Synthesis and amines enantiomeric recognition ability of binaphthyl-appended 22-crown-6 ethers derived from rosin acid

Article abstract of DOI:10.1007/s10847-011-0040-5

Novel chiral 22-crown-6 ethers (5a-b) bearing methoxycarbonyl side groups derived from rosin acid and 2,2-dihydroxy-1,1-binaphthyl (BINOL) were prepared in optically pure forms, and their enantiodiscriminating abilities toward protonated primary amines an

Full text of DOI:10.1007/s10847-011-0040-5

J Incl Phenom Macrocycl Chem (2012) 73:177–183
DOI 10.1007/s10847-011-0040-5
ORIGINAL ARTICLE
Synthesis and amines enantiomeric recognition ability
of binaphthyl-appended 22-crown-6 ethers derived
from rosin acid
•
Hengshan Wang Chunhuan He Yingming Pan
•
•
•
Guiyang Yao Qiang Wu Honggui Deng
•
Received: 17 September 2010 / Accepted: 8 September 2011 / Published online: 3 November 2011
Ó Springer Science+Business Media B.V. 2011
Abstract Novel chiral 22-crown-6 ethers (5a–b) bearing
methoxycarbonyl side groups derived from rosin acid and
2,20-dihydroxy-1,10-binaphthyl (BINOL) were prepared in
optically pure forms, and their enantiodiscriminating abil-
ities toward protonated primary amines and amino acid
methyl ester salts were examined by the UV–vis titration
method. These receptors exhibit good chiral recognition
towards the isomers (up to KL/KD = 5.23, DDG0 =
4.10 kJ mol-1) in CHCl3:MeOH = 2:1 at 25 °C.
compounds in enantiomeric separations have been dem-
onstrated by chromatographic methods [9–17]. Despite the
well-established supramolecular system, there is still a
strong requirement for novel types of host molecules in
order to improve the enantioselectivity and performance in
the enantiomer separation.
To prepare optically active crown ethers, especially the
chiral host molecular without C2-symmetric, natural prod-
ucts such as amino acids and carbohydrates [1, 18, 19] were
often used as chiral starting material. However, the use of
terpenoids as chiral pools has received fewer acceptances
[20]. Naturally occurring enantiomeric abietic acid, the
major diterpenoid components of rosin acid, promises to be
an excellent starting material for preparing chiral reagents
for enantiomeric separations because of its absolute optical
purity and very stable stereochemistry structure. Maleo-
pimaric acid, the Diels–Alder adduct of levopimaric acid
with maleic anhydride [21], has been applied in catalytic
asymmetric reaction [22]. In our prior works, we have
reported using maleopimaric acid in the separations of D/L
amino acids by CE [23–26]. Our interest has been focused on
the developing of the chiral crown ether for the chromato-
graphic uses, by using structural feature of maleopimaric
acid. We report here an efficient and short-step synthesis of
two optically pure crown ethers containing methoxycar-
bonyl groups, using maleopimaric acid and BINOL as start
materials, and the result of enantiomeric recognition.
Keywords Rosin acid ꢀ BINOL ꢀ Chiral crown ethers ꢀ
Enantiodiscriminating abilities ꢀ UV–vis spectroscopy
Introduction
Enantiomeric recognition and separation of amine com-
pounds are among the main topics of supramolecular
chemistry since these compounds are basic building blocks
of biological molecules and a number of them are known
to possess potent biological activities [1, 2]. Among the
numerous types of host molecules studied, chiral
18-crown-6 derivatives have been recognized as the most
successful for the enantiodiscrimination of protonated
primary amines [3–8] and high effectiveness of chiral 18C6
Electronic supplementary material The online version of this
article (doi:10.1007/s10847-011-0040-5) contains supplementary
material, which is available to authorized users.
Results and discussion
H. Wang (&) ꢀ C. He ꢀ Y. Pan ꢀ G. Yao ꢀ Q. Wu ꢀ H. Deng
Key Laboratory for the Chemistry and Molecular Engineering
of Medicinal Resources, School of Chemistry & Chemical
Engineering of Guangxi Normal University, Guilin 541004,
People’s Republic of China
Synthesis
The Diels–Alder addition product of rosin acid with maleic
acid anhydride (2 in Scheme 1) contain three functional
e-mail: wang_hengshan@yahoo.com.cn
123

