Helix formation in synthetic polymers by hydrogen bonding with native saccharides in protic media

Article abstract of DOI:10.1002/chem.200600315

Water-soluble poly(m-ethynylpyridine)s were designed to realize saccharide recognition in protic media. UV/Vis, ¹HNMR, and fluorescence measurements revealed that the polymer forms a helical higher order structure by solvophobic interactions between the ethynylpyridine units in the protic medium. The resulting pore in the helix behaves like a binding pocket in proteins, by taking advantage of inwardly directed hydrogen-bonding functional groups of the polymers. Molecular recognition of native saccharides by the polymers was investigated by circular dichroism (CD). The chirality of the saccharide was transferred to the helical sense of the polymers, accompanied by the appearance of induced CDs (ICDs) in the absorptive region of the polymers. In MeOH/water (10/1), mannose and allose showed intense ICDs, and the apparent association constant between the polymer and D-mannose was 14M^-1.

Full text of DOI:10.1002/chem.200600315

FULL PAPER
DOI: 10.1002/chem.200600315
Helix Formation in Synthetic Polymers by Hydrogen Bonding with Native
Saccharides in Protic Media
[
a]
[a, b]
[a]
Minoru Waki, Hajime Abe,*
andMasahiko Inouye*
Abstract: Water-soluble poly(m-ethy-
nylpyridine)s were designed to realize
saccharide recognition in protic media.
wardly directed hydrogen-bonding
functional groups of the polymers. Mo-
lecular recognition of native saccha-
rides by the polymers was investigated
by circular dichroism (CD). The chiral-
ity of the saccharide was transferred to
the helical sense of the polymers, ac-
companied by the appearance of in-
duced CDs (ICDs) in the absorptive
region of the polymers. In MeOH/
water (10/1), mannose and allose
showed intense ICDs, and the apparent
association constant between the poly-
1
UV/Vis, H NMR, and fluorescence
measurements revealed that the poly-
mer forms a helical higher order struc-
ture by solvophobic interactions be-
tween the ethynylpyridine units in the
protic medium. The resulting pore in
the helix behaves like a binding pocket
in proteins, by taking advantage of in-
Keywords: helical structures · hy-
drogen bonds · molecular recogni-
tion · Pi interactions · supramolecu-
lar chemistry
À1
mer and d-mannose was 14m .
Introduction
cially the recognition of saccharides by hydrogen bonding is
strongly affected, because the multiple hydroxyl groups of
saccharides are prone to interact with the surrounding sol-
vent molecules. Even biotic receptors bind to saccharides
with much difficulty: the binding constants between various
native proteins and monosaccharides have been reported to
Hydrogen bonds play an important role in structures and
functions of biopolymers such as DNA, proteins, and poly-
[
1]
saccharides. Examples include complementary bonding be-
tween base pairs in DNA and RNA duplexes and molecular
recognition of substrates by enzymes and antibodies. In the
field of molecular-recognition chemistry, mimicking biologi-
cal systems by hydrogen bonding with designed synthetic
7
À1
[3c,7]
be 10 m at most.
Thus, the development of artificial
host molecules that recognize saccharides in protic media is
[8]
an exciting and challenging subject.
[
2]
host molecules is subject to continuing interest. These
mimetics may provide not only information for understand-
ing biological events but also an approach for the develop-
ment of medical treatments. So far, hydrogen-bonding-
driven molecular recognition of biomolecules has been in-
Recently, Davis et al. reported a notable exception in
which a tricyclic polyamide host recognizes saccharides in
water by CH–p and probably some hydrogen-bonding inter-
[9]
actions. The binding event for this highly preorganized
host was mainly assessed by NMR titration. These “lock-
and-key” interaction modes would be favorable for forming
host–guest complexes without entropic loss caused by re-
[
3–5]
vestigated mainly in less polar media
and at air/water in-
[
6]
terfaces. However, the results should be no different than
those under abiotic conditions. In polar media, and more-
over in protic ones, hydrogen bonding suffers from over-
whelming competition of the bulk solvent molecules. Espe-
[10]
structuring of the conformations. At the same time, how-
ever, such a rigid frame in the host structure hardly changes
its optical properties when recognizing substrates. This
sometimes hides interactions, especially in the case of weak
interactions.
[
a] M. Waki, Dr. H. Abe, Prof. Dr. M. Inouye
Faculty of Pharmaceutical Sciences, University of Toyama
Sugitani 2630, Toyama 930-0194 (Japan)
Fax : (+81)76-434-5049
During the course of our studies on molecular recognition
[5]
[5a,b,c]
of saccharides, we have developed terpyridine
and
[5d,e]
polypyridine structures
with acetylene bridges, fashioned
E-mail: abeh@pha.u-toyama.ac.jp
to fit guest polyols. The poly(m-ethynylpyridine)s alone
adopt unfolded conformations in less polar media such as
[
b] Dr. H. Abe
PRESTO, Japan Science and Technology Agency (JST)
CH Cl and CHCl and can recognize saccharides by multi-
ple hydrogen bonds between the pyridine N atoms and sac-
Supporting information for this article is available on the WWW
under http://www.chemeurj.org/ or from the author.
2
2
3
Chem. Eur. J. 2006, 12, 7839 – 7847
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
7839
Pagination corrected Oct. 17, 2006

[
5d]
charide OH groups.
The resulting complexes are biased
media. Even if the recognition proceeds, detection of the
event might be difficult because of disturbance from bulk
solvent molecules. This problem could be overcome by
means of CD spectroscopy for detecting the chirality of the
helical structures, and this drastic conformational change in
the polymers was easily detected by circular dichroism
CD). The pore inside the helix will be isolated from bulk
(
[13]
solvent molecules and is expected to behave as a “binding
pocket”. Therefore, if the polymers prefer helical conforma-
tions to unfolded ones due to hydrophobic effects in aque-
ous media, it may be possible to import the polymers into
such conditions for saccharide recognition. Herein we report
the syntheses and saccharide-recognition abilities of amphi-
philic water-soluble poly(m-ethynylpyridine)s in 100%
protic media.
resulting higher order structures:
in a mixture of a
poly(m-ethynylpyridine) and a native saccharide, CD ob-
served in the wavelength range longer than 200 nm is only
attributable to complexation of the polymer with the saccha-
ride, because the polymer is achiral by itself and the saccha-
ride has no absorption in that wavelength region.
