Synthesis and Molecular Recognition of Pyrenophanes with Polycationic or Amphiphilic Functionalities: Artificial Plate-Shaped Cavitant Incorporating Arenes and Nucleotides in Water

Article abstract of DOI:10.1021/jo035188u

Water-soluble pyrenophanes possessing polycationic or amphiphilic side chains have been developed as synthetic host molecules to investigate hydrophobic and/or π-stacking interactions. By utilizing ω-acetalic alkyl side chains to retain solubility and ver

Full text of DOI:10.1021/jo035188u

Syn th esis a n d Molecu la r Recogn ition of P yr en op h a n es w ith
P olyca tion ic or Am p h ip h ilic F u n ction a lities: Ar tificia l
P la te-Sh a p ed Ca vita n t In cor p or a tin g Ar en es a n d Nu cleotid es in
Wa ter
Hajime Abe,† Yosuke Mawatari,† Haruna Teraoka,† Kazuhisa Fujimoto,† and
Masahiko Inouye*,†,‡
Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University,
Toyama 930-0194, J apan and Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical
University, and PRESTO, J apan Science and Technology Agency (J ST), Toyama 930-0194, J apan
inouye@ms.toyama-mpu.ac.jp
Received August 13, 2003
Water-soluble pyrenophanes possessing polycationic or amphiphilic side chains have been developed
as synthetic host molecules to investigate hydrophobic and/or π-stacking interactions. By utilizing
ω-acetalic alkyl side chains to retain solubility and versatility, water-soluble macrocyclic pyrenophanes
could be easily obtained by Stille coupling, followed by conversion of the acetal groups to hydrophilic
substituents. Among the pyrenophanes synthesized, hexaammonium-, bis(diazoniacrown)-, and
tetrakis[octa(oxyethylene)]-derived ones showed enough solubility in pure water. The former two
cationic pyrenophanes strongly recognized anionic arenes including nucleotides, while the latter
neutral one associated with monopyrenyl guests regardless of their electric natures. The strength
of recognition for nucleotides by bis(diazoniacrown)pyrenophane depended on the number of
phosphate moieties, decreasing in the following order: triphosphate . diphosphate ∼ monophos-
phate.
In tr od u ction
host molecules bearing a plate-shaped cavity have been
relatively rare.
Bondings are the most essential factor for the existence
of compounds and work in natural and artificial environ-
ments. The molecular recognition chemistry has focused
on noncovalent bonding and has succeeded in mimicking
various phenomena in nature.1 Among the noncovalent
bondings, hydrophobic and π-stacking interactions are
important ones for aromatic components, especially for
each plane of base pairs in DNA and RNA helices.2
Intercalation of some kinds of arenes into those planes
of a nucleic acid are also driven by π-stacking interaction.
For studying the π-stacking interaction, it is better to
apply such host molecules bearing a plate-shaped cavity
fitting the plane of guest arenes. In the field of host-
guest chemistry, there have been numerous studies about
synthetic hosts with a hydrophobic cavity to accom-
modate various kinds of guests.3 In most cases, however,
the shape of the cavity was spherical or cylindrical, while
Cyclophane is representative of a class of versatile
macrocyclic compounds on which various functionalities
could be conferred by the proper choice of arenes, bridges,
and substituents.4 These compounds have attracted much
attention from their moderately rigid cavity, especially
as hydrophobic host molecules.4-8 Some of them are con-
structed by use of polycyclic arenes such as acridine,9
phenanthridine,10 quinacridine,11 ethanoanthracene,12 or
flavin units,13 and proper arrangement of the polyaro-
matics produced a plate-shaped cavity on the cyclo-
phanes. During the course of our study about molecular
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* To whom correspondence should be addressed. Phone: +81-76-
434-7525. Fax: +81-76-434-5049.
† Toyama Medical and Pharmaceutical University.
‡ J ST.
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10.1021/jo035188u CCC: $27.50 © 2004 American Chemical Society
Published on Web 12/30/2003
J . Org. Chem. 2004, 69, 495-504
495

Abe et al.
meets another pyrene inter- or intramolecularly, the
interaction induces structureless broad excimer emission,
usually green-colored, in a longer wavelength area.18
Therefore the interaction between pyrenophanes and
guest molecules can be readily followed up by monitoring
the changes of the monomer and/or the excimer emis-
sions. Furthermore, on the absorption spectra, significant
hypochromism is often observed according to the com-
plexation. Thus our pyrenophane 1a could efficiently
sandwich various aromatic compounds in the plate-
shaped hydrophobic cavity, accompanied by such char-
acteristic spectral changes.14 However, we could not
examine the binding affinities of 1a in pure 100% water,
an ideal solvent for the hydrophobic interaction, because
1a scarcely dissolved in it.19 This frustration made us
decide to develop pyrenophanes soluble in pure 100%
water with the expectation of drawing out the full
potential of their hydrophobic cavities. Apart from their
molecular recognition abilities, the precoordinated pyreno-
phanes are also interesting from the viewpoint of pho-
tophysics for their intramolecular excimer or exciplex
formation.20
F IGURE 1. Macrocyclic pyrenophanes with cationic and
amphiphilic side chains.
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on its fluorescence spectrum. Once the excited pyrene
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496 J . Org. Chem., Vol. 69, No. 2, 2004

Synthesis and Molecular Recognition of Pyrenophanes
SCHEME 1. Syn th esis of P yr en op h a n esa
The solubility of the pyrenophane nucleus is inherently
poor not only in water but also in most organic solvents,
so some devices are necessary for improving its solubility.
This also will facilitate their synthetic and analytical
operations. To improve water solubility, hydrophilic
functionalities such as polyammonium and polyoxyeth-
ylene groups are introduced on the molecule. However,
the existence of highly polar functional groups frequently
brings about serious drawbacks for manipulations such
as reaction, isolation, and purification. Herein we report
the development of pure-water-soluble pyrenophanes
possessing a plate-shaped cavity that can incorporate
various aromatic compounds including biologically im-
portant nucleotides (Figure 1). The refined synthetic
strategy for overcoming insolubility problems and the
molecular recognition abilities of the pyrenophanes are
described.
Resu lts a n d Discu ssion
Syn th esis of Water -Solu ble P yr en oph an es. Polyam-
monium pyrenophane was the first target toward pure-
water-soluble compounds. The major issues in their
synthesis were how to construct the macrocyclic pyreno-
phane ring, when to introduce hydrophilic functionalities,
and how to handle highly polar intermediates. One route
(Scheme 1; 4 f 5 f (6 and 7) f 8 f 1c) was planned
following our previously reported synthesis of 1a , which
includes the Stille-type coupling reaction as the key
macrocyclization.14 Phenolic diacetylene 414 prepared
from 3,5-bis(hydroxymethyl)phenol was condensed with
triamino alcohol by the Mitsunobu reaction21 to give 5.
