Novel chiral fluorescent macrocyclic receptors: synthesis and recognition for amino acid anions

Article abstract of DOI:10.1016/j.tetasy.2006.07.037

New chiral fluorescence macrocycles 1 and 2 containing naphthalene and amino acid units were synthesized. The binding properties for amino acid anions were examined by the fluorescence and ¹H NMR spectra. The results indicated good enantioselec

Full text of DOI:10.1016/j.tetasy.2006.07.037

Tetrahedron: Asymmetry 17 (2006) 2143–2148
Novel chiral fluorescent macrocyclic receptors: synthesis
and recognition for amino acid anions
Haijuan Qin, Yongbing He,* Guangyan Qing, Chenguang Hu and Xi Yang
Department of Chemistry, Wuhan University, Wuhan, Hubei 430072, China
Received 29 June 2006; accepted 25 July 2006
Abstract—New chiral fluorescence macrocycles 1 and 2 containing naphthalene and amino acid units were synthesized. The binding
properties for amino acid anions were examined by the fluorescence and 1H NMR spectra. The results indicated good enantioselectivity
of 1 toward the N-protected phenylalanine anions.
ꢀ 2006 Elsevier Ltd. All rights reserved.
1. Introduction
ognition of chiral fluorescent macrocyclic receptors have
seldom been reported. Herein, we report the synthesis
and chiral recognition of new chiral fluorescent macro-
cyclic receptors 1 and 2 containing both an amino acid unit
and a fluorophore of naphthalene.
Chirality is a fundamental property of most biological
molecules, and chiral recognition has been widely studied
because it is one of the most significant processes in living
systems.1 The development of fluorescent chiral artificial
receptors with the properties of chiral recognition and opti-
cal change, has attracted increasing attention because of
their high sensitivity and potential applications in pharma-
ceuticals, analysis, biology, and catalysts.2 The chemical
and more important biological activities of many chiral
substances depend much on the stereochemistry. That is
why the design, synthesis, and structural activity relation-
ships of enantioselective receptors are still vital areas of
research.3 Much attention has been paid recently to the
development of the synthesis of molecular receptors with
the ability to recognize chiral molecules. Fluorescent sen-
sors are preferred because they are well suited to meet
the need for in vivo probes, such as mapping the spatial
and temporal distribution of the biological analyses.4
2. Results and discussion
2.1. Synthesis
The synthesis of chiral fluorescent receptors 1 and 2 is out-
lined in Scheme 1. Compounds 5a and 5b were synthesized
by a literature procedure.7
Intermediates 3, 4, 6a, and 6b were all obtained in high
yield. Compounds 6a and 6b were treated with diacid chlo-
ride 4 to afford target molecules 1 and 2, which were solu-
ble in common organic solvents such as CHCl3,
CH3CH2OH, DMSO, and DMF. These compounds were
characterized by IR, MS, 1H NMR, 13C NMR, and
elemental analysis.
Amino acids are often used as a chiral source in building
the desired chiral artificial receptors because of their acces-
sibility and biological relevance.5 Macrocyclic structures
have received much attention in the search for artificial
receptors, mainly because of their higher degree of preorga-
nization as compared to their acyclic counterparts. A great
number of artificial chiral receptors have been synthesized
and widely studied.6 However, the synthesis and chiral rec-
2.2. Fluorescence spectra
The chiral recognition properties of receptors 1 and 2 were
investigated for Boc-amino acid anions (D- and L-Phe
anions, D- and L-Ala anions). The fluorescence spectra
was recorded from a solution of receptors 1 and 2
(5 · 10ꢀ5 mol/L) in DMSO in the absence or presence of
Boc-amino acid anions, in each case the counter cations
were tetrabutylammonium.