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J Incl Phenom Macrocycl Chem (2012) 73:177–183
Scheme 1 Reagents and
conditions: (i) no solvent,
140 °C; (ii) PCl3, then MeOH,
reflux, 4 h; (iii) NaBH4 dioxane,
reflux, 0.5 h; (vi) NaH, 1, THF,
reflux, 50 h
groups in their multiple cyclic chiral structures, and their
reduction products 4 possessing two hydroxyl groups
served as linkage part of host molecular in present crown
ether synthesis. Introduction of a 2,20-dihydroxy-1,10-
binaphthyl (BINOL) unit on these crown ethers may result
in some interesting features: (i)formation of dual chiral
architectures with rosin terpenoid structure to control the
shape and the cavity of the crown, for observing special
selectivity to different guests (ii) providing supplementary
rigid steric and chiral barriers, which may allow different
enantioselective interactions with chiral guests enantio-
mers, (iii) facilitate photophysical studies involving intra-
molecular by UV–vis spectroscopy, because of the presence
of the photoactive 1,10-binaphthyl chromophore [27].
The ditosylate 1 was prepared according to the reported
procedure [28] in 27.2% overall yield, as shown in
Scheme 2. Maleopimaric acid 2 and its methyl ester were
prepared according to the reported procedure [21, 29]. The
conversion of methyl esters 3 to diol 4 was carried out by
the reported procedure [30] in 53% yield and followed by
the ring closure with (R) or (S) ditosylate 1 in the presence
of NaH in THF under high dilution conditions [31]. The
resulted host compound bears a methoxycarbonyl group in
the side chain, which can easily be used as linkage group
covalently bound to silica gel in the preparing chiral sta-
tionary phases or membranes [15].
The structures purposed for these new chiral macrocy-
cles are consistent with the data obtained from NMR, MS
and IR spectra. Structural assignment was further con-
1
firmed by compare with the NMR data (including H, 13C,
COSY, HSQC, HMBC and ROESY) of its methoxycar-
bonyl reduction products.
UV–vis
In the UV spectroscopic titration experiments, addition of
varying concentrations of guest molecules resulted in
gradual increase or decrease of characteristic absorptions
of the host molecules, the difference in the UV–vis spectra
of its free and complexed states is sufficient for the esti-
mation of molecular recognition thermodynamics.
Under the conditions employed herein, two primary
amines and two amino acid methyl ester hydrochlorides salts
were selected as the guest molecules. Absorption increased
upon addition of the selected guests to all the hosts in CHCl3:
MeOH (2:1) at 25 °C. Under this condition, the absorption
intensity at 327 nm for NEA–HCl and 281 nm for other
guests were collected. The behavior of crown ethers (6a–b,
7a–b) and the selected guests during the titration indicated
1:1 complexation. The association constants (Ka) all the
Scheme 2 Synthesis of the ditosylate (?)–(R)– or (-)–(S)–1:
(i) K2CO3/KI, 2-(2-chloroethoxy)ethanol, DMF, 150 °C, 48 h; (ii)
Et3N, TsCl, dichloromethane, rt., 24 h
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J Incl Phenom Macrocycl Chem (2012) 73:177–183
179
supramolecular system formed were determined by titration,
and analyzed by the Rose–Drago method [32]. The results of
Ka and free-energy changes (-DG0) of these hosts with
guest molecules are summarized in Table 1.
It was shown from the data of KD/KL in Table 1, these
receptors exhibit good chiral recognition towards most of
the isomers excepted 5a to NEA-HCl and 5b to PhenG-OMe
HCl (KD/KL = 1.01; entry 3 and 15). Encouragingly, there
were two cases of host–guest chiral recognition in which the
binding constants of the favorite enantiomer is more than
five times of the other (KD/KL = 5.23 and 5.22, respec-
tively; entry 1 and 13). That may be resulted from the huge
barrier provided by the multiple cyclic chiral structures of
rosin terpenoid and a combination of rigid steric effect and
p–p noncovalent interactions provided by BINOL moiety.
The chiral nature of crown ether and the rigidity of micro-
environment of its cavity are all expected to play an
important role in enantioselective induction. Moreover, a
broaden cavity of the 22-crown-6 can also be expected have
important recognition effects to aromatic amines and some
of the amino acid methyl ester hydrochlorides.
Taking into account the data in Table 1, it was shown
that crown ethers 5a–b formed complexes of appreciable
stability constants towards isomers of all the ammonium
ions hydrochloride (Ka = 2.81 9 103–1.69 9 104 dm3
mol-1; G0 = 24.13–19.68 kJ 9 mol-1). The data pre-
sented herein are competitively to those obtained with
chiral Eighteen member receptors [3–8], which implied