The triaminated derivative 5 was converted to a pair of
counterparts for Stille-type macrocyclization, i.e., one is
acetylenic stannane 6 by lithiation-transmetalation, and
the other is the iodopyrene derivative 7 by Sonogashira
coupling. After cyclization to pyrenophane 8, quarterna-
rization of each amine with methyl triflate afforded
hexaammonium pyrenophane 1c. The water solubility of
1c was actually increased compared to that of 1a because
of the increment of the number of cationic centers.
However, the low accessibility of 1c, such as low yields
and troublesome handling of each polyaminated inter-
mediate, spured us to develop a more convenient route.
In a new synthetic scheme, introduction of polar
moieties was followed by macrocyclization to make the
handling easier (Scheme 1; 4 f 9 f (10 and 11) f 12 f
13). Triisopropylsilyl(TIPS)-protected pyrenophane 12
was smoothly prepared via Stille coupling between TIPS-
protected 10 and 11. But once it was deprotected to 13,
the solubility tragically decreased, so any further ma-
nipulations ended in failure.
a
Reagents: (a) [Me2N(CH2)3]2N(CH2)3OH, Ph3P, DEAD,
THF; (b) i-Pr3SiCl, DMAP, Et3N, CH2Cl2; (c) Br(CH2)3CH(OMe)2,
NaI, 18-crown-6, K2CO3, acetone; (d) propargyl bromide, NaH,
THF, DMF; (e) n-BuLi, n-Bu3SnCl, THF; (f) 1,6-diiodopyrene,
PdCl2(PPh3)2, CuI, morpholine; (g) Pd(PPh3)4, toluene; (h) MeOTf,
CH2Cl2; (i) n-Bu4NF, H2O, THF; (j) CF3CO2H, H2O, CHCl3; (k)
octa(ethylene glycol), 10-camphorsulfonic acid.
17, which was deprotected by trifluoroacetic acid to 18.
Aldehyde 18 was easily soluble in CH2Cl2 and was
reductively aminated with 2 equiv of secondary amine
by using tetra-n-butylammonium cyanoborohydride (n-
Bu4NBH3CN)22 to afford the corresponding hexa-, tetra-,
and diaminated pyrenophanes 19b, 19d , and 19e (Table
1). The complete quarternarization by methyl triflate
gave targeted polyammonium pyrenophanes 1b,23 1d ,
and 1e. Purification of 1d ,e was carried out by a
preparative HPLC in a reverse phase. Azacrown and
azoniacrown rings were also introduced on the pyreno-
ω-Acetalic alkyl chains opened the door to the success-
ful route to hydrophilic pyrenophanes with synthetic
versatility and easy handling (Scheme 1; 14 f (15 and
16) f 17 f (18 and 3)). The key intermediate 14 was
prepared from 3,5-bis(hydroxymethyl)phenol via subse-
quent Williamson synthesis with 1-bromo-4,4-dimethox-
ybutane and propargyl bromide. Both the acetylenic ends
of 14 were stannylated to 15 and pyrenylated to 16,
which are two counterparts for the following macrocy-
clization. Stille coupling of 15 and 16 gave pyrenophane
(22) Hutchins, R. O.; Markowitz, M. J . Org. Chem. 1981, 46, 3571-
3574.
(23) Hexaammonium 1b could not be purified enough to permit
complexation studies because of its too high polarity. See the Sup-
porting Information.
(21) Hughes, D. L. Org. React. 1992, 42, 335-656.
J . Org. Chem, Vol. 69, No. 2, 2004 497

Abe et al.
TABLE 1. Syn th esis of P yr en op h a n es P ossessin g Am in o or Am m on iu m Gr ou p s
a
Not determined.
phane (Table 1). Indeed, diaza- and monoaza-18-crown-6
were condensed with 18 to afford 20a and 20b, respec-
tively. The quarternarization of 20a yielded a diazonia-
crown derivative 2a quantitatively.
Next was designed a neutral hydrophilic pyrenophane
3 possessing four octa(oxyethylene) side chains (Figure
1). The poly(oxyethylene) chain has been utilized for its
favorable amphiphilicity:24 affinity for both organic and
aqueous media. Fortunately, octa(oxyethylene) chains
could be directly introduced by acid-catalyzed transac-
F IGURE 2. Virtues of ω-acetalic alkyl branches.
etalization of diacetal 17 with octa(ethylene glycol)25
under reduced pressure to remove methanol (Scheme 1).
Thus, 17 is a versatile common intermediate for synthe-
sizing various functionalized pyrenophanes. This ap-
proach utilizing ω-acetalic alkyl chains generally would
be applicable for various compounds of poor solubility in
order to attach hydrophilic substituents (Figure 2).
Wa t er Solu b ilit y of P yr en op h a n es a n d Gu est
Molecu les. The pyrenophanes synthesized above were
studied for their water solubility. Each of the pyreno-
phanes 1-3 and 20 was suspended into Milli-Q pure
water and passed through a membrane filter, and the
filtrate was irradiated with UV light (365 nm). The water
solubility was judged from the presence or absence of
excimer emission. Among the pyrenophanes examined,
(24) (a) Uozumi, Y.; Nakai, Y. Org. Lett. 2002, 4, 2997-3000. (b)
Uozumi, Y.; Shibatomi, K. J . Am. Chem. Soc. 2001, 123, 2919-2920.
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281.
498 J . Org. Chem., Vol. 69, No. 2, 2004

Synthesis and Molecular Recognition of Pyrenophanes
F IGURE 3. Guest molecules.
hexaammonium 1b and 1c, bis(diazoniacrown)-substi-
tuted 2a , and poly(oxyethylene)-substituted 3 showed
pure-water solubilities, whereas tetraammonium 1d ,
diammonium 1e, and azacrown-substituted 20a and 20b
did not. Interestingly, amphiphilic 3 also dissolved into
organic solvents such as dichloromethane and ether. For
studying the recognition abilities of the pyrenophanes,
several types of guest molecules were subjected: those
include monomeric pyrenes 21 (neutral), 2214 (cationic),
and 23 (anionic), disulfonate 24, adenosine, and twelve
kinds of nucleotides. Figure 3 shows a series of guest
molecules used in this study.