*
Corresponding author. Fax: +86 27 68754076; e-mail: ybhe@
whu.edu.cn
0957-4166/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2006.07.037

2144
H. Qin et al. / Tetrahedron: Asymmetry 17 (2006) 2143–2148
COCl
EtOH, H2O, NaOH
COCl
O
O
O
O
O
O
reflux
CHCl3, 6 h
O
O
O
O
O
O
O
O
OH
OH
Cl
Cl
Et
Et
4
3
H
NH2
COOH
1) 2 N NaOH, EtOH
2) conc. HCl
SOCl2, MeOH
Cl
O
Cl
+
n
HS
5a: n = 1
5b: n = 2
7
O
O
H2N
H
S
H
S
NH2
COOMe
O
O
4
MeOOC
HN
MeOOC
H
S
H
S
NH
COOMe
O
CHCl3, TEA
n
O
6a: n = 1
6b: n = 2
n
1: n = 1
2: n = 2
Scheme 1. The synthesis of receptors 1 and 2.
500
400
300
200
100
0
Figures 1 and 2 show the fluorescence emission spectra of 1
with different concentrations of D- or L-Phe anions in
DMSO. When gradually increasing the concentration of
the anions, the fluorescence emission intensities of 1
(5 · 10ꢀ5 mol/L) at 343 nm (kex = 301 nm) decreased. The
quenching efficiency was 83% with 20 equiv of D-Phe anion
while it was 34% with 20 equiv of L-Phe anion. The differ-
ent quenching efficiencies (DID/DIL ꢁ 2.5) indicated that
receptor 1 has a good enantioselective recognition ability
between D- and L-Phe anions. Upon addition of 20 equiv
of D- or L-Ala anions to a solution of 1, the enantioselective
fluorescence response was 1.3 (DID/DIL).
500
400
300
200
100
0
0
100
200
300
400
[L-Phe anion]/[receptor 1]
500
500
325
350
375
400
425
450
400
Wavelength/nm
400
Figure 2. Fluorescence spectra of 1 (5 · 10ꢀ5 mol/L, DMSO) upon the
addition of various amounts of L-Phe anion in DMSO, kex = 301 nm,
equivalent of Bu4N+ (N-protected phenylalanine): 0 ! 325. The non-
linear fitting curve of change in the fluorescence intensity at 343 nm with
respect to the amount of Bu4N+ (N-protected phenylalanine) is shown in
the inset.
300
200
300
100
0
200
0
10 20 30 40 50
[D-Phe anion]/[receptor 1]
When the enantiomers of Phe or Ala anions were added
into a solution of 2 in DMSO, respectively, the fluorescence
changes were similar. More anions were needed when the
fluorescence of 2 was nearly completely quenched (Figs. 3
and 4), and the changes of quenching efficiencies were
smaller, which indicated that the recognition ability for an-
ions of 2 was weaker compared with receptor 1.
100
0
325
350
375
400
425
450
Wavelength/nm
Figure 1. Fluorescence spectra of 1 (5 · 10ꢀ5 mol/L, DMSO) upon the
addition of various amounts of D-Phe anion in DMSO, kex = 301 nm,
equivalent of Bu4N+ (N-protected phenylalanine): 0 ! 46. The non-linear
fitting curve of change in the fluorescence intensity at 343 nm with respect
to the amount of Bu4N+ (N-protected phenylalanine) is shown in the inset.
In the presence of amino acid anions, the fluorescence
quenching of receptors 1 and 2 most likely arose from
the change of the free energy (DGPET) of electron transfer
between the excited fluorophore and the receptor.8 When

H. Qin et al. / Tetrahedron: Asymmetry 17 (2006) 2143–2148
2145
400
300
200
100
0
400
300
200
100
0
100
80
D-Phe anion
L-Phe anion
60
I
I
40
0
40
80
120
[D-Phe anion]/[receptor 2]
20
0
0.0
0.2
0.4
0.6
0.8
1.0
325
350
375
400
425
450
[H]/([G]+[H])
Wavelength/nm
Figure 3. Fluorescence spectra of 2 (5 · 10ꢀ5 mol/L, DMSO) upon the
addition of various amounts of D-Phe anions in DMSO, kex = 299 nm,
equivalent of Bu4N+ (N-protected phenylalanine): 0 ! 109. The non-
linear fitting curve of change in fluorescence intensity at 342 nm with
respect to the amount of Bu4N+ (N-protected phenylalanine) is shown in
the inset.
