoside/
receptor ratio of 0.5, which is then gradually replaced by the
FIGURE 3. Examples of hydrogen-bonding motifs found by molecular
modeling studies in the 2:1 complex between receptor 1 and maltoside
2â (MacroModel V.6.5, Amber* force field, Monte Carlo conforma-
tional searches, 50 000 steps).
1:1 complex (see Figure 2b) with increasing maltoside/receptor
ratio. Similar complexation behavior and very strong binding
6
-1
of the maltoside 2â (Ka > 10 M ) could be also observed in
water-containing chloroform solutions ([receptor]:[water] )
molecules (see Figure 2a) in a similar way as in the protein-
sugar complexes.
1
4
1
:10, 1:20). Dodecyl R-D-maltoside (2R) is poorly soluble in
chloroform and could not be solubilized in this solvent in the
presence of receptor 1 in the concentration range required for
binding studies (contrary to the â-anomer, which is soluble in
the presence of 1), indicating weaker binding between 1 and
the R-anomer. Thus, receptor 1 shows R/â-anomer selectivity
in the recognition of maltosides.
The 3- and 4-OH groups of the glucosyl unit g2 (for labeling
see formula 2â), the 6-OH group, and the ring oxygen atom of
the g1 unit all participate in bidentate hydrogen bonds with the
amidopyridine subunits of the receptor (see Figure 3c and 3b,
respectively). The 2-OH of the g1 unit is involved in cooperative
hydrogen bonds, which results from the simultaneous participa-
tion of the OH as acceptor for the NH group of the receptor
and as donor for the pyridine nitrogen atom (Figure 3a). The
According to molecular modeling calculations, the disaccha-
ride 2â is encapsulated in the cavity between the two receptor
3
- and 2-OH groups of the g1 and g2 unit, respectively, are
(
12) Similar 1:1 and 2:1 receptor/substrate complexation behavior was
involved in the formation of an intramolecular hydrogen bond
observed for a guanidinium-based receptor and sulfate anion. See: Kobiro,
(Figure 3e). Furthermore, hydrogen bonds between the two
K.; Inoue, Y. J. Am. Chem. Soc. 2003, 125, 421-427.
(13) The linearity of the shift changes shows that the association constant
is very large and could not be precisely determined from the NMR titrations
data. For a review discussing the limitations of the NMR method, see:
Fielding, L. Tetrahedron 2000, 56, 6151-6170.
(14) The presence of water may lead to the formation of water-mediated
hydrogen bonds, in line with the observation in protein-carbohydrate
complexes.
7
856 J. Org. Chem., Vol. 71, No. 20, 2006

receptor molecules stabilize the 2:1 receptor/sugar complex
Figure 3f). In addition, the biphenyl units of both receptors
for 1 h. The organic layer was separated and washed three times
with water, dried with MgSO , filtered, and concentrated in vacuum.
(
4
The crude product was recrystallized three times from methanol,
stack on the sugar rings. Both sides of the pyranose rings are
1
involved in the CH-π interactions.15 Interestingly, in the crystal
giving 5 as light-brown crystals. Yield 49%. Mp 103-104 °C. H
NMR (400 MHz, CDCl ): δ ) 3.95 (s, 6H), 8.53 (d, 2H, J ) 1.5
3
structure of the MBP-maltose complex, the 3- and 4-OH groups
of the glucosyl unit g2 participate in bidentate hydrogen bonds,
the 2-OH group of the g1 unit is involved in cooperative
hydrogen bonds, and the 3-OH(g1) and 2-OH(g2) form an
intramolecular hydrogen bond, in line with observations in the
synthetic complex.
13
Hz), 8.61 (t, 1H, J ) 1.5 Hz). C NMR (100 MHz, CDCl
3
): δ )
5
2.6, 93.4, 129.8, 132.3, 142.4, 164.7. MS-EI, m/z (%): 320 (88)
+
[
M ], 289 (100), 261 (25). R
hexane 3:7 v/v).