F IGURE 4. (a) The absorption spectra of 3 (1.5 × 10-5 M, s)
and 21 (3 × 10-5 M, ‚‚‚) in water. (b) The fluorescent spectra
of 3 (1 × 10-5 M, s) and 21 (2 × 10-5 M, ‚‚‚) in water. The
excitation wavelength was 370 nm.
UV-Visible a n d F lu or escen ce Sp ectr a of P yr en o-
p h a n e 3. In the absorption spectrum of 3 (Figure 4a),
broadening of the bands slightly red-shifted and a
significant hypochromism, compared with that of the
monopyrenyl reference 21 were observed. These differ-
ences indicate transannular interaction between two
pyrene planes in 3.17e,h,i,20 As mentioned above, the optical
properties of pyrenophanes are well-characterized in
their fluorescence spectra. In a water solution, 3 almost
exclusively exhibited excimer emission (λmax ) 520 nm)
even at the concentration of 8 × 10-7 M, while monomer
emission was hardly observed (Figure 4b). Thus, the
excimer emission is obviously due to intramolecular
π-stacking on the precoordinated structure of 3, not due
to intermolecular stacking which should depend on the
concentration. On the other hand, monomeric pyrene 21
showed both monomer (λmax ) 395, 416 nm) and excimer
(λmax ) 520 nm) emissions at the concentration of 2 ×
10-5 M in water, and the proportion of these two
emissions depended on the concentration of 21. The
excimer emission of 21 disappeared under a diluted
condition, indicating the feature of the intermolecular
interaction.
Com p lexa t ion of P yr en op h a n es w it h Ar om a t ic
Gu ests. (i) Self-Associa tion Ten d en cies of P yr en o-
p h a n es 1-3 a n d Mon om er ic P yr en es 21-23. Enough
water solubility of the pyrenophanes 1b, 1c, 2a , and 3
enabled us to examine their hydrophobic interactions
under a 100% aqueous condition. All binding assays must
be carried out below this concentration so that the self-
association of each substrate is negligible under the
conditions of the following measurements. Therefore, self-
association tendencies of 3 and the monopyrenyl guests
21-23 were studied in advance. From UV-vis and
fluorescence spectra, the relations of the absorbance and
emission intensity upon the concentration were investi-
gated (for 3, see Figures S1 and S2 in the Supporting
Information). At a lower concentration of the substrate,
the absorbance fitted in proportion to the concentration,
obeying Beer’s law. If deviation is observed from the
J . Org. Chem, Vol. 69, No. 2, 2004 499

Abe et al.
TABLE 2. Th e Con cen tr a tion Ra n ges for 3 a n d 21-23 in
Wh ich th e Absor ba n ce a n d Em ission In ten sity Obey th e
Lin ea r Rela tion sh ip in Wa ter
by absorbance
by fluorescence intensity
λ (nm) linearity range (M) λ (nm) linearity range (M)
3
391
370
383
350
<2.5 × 10-4
<3.0 × 10-5
<2.5 × 10-4
<2.5 × 10-4
520
395
400
380
<1.0 × 10-5
<3.0 × 10-6
<6.4 × 10-6
<3.1 × 10-5
21
22
23
linearity over a certain concentration, it means self-
interaction becomes significant between two ground state
molecules. On the other hand, in the fluorescence inten-
sity, the divergence from the linearity corresponds to the
interaction between one excited molecule and another,
usually the ground-state one. Table 2 shows the ranges
in which the absorbance and emission intensity obey a
linear relationship with the concentration. In the cases
of monomeric pyrenes 21-23, excimer emissions were not
observed within those concentration ranges. Between the
neutral substances 3 and 21, monopyrenyl 21 tends to
self-associate more than pyrenophane 3. This may be
partly because the cavity inside the pyrenophane is not
so large to accommodate another pyrenophane. Among
the monomeric pyrenes, charged 22 and 23 showed
weaker self-association than 21 probably because of the
electrostatic repulsion. By analogy to that, the polyca-
tionic pyrenophanes 1b,c and 2a will be supposed to
perform weaker self-association than neutral 3. On the
basis of these results, all the following host-guest
complexation experiments were carried out within those
concentrations at which self-association is negligible.
F IGURE 5. Fluorimetric titration of 21 (3.1 × 10-6 M) with
3 (0-12 equiv) in water. The excitation wavelength was 370
nm. Inset: The relationship between [3] and the decrease in
intensity of the emission of 21 at 416 nm. The solid line shows
the fitted curve.
(ii) Com p lexa tion of P oly(oxyeth ylen e)-Su bsti-
tu ted P yr en op h a n e 3. When the neutral monomeric
pyrene 21 was titrated with the neutral poly(oxyethyl-
ene)-substituted pyrenophane 3, quenching of the mono-
mer emission of 21 was observed in the fluorescence
spectra (Figure 5). Curve-fitting analysis of the titration
curve supported 1:1 stoichiometry, and the association
constant was determined at 1.3 × 105 M-1. In reverse,
titration of 3 by 21 induced quenching of the excimer
emission of 3 as expected. As for the cationic and the
anionic monomeric pyrene guests 22 and 23, the spectral
changes were also observed in a similar manner. The
association constants for 22 and 23 were estimated close
to that for 21 (1 × 105 M-1). Thus, the poly(oxyethylene)-
substituted pyrenophane 3 can incorporate the mono-
meric pyrenes 21-23 to a similar extent, regardless of
their electric natures.
F IGURE 6. The postulated triply π,π,π-stacking coordination
between a pyrenophane host and a monopyrenyl guest.
cent band at longer wavelengths with dibenzoperylene26a,b
or triple-decked cyclophane.26c In our experiments, how-
ever, such an extra emission band could not be found, so
in the case of pyrene the π,π,π-excited trimer formation
by spectroscopy remains to be confirmed. The investiga-
tion of trilayer or more π-stacking pyrene systems is now
under way.
(iii) Com p lexa tion of P olyca tion ic P yr en op h a n es
1c a n d 2a w ith An ion ic Gu est 24. The complexation
of the pyrenophanes 1c and 2a bearing polycationic sites
was studied. These pyrenophanes were expected as
multipoint recognition hosts based on collaboration of the
π-stacking and the electrostatic interactions. Thus, 1c
and 2a may have an advantage in recognizing such a
molecule that has both aromatic and anionic moieties.