Preparation of m-ethynylpyridine polymers 2poly and3 poly
:
Polymers 2poly and 3poly were designed to have amphiphilicity
by introducing tri- and octaethylene glycol side chains, re-
spectively, and obtained by copolymerization of two types of
corresponding trimers (2poly from 9a and 11a; 3poly from 9b
Results andDiscussion
[14]
Molecular design of water-soluble m-ethynylpyridine poly-
mers: To render poly(m-ethynylpyridine)s soluble in protic
media, amphiphilic poly(ethylene glycol) chains were intro-
duced in the pyridine rings of the polymers 2poly and 3poly. In
and 11b; Scheme 1). Iridium-catalyzed direct boration of
commercially available 2,6-dibromopyridine (4) and subse-
quent oxidative cleavage of the CÀB bond afforded 2,6-di-
bromopyridin-4-ol (5). Halogen exchange of 5 with an
[15]
excess of CuI and KI
gave 2,6-diiodopyridin-4-ol (6),
which was converted to tri- and octaethylene glycolic deriva-
[16]
tives 7a and 7b
by Williamson and Mitsunobu reac-
[17]
tions, respectively. Diiodides 7 were ethynylated to 8 by
Sonogashira reaction with (trimethylsilyl)acetylene followed
by protiodesilylation. Diiodo trimers 9 were obtained by
coupling between 8 and an excess of 7. Further Sonogashira
reaction of 9a with tert-butyldimethylsilylacetylene afforded
disilylated trimer 10a, and deprotection of 10a yielded diac-
etylene-terminated trimer 11a. Copolymerization of 9a and
1
1a by Sonogashira reaction yielded polymer 2poly. On the
polar aqueous media, the polymers are expected to sponta-
other hand, Sonogashira reaction of 9b and tert-butyldime-
thylsilylacetylene was deliberately controlled to give a mix-
ture of trimers 10b and 12b, which were separated by re-
verse-phase HPLC. Protiodesilylation of 10b afforded diace-
tylene-terminated trimer 11b. Finally, copolymerization of
9b and 11b furnished target polymer 3poly. Monoacetylene-
terminated trimer 13b was also prepared as a short refer-
ence oligomer from spare 12b.
[11]
neously form a helical structure
by solvophobic interac-
tions between one pyridine ring and another at an interval
of one pitch (Figure 1). In the helix, pyridine rings line up in
cisoid conformation, so that all of the pyridine nitrogen
atoms are directed to the inside of the pore. The pore simul-
taneously provides a “low-entropy” location compared to
the outside for protic solvent molecules that can form hy-
drogen bonds with one another. Thus, the included solvent
molecules within the pore can be substituted by other hy-
drogen-bonding substrates of sufficient size to fill the pore
The molecular weights of amphiphilic polymers 2poly and
3poly were estimated by gel permeation chromatography
4
4
À1
(GPC) as M =2.6”10 , M =2.7”10 gmol for 2poly and
n
w
[12]
4
4
À1
volume.
With these speculations in mind, we expected
M =2.8”10 , M =3.4”10 gmol for 3poly (see Supporting
n w
that the recognition of native saccharides may be realizable
Information). Copolymerization of 9b and 11b yielded a
with water-soluble poly(m-ethynylpyridine)s in aqueous
polymer longer than that obtained by simple self-polymeri-
Figure 1. Conformation change of amphiphilic m-ethynylpyridine polymer driven by solvent effect, and saccharide recognition within the resulting pore.
7840
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ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2006, 12, 7839 – 7847

Molecular Recognition of Saccharides in Protic Media
FULL PAPER
Scheme 1. Preparation of amphiphilic poly(m-ethynylpyridine)s 2poly and 3poly. a) Pinacolborane, [{IrCl
A
H
R
U
G
2
], DPPE; b) Oxone, H
, toluene, iPr NEt; f) 2-methyl-3-butyn-2-
NH, THF; i) TBAF, H O, THF; j) [Pd
NH, THF; l) [Pd(PPh ], CuI, iPr NH, THF.
2
O, THF; c) KI, CuI,
DMF; d) TsO
ol, [PdCl (PPh
(dba) ]·CHCl , PPh
A
C
H
T
R
E
U
N
G
(C
2
H
4
O)
], CuI, Et
, CuI, iPr
3
CH
3
, K
NH; g) NaH, toluene; h) (trimethylsilyl)acetylene, [PdCl
NH, THF; k) (tert-butyldimethylsilyl)acetylene, [PdCl (PPh
2
CO
3
, acetone; e) HO
A
H
R
U
G
2
H
4
O)
8
CH
3
, DIAD (diisopropyl azodicarboxylate), PPh
(PPh ], CuI, Et
], CuI, iPr
3
2
2
A
C
H
T
R
E
U
N
G
3
)
2
2
2
A
H
E
N
3
)
2
2
2
2
-
A
C
H
T
R
E
U
N
G
3
3
3
2
2
A
H
R
N
3
2
2
A
H
R
U
G
3
)
4
2
zation of trimer 13b bearing both iodo and ethynyl groups
and 317 nm. In MeOH, hypochromism occurred for the
latter lmax accompanied by a small red shift, which became
more significant in water. The possible reasons for this red
shift are 1) hydrogen bonding between the solvents and the
nitrogen atoms of the chromophoric pyridine rings of the
polymer and/or 2) intra- and/or intermolecular p-stacking
4
4
À1
(
M =1.0”10 , M =1.8”10 gmol ). As expected, 2
and
n
w
poly
3poly are soluble in various less polar and polar solvents such
as CH Cl , CHCl , AcOEt, CH CN, and MeOH. With
2
2
3
3
regard to aqueous solvent systems, 2poly is soluble in MeOH/
water (10/1), and 3poly is freely soluble even in pure water.
[11f,18]
interactions between the pyridine rings of the polymer.
Structure of amphiphilic polymer 3
H NMR, and fluorescence analyses were performed on 3poly
to clarify its higher order structure. The shape of the UV/
in solution: UV/Vis,
To evaluate the influence of hydrogen bonding on the UV
spectra, solvent effects were also studied for reference
trimer 13b, which is too short for intramolecular p stacking.
If the red shift observed for 3poly were due to merely the hy-
drogen-bonding interactions with solvents and independent
of p-stacking interactions, the UV/Vis spectrum of 13b
should reveal similar solvent effects to those for 3poly. When
the UV/Vis spectrum of 13b was measured in various sol-
vents, the red shift was very small even in water (see Sup-
porting Information). Therefore, hydrogen bonding has only
little influence on the red shift observed in Figure 2, which
is mainly due to p-stacking interactions between the pyri-
poly
1
Vis absorbance spectrum of 3poly depended on the solvent
À5
(
Figure 2). In CH Cl (3.0”10 m monomer-unit concentra-
2
2
tion), two absorption maxima (lmax) were observed at 275
dine rings in 3poly
.
However, there are still two possible p-stacking modes for
3poly: intra- and intermolecular. To rule out a contribution
from the intermolecular interaction, the dependence of the
UV/Vis absorbance of 3poly on concentration was studied in
various solvents. In CH Cl , MeOH, and water, the absor-
2
2
bances at 275 and 323 nm obeyed Beerꢁs lawat concentra-
À3
tions below1.0”10 m (monomer-unit concentration). This
rules out the possibility that intermolecular interaction of
3poly caused the red shift in Figure 2. Therefore, the observed
red shift should be attributed to the intramolecular p-stack-
ing interaction in 3poly. This conclusion was further supported
Figure 2. UV/Vis spectra of 3poly in CH
water (blue). Conditions: 3poly (3.0”10 m, monomer-unit concentration),
2
Cl
2
(black), MeOH (red), and
À5
2
58C, light path length=10 mm.
Chem. Eur. J. 2006, 12, 7839 – 7847
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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7841

H. Abe, M. Inouye, and M. Waki
1
on the basis of the following H NMR and fluorescence
analyses.
1
H NMR analyses were carried out for polymer 3poly and
short reference trimers 9b and 11b. For the trimers 9b and
1
1b in CD OD, the signals of the protons on the central pyr-
3
idine rings were observed at d=7.40 and 7.41 ppm, respec-
tively (Figure 3a, b). In the spectrum of polymer 3poly, the
Figure 4. Fluorescence emission spectra of 3poly in CH
2
Cl
2
(black), MeOH
À5
(
red), and water (blue). Conditions: lex =300 nm, 3poly (3.0”10 m, mono-
mer-unit concentration), 258C, light path length=10 mm. The inset ex-
pands the region of the excimer-like emission.
