Formation of higher-order structures of chiral poly(ethynylpyridine)s depending on size, temperature, and saccharide recognition

Article abstract of DOI:10.1039/c2ob25816a

Amphiphilic 2,6-pyridylene ethynylene "meta-ethynylpyridine" polymers having chiral oligo(oxyethylene) side chains were developed as hosts for saccharide recognition. The polymers were prepared via a Sonogashira reaction and fractionated by gel permeation

Full text of DOI:10.1039/c2ob25816a

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PAPER
Formation of higher-order structures of chiral poly(ethynylpyridine)s
depending on size, temperature, and saccharide recognition†
Hajime Abe,* Kotaro Okada, Hiroki Makida and Masahiko Inouye*
Received 28th April 2012, Accepted 5th July 2012
DOI: 10.1039/c2ob25816a
Amphiphilic 2,6-pyridylene ethynylene “meta-ethynylpyridine” polymers having chiral oligo
(oxyethylene) side chains were developed as hosts for saccharide recognition. The polymers were
prepared via a Sonogashira reaction and fractionated by gel permeation chromatography (GPC). They
showed circular dichroism (CD) activity due to their higher-order chiral helical structures, and their CD
and UV-vis spectra changed depending on not only saccharide recognition but also molecular size,
temperature, and metal cation recognition.
stabilize the higher-order chiral helical structure,9–11 improving
recognition ability. Herein we would like to report the prep-
Introduction
A variety of biopolymers such as nucleic acids, proteins, and
aration of the chiral polymers 2R and 2S, which showed CD-
polysaccharides performs molecular recognition based on their
higher-order structure. In the field of supramolecular chemistry,
many kinds of synthetic polymers have been studied for the mo-
lecular recognition abilities based on their architecture.1,2
Recently, our group has been interested in the development of
synthetic hosts responsive to saccharide recognition,3 especially
under aqueous conditions.4–7 During the course of our study on
2,6-pyridylene ethynylene “meta-ethynylpyridine” polymers and
oligomers,7,8 we have developed polymer 1 having octaethylene
glycol chains (Fig. 1). This water-soluble polymer spontaneously
forms a helix in polar solvents and could associate with mono-
saccharides in aqueous MeOH by accommodating the guests
within the cavity of the helix.7
response to saccharide recognition in an aqueous solution. Fur-
thermore, CD-response was also observed depending on molecu-
lar size, temperature, and association with metal ions.
For recognizing oligosaccharide guests, oligomeric architec-
tures have been applied to the design of host molecules.5 In
reverse, polysaccharides which spontaneously form helical struc-
tures have been reported to play a role as a host molecule to
form an inclusion complex with synthetic polymer as a guest.12
Results and discussion
Chiral polymer 2R was prepared as shown in Scheme 1. Ring-
opening reductive condensation of (R)-propylene oxide (3R)
with benzaldehyde yielded (R)-2-benzyloxy-1-methylethanol
(4R).13 This alcohol was coupled with tosylated octaethylene
glycol monomethyl ether to 5R, and the benzyl group was
removed to give elongated chiral alcohol 6R. The alcohol 6R
was condensed with 2,6-diiodo-4-pyridinol (7)7b to afford 8R,
which was diethynylated to yield 10R by the Sonogashira reac-
tion with tert-butyldimethylsilylacetylene followed by protio-
desilylation. The diacetylene 10R was subjected to reaction with
an excess of the diiodide 8R, and the resulting trimeric diiodide
11R was diethynylated to 13R. Finally, co-polymerization of
11R and 13R by the Sonogashira reaction under aqueous con-
ditions yielded R-polymer 2R. As well as 1,7 2R was soluble in
various apolar and polar solvents including water. The product
of the co-polymerization was separated into four fractions 2R(1)–
2R(4) by gel permeation chromatography (GPC). The
average molecular weights Mn for 2R(1)–2R(4) were estimated
as 18 100, 23 300, 29 000, and 36 500 g mol−1 versus poly-
styrene standards, respectively. The Mn value for 2R(4) corre-
sponds to an approximately 67-mer of pyridylene ethynylene
As the next step, we designed chiral polymers 2R and 2S,
which have a chiral side chain at the 4-positions of their pyridine
rings (Fig. 1). We expected that repeating chiral centers would
Fig. 1 Water-soluble ethynylpyridine polymers 1, 2R, and 2S.