Figure 5. Job plots of 1 with D- and L-Phe anions (at 343 nm). The total
concentration of the host and guest is 1.0 · 10ꢀ4 mol/L in DMSO. I0:
fluorescence intensity of 1; I: fluorescence intensity of 1 in the presence of
the guest.
D- and L-Phe anions (at 343 nm). When the molar fraction
of the host was 0.50, the fluorescence intensity reached a
maximum, which demonstrated that receptors 1 formed a
1:1 complex with D- and L-Phe anions, respectively.10
400
400
Assuming the complex stoichiometry was 1:1, the associa-
tion constant (Kass) can be calculated by the following
equation:11
300
300
200
100
X ¼ X0 þ ðXlim ꢀ X0Þ=2c0fcH þ cG þ 1=Kass
2
1=2
200
ꢀ ½ðcH þ cG þ 1=KassÞ ꢀ 4cHcGꢂ
g
ð1Þ
0
0
100
200
300
400
where X represents the fluorescence intensity, cH and cG
represent the corresponding concentration of host and
guest. The non-linear curve fitting results of the fluores-
cence intensity (at 342 nm) of the interaction between 1
or 2 and D-, L-amino acid anions are shown in Table 1.
The correlation coefficients of the non-linear curve fitting
were all larger (>0.99), which indicated that the 1:1 com-
plex between 1 or 2 and the amino acid anions has been
formed.11,12 The data in Table 1 illustrate that the two
receptors exhibited good enantioselective recognition for
D- or L-Phe anions. The association constants (Kass) of 1
and 2 with D-Phe were much higher than those of 1 and
2 with L-Phe anion, which is probably due to the more
complementary structure of the D-Phe anion with receptors
[L-Phe anion]/[receptor 2]
100
0
325
350
375
400
425
450
Wavelength/nm
Figure 4. Fluorescence spectra of 2 (5 · 10ꢀ5 mol/L, DMSO) upon the
addition of various amounts of L-Phe anions in DMSO, kex = 299 nm,
equivalent of Bu4N+ (N-protected phenylalanine): 0 ! 408. The non-
linear fitting curve of change in the fluorescence intensity at 342 nm with
respect to the amount of Bu4N+ (N-protected phenylalanine) is shown in
the inset.
1 and 2. Receptor 1 gave the enantioselectivity Kass(
/
D
-Phe)
the amino acid anion interacted with either receptor 1 or 2,
the reductive potential of the amide group increased along
with the ratio of the electron transfer from the HOMO
orbital of receptors to the excited naphthalene group,
which in turn led to a more easy intramolecular PET
(photo-induced electron transfer) process.9
Kass( -Phe) = 4.94. However, the small association constant
L
Table 1. Association constants (Kass) and correlation coefficients (R) of 1
and 2 with amino acid anions in DMSO
Aniona
1
2
Kass
R
Kass
R
The continuous variation methods were employed to deter-
mine the stoichiometric ratio of the receptor 1 with guests
(D- and L-Phe anions). The total concentration of host and
guest was constant (1.0 · 10ꢀ4 mol/L) in DMSO, with a
continuously variable molar fraction of host ([H]/
([H]+[G])). Figure 5 shows the Job plots of receptor 1 with
D-Phe
L-Phe
D-Ala
D-Ala
(2.55 0.17b) · 103 0.9948 (0.39 0.02b) · 103 0.9966
(0.52 0.02b) · 103 0.9956 (0.28 0.01b) · 103 0.9948
47.07 3.07
16.23 1.19
0.9930 48.09 2.98
0.9924 40.21 3.14
0.9949
0.9977
a Anions were used as their tetrabutylammonium salts.
b All error values were obtained by the results of non-linear curve fitting.