[5d,11d]
this emission.
Based on this similarity, the broad emis-
sion of 3poly could be due to intramolecular p interaction be-
tween one excited segment and another, usually the ground
state in 3poly. Indeed, the trimer 13b did not exhibit such an
excimer-like emission because it is too short to interact in-
tramolecularly (see Supporting Information). Furthermore,
the monomer emission significantly decreased in polar sol-
vents, especially in water. This suppression would result
from the enforced solvophobic intramolecular p-stacking in-
[11f]
teractions between two ground-state segments in 3poly
.
These three spectroscopic investigations indicated the
contribution of intramolecular p-stacking interactions in 3poly
in polar solvents, and these interactions probably arise from
the helical structure of 3poly shown in Figure 1. In the helical
structure, the pyridine rings located near the inside pore
overlap with each other, and the amphiphilic side chains
extend from the helix to the outside, where they interact
with polar solvents. Thus, one might expect that the inside
pore would effectively incorporate saccharides in polar sol-
vents to form chiral helical complexes biased by the chirality
of the saccharides.
1
Figure 3. H NMR (300 MHz) spectra in CD
1
3
OD for trimers 9b (a) and
1b (b) and polymer 3poly (c) at 238C.
signal for the aromatic protons appeared as a broad peak
around 7.23 ppm (Figure 3c). This upfield shift can be ra-
tionalized by an anisotropic effect in the p-stacked pyridine
rings of 3poly. Similar observations have been reported for
other kinds of intramolecularly p-stacked oligomers and pol-
[
11c,19]
ymers.
Moreover, the broadening of the aromatic signal
for 3poly would reflect the slowness of its molecular motion
in the ordered structure.
[4a,11g]
On the other hand, the spectra
of 9b, 11b, and 3poly in CDCl3 showed almost the same
chemical shift for the protons on the pyridine rings, at d=
Saccharide recognition with amphiphilic polymer 3poly: Pre-
viously, we reported that the butoxy-substituted polymer
1poly forms biased helical complexes with octyl glycosides
7.16 ppm for 9b, d=7.17 ppm for 11b, and d=7.18 ppm for
[5d]
3poly. This finding means that 3poly in CDCl does not form
that showICDs in the absorptive region of 1
.
poly
Polymer
3
À3
higher order structures, in agreement with the previous
3poly (1.0”10 m, monomer-unit concentration) and each of
naturally occurring monosaccharides (0.30m) in Figure 5
were mixed in MeOH/water (10/1), and the mixtures were
subjected to CD measurements. The saccharides were used
as an a/b and furanose/pyranose equilibrium mixture after
[5d]
1
result for 1poly in less polar solvents. Thus, H NMR analy-
ses gave further evidence for the p-stacked higher order
structure of 3poly in polar solvents.
The fluorescence emission spectra of 3poly gave additional
information on the intramolecular p interactions from the
[20]
the solution had been left for 48 h. As shown in Figure 6,
the mixed solutions showed significant ICDs in the absorp-
tive region of 3poly. These ICDs indeed demonstrate that 3poly
associates with native saccharides even in a 100% protic
medium. With the enantiomeric pairs of mannose (d-Man
and l-Man) and fructose (d-Fru and l-Fru), we observed
pairs of spectra as mirror images (Figure 6A). Thus, the
ICDs must result from the chirality of the saccharides. The
À5
viewpoint of its excited state. When 3poly (3.0”10 m, mono-
mer-unit concentration) was excited at 300 nm in various
solvents, the fluorescence emission spectrum exhibited two
bands at Fmax ꢀ330 and 520 nm, and the latter was broad
and structureless (Figure 4). A similar broad emission was
also observed for 1poly around 525 nm, and in that case intra-
molecular excimer-like p interaction was assumed to cause
7842
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Chem. Eur. J. 2006, 12, 7839 – 7847

Molecular Recognition of Saccharides in Protic Media
FULL PAPER
Figure 5. Native hexoses and pentoses as guest saccharides (pyranose
forms).
CD spectra of the mixtures of 3poly and other saccharides are
shown in Figure 6B. Of the hexoses, d-allose (d-All) exhibit-
ed the strongest positive ICD, while d-glucose (d-Glc), the
most common monosaccharide, showed only a weak nega-
tive ICD with the longest wavelength. Unfortunately, d-gal-
actose (d-Gal) was scarcely soluble in the mixed solvent and
showed no meaningful ICD. Pentoses also revealed ICDs by
interacting with 3poly under the same conditions, and the ob-
served ellipticities were relatively strong for d-ribose (d-
Rib) and d-lyxose (d-Lyx), weak for d-xylose (d-Xyl), and
negligible for d-arabinose (d-Ara).
Figure 6. A) ICDs of the complexes between 3poly and the enantiomeric
pairs of mannose and fructose: d-Man (red solid line), l-Man (red
broken line), d-Fru (blue solid line), and l-Fru (blue broken line). Condi-
À3
tions:
3
poly (1.0”10 m, monomer-unit concentration), saccharides
(
0.30m), MeOH/water (10/1), 258C, light path length=1 mm. B) ICDs of
the complexes between 3poly and various monosaccharides. Conditions:
À3
3poly (1.0”10 m, monomer-unit concentration), saccharide [0.30m except
for d-All (0.22m) and d-Gal (virtually insoluble)], MeOH/water (10/1),
2
58C, light path length=1 mm.
The shapes of these ICDs are similar to those for 1poly
with saccharide derivatives in less polar media. This resem-
blance would suggest that the complexes between poly(m-
ethynylpyridine)s and saccharides in both protic and aprotic
media have similar biased helical structures. Therefore, it
would be reasonable to assume that saccharide recognition
by 3poly in MeOH/water is also driven by hydrogen bonding,
as in the case of 1poly. To support this assumption, solvent ef-
fects were examined for the ICDs of the complex between
3poly and d-Man in MeOH/water mixtures of various ratios
(
Figure 7). With increasing fraction of water, the ICD
around 337 nm gradually decreased and almost disappeared
in MeOH/water (2/1). This shows that complex formation
between 3poly and native saccharides was disturbed by the
bulk water and implies that hydrogen bonding is one of the
driving forces for the complexation. When the ratio of
MeOH to water was increased, the ICD again began to de-
crease above MeOH/water=10/1 (see Supporting Informa-
tion). Thus, the two interactions may operate in a conflicting
manner for the recognition process in protic media: solvo-
phobic interactions causing helix formation in 3poly (advanta-
Figure 7. ICDs of the complexes between 3poly and d-Man in aqueous
MeOH of various ratios. Conditions: 3poly (1.0”10 m, monomer-unit
concentration), d-Man (0.30m), MeOH/water (10/1 to 2/1), 258C, light
path length=1 mm.
À3
geous in water, disadvantageous in MeOH) and hydrogen
bonding of 3poly to saccharides with biasing of the sense of
the helicity (disadvantageous in water, advantageous in
MeOH). The net attractive interaction would be a maximum
Chem. Eur. J. 2006, 12, 7839 – 7847
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
7843

H. Abe, M. Inouye, and M. Waki
for the formation of chiral complexes at a MeOH/water
ratio of about 10/1.