Graduate School of Pharmaceutical Sciences, University of Toyama,
Sugitani 2630, Toyama, Toyama 930-0194, Japan.
E-mail: abeh@pha.u-toyama.ac.jp; Fax: +81 76 434 5049;
Tel: +81 76 434 7527
†Electronic supplementary information (ESI) available: The experimen-
tal detail of preparation of 2S, characteristics of new compounds,
Fig. S1–S13. See DOI: 10.1039/c2ob25816a
6930 | Org. Biomol. Chem., 2012, 10, 6930–6936
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Fig. 3 Temperature dependence of (A) UV-vis and (B) CD spectra of
2R(4). Conditions: 2R(4) (1.0 × 10−3 M, unit conc.), H2O, 25 to 70 °C,
path length = 1 mm. Red lines show spectra for 2R(1) normalized at
260 nm absorption.
323 to 332 nm was observed with increase of absorption. More
remarkable is that the shape of the CD spectrum drastically
changed by molecular size, and the characteristic CD band
around 333 nm showed inversion of the sign for the heavier frac-
tions. These findings suggested that there was a contribution of a
different type of chiral higher-order structure for the case of
heavier polymer, in addition to the conventional single-helical
higher-order structure that 1 forms.7 On the other hand, the
trimers 11R and 13R showed only weak CDs (Fig. S1 in the
ESI†) probably because they are too short to form a helical
higher-order structure, therefore the CDs shown in Fig. 2B were
due to the chiral higher-order structures of the polymer 2R.
The temperature dependence of UV-vis and CD spectra was
studied for the heaviest fraction 2R(4). As mentioned above, this
fraction showed a positive CD band around 333 nm. When an
aqueous solution of 2R(4) (1.0 × 10−3 M) was heated from
25 °C, both hypochromism and a blue-shift were observed in the
first absorptive band. At 70 °C the shape of the UV-vis spectrum
became close to that for the lightest fraction 2R(1) at 25 °C
(Fig. 3A). In the CD experiment, heating the solution of 2R(4)
from 25 °C to 70 °C caused transformation of the spectrum as
shown in Fig. 3B. During this process, the positive CD around
333 nm decreased and turned negative, approaching the CD of
2R(1) at 25 °C as in the case of the UV-vis experiment. Thus,
heating 2R(4) and decreasing molecular size from 2R(4) to
2R(1) caused similar changes in optical properties. When the
concentration effect was studied for 2R(4), the absorbance showed
linearity with the concentration of the polymer from 2.2 × 10−6
to 1.0 × 10−3 M (unit conc.) (Fig. S2 in the ESI†). Thus, inter-
molecular interaction was judged to be negligible for the
polymer up to 1.0 × 10−3 M. The size and temperature depen-
dences of UV-vis and CD spectra were also studied for the frac-
tions of the antipodal polymer 2S(1)–2S(4). As shown in Fig. 4
and 5, changes were observed for UV-vis spectra in a similar
manner to the cases of the 2R series. In the CD experiments,
spectral changes were observed in a mirror-image manner to that
for 2R.
Scheme 1 Preparation of chiral polymer 2R. DIAD = diisopropyl azo-
dicarboxylate, TBS = tert-butyldimethylsilyl, TBAF = tetra-n-butylam-
monium fluoride, dba = dibenzalacetone.