,3′,5,5′-Tetrakis(methoxycarbonyl)biphenyl (8). A mixture of
f
) 0.54 (silica gel, ethyl acetate/
3
dimethyl 5-iodobenzene-1,3-dicarboxylate (5) (320 mg, 1.00 mmol),
bis(pinacolato)diborane (6) (279 mg, 1.10 mmol), potassium acetate
(294 mg, 3.00 mmol), PdCl (dppf) (24 mg, 0.03 mmol), and dried
2
DMF (6 mL) was stirred at 80 °C for 2 h. The reaction mixture
was cooled to room temperature. Then, dimethyl 5-iodobenzene-
1
The H NMR titration experiments with â-glucopyranoside
were carried out by adding increasing amounts of the sugar
3
to a solution of receptor 1. During titration, the signal due to
the amide NH of 1 moved downfield by about 0.66 ppm (after
the addition of 5 equiv of sugar; see Figure S2). Furthermore,
1
0
,3-dicarboxylate (5) (640 mg, 2.00 mmol), PdCl
.03), and CsF (456 mg, 3.0 mmol; dissolved in 2.5 mL of water)
2
(dppf) (24 mg,
1
the H NMR spectra showed changes in the chemical shifts of
were added. The mixture was stirred at 80 °C overnight and
afterward extracted four times with diethyl ether (4 × 25 mL). The
the biphenyl/pyridine CH’s and the CH3 protons (upfield shifts,
in the range of 0.04-0.15 ppm), as illustrated in Figure S2.
Typical titration curves are shown in Figure S3. Both the curve
fitting of the titration data1 and the mole ratio plots (see Figure
S13b) suggest the existence of 1:1 and 1:2 receptor/sugar
complexes in chloroform. The binding constants for 1•3 were
4
organic layer was dried with MgSO , and the solvent was removed
in vacuum. The crude product was purified by column chroma-
tography (silica gel, ethyl acetate/hexane, 3:7 v/v). Yield 82%. Mp
1e
1
214-215 °C. H NMR (400 MHz, CDCl ): δ ) 4.00 (s, 12H),
3
13
8.51 (d, 4H, J ) 1.5 Hz), 8.72 (d, 2H, J ) 1.5 Hz). C NMR (100
-
1
found to be 8800 (Ka1) and 300 (Ka2) M [in water-containing
chloroform solutions ([receptor]:[water] ) 1:10), the binding
MHz, CDCl
0
3
): δ ) 52.5, 130.2, 131.5, 132.3, 139.9, 165.9. R
f
)
.50 (silica gel, ethyl acetate/hexane, 3:7 v/v). MS-EI, m/z (%):
+
-1
11b,d
386 (75) [M ], 355 (100), 327 (15), 194 (10).
constants amount to 11 400 (Ka1) and 480 (Ka2) M ].
Thus,
Biphenyl-3,3′,5,5′-tetracarboxylic acid (9). A mixture of 3,3′,5,5′-
tetrakis(methoxycarbonyl)biphenyl (8) (0.96 g, 2.5 mmol), THF (40
mL), and NaOH (1.6 g, 40 mmol) dissolved in water (40 mL) was
refluxed for 1 h. Then, the organic solvent was removed under
reduced pressure, and the aqueous solution was refluxed again for
the binding affinity of 1 for the monosaccharide 3 is expectedly
16a
significantly lower than that observed for the disaccharide 2â.
In conclusion, the biphenyl-based receptor 1 has been
established as a highly effective receptor for dodecyl â-D-
maltoside (2â) in chloroform and water-containing chloroform
solutions, showing successive 1:1 and 2:1 receptor/sugar binding
4
2
h. The reaction mixture was cooled and acidified with 50% H -
SO . The precipitate was filtered and dried to obtain 9 as a white
powder. Yield 89%. Mp > 350 °C. H NMR (400 MHz, DMSO-
d ): δ ) 8.44 (d, 4H, J ) 1.5 Hz), 8.53 (t, 2H, J ) 1.5 Hz), 13.48
4
6
-1
1
behavior toward the disaccharide (Ka > 10 M ). This receptor
provides both hydrogen bonding sites and aromatic units for
facilitating stacking interactions with the sugar rings. This
receptor type is able to bind both â-glucopyranoside 3 and
6
13
(
1
br s, 4 H). C NMR (100 MHz, DMSO-d
32.3, 139.2, 166.3. MS-EI, m/z (%): 330 (100) [M ], 313 (40),
285 (15) 240 (5).
6
): δ ) 129.5, 131.4,
+
1
6a
â-maltoside 2â, with a preference for the disaccharide.