Conclusion
To examine the influence of the amphiphilic side chains
on saccharide recognition, triethylene glycol-derived poly-
mer 2poly was subjected to CD measurement under the same
Amphiphilic poly(m-ethynylpyridine)s spontaneously form
helical conformations in protic media. In the resulting heli-
cal pore, native saccharides interact with the polymer, and
this association could be clearly and easily detected by CD
spectroscopy. In MeOH/water (10/1), the complexes with
native saccharides showed substantial ICDs in the absorp-
tive region of the polymer. In these complexes, the chirality
of the saccharides was transferred to the helical sense of the
polymer. Several experiments revealed that this recognition
event might, at least partially, be driven by hydrogen-bond-
ing interactions even in 100% protic media. By further
modification of the polymer backbone or side chains, sac-
charide recognition may be performable in 100% water,
which would extend the molecular recognition of saccha-
rides to the next stage.
À3
conditions as 3poly. Mixtures of 2poly (1.0”10 m, monomer-
unit concentration) and d-Man or d-Fru (0.30m) in MeOH/
water (10/1) gave ICDs similar to those with 3poly (see Sup-
porting Information). Thus, the contribution of the longer
amphiphilic side chains in 3poly is limited to solubility in
water, and is irrelevant not only to saccharide recognition
but also to formation of the higher order structure of the
polymer.
To obtain quantitative information on the associations,
the apparent association constants K between 3 and vari-
a
poly
ous hexoses were evaluated by CD titration experiments
see Supporting Information). When a hexose (d-Man, d-
(
Fru, or d-All) was added incrementally to a solution of 3
poly
À3
(
1.0”10 m, monomer-unit concentration) in MeOH/water
(
10/1), the ICD band around 337 nm increased gradually
Experimental Section
and showed isodichroic points at 274 and 310 nm (see Sup-
porting Information). From these titrations, the apparent as-
sociation constants were evaluated by using a least-squares
curve-fitting method based on the assumptions of a 1/1 bind-
ing model and a molecular weight of 3
1
1
13
General: H and C NMR analyses were performed in CDCl , CD OD,
3
3
and [D
6
]DMSO at 238C and 300 and 75 MHz, respectively. UV/Vis, fluo-
Cl and MeOH
rescence and CD spectra were measured at 258C in CH
2
2
of commercial spectroscopic grade or in Milli-Q water by using a quartz
cell of 1 or 10 mm path length. IR spectra were recorded with NaCl
plates or as KBr pellets. High-resolution MS analyses were carried out
on an ESI-TOF instrument.
of M =2.8”
n
poly
4
À1
0 gmol (from GPC analysis, see above). The free-energy
changes DG were calculated from the K values by using
a
[
5b]
2
,6-Dibromopyridin-4-ol (5): This compound was prepared by Ir-cata-
[14]
lyzed direct boration of 2,6-dibromopyridine (4) and subsequent oxida-
tion. A mixture of 4 (12 g, 51 mmol), pinacolborane (32 g, 250 mmol),
Table 1. Apparent association constants and thermodynamic parameters
for 3poly and saccharides.
[
a]
[
A
H
R
U
G
2
{IrCl(cod)} ] (cod=1,5-cyclooctadiene; 0.68 g, 1.0 mmol), and 1,2-bis(di-
Guest
K
a298
DG298
DH
[kJmol
TDS
[kJmol ]
DH/TDS
phenylphosphino)ethane (0.81 g, 2.0 mmol) was stirred under Ar for 4 h
at 1308C. The resulting mixture was allowed to cool to room temperature
and evaporated in vacuo. The concentrated residue was diluted with
THF (190 mL). To the THF solution was added aqueous Oxone (34 g,
À1
À1
À1
À1
A
C
H
T
R
E
U
N
G
[m
14
5.5
4.4
]
A
C
H
T
R
E
U
N
G
[kJmol
]
A
H
R
U
G
]
A
H
R
U
G
d-Man
d-Fru
d-All
À6.5
À4.2
À3.7
À24
À24
À25
À17
À20
À21
1.4
1.2
1.2
5
6 mmol in 170 mL) slowly over 5 min. After stirring for 7 min at room
temperature, the mixture was quenched with aqueous NaHSO and ex-
tracted with diethyl ether. The separated ethereal layer was washed with
water and brine, dried over MgSO , evaporated, and purified by silica-gel
column chromatography (eluent: AcOEt/hexane 1/5) to afford 5 (12 g,
3
[
a] All apparent association constants were evaluated by using nonlinear
least-square analyses fitting to the 1/1 binding model. Thermodynamic
parameters were estimated by a van’t Hoff plot using the K values at
83, 288, 293, and 298 K (see Supporting Information).
4
a
2
9
2%) as a colorless solid. This product was identical to that previously
[
5b]
synthesized by us.
2
,6-Diiodopyridin-4-ol (6): This compound was prepared by a modifica-
[15]
DG=ÀRTlnK (Table 1). Although the values of K and
a
a
tion of the published procedure by Suzuki, Inouye et al. A mixture of
5 (6.1 g, 24 mmol), CuI (106 g, 0.56 mol), and KI (214 g, 1.30 mol) in
DMF (400 mL) was stirred for 24 h at 1208C. The resulting brown mix-
ture was concentrated in vacuo, diluted with AcOEt, and filtered. The
precipitate was further extracted with AcOEt in a Soxhlet extractor for
the binding energies ÀDG were small, association was found
to be clearly preferred even in 100% protic medium. To de-
termine the thermodynamic parameters for the association,
a van’t Hoff plot was performed at several temperatures
2
4 h. The combined AcOEt extract was evaporated, and the residue was
(
Table 1). The ratios DH/TDS lie in the range of 1.2–1.4 and
purified by silica-gel column chromatography (eluent: AcOEt/hexane 1/
are much larger than those in cyclodextrin/monosaccharide
complexes mainly formed by hydrophobic interactions in
4) to afford 6 (6.1 g, 87%) as a yellowsolid. M.p. 234–237 8C; IR (KBr):
À1
1
n˜ =1579, 1532 cm
11.43 ppm (s, 1H); C NMR (75 MHz, [D
64.5 ppm; ESI-HRMS: m/z: calcd for C
found: 347.8337.
Triethylene glycol-derived 2,6-diiodopyridine 7a: Triethylene glycol mon-
;
H NMR (300 MHz, [D
6
]DMSO): d=7.22 (s, 2H),
1
3
[21]
6
]DMSO): d=117.4, 121.7,
water (DH/TDS=À0.01). Thus, saccharide recognition by
+
1
5 4 2
H I NO [M+H] : 347.8383;
3
is largely attributed to enthalpic affinities, that is, hydro-
poly
gen bonds will make a substantial contribution to the inter-
action even in aqueous media.