When disulfonate 24 was added to a solution of the bis-
(diazoniacrown)-substituted pyrenophane 2a , hypochrom-
ism in the absorption spectra of 2a was observed (Figure
7a). This should be due to the complexation, and the
association constant was determined to be 1.5 × 106 M-1
by curve-fitting analysis. On fluorimetric titration, quench-
ing of the excimer emission of 2a was observed under
The complexation mode would be depicted as a sand-
wich form (Figure 6).14 The other possibility is that the
monomeric pyrenes merely nest on one side of 3. How-
ever, this type of nesting association could be rejected
because this mode resembles self-association of the
monomeric pyrenes. Indeed, the host-guest cross-as-
sociation is far preferred to the self-association. (The
cross-association was observable even at [3] ) [21] ) 8.3
× 10-7 M as quenching of the excimer emission of 3.
Compare this with the results in Table 2.) The quenching
of fluorescence during the titration means that the
complexation lost the excitation energy thermally in the
tripyrenyl stack, while the π,π,π-stacking excited trimer
has been reported to induce a very weak broad fluores-
(26) (a) Abu-Zeid, M. E.; Lopez, J . R.; Marafi, M. A. J . Chem. Phys.
1981, 75, 2237-2241. (b) Abu-Zeid, M. E.; Lopez, J . R. J . Chem. Phys.
1980, 73, 4141-4142. (c) Otsubo, T.; Kohda, T.; Misumi, S. Bull. Chem.
Soc. J pn. 1980, 53, 512-517.
500 J . Org. Chem., Vol. 69, No. 2, 2004

Synthesis and Molecular Recognition of Pyrenophanes
F IGURE 8. Multipoint recognition of 2a for nucleotide.
which recognize phosphate moieties, for example, azonia-
crowns,28-30 azoniacyclophanes,8 and protonated sapphy-
rins.31 Lehn, Hosseini, and co-workers have reported a
series of azoniacyclophanes.5b,9-11 Furthermore, acridine-
armed azoniacyclophanes28d,e associated with nucleotides
as multipoint recognition hosts by both electrostatic and
π-stacking interactions.
Two kinds of three recognition sites in 2a are placed
at appropriate positions, i.e., two azoniacrown sites at
both ends and one pyrenophane site at the center. If these
sites work synergistically, the form of the complex would
be featured as in Figure 8 in expectation of effective
distinction of nucleotides by size.
When 2a was titrated with ATP in water, the UV-vis
spectra changed in a hypochromic way according to
(27) Teulade-Fichou, M.-P.; Vigneron, J .-P. In DNA and RNA
Binders; Demeunynck, M., Bailly, C., Wilson, W. D., Eds.; Wiley-
VCH: Weinheim, Germany, 2003; Vol. 1, pp 278-314. Hosseini, M.
W. In Supramolecular Chemistry of Anions; Bianchi, A., Bowman-
J ames, K., Garc´ıa-Espan˜a, E., Eds.; Wiley-VCH: New York, 1997; pp
421-448. For intercalating agents for DNA, see: J ohnson, D. S.; Boger,
D. L. In Comprehensive Supramolecular Chemistry; Atwood, J . L.,
Davies, J . E. D., MacNicol, D. D., Vo¨gtle, F., Lehn, J .-M., Murakami,
Y., Eds.; Pergamon: Oxford, UK, 1996; Vol. 4, pp 73-176. Aoki, S.;
Kimura, E. Rev. Mol. Biotechnol. 2002, 90, 129-155.
(28) (a) Hosseini, M. W.; Lehn, J .-M. Helv. Chim. Acta 1987, 70,
1312-1319. (b) Brand, G.; Hosseini, M. W.; Ruppert, R. Helv. Chim.
Acta 1992, 75, 721-728. (c) Cordier, D.; Hosseini, M. W. New J . Chem.
1990, 14, 611-616. (d) Hosseini, M. W.; Blacker, A. J .; Lehn, J .-M. J .
Am. Chem. Soc. 1990, 112, 3896-3904. (e) Fenniri, H.; Hosseini, M.
W.; Lehn, J .-M. Helv. Chim. Acta 1997, 80, 786-803.
(29) (a) Bazzicalupi, C.; Bencini, A.; Bianchi, A.; Fedi, V.; Fusi, V.;
Giorgi, C.; Paoletti, P.; Tei, L.; Valtancoli, B. J . Chem. Soc., Dalton
Trans. 1999, 1101-1108. (b) Andore´s, A.; Bazzicalupi, C.; Bencini, A.;
Bianchi, A.; Fusi, V.; Garcia-Espan˜a, V.; Giorgi, C.; Nardi, N.; Paoletti,
P.; Ramirez, J . A.; Valtancoli, B. J . Chem. Soc., Perkin Trans. 2 1994,
2367-2373. (c) Andore´s, A.; Arago´, J .; Bencini, A.; Bianchi, A.;
Domenech, A.; Fusi, V.; Garc´ıa-Espan˜a, E.; Paoletti, P.; Ram´ırez, J .
A. Inorg. Chem. 1993, 32, 3418-3424. (d) Bencini, A.; Bianchi, A.;
Garcia-Espana, E.; Scott, E. C.; Morales, L.; Wang, B.; Deffo, T.;
Takusagawa, F.; Mertes, M. P.; Mertes, K. B.; Paoletti, P. Bioorg.
Chem. 1992, 20, 8-29. (e) Bencini, A.; Bianchi, A.; Burguete, M. I.;
Domenech, A.; Garc´ıa-Espan˜a, E.; Luis, S. V.; Nin˜o, M. A.; Ram´ırez,
J . A. J . Chem. Soc., Perkin Trans. 2 1991, 1445-1451. (f) Bianchi, A.;
Micheloni, M.; Paoletti, P. Inorg. Chim. Acta 1988, 151, 269-272.
(30) (a) Kimura, E.; Kuramoto, Y.; Koike, T.; Fujioka, H.; Kodama,
M. J . Org. Chem. 1990, 55, 42-46. (b) Umezawa, Y.; Kataoka, M.;
Takami, W.; Kimura, E.; Koike, T.; Nada, H. Anal. Chem. 1988, 60,
2392-2396. (c) Kimura, E.; Komada, M.; Yatsunami, T. J . Am. Chem.
Soc. 1982, 104, 3182-3187. (d) Marecek, J . F.; Fischer, P. A.; Burrows,
C. J . Tetrahedron Lett. 1988, 29, 6231-6234. (e) Marecek, J . F.;
Burrows, C. J . Tetrahedron Lett. 1986, 27, 5943-5946. (f) Yohannes,
P. G.; Plute, K. E.; Mertes, M. P.; Mertes, K. B. Inorg. Chem. 1987,
26, 1751-1755. (g) Yohannes, P. G.; Mertes, M. P.; Mertes, K. B. J .