Fig. 2 Molecular size dependence of (A) UV-vis and (B) CD spectra
of 2R. Conditions: 2R (2R(4): 1.0 × 10−3 M (unit conc.), Abs260
=
1.20; 2R(1), 2R(2), 2R(3): ca. 1 × 10−3 M (unit conc., normalized as
Abs260 = 1.20)), H2O, 25 °C, path length = 1 mm.
units. The antipodal polymer 2S was similarly prepared from
(S)-propylene oxide (3S) (see the ESI†), and the Mn values of
GPC fractions 2S(1)–2S(4) were 17 100, 23 000, 26 500, and
33 100 g mol−1 versus polystyrene standards, respectively.
To study the influence of the molecular size, each of the GPC
fractions 2R(1)–2R(4) was subjected to UV-vis and CD ana-
lyses. Fig. 2 shows the comparison of the spectra after normali-
zation as Abs260 = 1.20. When the first absorptive band for
2R(4) was compared with that for 2R(1), a red-shift of λmax from
The association abilities of the longer polymers with various
saccharides were studied in aqueous solutions of 2R(4) and
2S(4). When D- or L-mannose was added to the solution of 2R(4),
the CD spectrum changed as shown in Fig. 6. L-Mannose
induced a little bigger CD change around 333 nm than
D-mannose did. Other kinds of monosaccharides such as glucose
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Fig. 4 Molecular size dependence of (A) UV-vis and (B) CD spectra
of 2S. Conditions: 2S (2S(4): 1.0 × 10−3 M (unit conc.), Abs260 = 1.20;
Fig. 6 CD responses of 2R(4) to the addition of (blue) D-mannose and
(red) L-mannose. Conditions: 2R(4) (1.0 × 10−3 M, unit conc.), mannose
(3.0 M), H2O, 25 °C, path length = 1 mm.
2S(1), 2S(2), 2S(3): ca. 1 × 10−3 M (unit conc., normalized as Abs260
=
1.20)), H2O, 25 °C, path length = 1 mm.
Fig. 7 CD responses of (A) 2R(4) and (B) 2S(4) to the addition of
polysaccharides. Conditions: 2R(4) or 2S(4) (1.0 × 10−3 M, unit conc.),
saccharide (4.9 w/v%), H2O, 25 °C, path length = 1 mm. (black) Only
2R(4) or 2S(4), (orange) with glycogen, (green) with pullulan, (purple)
with hyaluronic acid.
Fig. 5 Temperature dependence of (A) UV-vis and (B) CD spectra of
2S(4). Conditions: 2S(4) (1.0 × 10−3 M, unit conc.), H2O, 25 to 70 °C,
path length = 1 mm. Red lines show spectra for 2S(1) normalized at
260 nm absorption.
and galactose induced only little CD changes. Next we studied
the treatment of poly- and cyclooligosaccharides with 2R(4) and
2S(4). The polysaccharides examined were glycogen, pullulan,
and hyaluronic acid. Upon addition of these polysaccharides to
the polymer solutions, we observed remarkable CD responses as
shown in Fig. 7. The CD band around 333 nm showed sign
inversion, when the polysaccharide guests were added. Among
two kinds of cyclodextrins (α- and γ-CyD), γ-CyD induced
much bigger CD responses (Fig. 8).
The additive effects of pullulan and hyaluronic acid also pro-
duced a hypochromic effect in the absorption spectra as shown
in Fig. S3 in ESI.† In the case of mannose, a similar hypochro-
mic effect was observed for the shorter oligomer (see below).
Titration experiments were performed by using glycogen with
2R(4) and 2S(4). When glycogen was added into aqueous sol-
utions of 2R(4) and 2S(4), the CD spectra gradually changed
(Fig. S5 and S6 in the ESI†). The titration curves outwardly
fitted well with 1 : 1 binding isotherms. The changes of CD
spectra during these titrations resembled those observed in the
heating experiments (Fig. 3 and 5) and in the experiment
decreasing the molecular size of the polymers (Fig. 2 and 4) as
mentioned above. In every case the characteristic CD band
around 335 nm decreased and finally its sign was inverted.