[
16]
omethyl ether monotosylate (0.55 g, 1.7 mmol) was added to a suspen-
sion of 6 (0.60 g, 1.7 mmol) and potassium carbonate (1.2 g, 8.7 mmol) in
acetone (5 mL), and then the mixture was refluxed for 24 h. The mixture
was filtered and evaporated, and the resulting residue was purified by
silica-gel column chromatography (eluent: AcOEt/hexane 2/1) to afford
7
a (0.82 g, 96%) as a yellowoil. IR (neat): n˜ =2878, 1566, 1525, 1371,
À1
1
1
3
280, 1199, 1152 cm ; H NMR (300 MHz, CDCl ): d=3.38 (s, 3H),
7844
www.chemeurj.org
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2006, 12, 7839 – 7847

Molecular Recognition of Saccharides in Protic Media
FULL PAPER
3
2
6
.53–3.56 (m, 2H), 3.63–3.71 (m, 6H), 3.81–3.85 (m, 2H), 4.12–4.18 (m,
(300 MHz, CDCl
3
): d=3.14 (s, 2H), 3.38 (s, 3H), 3.54 (t, J=5.1 Hz, 2H),
1
3
H), 7.26 ppm (s, 2H); C NMR (75 MHz, CDCl
3
): d=59.2, 68.3, 68.5,
3.60–3.73 (m, 26H), 3.86 (t, J=4.8 Hz, 2H), 4.17 (t, J=4.8 Hz, 2H),
7.01 ppm (s, 2H); C NMR (75 MHz, CDCl
70.65, 71.0, 72.0, 82.2, 114.2, 143.6, 165.0 ppm; ESI-HRMS: m/z: calcd for
26 9
C H39NNaO [M+Na] : 532.2523; found: 532.2481.
1
3
9.2, 70.7, 71.1, 72.0, 121.4, 140.9, 164.7 ppm; ESI-HRMS: m/z: calcd for
3
): d=59.1, 68.0, 69.3, 70.58,
+
C
12
H
17
I
2
NNaO
Octaethylene glycol-derived 2,6-diiodopyridine 7b: Diisopropyl azodicar-
boxylate (3.0 g, 15 mmol) was added to a mixture of iPr NEt (15 mL), 6
5.2 g, 15 mmol), and PPh (3.9 g, 15 mmol) in toluene (270 mL), and
then the mixture was stirred for 1 h at room temperature. Octaethylene
4
[M+Na] : 515.9145; found: 515.9221.
+
2
Triethylene glycol-derived diiodo trimer 9a: Compounds 7a (0.82 g,
1.7 mmol) and 8a (0.12 g, 0.42 mmol) were added successively to a mix-
(
3
ture of [Pd
8.6 mg, 8.3 mmol), PPh
iPr NH (25 mL)/THF (5 mL). The mixture was stirred for 3 h at room
2
A
H
R
U
G
3
]·CHCl
3
(dba=trans,trans-dibenzylideneacetone;
[
16]
glycol monomethyl ether (4.8 g, 12 mmol) was added, and the resulting
mixture stirred for an additional 12 h at room temperature and concen-
trated. The residue was purified by silica-gel column chromatography
3
(8.7 mg, 33 mmol), and CuI (0.2 mg, 1.1 mmol) in
2
temperature, diluted with AcOEt, and filtered to remove insoluble salts.
The filtrate was evaporated and the residue purified by silica-gel column
chromatography to afford recovered 7a (0.52 g, 80% recovery, eluent:
AcOEt/hexane 2/1) and 9a (0.33 g, 79% based on 8a, eluent: AcOEt) as
(
eluent: AcOEt) to afford 7b (7.2 g, 81%) as a yellowoil. IR (neat): n˜ =
À1
1
2
3
873, 1574, 1536, 1287, 1108 cm ; H NMR (300 MHz, CDCl ): d=3.38
(
s, 3H), 3.54 (t, J=4.2 Hz, 2H), 3.63–3.69 (m, 26H), 3.82 (t, J=4.8 Hz,
1
3
À1
1
2
H), 4.14 (t, J=4.8 Hz, 2H), 7.26 ppm (s, 2H); C NMR (75 MHz,
): d=59.1, 68.3, 69.2, 70.6, 70.7, 71.0, 72.0, 115.7, 141.0, 164.6 ppm;
a
yellowoil. IR (neat):
n˜ =2879, 1577, 1532, 1105 cm
;
H NMR
CDCl
ESI-HRMS: m/z: calcd for C22
36.0448.
3
(300 MHz, CDCl
3
): d=3.38 (d, J=1.2 Hz, 9H), 3.54–3.58 (m, 6H), 3.64–
+
H
37
I
2
NNaO
9
[M+Na] : 736.0456; found:
3.75 (m, 18H), 3.86–3.90 (m, 6H), 4.18–4.25 (m, 6H), 7.17 (d, J=2.1 Hz,
1
3
7
2H), 7.18 (s, 2H), 7.31 ppm (d, J=2.1 Hz, 2H); C NMR (75 MHz,
CDCl ): d=59.0, 60.3, 68.1, 69.0, 70.45, 70.49, 79.8, 71.8, 86.7, 87.9,
14.56, 114.61, 117.6, 121.4, 143.2, 143.4, 164.5, 164.9 ppm; ESI-HRMS:
Triethylene glycol-derived 2,6-bis(3-hydroxy-3-methyl-1-butynyl)pyridine:
Compounds 7a (2.5 g, 5.1 mmol) and 2-methyl-3-butyn-2-ol (1.7 g,
3
1
+
m/z: calcd for C40
51 2 3
H I N NaO12 [M+Na] : 1042.2146; found: 1042.2078.
2
1 mmol) were added successively to a suspension of [PdCl
2
A
H
R
U
G
3 2
(PPh ) ]
(
144 mg, 0.21 mmol) and CuI (20 mg, 0.10 mmol) in Et NH (100 mL).
2
Octaethylene glycol-derived diiodo trimer 9b: Compounds 7b (2.0 g,
2.7 mmol) and 8b (0.35 g, 0.69 mmol) were added successively to a mix-
The mixture was stirred for 5 h at room temperature and evaporated, the
residue diluted with AcOEt, and insoluble salts filtered off. The filtrate
was concentrated and subjected to silica-gel column chromatography
ture of [Pd
2
A
H
R
U
(dba)
3
]·CHCl
3
(28 mg, 0.027 mmol), PPh
3
(29 mg, 0.11 mmol),
and CuI (5.2 mg, 0.027 mmol) in iPr
2
NH (20 mL)/THF (20 mL). The mix-
(
eluent: AcOEt) to afford triethylene glycol-derived 2,6-bis(3-hydroxy-3-
ture was stirred for 12 h at room temperature, diluted with AcOEt, and
filtered to remove insoluble salts. The filtrate was evaporated, and the
residue purified by silica-gel column chromatography (eluent: AcOEt to
acetone) to afford recovered 7b (0.76 g, 48% recovery) and 9b (0.86 g,
75% based on 8b) as a yellowoil. IR (neat): n˜ = 2873, 1573, 1531,
methyl-1-butynyl)pyridine (2.1 g, 100%) as a yellowoil. IR (neat): n˜ =
3
CDCl
3
6
6
À1
1
371, 2981, 2931, 2881, 2229, 1584, 1554 cm
;
H NMR (300 MHz,
3
): d=1.61 (s, 12H), 3.15 (s, 2H), 3.38 (s, 3H), 3.53–3.56 (m, 2H),
.63–3.72 (m, 6H), 3.84 (t, J=4.7 Hz, 2H), 4.16 (t, J=4.7 Hz, 2H),
1
3
À1
1
.87 ppm (s, 2H); C NMR (75 MHz, CDCl
3
): d=31.3, 59.2, 65.1, 68.0,
3
1107 cm ; H NMR (300 MHz, CDCl ): d=3.38 (s, 9H), 3.53–3.56 (m,
9.4, 70.7, 70.8, 71.1, 72.1, 80.7, 94.8, 113.2, 144.0, 165.1 ppm; ESI-HRMS:
6H), 3.61–3.72 (m, 78H), 3.83–3.91 (m, 6H), 4.14–4.22 (m, 6H), 7.13 (d,
+
13
m/z: calcd for C22
H31NNaO
6
[M+Na] : 428.2049; found: 428.1995.