Am. Chem. Soc. 1985, 107, 8288-8289.
F IGURE 7. (a) UV-vis titration of 2a (1.1 × 10-5 M) with
24 (0-1.5 equiv) in water. (b) Fluorimetric titration of 2a (1.6
× 10-5 M) with 24 (0-1.5 equiv) in water. The excitation
wavelength was 370 nm.
similar conditions (Figure 7b). The branched polycationic
pyrenophane 1c also displayed a similar affinity for 24,
and the association constant between 1c and 24 was
estimated as over 1 × 106 M-1 from the fluorimetric
titration. Thus, the multipoint recognition by 1c and 2a
takes place for anionic arenes, while neutral pyrenophane
3 showed no observable interaction with 24 by both UV-
vis and fluorimetric titrations.
Com p lexa tion of P yr en op h a n e 2a w ith Nu cle-
otid es. Nucleotides are the most important class of
biomolecules possessing both aromatic and anionic moi-
eties. So they are suitable guest molecules for demon-
strating the host ability of the bis(diazoniacrown)-
substituted pyrenophane 2a . There have already been
numerous studies about the development of host mol-
ecules for nucleotides.27 One efficient strategy for the
recognition of nucleotides is to use cationic macrocycles
(31) Kra´l, V.; Furuta, H.; Shreder, K.; Lynch, V.; Sessler, J . L. J .
Am. Chem. Soc. 1996, 118, 1595-1607. Iverson, B. L.; Shreder, K.;
Kra´l, V.; Sansom, P.; Lynch, V.; Sessler, J . L. J . Am. Chem. Soc. 1996,
118, 1608-1616. Kra´l, V.; Andrievsky, A.; Sessler, J . L. J . Chem. Soc.,
Chem. Commun. 1995, 2349-2351.
J . Org. Chem, Vol. 69, No. 2, 2004 501

Abe et al.
TABLE 3. Associa tion Con sta n ts a n d F r ee-En er gy
Ch a n ges for th e Com p lexa tion of 2a w ith Nu cleotid esa
association
-∆G293
nucleotide
constant (M-1
)
(kJ mol-1
)
ATP
1.0 × 106
5.3 × 103
1.9 × 103
1.3 × 106
4.0 × 103
2.7 × 103
2.6 × 105
7.7 × 103
4.0 × 103
7.7 × 105
2.2 × 104
3.0 × 103
34
21
18
34
20
19
30
22
20
33
24
20
ADP
AMP
GTP
GDPb
GMP
CTP
CDP
CMPb
UTP
UDP
UMP
a
Calculated by curve-fitting analysis of hypochromism on 390
nm. Conditions: 2a (1.0 × 10-5 M), nucleotide, 20 °C in water.
b The association constant was estimated by the Benesi-Hildebrand
method.
to ATP. On the other hand, bindings of 2a to di- and
monophosphate nucleotides (ADP, GDP, CDP, UDP,
AMP, GMP, CMP, and UMP) appeared much weakly
than those to triphosphates. The association constants
for the di- and monophosphate nucleotides were close to
that between 2a and adenosine (6.5 × 103 M-1) rather
than those for triphosphates whether the type of nucleo-
base had only a little effect on the binding or purine bases
were slightly preferred to pyrimidine ones. Thus, the
recognition selectivities of 2a would be due to a structural
reason: the distance between the pyrenophane cavity and
diazoniacrown sites in 2a may fit in with the size of the
triphosphate nucleotides along with synergistic coordina-
tion.
Con clu sion
To investigate the molecular recognition abilities of
pyrenophanes in pure water, several types of pyreno-
phanes possessing various hydrophilic functionalities
were synthesized. The construction of the pyrenophane
nucleus was achieved by macrocyclization applying Stille-
type coupling. The use of ω-acetalic alkyl chains was effi-
cient for retaining the solubility on pyrenophane inter-
mediates, and the side chains could be readily converted
to polyammonium-, azoniacrown-, and poly(oxyethylene)-
substituted hydrophilic substituents. In the study of
molecular recognition abilities, amphiphilic poly(oxyeth-
ylene)-substituted pyrenophane 3 showed good affinities
for monopyrenyl guests, regardless of the guest being
cationic, anionic, or neutral. Polycationic hexaammonium
pyrenophane 1c and bis(diazoniacrown)-substituted one
2a associated well with anionic arenes. It is remarkable
that 2a much preferred triphosphate nucleotides rather
than di- or monophosphate ones. These pyrenophanes are
the optical probe of interest, not only for recognition
ability, but also for their optical uniqueness. They
displayed characteristic excimer emission owing to the
two precoordinated pyrene rings, which were susceptibly
affected by association with guest arenes. This makes the
study of its host-guest chemistry straightforward. Fur-
ther development of polypyrenyl architectures for bioor-
ganic applications is now under way in our laboratory.
F IGURE 9. (a) UV-vis titration of 2a (1.0 × 10-5 M) with
ATP (0-1.4 equiv) in water. (b) Fluorimetric titration of 2a (1
× 10-5 M) with ATP (0-6.0 equiv) in water. The excitation
wavelength was 370 nm.
π-stacking coordination (Figure 9a), and the association
constant was determined (1.0 × 106 M-1 by curve-fitting
analysis) as high as the disulfonate guest 24. The
quenching of the excimer fluorescence was also observed
under similar conditions (Figure 9b).32 On the other hand,
the neutral host 3 showed no observable interaction with
ATP on the UV-vis titration, possibly because the
π-plane of adenine is not large enough to complex with
3 by only π-stacking.