Generally, when a guest saccharide is treated with an achiral
ethynylpyridine polymer, the sign of induced CD is determined
by the chirality of the guest.7,8 On the other hand, in the cases of
chiral polymers 2R and 2S, the direction of the CD changes was
determined by the chirality of the host. When a guest saccharide
was treated with a pair of solutions of 2R(4) and 2S(4), the CD
changes were induced roughly in a mirror image manner to each
other corresponding to the chirality of the host polymers
(Fig. 6–8). Therefore, the helical sense of the resulting polymer–
saccharide complexes was determined by the chirality of the host
polymers, not by that of the guest, in other words, independent
of the chirality of the guest. These findings indicate the possi-
bility that an achiral guest may affect the chiral higher-order
structure of 2R and 2S. So we studied the influence of inorganic
salts as an additive. When NaClO4 or Ca(ClO4)2 was added to
an aqueous solution of 2R(4), the inversion of the CD band was
clearly observed (Fig. 9A). In experiments using 2S(4), similar
CD inversion was also observed in a mirror image manner
(Fig. 9B). Ca(ClO4)2 gave much more improvement than
NaClO4 did, in both cases.
In our recent reports, it was found that the helical structure of
ethynylpyridine oligomers with (or without) coordinating side
chains could be stabilized by the addition of a Cu2+ cation,
which works as a center of the complex outside (or inside) the
helix.8a,c,e The additive effects of NaClO4 and Ca(ClO4)2 would
be also due to the complexation at the side oligo(oxyethylene)
chains and/or the bridging between the pyridine nitrogen atoms
and the saccharide hydroxy groups. The stronger Lewis acid
Ca2+ gave bigger CD bands by stronger chelation.
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Fig. 8 CD responses of (A) 2R(4) and (B) 2S(4) to the addition of
cyclodextrins (CyDs). Conditions: 2R(4) (1.0 × 10−3 M, unit conc.) or
2S(4) (1.0 × 10−3 M, unit conc.), cyclodextrin (0.1 M), H2O, 25 °C,
path length = 1 mm. (black) Only 2R(4) or 2S(4), (purple) with α-cyclo-
dextrin, (green) with γ-cyclodextrin.
Scheme 2 A possible transformation mechanism of higher-order struc-
tures of polymers 2R and 2S of bigger size which were heated or associ-
ated with a guest on the assumption of contribution of an intramolecular
duplex. For molecular models depicted for these single and double
helices by using Monte-Carlo MM analyses, see Fig. S13 in ESI.†
more-ordered structures such as an intramolecular double
helix11a,15 and transform into a less-ordered simple single helix
at higher temperature (Scheme 2).11a The single helix can be
also stabilized by host–guest association with a saccharide as
shown in our previous work,7,8 thus the addition of saccharide
guests induced the changes of CD spectra as mentioned above.
Conclusion
Fig. 9 CD responses of (A) 2R(4) and (B) 2S(4) to the addition of
(red) NaClO4 or (blue) Ca(ClO4)2. Conditions: 2R(4) or 2S(4) (1.0 ×
10−3 M, unit conc.), NaClO4 or Ca(ClO4)2 (1.0 × 10−1 M), H2O, 25 °C,
path length = 1 mm.
meta-Ethynylpyridine polymers 2R and 2S having chiral centers
at the side chains were prepared and separated into fractions by
GPC. The CD spectra of the polymers changed their shape,
depending on the molecular size of the polymer and the tempera-
ture of the sample solution examined. In addition, the heaviest
fractions 2R(4) and 2S(4) showed CD responses to the addition
of mannose, cyclodextrins, and polysaccharides such as glyco-
gen even in water. These saccharide-induced CD responses
resembled those according to heating of the sample solution and
decreasing of the molecular size, suggesting that a similar ten-
dency of structural change of the higher-order chiral structure
took place. In host–guest chemistry, synthetic host molecules
recognizing polysaccharide guests have been relatively un-
explored. The use of chiral polymeric hosts will promote this
objective.