J=2.3 Hz, 2H), 7.16 (s, 2H), 7.30 ppm (d, J=2.3 Hz, 2H); C NMR
(
1
75 MHz, CDCl
3
): d=59.2, 68.3, 69.3, 70.6, 70.7, 71.1, 72.1, 86.8, 88.2,
Triethylene glycol-derived 2,6-diethynylpyridine 8a: Triethylene glycol-
derived 2,6-bis(3-hydroxy-3-methyl-1-butynyl)pyridine (2.3 g, 5.8 mmol)
was added to a suspension of NaH (23 mg, 0.58 mmol; commercial 60%
dispersion was washed thoroughly with hexane prior to use) in toluene
14.7, 114.8, 117.7, 121.6, 143.5, 143.8, 164.7 ppm; ESI-HRMS: m/z: calcd
+
for C70
111 2 3
H I N NaO27 [M+Na] : 1702.4992; found: 1702.5271.
Triethylene glycol-derived bis(silylethynyl) trimer 10a: Compounds 9a
(0.41 g, 0.40 mmol) and (tert-butyldimethylsilyl)acetylene (0.28 g,
(
60 mL). The mixture was stirred at 808C for 30 min and evaporated.
The evaporation residue was purified by silica-gel column chromatogra-
2.0 mmol) were added successively to a mixture of [PdCl
2
A
H
R
U
G
3 2
(PPh ) ] (11 mg,
phy (eluent: AcOEt/hexane 1/1) to afford 8a (1.3 g, 88%) as a yellow
16 mmol) and CuI (1.5 mg, 8.0 mmol) in iPr NH (20 mL)/THF (10 mL).
2
À1
1
oil. IR (neat): n˜ =3234, 2882, 2112, 1582, 1556 cm ; H NMR (300 MHz,
CDCl ): d=3.12 (s, 2H), 3.38 (s, 3H), 3.53–3.56 (m, 2H), 3.63–3.71 (m,
H), 3.86 (t, J=4.7 Hz, 2H), 4.18 (t, J=4.7 Hz, 2H), 7.01 ppm (s, 2H);
The mixture was stirred for 12 h at room temperature and concentrated,
and the concentrated residue was diluted with AcOEt and filtered to
remove insoluble salts. The filtrate was evaporated and the residue puri-
fied by silica-gel column chromatography (eluent: AcOEt) to afford 10a
(0.29 g, 70%) as a yellowoil. IR (neat): n˜ =2929, 2884, 2246, 2163, 1581,
3
6
1
3
C NMR (75 MHz, CDCl
3
): d=59.2, 68.0, 69.3, 70.76, 70.81, 71.1, 72.1,
8
C
2.3, 100.7, 114.2, 143.7, 165.1 ppm; ESI-HRMS: m/z: calcd for
+
À1
1
16
H
19NNaO
4
[M+Na] : 312.1212; found: 312.1208.
3
1550, 1128 cm ; H NMR (300 MHz, CDCl ): d=0.20 (s, 12H), 1.00 (s,
1
3
8H), 3.38 (d, J=2.1 Hz, 9H), 3.54–3.58 (m, 6H), 3.64–3.75 (m, 18H),
.86–3.90 (m, 6H), 4.19 (t, J=4.5 Hz, 6H), 7.01 (d, J=2.1 Hz, 2H), 7.13
Octaethylene glycol-derived 2,6-bis(trimethylsilylethynyl)pyridine: Com-
pounds 7b (2.9 g, 4.6 mmol) and (trimethylsilyl)acetylene (2.3 g,
1
3
(
d, J=2.1 Hz, 2H), 7.16 ppm (s, 2H); C NMR (75 MHz, CDCl
À4.5, 26.4, 59.2, 60.5, 68.0, 68.1, 69.3, 70.8, 71.1, 72.0, 87.2, 87.6, 93.7,
03.9, 113.9, 114.6, 114.7, 143.7, 143.9, 144.6, 164.9, 165.0 ppm; ESI-
3
): d=
2
3 mmol) were added successively to
a
mixture of [PdCl
2
A
H
R
U
G
3 2
(PPh ) ]
(
130 mg, 0.19 mmol) and CuI (18 mg, 0.093 mmol) in Et
2
NH (80 mL).
1
The mixture was stirred for 3.5 h at room temperature and evaporated.
The evaporation residue was diluted with AcOEt and filtered to remove
insoluble salts. The filtrate was concentrated and purified by silica-gel
column chromatography (eluent: AcOEt) to afford octaethylene glycol-
derived 2,6-bis(trimethylsilylethynyl)pyridine (2.5 g, 84%) as a yellowoil.
+
HRMS: m/z: calcd for C56
066.5141.
Triethylene glycol-derived diethynyl trimer 11a: nBu
0.47 mL, 0.47 mmol) and a fewdrops of H O were added to a solution of
3 2
H81IN NaO12Si [M+Na] : 1066.5257; found:
1
4
NF (1.0m in THF,
2
-1
1
IR (neat): n˜ = 2874, 2110, 1581, 1555, 1333, 1108 cm ; H NMR (300
MHz, CDCl ): d = 0.24 (18H), 3.38 (s, 3H), 3.55 (t, J = 2.7 Hz, 2H),
.59–3.72 (m, 26H), 3.84 (t, J = 5.1 Hz, 2H), 4.17 (t, J = 5.1 Hz, 2 H),
10a (0.22 g, 0.21 mmol) in THF (6 mL). The mixture was stirred for 5 h
at room temperature, concentrated, and the residue purified by silica-gel
column chromatography (eluent: acetone) to afford 11a (0.12 g, 71%) as
3
3
6
7
1
3
À1
.95 ppm (s, 2H); C NMR (75 MHz, CDCl
3
): d= À0.1, 59.2, 68.0, 69.3,
a yellowoil. IR (neat): n˜ =3232, 2879, 2110, 1582, 1552, 1126 cm
;
1
0.6, 70.7, 71.1, 72.1, 95.1, 103.1, 113.8, 144.2, 164.9 ppm; ESI-HRMS: m/
H NMR (300 MH, CDCl
3
): d=3.16 (s, 2H), 3.38 (s, 9H), 3.54–3.58 (m,
+
9 2
z: calcd for C32H55NNaO Si [M+Na] : 676.3313; found: 676.3368.
6H), 3.64–3.75 (m, 18H), 3.87–3.90 (m, 6H), 4.20 (t, J=4.5 Hz, 6H), 7.04
1
3
(
(
8
d, J=2.6 Hz, 2H), 7.16 (d, J=2.6 Hz, 2H), 7.17 ppm (s, 2H); C NMR
75 MHz, CDCl ): d=59.2, 68.1, 68.2, 69.3, 70.71, 70.74, 71.1, 72.0, 82.2,
7.3, 87.4, 114.2, 114.6, 114.7, 143.7, 143.8, 165.0, 165.1 ppm; ESI-HRMS:
Octaethylene glycol-derived 2,6-diethynylpyridine 8b: nBu NF (1.0m in
THF, 8.5 mL, 8.5 mmol) and a fewdrops of H O were added to a solu-
tion of octaethylene glycol-derived 2,6-bis(trimethylsilylethynyl)pyridine
2.5 g, 3.9 mmol) in THF (35 mL). The mixture was stirred for 3 h at
4
3
2
+
m/z: calcd for C44
Triethylene glycol-derived polymer
0.13 mmol) and 11a (0.11 g, 0.13 mmol) were added to a mixture of [Pd-
(PPh (6.2 mg, 5.3 mmol) and CuI (1.0 mg, 5.3 mmol) in iPr NH
H53IN
3
NaO12 [M+Na] : 838.3527; found: 838.3534.