These results encouraged us to investigate the recogni-
tion ability of 2a for other nucleotides comprehensively
in a similar manner as for ATP. The association constants
were lined up in Table 3. Triphosphate nucleotides GTP,
CTP, and UTP associated with 2a at comparable levels
Exp er im en ta l Section
Eva lu a tion of Associa tion Con sta n ts. Milli-Q pure water
was used as a common aqueous solvent. The analyses for 3
(32) Similar optical behavior was observed in our previous work.14
502 J . Org. Chem., Vol. 69, No. 2, 2004

Synthesis and Molecular Recognition of Pyrenophanes
were performed by fluorimetric titration at 25 °C, measuring
the quenching of the emission at 520, 416, and 380 nm for 3,
21, and 23, respectively. The analyses for 2a were performed
by UV-vis titration at 20 °C by measuring hypochromism of
the absorption at 390 nm. The association constants were
calculated by using iterative least-squares curve-fitting or the
Benesi-Hildebrand method.33
mL) suspension of 14 (1.1 g, 3.2 mmol), 1,6-diiodopyrene35 (5.25
g, 11.6 mmol), Pd(PPh3)4 (370 mg, 0.32 mmol), and CuI (30
mg, 0.16 mmol) was stirred at 110 °C for 5 h. After evapora-
tion, the residue was diluted with brine and extracted with
CHCl3. The CHCl3 extract was concentrated and purified by
repeated column chromatography (silica gel; CH2Cl2:MeOH
1
100:1) to give 16 as a solid (1.0 g, 32%). Mp 154-158 °C; H
1-(4,4-Dim eth oxybu tyloxy)-3,5-bis(h ydr oxym eth yl)ben -
zen e. To an acetone (70 mL) suspension of 1-bromo-4,4-
dimethoxybutane34 (16 g, 81 mmol), NaI (0.61 g, 4.1 mmol),
18-crown-6 (1.1 g, 4.1 mmol), and finely ground K2CO3 (28 g,
203 mmol) was added an acetone (70 mL) solution of 3,5-bis-
(hydroxymethyl)phenol14 (6.1 g, 41 mmol). The suspension was
refluxed for 12 h and filtered, and the concentrated filtrate
was purified on column chromatography (silica gel; CH2Cl2:
MeOH 50:1) to give 1-(4,4-dimethoxybutyloxy)-3,5-bis(hy-
NMR (300 MHz, CDCl3) δ 8.43 (d, J ) 5.4 Hz, 2 H), 8.36 (d, J
) 8.3 Hz, 2 H), 8.15 (d, J ) 9.3 Hz, 2 H), 8.01 (d, J ) 8.1 Hz,
2 H), 7.96-7.67 (m, 6 H), 7.24 (s, 1 H), 7.00 (s, 2 H), 4.85 (s, 4
H), 4.65 (s, 4 H), 4.43 (t, J ) 5.5 Hz, 1 H), 4.04 (t, J ) 6.1 Hz,
2 H), 3.32 (s, 6 H), 1.87-1.76 (m, 4 H); 13C NMR (75 MHz,
CDCl3) δ 159.6, 139.2, 137.0, 132.3, 131.7, 131.6, 131.0, 130.9,
130.2, 128.9, 127.9, 126.3, 125.7, 124.8, 124.7, 123.4, 120.4,
117.7, 113.8, 104.2, 97.0, 91.1, 85.5, 71.5, 67.6, 58.1, 52.8, 29.1,
24.5; IR (KBr) 2929, 2873, 2834, 2215 cm-1; FABMS (2-
nitrophenyl octyl ether) m/z 998 (M+, 100); ESI-HRMS m/z
calcd for C52H40I2NaO5 (M + Na+) 1021.0863, found 1021.0817.
Aceta lic P yr en op h a n e 17. Stille-Typ e Ma cr ocycliza -
tion . To a toluene (500 mL) solution of 16 (2.6 g, 2.6 mmol)
and Pd(PPh3)4 (300 mg, 0.26 mmol) was added a toluene (100
mL) solution of 15 (2.6 g, 2.9 mmol) at room temperature, and
the mixture was stirred at 60 °C for 2 days. After evaporation,
the residue was diluted with brine and extracted with CHCl3.
The CHCl3 extract was concentrated and subjected to column
chromatography (silica gel; CH2Cl2:MeOH 50:1) to give 17 as
a solid (0.23 g, 8%). Mp 169-171 °C; 1H NMR (300 MHz,
CDCl3) δ 8.20 (d, J ) 9.0 Hz, 4 H), 7.84 (d, J ) 7.8 Hz, 4 H),
7.54 (d, J ) 9.3 Hz, 4 H), 7.50 (d, J ) 8.1 Hz, 4 H), 7.44 (s, 2
H), 7.04 (s, 4 H), 4.94 (s, 8 H), 4.63 (s, 8 H), 4.48 (t, J ) 5.5
Hz, 4 H), 4.09 (t, J ) 6.1 Hz, 2 H), 3.37 (s, 12 H), 1.94-1.81
(m, 8 H); 13C NMR (75 MHz, CDCl3) δ 159.9, 138.9, 131.6,
130.4, 129.5, 127.6, 125.5, 124.7, 123.0, 121.6, 117.1, 114.3,
104.2, 90.5, 85.8, 71.0, 67.7, 57.4, 52.8, 29.1, 24.5; IR (KBr)
2929, 2873, 2838, 2215 cm-1; FABMS (2-nitrophenyl octyl
1
droxymethyl)benzene as a colorless oil (7.6 g, 69%). H NMR
(300 MHz, DMSO-d6) δ 6.81 (s, 1 H), 6.71 (s, 1 H), 5.13 (t, J )
5.7 Hz, 2 H), 4.43-4.39 (m, 5 H), 3.93 (t, J ) 6.2 Hz, 2 H),
3.22 (s, 6 H), 1.71-1.63 (m, 4 H); 13C NMR (75 MHz, DMSO-
d6) δ 158.48, 143.85, 116.46, 110.57, 103.66, 66.91, 62.83, 52.42,
28.67, 24.02; IR (KBr) 3396, 2939, 2879 cm-1; FABMS (3-
nitrobenzyl alcohol) m/z 270 (M+, 100).
1-(4,4-Dim et h oxybu t yloxy)-3,5-b is(2-p r op yn yloxym e-
th yl)ben zen e (14). NaH (60% oil dispersion; 2.64 g, 66 mmol)
was washed thoroughly with hexane and suspended with THF
(50 mL), to which was added a DMF (65 mL) solution of 1-(4,4-
dimethoxybutyloxy)-3,5-bis(hydroxymethyl)benzene (4.45 g,
16.5 mmol) dropwise at 0 °C. After the solution was stirred at
that temperature for 1 h, propargyl bromide (7.8 g, 66 mmol)
was added dropwise at -78 °C. The mixture was stirred
additionally for 12 h, being allowed to reach room temperature.
After evaporation, the residue was diluted with water and
extracted with CHCl3. The CHCl3 extract was concentrated
and subjected to column chromatography (silica gel; CH2Cl2)
1
ether) m/z 1088 (M+, 100); ESI-HRMS m/z calcd for C72H64
NaO10 (M + Na+) 1111.4397, found 1111.4349.