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H. Qin et al. / Tetrahedron: Asymmetry 17 (2006) 2143–2148
and lower enantioselectivity of the receptors 1 and 2 to the
enantiomers of the Ala anions were discovered, which indi-
cated that the cyclic space of the receptors did not match
with the structure of the Ala anion. Since the bridge chain
in receptor 1 is shorter than that of receptor 2, a larger
rigidity and a good preorganization property in the cycle
of receptor 1 may result in the good enantioselective recog-
nition of receptor 1 for the enantiomers of the Phe anion.
anion because it can provide structural and dynamic infor-
mation.13 The study was carried out on a 300 MHz NMR
spectrometer in DMSO at room temperature using recep-
tor 1 as a chiral solvating agent.
1
The H NMR spectra of receptor 1 (4 · 10ꢀ2 mol/L) and
its complex with equimolar amounts of racemic, D- or L-
Phe anions (4 · 10ꢀ2 mol/L) in DMSO-d6 are shown in
Figure 6. Figure 6A shows the 1H NMR spectra of racemic
Phe anions, only one broad singlet (d 3.98 ppm) is present
for the CH proton resonance of racemic Phe anions. When
treated with equimolar amounts of receptor 1, the CH
proton signal was cleaved into two singlets (d 3.99 and
1
2.3. H NMR study
1H NMR experiments were undertaken to assess the chiral
recognition properties between receptor 1 and the Phe
Figure 6. 1H NMR spectra of 1 and its guest complex at 25 ꢁC ([1] = [guest] = 4.0 · 10ꢀ2 mol/L) in DMSO-d6 at 300 MHz: (A) racemic Phe anions; (B)
receptor 1; (C) receptor 1 + racemic Phe anions; (D) receptor 1 + D-Phe anions; (E) receptor 1 + L-Phe anions.

H. Qin et al. / Tetrahedron: Asymmetry 17 (2006) 2143–2148
2147
3.95 ppm) (Fig. 6C), and the separation between the two
peaks was 12 Hz. The interaction of 1 with the D-Phe anion
showed that the CH proton signal shifted upfield (Fig. 6D),
but shifted downfield when interacted with the L-Phe anion
(Fig. 6E), which indicated that the interactions of 1 with
D- and L-Phe anion were different. The different shift of
the CH proton of D- and L-enantiomers revealed the good
enantioselective recognition ability of receptor 1. At the
same time, the peak of the amide (NH) at 8.58 ppm was
shifted downfield to 8.64 ppm, and the proton signals of
naphthalene ring were cleaved and moved upfield. This
indicated that the interaction between the host and guest
was also through multiple hydrogen bonding and p–p
stacking of aromatic ring interactions.14
washed with cold water to give compound 3: 2.70 g, yield:
1
97.8%. Mp: 223–225 ꢁC. H NMR (DMSO-d6): d (ppm):
7.72 (d, J = 8.7 Hz, 2H, naph 4, 5-H), 7.12 (s, 2H, naph
1, 8-H), 6.98 (d, J = 8.7 Hz, 2H, naph 3, 6-H), 4.75 (s,
4H, OCH2).
4.2.2. Synthesis of compound 4. Diacid
3 (0.55 g,
2.0 mmol) was suspended in dry CHCl3 (10 mL) under an
ice-bath, and DMF (two drops) was added. A solution of
oxalyl chloride (2 mL, 23.3 mmol) in dry CHCl3 (10 mL)
was added dropwise and then stirred at room temperature
for 6 h. The volatile materials were removed under reduced
pressure and the residue dried under high vacuum for 3 h.
Diacid chloride 4 was used without further purification.