(
room temperature, concentrated, and purified by silica-gel column chro-
poly
2 :
Compounds 9a (0.14 g,
matography (eluent: AcOEt) to afford 8b (1.7 g, 87%) as a yellowoil.
À1
1
IR (neat): n˜ =3230, 2874, 2111, 1581, 1555, 1334, 1108 cm
;
H NMR
A
H
R
U
G
3
)
4
]
2
Chem. Eur. J. 2006, 12, 7839 – 7847
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
7845

H. Abe, M. Inouye, and M. Waki
(
30 mL)/THF (30 mL). The mixture was stirred for four days at room
(20 mL)/THF (40 mL). The mixture was stirred for three days at room
temperature and concentrated. The concentrated residue was diluted
with AcOEt and filtered to remove insoluble salts. The filtrate was
temperature and concentrated, and the concentrated residue diluted with
AcOEt and filtered to remove insoluble salts. The filtrate was evaporated
and treated with a Sephadex LH-20 column (eluent: CHCl
tarry impurities. The eluent was evaporated, and the residue was purified
3
) to remove
evaporated and treated with a Sephadex LH-20 column (eluent: CHCl
to remove tarry impurities. The eluent was evaporated, and the residue
purified by preparative GPC (eluent: CHCl ) to afford 3poly (0.10 g, 43%
by weight) as a dark brown oil. IR (neat): n˜ =2873, 2351, 1582, 1550,
3
)
by preparative GPC (eluent: CHCl
3
) to afford 2poly (0.10 g, 40% by
3
À1
weight) as dark brown oil. IR (neat): n˜ =2877, 2225, 1583, 1109 cm
;
1
À1
1
H NMR (300 MHz, CDCl
.73 (m, 6nH), 3.89 (s, 2nH), 4.21 (s, 2nH), 7.05–7.19 ppm (m, 2nH);
3
): d=3.38 (s, 3n H), 3.55–3.58 (m, 2nH), 3.64–
1108 cm
3
; H NMR (300 MHz, CDCl ): d=3.37 (s, 3nH), 3.52–3.57 (m,
3
2nH), 3.62–3.72 (m, 26nH), 3.89 (s, 2nH), 4.20 (s, 2nH), 7.15–7.35 ppm
1
3
13
C NMR (75 MHz, CDCl
14.8, 143.9, 165.2 ppm.
3
): d=59.2, 68.3, 69.3, 70.8, 71.2, 72.1, 87.5,
(m, 2nH); C NMR (75 MHz, CDCl
3
): d=59.2, 68.3, 69.3, 70.7, 71.1,
1
72.1, 87.5, 100.7, 114.8, 143.9, 165.1 ppm.
Octaethylene glycol-derived bis(silylethynyl) trimer 10b and octaethy-
lene glycol-derived iodo silylethynyl trimer 12b: Compound 9b (0.74 g,
0
.44 mmol) and (tert-butyldimethylsilyl)acetylene (93 mg, 0.66 mmol)
were added to a mixture of [PdCl (PPh ] (12 mg, 18 mmol) and CuI
1.7 mg, 8.8 mmol) in iPr NH (20 mL)/THF (15 mL). The mixture was
stirred for 15 h at room temperature and concentrated. The concentrated
residue was diluted with AcOEt and filtered to remove insoluble salts.
The filtrate was evaporated and treated by silica-gel column chromatog-
raphy (eluent: AcOEt to acetone) to remove impurities. The eluent was
evaporated, and the residue purified by preparative reverse-phase HPLC
to afford 9b (98 mg, 13% recovery), 10b (0.15 g, 20%), and 12b (0.27 g,
2
A
H
R
U
G
3 2
)
[
[
1] a) G. A. Jeffrey, An Introduction to Hydrogen Bonding, Oxford Uni-
versity Press, NewYork, 1997; b) A. Fersht, Enzyme Structure and
Mechanism, 2nd ed., W. H. Freeman and Co., NewYork, 1985;
c) A. Kobata, Acc. Chem. Res. 1993, 26, 319–324.
2] a) Comprehensive Supramolecular Chemistry, Vol. 2 (Eds.: J. L.
Atwood, J. E. D. Davies, D. D. MacNicol, F. Vçgtle, J.-M. Lehn),
Pergamon, Oxford, 1996; b) Host–Guest Chemistry—Mimetic Ap-
proaches to Study Carbohydrate Recognition, Topics in Current
Chemistry 218 (Ed.: S. PenadØs), Springer, Berlin, 2002; c) F.
Vçgtle, Supramolecular Chemistry, Wiley, NewYork, 1991.
(
2
3
4%).
À1
1
0b: yellowoil; IR (neat): n˜ = 2878, 2163, 1582, 1550, 1133 cm ;
1
H NMR (300 MHz, CDCl
3
): d=0.20 (s, 12H), 1.0 (s, 18H), 3.37 (s, 9H),
[3] a) A. D. Hamilton in Advances in Supramolecular Chemistry, Vol. 1
(Ed.: G. W. Gokel), JAI Press, London, 1990, pp. 1–64; b) Y.
Aoyama in Advances in Supamolecular Chemistry, Vol. 2 (Ed.:
G. W. Gokel), JAI Press, London, 1992, pp. 65–92; c) A. P. Davis,
R. S. Wareham, Angew. Chem. 1999, 111, 3160–3179; Angew. Chem.
Int. Ed. 1999, 38, 2978–2996.
[4] For recent examples of artificial host molecules for saccharides, see:
a) J.-L. Hou, X.-B. Shao, G.-J. Chen, Y.-X. Zhou, X.-K. Jiang, Z.-T.
Li, J. Am. Chem. Soc. 2004, 126, 12386–12394; b) J.-M. Fang, S.
Selvi, J.-H. Liao, Z. Slanina, C.-T. Chen, P.-T. Chou, J. Am. Chem.
Soc. 2004, 126, 3559–3566; c) K. Ladomenou, R. P. Bonar-Law,
Chem. Commun. 2002, 2108–2109; d) Y.-H. Kim, J.-I. Hong, Angew.
Chem. 2002, 114, 3071–3074; Angew. Chem. Int. Ed. 2002, 41, 2947–
3
4
.53–3.57 (m, 6H), 3.61–3.72 (m, 78H), 3.86–3.90 (m, 6H), 4.19 (t, J=
.5 Hz, 6H), 7.01 (d, J=2.4 Hz, 2H), 7.12 (d, J=2.4 Hz, 2H), 7.16 ppm
1
3
(
7
1
s, 2H); C NMR (75 MHz, CDCl
3
): d=À4.6, 16.9, 26.3, 59.1, 68.0, 69.2,
0.57, 70.63, 71.0, 72.0, 87.2, 87.6, 93.7, 103.8, 113.9, 114.6, 143.7, 143.9,
44.5, 164.8, 165.0 ppm; ESI-HRMS: m/z: calcd for C86 NaO27Si
2
H
141
N
3
+
[
M+Na] : 1726.9189; found: 1726.9137.