-
to give 14 as a colorless oil (4.0 g, 70%). H NMR (300 MHz,
CDCl3) δ 6.91 (s, 1 H), 6.84 (s, 2 H), 4.57 (s, 4 H), 4.40 (t, J )
5.2 Hz, 1 H), 4.18 (d, J ) 2.4 Hz, 4 H), 3.99 (t, J ) 6.0 Hz, 2
H), 3.34 (s, 6 H), 2.47 (t, J ) 2.4 Hz, 2 H), 1.88-1.76 (m, 4 H);
13C NMR (75 MHz, CDCl3) δ 159.4, 139.0, 119.7, 113.5, 104.2,
79.6, 74.7, 71.3, 67.5, 57.2, 52.8, 29.1, 24.5; IR (KBr) 3290,
2944, 2117 cm-1; FABMS (3-nitrobenzyl alcohol) m/z 345 (M
- H-, 100); ESI-HRMS m/z calcd for C20H26NaO5 (M + Na+)
369.1678, found 369.1637.
Ald eh yd ic P yr en op h a n e 18. To a CHCl3 (5 mL) solution
of 17 (50 mg, 0.046 mmol) was added aqueous 50% CF3CO2H
(2.5 mL) dropwise at 0 °C, and the mixture was stirred at that
temperature for 18 h. To the mixture was added aqueous K2-
CO3 at room temperature until no more CO2 evolved. The
reaction mixture was extracted with CH2Cl2, and the CH2Cl2
extract was concentrated and subjected to column chromatog-
raphy (silica gel; CH2Cl2:MeOH 20:1) to give 18 (45 mg, 95%).
1-(4,4-Dim eth oxybu tyloxy)-3,5-bis(3-tr ibu tylsta n n yl-2-
p r op yn yloxym eth yl)ben zen e (15). To a THF (5 mL) solu-
tion of 14 (900 mg, 2.6 mmol) was added a hexane solution of
n-BuLi (5.7 mmol) dropwise at 0 °C. After the solution was
stirred at that temperature for 1 h, n-Bu3SnCl (1.9 g, 5.7 mmol)
was added dropwise. The reaction mixture was stirred ad-
ditionally for 14 h, being allowed to reach room temperature.
After evaporation, the residue was treated with saturated
aqueous KF and extracted with Et2O. The Et2O extract was
evaporated to give crude 15 as a colorless oil (2.25 g, 94%),
which was used in the next reaction without further purifica-
1
Mp >240 °C dec; H NMR (300 MHz, CDCl3) δ 9.88 (s, 2 H),
8.20 (d, J ) 9.0 Hz, 4 H), 7.78 (d, J ) 8.1 Hz, 4 H), 7.59 (d, J
) 9.0 Hz, 4 H), 7.51 (d, J ) 8.5 Hz, 4 H), 7.44 (s, 2 H), 7.03 (s,
4 H), 4.93 (s, 8 H), 4.63 (s, 8 H), 4.11 (t, J ) 6.0 Hz, 4 H), 2.71
(t, J ) 7.0 Hz, 4 H), 2.21-2.14 (m, 4 H); 13C NMR (75 MHz,
CDCl3) δ 201.8, 159.6, 139.0, 131.6, 130.5, 129.5, 127.6, 125.5,
124.8, 123.0, 121.8, 117.1, 114.2, 90.5, 85.8, 71.0, 66.9, 57.5,
40.7, 22.1; IR (KBr) 2210, 1718 cm-1; FABMS (2-nitrophenyl
octyl ether) m/z 996 (M+, 100); ESI-HRMS m/z calcd for C68H52
NaO8 (M + Na+) 1019.3560, found 1019.3560.
-
1
tion. H NMR (300 MHz, CDCl3) δ 6.90 (s, 1 H), 6.84 (s, 2 H),
7-Be n zyl-1,4,10,13-t e t r a oxa -7,16-d ia za cyclooct a d e -
ca n e.36 NaH (60% oil dispersion; 26 mg, 0.64 mmol) was
washed thoroughly with hexane and suspended in THF (2 mL).
At 0 °C a THF (9 mL) solution of 1,4,10,13-tetraoxa-7,16-
diazacyclooctadecane (500 mg, 1.91 mmol) was added to the
suspension dropwise, and the mixture was stirred for 30 min.
To the resulting mixture was added benzyl bromide (120 mg,
0.70 mmol), and the reaction mixture was further stirred for
24 h, being allowed to reach room temperature. The concen-
trated residue was subjected to reverse-phase HPLC (ODS
4.57 (s, 4 H), 4.44 (t, J ) 5.2 Hz, 1 H), 4.19 (t, J ) 3.9 Hz, 4
H), 3.98 (t, J ) 5.7 Hz, 2 H), 3.34 (s, 6 H), 1.83-1.77 (m, 4 H),
1.66-1.59 (m, 12 H), 1.39-1.19 (m, 12 H), 1.12-0.99 (m, 12
H), 0.96-0.84 (m, 18 H); 13C NMR (75 MHz, CDCl3) δ 159.3,
139.4, 119.9, 113.5, 104.4, 90.3, 71.2, 68.2, 67.7, 58.5, 53.0, 29.2,
27.4, 27.3, 24.8, 14.0, 11.4; IR (neat) 2954, 2924, 2853, 2148
cm-1; ESI-HRMS m/z calcd for C44H78NaO5118Sn120Sn (M +
Na+) 947.3785, found 947.3768.
1-(4,4-Dim et h oxyb u t yloxy)-3,5-b is[3-(6-iod op yr en -1-
yl)-2-p r op yn yloxym eth yl]ben zen e (16). A morpholine (120
(33) Connors, K. A. Binding Constants; J ohn Wiley & Sons: New
York, 1987.
(35) This compound was prepared by a modification of the published
procedure. See: Suzuki, H.; Kondo, A.; Inouye, M.; Ogawa, T. Synthesis
1986, 121-122.
(36) Ihara, M.; Takahashi, T.; Shimizu, N.; Ishida, Y.; Sudow, I.;
Fukumoto, K.; Kametani, T. J . Chem. Soc., Perkin Trans. 1 1989, 529-
535. Niwa, H.; Hasegawa, T.; Ban, N.; Yamada, K. Tetrahedron 1987,
43, 825-834.
(34) Quici, S.; Manfredi, A.; Pozzi, G.; Cavazzini, M.; Rozzoni, A.
Tetrahedron 1999, 55, 10487-10496. Solov’ev, V. P.; Strakhova, N.
N.; Kazachenko, V. P.; Solotnov, A. F.; Baulin, V. E.; Raevsky, O. A.;
Ru¨diger, V.; Eblinger, F.; Schneider, H.-J . Eur. J . Org. Chem. 1998,
1379-1389.