Several additional titration experiments were carried out by
using the fraction of 2R of smaller molecular weight (Mn
=
8800 g mol−1). As shown in Fig. S8–S10 in ESI,† the titrations
with D-mannose and D-glucose to 2R caused a hypochromic
effect around 330 nm in UV-vis spectra. The binding constants
were estimated as Ka = 3.7 M−1 vs. D-mannose and 1.9 M−1 vs.
D-glucose on the assumption of 1 : 1 binding. During these titra-
tions, no meaningful change of the CD spectrum was observed.
On the other hand, the titration with NaClO4 to 2R caused
changes both of CD and UV-vis spectra as shown in Fig. S11 in
ESI.† The absence of an isoabsorptive point and an isodichroic
point suggests the involvement of several kinds of complexes of
different molar ratios of the oligomer and metal.
Experimental section
The solvent effect was studied for H2O, CH3CN, MeOH, and
CH2Cl2 solutions of 2S as shown in Fig. S12 in ESI.† In polar
solvents CH3CN and MeOH, weak CD was still found, while in
apolar CH2Cl2 CD activity was not observed probably due to the
lack of a solvophobic effect.
As shown in Fig. 2–8, the similarity of the optical responses
to size, temperature, and recognition would correspond to the
similarity of structural changes, however, it is not clear how the
polymers in the heaviest fractions 2R(4) and 2S(4) change their
structure. The temperature dependence of UV-vis and CD pro-
perties observed in Fig. 3 and 5 would suggest the contribution
of some entropic factors. A possible explanation is: at lower
temperature the longer polymers in 2R(4) and 2S(4) may form
General
1H NMR spectra were recorded on a 300 MHz NMR spec-
trometer using tetramethylsilane (TMS) as an internal reference.
13C NMR spectra were recorded on a 75 MHz NMR spec-
trometer. THF was freshly distilled before use from sodium ben-
zophenone ketyl. (R)- and (S)-1-Benzyloxypropan-2-ol (4R, 4S)
were prepared from (R)- and (S)-propylene oxide (3R, 3S),
respectively, and benzaldehyde by reductive condensation cata-
lyzed by Wilkinson catalyst.13 Tosylate ester of octaethylene
glycol monomethyl ether was prepared from octaethylene glycol
monomethyl ether.16,17 All reactions were carried out under an
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argon atmosphere. Glycogen, pullulan, and hyaluronic acid were
purchased from TCI.
was stirred for 3 h at room temperature. The resulting mixture
was filtered and the filtrate was concentrated with a rotary evap-
orator. The resulting residue was subjected to silica gel column
chromatography (eluent: AcOEt–hexane = 1 : 1 to AcOEt) to
afford 9R (0.62 g, 85%) as a yellow oil. IR (neat) ν 2929, 2859,
Preparation of chiral polymer 2R
1
2162, 1578, 1551, 1112 cm−1; H NMR (CDCl3, 300 MHz) δ
(R)-27-Methyl-28-benzyloxy-2,5,8,11,14,17,20,23,26-nonaoxa-
octacosane (5R). A suspension of NaH (0.33 g of 60% oil sus-
pension was washed with hexane before use, 8.4 mmol) in THF
(22 mL) was added to (R)-1-benzyloxypropan-2-ol (4R, 0.93 g,
5.6 mmol), and the mixture was stirred for 6 h at room tempera-
ture. Then, tosylated octaethylene glycol monomethyl ether
(3.0 g, 5.6 mmol) was added to the reaction mixture. After stir-
ring for 2 days at room temperature, the reaction mixture was
filtered with rinsing by AcOEt. The combined filtrate was evap-
orated, and the resulting residue was purified by silica gel
column chromatography (eluent: AcOEt–hexane = 1 : 1 to
AcOEt) to afford 5R (2.1 g, 71%) as a yellow oil. IR (neat)
0.18 (s, 12 H), 0.99 (s, 18 H), 1.27 (d, J = 6.3 Hz, 3 H), 3.38 (s,
3 H), 3.53–4.19 (m, 35 H), 6.93 (s, 2 H); 13C NMR (CDCl3,
100 MHz) δ −4.8, 16.7, 17.1, 26.1, 59.0, 68.9, 70.5, 70.6, 70.8,
71.6, 71.9, 73.9, 93.4, 104.0, 113.9, 144.4, 164.8; ESI-HRMS
m/z calcd for C41H73NNaO10Si2 (M + Na+): 818.4671; found:
818.4669.