4.2.3. General procedure for preparing 6. A solution of
compound 5 (16.5 mmol) in C2H5OH (10 mL) was added
3. Conclusion
dropwise into the mixture of L-cysteine
7 (4.0 g,
Two chiral fluorescence receptors 1 and 2 containing
amides and L-cysteine were synthesized. The enantioselec-
tive recognition of these receptors was studied by fluores-
33.0 mmol), 2 M NaOH solution (25 mL), and C2H5OH
(20 mL) under ice-bath. After addition, the mixture was
stirred at room temperature for 24 h, then adjusted to
pH = 9 with concd HCl, the precipitated white solid was
isolated and washed with anhydrous ether, then dried
under vacuum. The solid obtained was used without further
purification. SOCl2 (9.5 mL) was slowly added into the
solution of the above solid (2.0 g) in dry CH3OH (40 mL)
under an ice-bath, after addition, the mixture was stirred
for 24 h at room temperature. The solvent was removed
under reduced pressure, the residue was dissolved in water
(30 mL), adjusted to pH = 9 with 2 M NaOH solution, and
extracted by CHCl3 (15 mL · 3). The combined extracts
were dried over anhydrous Na2SO4. The final product 6
was afforded after being purified by column chromato-
graphy on silica gel (eluent: CHCl3/CH3OH 20:1).
1
cence spectra and H NMR spectra, the result indicated
that receptors 1 and 2 can form a 1:1 complex between host
and guest. The enantioselective recognition ability of recep-
tor 1 toward the Phe anions was better in comparison to 2.
The complementary structure and p–p stacking of the aro-
matic rings between host and guest, the relative rigidity and
the good preorganization property of the host, and the
cooperative effect of multiple hydrogen bondings in the
complexation may result in the good enantioselective rec-
ognition of receptor 1 for the enantiomers of the Phe anion.
4. Experimental
1
4.1. Materials and methods
4.2.3.1. Compound 6a. Yield: 54%; H NMR (CDCl3):
d (ppm): 3.74 (dd, J = 4.8, 4.2 Hz, 2H, CHN), 3.68 (s, 6H,
OCH3), 3.59–3.63 (m, 2H, OCH2CH2S), 3.55–3.59 (m, 2H,
OCH2CH2S), 3.05 (dd, J = 4.8, 14.5 Hz, 2H, SCH2CH),
2.88 (dd, J = 4.2, 14.5 Hz, 2H, SCH2CH), 2.68–2.72 (m,
4H, 2SCH2CH2O), 1.78 (s, 4H, 2NH2). Elemental analysis
calcd (%) for C12H24N2O5S2: C, 42.33; H, 7.12; N, 8.23.
Found: C, 42.32; H, 7.41; N, 7.91.
CHCl3 and Et3N were dried and distilled from CaH2. All
other commercially available reagents were used without
further purification. 2,7-Bis(ethoxycarbonyl methoxy)-
naphthalene and compounds 5a and 5b were synthesized
by a literature procedure.7,14b Melting points were deter-
mined with a Reichert 7905 melting-point apparatus and
are uncorrected. Optical rotations were taken on a
Perkin–Elmer Model 341 polarimeter. IR spectra were
1
4.2.3.2. Compound 6b. Yield: 61%; H NMR (CDCl3):
1
obtained on a Nicolet 670 FT-IR spectrophotometer. H
d (ppm): 3.71 (dd, J = 4.5, 4.8 Hz, 2H, CHN), 3.65 (s, 6H,
OCH3), 3.61–3.65 (m, 4H, OCH2CH2O), 3.52–3.56 (m, 2H,
OCH2CH2S), 3.48–3.52 (m, 2H, OCH2CH2S), 3.02 (dd,
J = 4.5, 14.7 Hz, 2H, SCH2CH), 2.79 (dd, J = 4.8,
14.7 Hz, 2H, SCH2CH), 2.62–2.66 (m, 4H, 2SCH2CH2O),
1.75 (s, 4H, 2NH2). Elemental analysis calcd (%) for
C14H28N2O6S2: C, 43.72; H, 7.35; N, 7.29. Found: C,
43.70; H, 7.51; N, 7.12.