J . Org. Chem, Vol. 69, No. 2, 2004 503

Abe et al.
column (Shinwa Chemical Industries, Ltd.); MeOH) to give
7-benzyl-1,4,10,13-tetraoxa-7,16-diazacyclooctadecane as a light
yellow oil (121 mg, 49%).
3.11 (s, 6 H), 3.00 (s, 6 H), 1.95-1.89 (m, 8 H); IR (KBr) 3477,
2870, 1262, 1160, 1031 cm-1; ESI-HRMS m/z calcd for
C
112H128F6N4O20S2 ((M - 2TfO-)2+) 1013.4234, found 1013.4210.
Dia za cr ow n P yr en op h a n e 20a . Red u ctive Am in a tion .
To a CH2Cl2 (2 mL) solution of 18 (11 mg, 0.011 mmol) were
successively added 7-benzyl-1,4,10,13-tetraoxa-7,16-diazacy-
clooctadecane (49 mg, 0.14 mmol), 1 N HCl in Et2O (0.044 mL,
0.044 mmol), finely ground molecular sieves 4A (5 mg), and
n-Bu4NBH3CN (6.2 mg, 0.022 mmol). The mixture was stirred
at room temperature for 30 h and filtered. To the filtrate was
added additional CH2Cl2, and the combined CH2Cl2 layer was
washed with water, concentrated, and subjected to column
chromatography (silica gel; CH2Cl2:MeOH:Et3N 50:1:1) to give
19e (5 mg, 27%). Mp 71-73 °C; 1H NMR (300 MHz, CDCl3) δ
8.21 (d, J ) 9.0 Hz, 4 H), 7.78 (d, J ) 7.7 Hz, 4 H), 7.59 (d, J
) 9.0 Hz, 4 H), 7.51 (d, J ) 7.7 Hz, 4 H), 7.44 (s, 2 H), 7.34-
7.23 (m, 10 H), 7.04 (s, 4 H), 4.94 (s, 8 H), 4.63 (s, 8 H), 4.07
(t, J ) 6.0 Hz, 4 H), 3.68-3.61 (m, 32 H), 3.49 (s, 4 H), 2.83-
2.81 (m, 16 H), 2.61 (t, J ) 7.1 Hz, 4 H), 1.84-1.68 (m, 8 H);
13C NMR (75 MHz, CDCl3) δ 160.0, 139.5, 138.9, 131.6, 130.5,
129.5, 128.9, 128.2, 127.6, 126.9, 125.5, 124.8, 123.0, 121.6,
117.1, 114.3, 90.5, 85.8, 76.8, 71.0, 70.7, 70.0, 68.0, 59.9, 57.4,
55.6, 54.0, 53.8, 27.2, 23.5; IR (KBr) 3434, 2924, 2863, 1097
cm-1; ESI-HRMS m/z calcd for C106H117N4O14 (M + H+)
1669.8566, found 1669.8571.
Dia zon ia cr ow n P yr en op h a n e 2a . Qu a r ter n a r iza tion
to Am m on iu m Sa lt. To a CH2Cl2 (1 mL) solution of 20a (5
mg, 0.003 mmol) was added MeOTf (10 mg, 0.06 mmol)
dropwise at 0 °C. The resulting precipitate was filtered and
washed sequentially with hexane and ether to afford 1e (7 mg,
99%) as a solid. Mp >230 °C dec; 1H NMR (300 MHz, CD3OD)
δ 7.93 (d, J ) 8.5 Hz, 4 H), 7.70 (d, J ) 7.7 Hz, 4 H), 7.55-
7.46 (m, 20 H), 7.11 (s, 4 H), 4.95 (s, 8 H), 4.66 (s, 8 H), 4.59
(d, J ) 6.8 Hz, 4 H), 4.17-4.15 (m, 4 H), 4.09-3.44 (m, 52 H),
P oly(oxyeth ylen e) P yr en op h a n e 3. Tr a n sa ceta liza -
tion . To octa(ethylene glycol)25 (200 mg, 0.53 mmol) were
successively added 17 (14 mg, 0.013 mmol) and 10-camphor-
sulfonic acid (21 mg, 0.093 mmol), and the mixture was stirred
at 80 °C under reduced pressure for 20 min. After the mixture
had cooled to room temperature, finely ground K2CO3 was
added. The resulting mixture was stirred for an additional 10
min and filtered. The filtrate was concentrated and subjected
to column chromatography (silica gel; CH2Cl2:MeOH:Et3N 50:
1:1), followed by reverse-phase HPLC (ODS column (Shinwa
Chemical Industries, Ltd.); MeOH:Et3N 100:0.3) to give 3 as
a yellowish viscous oil (7.1 mg, 22%). 1H NMR (300 MHz,
CDCl3) δ 8.20 (d, J ) 9.0 Hz, 4 H), 7.78 (d, J ) 8.1 Hz, 4 H),
7.59 (d, J ) 9.0 Hz, 4 H), 7.50 (d, J ) 8.1 Hz, 4 H), 7.44 (s, 2
H), 7.02 (s, 4 H), 4.93 (s, 8 H), 4.70 (t, J ) 5.6 Hz, 4 H), 4.62
(s, 8 H), 4.07 (t, J ) 6.0 Hz, 4 H), 3.80-3.76 (m, 4 H), 3.75-
3.69 (m, 12 H), 3.68-3.59 (m, 112 H), 2.98 (br, 4 H), 1.95-
1.84 (m, 8 H); 13C NMR (75 MHz, CDCl3) δ 160.1, 139.0, 131.8,
130.6, 129.7, 127.8, 125.7, 125.0, 123.2, 121.8, 117.3, 114.5,
90.7, 86.0, 72.8, 71.1, 70.8, 70.74, 70.73, 70.70, 70.67, 70.4, 67.9,
64.7, 61.9, 57.6, 30.0, 24.8; IR (KBr) 3380, 2218 cm-1; ESI-
HRMS m/z calcd for C132H184NaO42 (M + Na+) 2464.2160,
found 2464.2099.
Su p p or tin g In for m a tion Ava ila ble: Preparation of 1b-
1
e, 5-13, 19b, 19d , 19e, 20b, 21, and 23, and H NMR spectra
of 1d , 1e, 2a , 3, 5-18, 19b, 19d , 19e, 20a , and 20b. This
material is available free of charge via the Internet at
http://pubs.acs.org.
J O035188U
504 J . Org. Chem., Vol. 69, No. 2, 2004