(R)-Amphiphilic chain-derived 2,6-diethynylpyridine 10R. To
a THF (8.8 mL) solution of 9R (0.62 g, 0.78 mmol) were added
two drops of water and nBu4NF (1.7 mL of 1 M THF solution,
1.7 mmol) dropwise. The mixture was stirred for 3 h at room
temperature, evaporated, and instantly subjected to silica gel
column chromatography (eluent: AcOEt to AcOEt–acetone =
4 : 1) to afford 10R (0.47 g, 100%) as a brown oil. IR (neat)
ν 3229, 2873, 2110, 1581, 1556, 1107; 1H NMR (CDCl3,
300 MHz) δ 1.27 (d, J = 6.3 Hz, 3 H), 3.12 (s, 2 H), 3.38 (s,
3 H), 3.53–4.20 (m, 35 H), 7.01 (s, 2 H); 13C NMR (CDCl3,
100 MHz) δ 16.9, 59.0, 69.0, 70.46, 70.52, 70.6, 70.8, 71.8,
71.9, 73.9, 77.3, 82.1, 114.1, 143.6, 165.1; ESI-HRMS m/z
1
ν 2870, 1107 cm−1; H NMR (CDCl3, 300 MHz) δ 1.17 (d, J =
6.3 Hz, 3 H), 3.38–3.71 (m, 38 H), 4.55 (s, 2 H), 7.26–7.34 (m,
5 H); 13C NMR (CDCl3, 100 MHz) δ 17.3, 59.0, 68.6, 70.5,
70.6, 70.8, 71.9, 73.3, 74.1, 75.1, 127.5, 127.6, 128.3, 138.4;
ESI-HRMS m/z calcd for C27H48NaO10 (M + Na+): 555.3145;
found: 555.3165.
(R)-2-Methyl-3,6,9,12,15,18,21,24,27-nonaoxaoctacosan-1-ol
(6R). A mixture of 5R (3.2 g, 6.1 mmol), Pd(OH)2 20% on
carbon (0.43 g), and cyclohexene (47 mL) in EtOH (79 mL) was
refluxed for 24 h. The reaction mixture was filtered through a
Celite bed. The filtrate was evaporated, and the residue was
purified by silica gel column chromatography (eluent: CH2Cl2 →
AcOEt → AcOEt–acetone = 1 : 1 → acetone) to afford 6R
(2.0 g, 74%) as a yellow oil. [α]2D8 = −6.0 (c = 3.0, CHCl3); IR
(neat) ν 3483, 2872, 1106 cm−1; 1H NMR δ 1.12 (d, J = 6.3 Hz,
3 H), 3.38 (s, 3 H), 3.53–3.82 (m, 35 H); 13C NMR (CDCl3,
100 MHz) δ 16.3, 59.0, 61.8, 66.3, 68.2, 70.4, 70.5, 70.6, 70.8,
71.9, 72.5; ESI-HRMS m/z calcd for C20H42NaO10 (M + Na+):
465.2676; found: 465.2694.
calcd for C29H45NNaO10 (M
590.2959.