NMR and 13C NMR spectra were performed on a Varian
Mercury VX 300 MHz spectrometer in CDCl3 and DMSO-
d6. Mass spectra were recorded on a Finnigan LCQ advan-
tage mass spectrometer. Elemental analysis was determined
with a FlashEA 1112 instrument. Fluorescence spectra
were obtained on a Schimadzu RF-5301 spectrometer.
4.2. Syntheses
4.2.4. Synthesis of compounds 1 and 2. Under an argon
atmosphere and ice-bath, a solution of compound 6
(2.3 mmol) in dry CHCl3 (110 mL) and diacid chloride 4
(2.3 mmol) in dry CHCl3 (110 mL) were simultaneously
added dropwise (about 3 h) into a vigorously stirring solu-
tion of CHCl3 (100 mL) and triethylamine (5.0 mmol).
After addition, the mixture was stirred at room tempera-
ture for a further 12 h, and then washed with cold 2 M
4.2.1. Synthesis of compound 3. 2,7-Bis(ethoxycarbonyl-
methoxy)naphthalene (3.32 g, 10.0 mmol) was dissolved
in a mixture of 10% NaOH (100 mL) and CH3CH2OH
(100 mL) solution and heated at reflux for 24 h. The sol-
vents were removed and followed by the addition of water
(30 mL). A white precipitate was afforded after being acid-
ified with HCl. The precipitate was filtered and then

2148
H. Qin et al. / Tetrahedron: Asymmetry 17 (2006) 2143–2148
H2SO4, saturated sodium bicarbonate solution, and water,
and the organic layer was dried over anhydrous Na2SO4.
The crude product was purified by column chromatogra-
phy on silica gel (eluent: CHCl3/CH3CH2OH 100:1) to give
the pure products 1 and 2 as a white powder, respectively.
Acknowledgments
We thank the National Natural Science Foundation for
financial support (Grant No. 20572080).
References
4.2.4.1. Compound 1. Yield: 46.5%; mp: 180–181 ꢁC;
20
½aꢂD ¼ þ43:0 (c 0.05, CHCl3); IR (KBr): m 3420, 3323,
1. (a) Beer, P. D.; Smith, D. K. Prog. Inorg. Chem. 1997, 46, 1–
96; (b) Beer, P. D.; Gale, P. A. Angew. Chem., Int. Ed. 2001,
40, 486–516; (c) Lee, D. H.; Lee, H. Y.; Hong, J. I.
Tetrahedron Lett. 2002, 43, 7273–7276; (d) Martinez, M. R.;
Sancenon, F. Chem. Rev. 2003, 103, 4419–4476; (e) Schmidt-
chen, F. P. Top. Curr. Chem. 2005, 255, 1–29.
2. (a) Stoddart, J. F. Angew. Chem., Int. Ed. 1996, 35, 1154–
1198; (b) McCoy, C. P.; Rademacher, J. T.; Rice, T. E. Chem.
Rev. 1997, 97, 1515–1566; (c) Martiner-Manez, R.; Sancenon,
F. Chem. Rev. 2003, 103, 4419–4476; (d) Pu, L. Chem. Rev.
2004, 104, 1687–1716.
3. (a) Tye, H.; Eldred, C.; Wills, M. J. Chem. Soc., Perkin Trans.
1 1998, 457–465; (b) Chin, J.; Lee, S. S.; Lee, K. J.; Park, S.;
Kim, D. H. Nature 1999, 401, 254–257; (c) Schmuck, C.
Chem. Eur. J. 2000, 6, 709–718; (d) Kyne, G. M.; Light, M.
E.; Hursthouse, M. B.; Mendoza, J.; Kilburn, J. D. J. Chem.