N,N′,N′′,N′′′-Tetrakis-[(4,6-dimethylpyridin-2-yl)biphenyl-
,3′,5,5′-tetracarboxamide (1). (a) Synthesis of 10. A mixture of
Furthermore, receptor 1 shows â versus R binding selectivity
in the recognition of maltosides 2â and 2R.1 The simple acyclic
structure offers the possibility of an easy variation of the receptor
structure. The results obtained with receptor 1 serve as a basis
for the construction of new biphenyl-based receptors, incorpo-
rating both neutral and ionic hydrogen-bonding sites, for the
recognition of saccharides in organic and aqueous media.
Binding studies with this type of receptor and different
oligosaccharides are now in progress.
3
6b
biphenyl-3,3′,5,5′- tetracarboxylic acid (9) (0.30 g, 0.90 mmol) and
thionyl chloride (0.53 mL, 7.20 mmol) in THF (20 mL) was heated
under reflux for 3 h. The solvent was removed in vacuum. Then,
THF (4 × 20 mL) was added, and again the solvent was removed
in vacuum. The crude product was used directly for further reaction.
(b) Synthesis of 1. A solution of 10 in THF (20 mL) was added
dropwise to a solution of 2-amino-4,6-dimethylpyridine (11) (0.47
g, 3.81 mmol) and triethylamine (0.76 mL) in THF (20 mL). After
complete addition, the mixture was stirred at room temperature for
48 h. The reaction mixture was treated with water (100 mL), stirred
for 15 min, and THF was removed in vacuum. The resulting
precipitate was filtered, washed with water, dried, and recrystallized
Experimental Section
Dimethyl 5-Iodobenzene-1,3-dicarboxylate (5). A solution of
6
sodium nitrite (8.63 g, 0.125 mol) in water (150 mL) was added to
a suspension of 5-aminobenzene-1,3-dicarboxylate (4) (26.16 g,
1
from THF/hexane or chloroform. Yield 76%. Mp 181-182 °C. H
NMR (500 MHz, CDCl
3
): δ ) 2.31 (s, 12 H), 2.37 (s, 12 H), 6.72
0
.125 mol) in 20% HCl (75 mL) at -5 °C. Toluene (200 mL) and
then a solution of potassium iodide (42.00 g, 0.50 mol) in water
100 mL) were slowly added to the suspension. After the addition,
the reaction mixture was stirred for 12 h and afterward refluxed
(
s, 4H), 8.01 (s, 4H,), 8.47 (d, 4H, J ) 1.8 Hz), 8.53 (t, 2H, J )
1
2
1
7
.8 Hz), 8.91 (br s, 4H). 13C NMR (125 MHz, DMSO-d
0.9, 23.2, 111.9, 120.4, 127.2, 129.8, 135.1, 139.1, 149.6, 151.4,
56.1, 165.3. HR-MS calcd for C44 746.3329; found
46.3334. R ) 0.94 (silica gel, methanol/chloroform 1:7 v/v).
6
): δ )
(
42 8 4
H N O
f
(15) (a) For examples of CH-π interactions in the crystal structures of
Acknowledgment. This work was supported by the Deutsche
Forschungsgemeinschaft.
the complexes formed between artificial receptors and carbohydrates, see
ref 2c. (b) For a recent discussion on the importance of carbohydrate-
aromatic interactions, see: Ch a´ vez, M. I.; Andreu, C.; Vidal, P.; Aboitiz,
N.; Freire, F.; Groves, P.; Asensio, J. L.; Asensio, G.; Muraki, M.; Ca o` ada,
F. J.; Jim e´ nez-Barbero, J. Chem.sEur. J. 2005, 11, 7060-7074.
Supporting Information Available: 1H NMR titration data
1
13
(
Figures S1-S3). Copies of the H and C NMR spectra of all
(
16) (a) For an example of a macrocyclic receptor, which is able to
compounds (Figures S4-S12). Representative mole ratio plots
(Figure S13). Description of a titration experiment with dodecyl
â-D-maltoside (2â). This material is available free of charge via
the Internet at http://pubs.acs.org.
-
1
distinguish between the octyl â-D-maltoside (Ka ) 11 000 M ) and octyl
â-D-glucopyranoside (no binding) in organic media (CD3CN/CD3OD, 88:
1
1
2 v/v), see: Neidlein, U.; Diederich, F. Chem. Commun. 1996, 1493-
494. (b) Selective recognition of oligosaccharides is still rare; for a recent
review, see ref 1a.
JO0610309
J. Org. Chem, Vol. 71, No. 20, 2006 7857