+
Na+): 590.2941; found:
(R)-Amphiphilic chain-derived diiodo-trimer 11R. To
a
mixture of 8R (5.5 g, 7.1 mmol) and 10R (0.78 g, 1.4 mmol) in
iPr2NH (58 mL) and THF (29 mL) were added Pd2(dba)3·CHCl3
(28 mg, 0.027 mmol), PPh3 (29 mg, 0.11 mmol), and CuI
(5 mg, 0.027 mmol). The reaction mixture was stirred for 18 h at
room temperature and filtered. The filtrate was evaporated with a
rotary evaporator, and the residue was subjected to silica gel
column chromatography (eluent: AcOEt–hexane = 1 : 1 →
AcOEt → AcOEt–acetone = 1 : 1 → acetone) to afford 11R
(1.6 g, 64%) as a brown oil. [α]2D8 = +4.2 (c = 1.0, CHCl3); IR
(neat) ν 2872, 1577, 1532, 1108 cm−1 1H NMR (CDCl3,
;
(R)-Amphiphilic chain-derived 2,6-diiodopyridine 8R. Mitsu-
nobu reaction with 2,6-diiodo-4-pyridinol (7). To a mixture of
2,6-diiodo-4-pyridinol (7, 1.6 g, 4.5 mmol), PPh3 (1.2 g,
4.5 mmol), and iPr2NEt (5.0 mL) in toluene (97 mL) was added
diisopropyl azodicarboxylate (DIAD, 0.91 g, 4.5 mmol), and the
mixture was stirred for 1 h at room temperature. Then, to the
reaction mixture was added 6R (2.0 g, 4.5 mmol), and the
mixture was stirred for 14 h at room temperature and evaporated.
The residue was subjected to silica gel column chromatography
(eluent: AcOEt–hexane = 1 : 1 → AcOEt → AcOEt–acetone =
4 : 1) to afford 8R (2.6 g, 76%) as a yellow oil. IR (neat) ν 2871,
300 MHz) δ 1.26–1.30 (m, 9 H), 3.38 (s, 9 H), 3.53–4.20 (m,
105 H), 7.12 (d, J = 2.1 Hz, 2 H), 7.16 (s, 2 H), 7.29 (d, J =
2.1 Hz, 2 H); 13C NMR (CDCl3, 100 MHz) δ 16.91, 16.94,
59.0, 68.1, 69.00, 69.05, 69.1, 70.5, 70.6, 70.8, 70.9, 71.9, 72.1,
73.9, 86.6, 88.1, 114.7, 117.7, 121.5, 143.5, 143.8, 164.8, 165.2;
ESI-HRMS m/z calcd for C79H129I2N3Na2O30 (M + 2Na+):
949.8273; found: 949.8275.
(R)-Amphiphilic chain-derived bis(TBS-ethynyl)trimer 12R.
A solution of 11R (1.1 g, 0.57 mmol) in iPr2NH (87 mL) and
THF (55 mL) was added to a mixture of PdCl2(PPh3)2
(16 mg, 0.023 mmol), CuI (4 mg, 0.023 mmol), and tert-butyl-
dimethylsilylacetylene (0.40 g, 2.9 mmol). The reaction mixture
was stirred for 13 h at room temperature. The resulting mixture
was filtered, and the filtrate was evaporated with a rotary evapor-
ator. The residue was subjected to silica gel column chromato-
graphy (eluent: AcOEt–hexane = 2 : 1 → AcOEt → AcOEt–
acetone = 1 : 1 → acetone) to afford 12R (0.94 g, 87%) as a
1
1560, 1522, 1107 cm−1; H NMR (CDCl3, 300 MHz) δ 1.25 (d,
J = 6.3 Hz, 3 H), 3.38 (s, 3 H), 3.53–4.01 (m, 35 H), 7.25 (s,
2 H); 13C NMR (CDCl3, 100 MHz) δ 16.9, 59.0, 69.0, 70.5,
70.6, 70.7, 70.8, 71.0, 71.9, 72.1, 73.9, 114.2, 115.7, 121.3,
164.7; ESI-HRMS m/z calcd for C25H43I2NNaO10 (M + Na+):
794.0874; found: 794.0876.