Soc., Perkin Trans. 1 2001, 1258–1263; (e) Kim, H. J.; Asif,
R.; Chung, D. S.; Hong, J. I. Tetrahedron Lett. 2003, 44,
4335–4338; (f) Khatri, V. K.; Upreti, S.; Pandey, P. S. Org.
Lett. 2006, 8, 1755–1758.
2923, 1741, 1667, 1633, 1541, 1514, 1436, 1256, 1210,
1053, 827, 470. 1H NMR (CDCl3, 300 MHz): d (ppm):
7.62 (d, J = 7.8 Hz, 2H, naph 4, 5-H), 7.40 (s, 2H, NH),
6.91–7.00 (m, 4H, naph 1, 3, 6, 8-H), 4.82–4.84 (m, 2H,
CHNH), 4.55 (s, 4H, COCH2), 3.68 (s, 6H, CH3), 3.45–
3.47 (m, 4H, OCH2CH2), 2.97–3.01 (m, 4H, SCH2CH2),
2.57–2.60 (m, 4H, SCH2CH); 13C NMR (CDCl3,
75 MHz): d (ppm): 171.5, 168.7, 157.0, 135.8, 129.8,
125.1, 117.0, 107.5, 70.3, 67.5, 52.7, 33.6, 31.9. ESI-MS
m/z (%): 581 (M++1, 100); Elemental analysis calcd (%)
for C26H32N2O9S2: C, 53.79; H, 5.52; N, 4.82. Found: C,
53.58; H, 5.61; N, 4.78.
4.2.4.2. Compound 2. Yield: 26.5%; mp: 160–161 ꢁC;
20
½aꢂD ¼ þ57:4 (c 0.05, CHCl3); IR (KBr): m 3422, 3263,
3084, 2921, 1738, 1681, 1669, 1554, 1516, 1385, 1257,
1
1209, 1174, 1105, 856, 831, 555, 471; H NMR (CDCl3,
300 MHz): d (ppm): 7.72 (d, J = 8.7 Hz, 2H, naph-4,
5H), 7.38–7.40 (d, 2H, CONH), 7.10–7.21 (m, 4H, naph
1, 3, 6, 8-H), 4.86–4.88 (m, 2H, CHNH), 4.71 (s, 4H,
COCH2), 3.77 (s, 6H, CH3), 3.26–3.36 (m, 8H,
OCH2CH2S, OCH2CH2O), 3.01–3.06 (m, 4H, SCH2CH2),
2.44–2.48 (m, 4H, SCH2CH); 13C NMR (CDCl3,
75 MHz): d (ppm): 170.9, 168.9, 156.5, 135.7, 129.8,
116.5, 108.4, 71.2, 70.0, 68.2, 53.0, 52.5, 34.1, 32.0. ESI-
MS m/z (%): 625 (M++1, 100); Elemental analysis calcd
(%) for C28H36N2O10S2: C, 53.85; H, 5.77; N, 4.49; O,
25.64; S, 10.26. Found: C, 53.96; H, 5.63; N, 4.62; O,
25.54; S, 10.34.
4. (a) Silva, A. P.; Gunaratne, H. Q. N.; Gunnlaugsson, T.;
Huxley, A. J. M.; McCoy, C. P.; Rademacher, J. T.; Rice, T.
´
E. Chem. Rev. 1997, 97, 1515–1566; (b) Martınez, R.;
´
Sancenon, F. Chem. Rev. 2003, 103, 4419–4476.
5. (a) Bhattacharyya, T.; Nilsson, U. J. Tetrahedron Lett. 2001,
42, 2873–2875; (b) Narumi, F.; Hattori, T.; Matsumura, N.;
Onodera, T.; Katagiri, H.; Kabuto, C.; Kameyama, H.;
Miyano, S. Tetrahedron 2004, 60, 7827–7833; (c) Xu, K. X.;
Wu, X. J.; He, Y. B.; Liu, S. Y.; Qing, G. Y.; Meng, L. Z.