À1
1
2b: yellowoil; IR (neat):
n˜ =2873, 2160, 1582, 1550, 1109 cm
): d=0.20 (s, 6H), 1.00 (s, 9H), 3.37 (s, 9H),
.52–3.58 (m, 6H), 3.61–3.72 (m, 78H), 3.84–3.92 (m, 6H), 4.16–4.22 (m,
H), 7.01 (d, J=2.4 Hz, 2H), 7.11 (d, J=2.7 Hz, 2H), 7.17 ppm (s, 2H);
;
1
H NMR (300 MHz, CDCl
3
3
6
1
3
C NMR (75 MHz, CDCl
3
): d=À4.7, 14.3, 16.7, 21.1, 26.2, 59.0, 60.3,
6
9
1
7.9, 68.1, 68.3, 69.1, 70.4, 70.5, 70.6, 70.9, 71.9, 86.3, 87.0, 87.5, 88.0, 88.3,
3.5, 103.7, 113.9, 114.5, 117.5, 142.3, 143.1, 143.4, 143.5, 143.8, 144.4,
2
950; e) J.-D. Lee, N. T. Greene, G. T. Rushton, K. D. Shimizu, J.-I.
Hong, Org. Lett., 2005, 7, 963–966; f) M. Mazik, W. Radunz, R.
Boese, J. Org. Chem. 2004, 69, 7448–7462; g) M. Segura, B. Bricoli,
A. Casnati, E. M. MuÇoz, F. S. Sansone, R. Ungaro, C. Vicent, J.
Org. Chem. 2003, 68, 6296–6303; h) T. Ishi-i, M. A. Mateos-Timone-
da, P. Timmerman, M. Crego-Calama, D. N. Reinhoudt, S. Shinkai,
Angew. Chem. 2003, 115, 2402–2407; Angew. Chem. Int. Ed. 2003,
64.5, 164.7, 164.9, 165.8, 170.8 ppm; ESI-HRMS: m/z: calcd for
+
C
78
H
126
N
3
NaIO27Si [M+Na] : 1714.7291; found: 1714.7343.
Octaethylene glycol-derived diethynyl trimer 11b: nBu
4
NF (1.0m in THF,
0
1
5
.23 mL, 0.23 mmol) and a fewdrops of H O were added to a solution of
0b (0.163 g, 0.096 mmol) in THF (5 mL). The mixture was stirred for
h at room temperature, concentrated, and purified by silica-gel column
2
4
2, 2300–2305; i) S. Tamaru, S. Shinkai, A. B. Khasanov, T. W. Bell,
chromatography (eluent: acetone) to afford 11b (0.12 g, 83%) as a dark
À1
Proc. Natl. Acad. Sci. USA 2002, 99, 4972–4976; j) A. P. Davis, R. S.
Wareham, Angew. Chem. 1998, 110, 2397–2401; Angew. Chem. Int.
Ed. 1998, 37, 2270–2273; k) T. Velasco, G. Lecollinet, T. Ryan, A. P.
Davis, Org. Biomol. Chem. 2004, 2, 645–647; l) G. Lecollinet, A. P.
Dominey, T. Velasco, A. P. Davis, Angew. Chem. 2002, 114, 4267–
yellowoil. IR (neat): n˜ =3526, 2874, 2115, 1582, 1551, 1108 cm
H NMR (300 MHz, CDCl
;
1
3
): d=3.17 (s, 2H), 3.53 (s, 9H), 3.52–3.58 (m,
6
H) 3.60–3.73 (m, 78H), 3.84–3.91 (m, 6H), 4.16–4.22 (m, 6H), 7.05 (d,
1
3
J=2.1 Hz, 2H), 7.15 (d, J=2.1 Hz, 2H), 7.17 ppm (s, 2H); C NMR
75 MHz, CDCl ): d=59.1, 68.1, 69.2, 70.55, 70.62, 70.7, 71.0, 72.0, 82.2,
7.4, 114.1, 114.6, 143.7, 143.78, 143.81, 165.0 ppm; ESI-HRMS: m/z:
(
8
3
4
270; Angew. Chem. Int. Ed. 2002, 41, 4093–4096; m) T. J. Ryan, G.
Lecollinet, T. Velasco, A. P. Davis, Proc. Natl. Acad. Sci. USA 2002,
+
calcd for C74
H
113
N
3
NaO27 [M+Na] : 1498.7460; found: 1498.7086.
NF (1.0m in
O were added to a solu-
9
2
9, 4863–4866; n) K. Wada, T. Mizutani, S. Kitagawa, J. Org. Chem.
003, 68, 5123–5131.
Octaethylene glycol-derived ethynyl iodo trimer 13b: nBu
THF, 83 mL, 0.083 mmol) and a fewdrops of H
4
2
[
5] a) M. Inouye, T. Miyake, M. Furusyo, H. Nakazumi, J. Am. Chem.
Soc. 1995, 117, 12416–12425; b) M. Inouye, K. Takahashi, H. Naka-
zumi, J. Am. Chem. Soc. 1999, 121, 341–345; c) M. Inouye, J. Chiba,
H. Nakazumi, J. Org. Chem. 1999, 64, 8170–8176; d) M. Inouye, M.
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tion of 12b (0.12 g, 0.069 mmol) in THF (3 mL). The mixture was stirred
for 4 h at room temperature, concentrated, and purified by silica-gel
column chromatography (eluent: acetone) to afford 13b (0.085 g, 78%)
as
a dark yellowoil. IR (neat): n˜ =3235, 2873, 2114, 1581, 1551,
À1
1
1
3
6
2
7
1
1
3
109 cm , H NMR (300 MHz, CDCl ): d=3.16 (s, 1H), 3.37 (s, 9H),
.53–3.57 (m, 6H), 3.62–3.72 (m, 78H), 3.84–3.90 (m, 6H), 4.15–4.21 (m,
H), 7.04–7.06 (m, 2H), 7.12–7.15 (m, 2H), 7.16 (s, 1H), 7.30 ppm (d, J=
.4 Hz, 1H); C NMR (75 MHz, CDCl
1.1, 72.0, 86.6, 87.2, 88.2, 114.2, 114.7, 142.5, 143.7, 143.8, 164.7,
65.1 ppm; ESI-HRMS: m/z: calcd for
600.6426; found: 1600.6464.
1
6189–16196; f) H. Abe, Y. Aoyagi, M. Inouye, Org. Lett. 2005, 7,
5
9–61.
1
3
3
): d=59.2, 68.1, 68.4, 69.2, 70.7,
[
6] a) S. Shinkai, K. Tsukagoshi, Y. Ishikawa, T. Kunitake, J. Chem. Soc.
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+
72 3
C H112IN NaO27 [M+Na] :
[
7] F. A. Quiocho, Pure Appl. Chem. 1989, 61, 1293–1306.
Octaethylene glycol-derived polymer
.076 mmol) and 11b (0.11 g, 0.076 mmol) were added to a mixture of
Pd(PPh ] (3.5 mg, 3.1 mmol) and CuI (0.6 mg, 3.1 mmol) in iPr NH
3
poly
:
Compounds 9b (0.18 g,
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0
[
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ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2006, 12, 7839 – 7847

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Published online: July 18, 2006
Chem. Eur. J. 2006, 12, 7839 – 7847
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
7847