(R)-Amphiphilic chain-derived 2,6-bis(TBS-ethynyl)pyridine
9R. A mixture of 8R (0.71 g, 0.92 mmol), PdCl2(PPh3)2
(26 mg, 0.037 mmol), CuI (3.5 mg, 0.018 mmol), and tert-butyl-
dimethylsilylacetylene (0.64 g, 4.6 mmol) in Et2NH (32 mL)
1
brown oil. IR (neat) ν 2871, 1581, 1550, 1109 cm−1; H NMR
(CDCl3, 300 MHz) δ 0.20 (s, 12 H), 1.00 (s, 18 H), 1.27–1.29
(m, 9 H), 3.38 (s, 9 H), 3.53–4.20 (m, 105 H), 6.99 (d, J =
6934 | Org. Biomol. Chem., 2012, 10, 6930–6936
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2.4 Hz, 2 H), 7.11 (d, J = 2.4 Hz, 2 H), 7.15 (s, 2 H); 13C NMR
(CDCl3, 100 MHz) δ −4.8, 16.7, 16.96, 17.02, 19.1, 26.2, 59.0,
68.99, 69.03, 70.5, 70.6, 70.8, 71.9, 73.88, 73.94, 87.2, 87.6,
93.7, 103.8, 114.0, 114.6, 143.7, 144.0, 144.6, 165.0;
ESI-HRMS m/z calcd for C95H159N3Na2O30Si2 (M + 2Na+):
962.0171; found: 962.0161.
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3 For reviews on saccharide recognition by synthetic host molecules, see:
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(R)-Amphiphilic chain-derived diethynyl-trimer 13R. To a
THF (29 mL) solution of 12R (0.89 g, 0.47 mmol) were sub-
sequently added ten drops of water and nBu4NF (1.0 mL of 1 M
THF solution, 1.0 mmol) dropwise. The mixture was stirred for
3 h at room temperature, evaporated, and instantly subjected to
silica gel column chromatography (eluent: AcOEt–acetone =
1 : 1 → acetone → acetone–MeOH = 10 : 1) to afford 13R
(0.76 g, 98%) as a brown oil. IR (neat) ν 2872, 2110, 1582,
1
1551, 1107 cm−1; H NMR (CDCl3, 300 MHz) δ 1.27–1.29 (m,
9 H), 3.15 (s, 2 H), 3.38 (s, 9 H), 3.53–4.19 (m, 105 H), 7.03 (d,
J = 2.3 Hz, 2 H), 7.14 (d, J = 2.3 Hz, 2 H), 7.16 (s, 2 H); 13C
NMR (CDCl3, 100 MHz) δ 16.9, 59.0, 69.0, 70.5, 70.6, 70.8,
71.9, 73.9, 82.1, 87.2, 87.3, 114.2, 114.5, 114.6, 143.7, 143.78,
143.83, 165.1. ESI-HRMS m/z calcd for C83H131N3Na2O30
(M + 2Na+): 847.9306; found: 847.9275.
(R)-Amphiphilic ethynylpyridine polymer 2R. A mixture of
11R (54 mg, 0.029 mmol), 13R (59 mg, 0.036 mmol), Pd
(PtBu3)2 (9.1 mg, 0.018 mmol), sodium 2′-(dicyclohexylphos-
phanyl)-2,6-diisopropylbiphenyl-4-sulfonate14
(14
mg,
0.027 mmol), and Cs2CO3 (38 mg, 0.11 mmol) was dispersed
with a mixed solvent of CH3CN (1.25 mL) and H2O (1.25 mL)
which were bubbled with argon before use. The mixture was
stirred for 3 days at room temperature with a water bath. The
resulting mixture was evaporated, and the residue was dissolved
in CHCl3 and purified by using a Sephadex LH-20 column to
afford 2R (99 mg, 88% yield by weight) as a brown oil. The
crude product was further purified and fractionated by prepara-
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1
tive GPC (Shodex K-2003, K-2002.5, eluent: CHCl3). H NMR
(CDCl3, 300 MHz) δ 1.27–1.33 (m, 3n H), 3.37 (s, 3n H),
3.5–4.2 (m, 35n H), 7.16–7.20 (m, 2n H).
Notes and references
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This journal is © The Royal Society of Chemistry 2012