Tetrahedron: Asymmetry 2005, 16, 833–839.
6. (a) Pu, L. J. Photochem. Photobiol. A: Chem. 2003, 155, 47–
´
55; (b) Baudequin, C.; Bregeon, D.; Levillain, J.; Guillen, F.;
Plaqueventb, J. C.; Gaumont, A. C. Tetrahedron: Asymmetry
2005, 16, 3921–3945; (c) Luo, J.; Zheng, Q. Y.; Chen, C. F.;
Huang, Z. T. Tetrahedron 2005, 6, 8517–8528.
4.3. Tetrabutylammonium salts
7. Pederson, C. J. J. Am. Chem. Soc. 1967, 89, 7017–7035.
8. (a) Amendola, V.; Fabbrizzi, L.; Mangano, C.; Pallavicini, P.
Acc. Chem. Res. 2001, 34, 488–493; (b) Gunnlaugsson, T.;
Davis, A. P.; O’Brien, J. E.; Glynn, M. Org. Lett. 2002, 4,
2449–2452.
9. (a) Martinez, R.; Sancenon, F. Chem. Rev. 2003, 103, 4419–
4476; (b) Gunnlaugsson, T.; Davis, A. P.; Hussey, G. M.;
Tierney, J.; Glynn, M. Org. Biomol. Chem. 2004, 2, 1856–
1863; (c) Kang, J.; Kima, H. S.; Jang, D. O. Tetrahedron Lett.
2005, 46, 6079–6082; (d) Liu, S. Y.; Fang, L.; He, Y. B.;
Chan, W. H.; Yeung, K. T.; Cheng, Y. K.; Yang, R. H. Org.
Lett. 2005, 7, 5825–5828.
All tetrabutylammonium salts were prepared by adding
1 equiv of tetrabutylammonium hydroxide in methanol to
a solution of the corresponding N-protected (by Boc) ami-
no acid derivatives (1 equiv) in methanol. The mixture was
stirred at room temperature for 4 h and evaporated to dry-
ness under reduced pressure. The resulting syrup was dried
at high vacuum for 24 h, checked by NMR and stored in a
desiccator.
4.4. Binding studies
10. Fang, L.; Chan, W. H.; He, Y. B.; Kwong, D. W. J.; Lee, A.
W. M. J. Org. Chem. 2005, 70, 7640–7646.
11. Valeur, B.; Pouget, J.; Bourson, J. J. Phys. Chem. 1992, 96,
6545–6549.
12. Collins, E. M.; Mckervey, M. A.; Madigan, E.; Moran, M.
B.; Mowens, M.; Ferguaon, G.; Harris, S. J. Chem. Soc.,
Perkin Trans. 1 1991, 2, 3137–3142.
13. Pirkle, W. H.; Pochapsky, T. C. Chem. Rev. 1989, 89, 347–
362.
14. (a) Cho, E. J.; Moon, J. W.; Ko, S. W.; Lee, J. Y.; Kim, S. K.;
Joon, Y.; Nam, K. C. J. Am. Chem. Soc. 2003, 125, 12376–
12377; (b) Wu, J. L.; He, Y. B.; Zeng, Z. Y.; Wei, L. H.;
Meng, L. Z.; Yang, T. X. Tetrahedron 2004, 60, 4309–4314.
The studies on the binding properties of 1 and 2 were
carried out in DMSO. The fluorescence titration was
performed with a series of 5 · 10ꢀ5 mol/L solutions of
receptors 1 and 2 containing different amounts of chiral an-
ions (the excited wavelength was 301 or 299 nm, the excita-
1
tion and emission slit widths were 5 nm). H NMR studies
were recorded after adding equivalent racemic Phe or Ala
anions into receptors (4 · 10ꢀ2 mol/L). Association con-
stants were calculated by means of a non-linear least-
square curve fitting method with Origin 7.0 (Origin-Lab
Corporation).