that these 22-membered crown ethers coordinate the cation
in a similar fashion as that for 18-crown-6, and founded the
basis of chiral recognition.
However, the extent of enantiomeric recognition varies
greatly, depending on different host–guest systems. It was
mainly affected by the variation of their structure com-
plementarity and displayed by the complex formed
between the guest and the given ligand. The main structural
feature governing effective enantiomeric recognition of the
two crown ethers are broaden cavity of the 22-crown-6 and
the special configurational characteristics of the ether chain
with different diasteretopic faces, which formed by the
combination of the dissimilar chiral units of the rosin and
BINOL side chain.
The data in Table 1 show that important differences in
the enantiomeric recognition of crown ethers towards the
different guest. The different structural complementarity of
chiral crown ethers with different configuration in the side
chain to the guests with varies structure can be observed.
Comparing the KD/KL values of NEA HCl (1.01 for 5a;
1.40 for 5b; see in Table 1, entry, 3; 11) with that of PEA
HCl, PhenG-OMe HCl and PhenA-OMe HCl (5.23, 1.39
Table 1 Binding constants (Ka), free-energy changes (-DGo), enantioselectivities KL/KD and DDG0 calculated from -DGo, for complexation
for 1:1 complexes between L/D- amines salts and chiral host 5a and 5b in CHCl3:MeOH (2:1) at 25 °C
Entry
Host
Guest
Ka (L mol-1
)
KD/KL
-DG0 (KJ mol-1
)
DDG0 (KJ mol-1
)
1
5a
R-PEA-HCl
(1.69 0.61) 9 104
(3.23 0.9) 9 103
(1.17 0.18) 9 104
(1.15 0.34) 9 104
(1.17 0.17) 9 104
(1.55 0.75) 9 104
(5.88 0.87) 9 103
(4.23 0.74) 9 103
(7.40 0.96) 9 103
(4.50 0.70) 9 103
(1.40 0.18) 9 104
(1.00 0.06) 9 104
(1.47 0.20) 9 104
(2.81 0.81) 9 103
(4.08 0.69) 9 103
(3.86 0.81) 9 103
5.23
24.13
20.03
23.21
23.19
23.22
23.91
21.51
20.70
22.09
20.85
23.67
22.84
23.78
19.68
20.61
20.47
4.10
2
S-PEA-HCl
3
R-NEA-HCl
1.01
1.03c
1.39
1.65
1.40
5.22
1.06
0.02
-0.69
0.82
4
S-NEA-HCl
5
D -PhenA-OMeꢀHCl
L-PhenA-OMeꢀHCl
D-PhenG-OMeꢀHCl
L-PhenG-OMeꢀHCl
R-PEA-HCl
6
7
8
9
5b
1.24
10
11
12
13
14
15
16
S-PEA-HCl
R-NEA-HCl
0.84
S-NEA-HCl
D-PhenA-OMeꢀHCl
L-PhenA-OMeꢀHCl
D-PhenG-OMeꢀHCl
L-PhenG-OMeꢀHCl
4.10
0.14
PEA-HCl 1-phenylethylamine hydrochloride salts, NEA-HCl 1-(1-naphthyl)ethylamine hydrochloride salts, PhenA-OMeꢀHCl phenylalanine
methyl ester hydrochloride salts, PhenG-OMeꢀHCl phenylglycine methyl ester hydrochloride salts
a
Concentration of the receptor (5a, 5b: 5 9 10-5
)
b
c
d
KR=KS
KL=KD
DDG0 ¼ DG0ðD=RÞ ꢁ DG0ðL=SÞ
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J Incl Phenom Macrocycl Chem (2012) 73:177–183
and 1.32 for 5a; 1.65, 1.06 and 5.22 for 5b; see in Table 1,
entry 1, 7, 5; 9, 15, 13), it was shown that 5a and 5b
showed better enantiomeric discrimination in average to
the selected guests with relatively small group than to those
with large group, crown ether with S-form of 1,10-
binaphthyl group (5a) showed better enantiomeric dis-
crimination to the small-sized molecules, while the crown
ether with R-form of 1,10-binaphthyl group (5b) have
advantage in recognition of middle-sized molecules. It may
be result of the deferent configurational characteristics of
the ether chain between 5a and 5b1. The highest enanti-
oselectivity was achieved in the case of 5a to PEA HCl.
Since the crown ethers possess two diasteretopic, non
equivalent faces, it is essential that the complexation for an
efficient enantiodiscrimination should occur in such a
manner that two guest enantiomers selectively complex to
one of the different faces or to the same faces of the crown
ether with different steric interaction and stability. The
attitude of macrocycle 5a to the small-sized molecules and
5b to middle-sized molecules deserves a special consider-
ation in its application.
investigated using UV spectroscopic titration [12] The
UV–vis spectra were measured at 25 0.1 °C with thermo-
stated cell compartment by CARY 100 spectrophotometer.
The same concentration of guest solution was added to the
sample cell and reference cell. The maximum wavelengths
are 327 nm for 5a and 5b to NEA HCl and 281 nm for other
host–guest systems. CHCl3:MeOH (2:1) was used as the
solvent. The concentration of the hosts is 5.0 9 10-5 mol
dm-3 with the increasing concentration of the added guest.
4-Methyl-13-(1-methylethyl)-4-methoxycarbonyl-
16aH-atis-13-ene-23, 24-diol
4.04 g (0.01 mmol) 3 were dissolved in 100 mL dry diox-
ane; this mixture was added dropwise to 1.51 g
(0.0376 mmol, 98%) NaBH4 under cooling with ice. This
mixture was stirred and heated at refluxing temperature for
30 min, and then the reaction mixtures was poured into ice
water and conc. HCl were added before the mixture was
extracted five times with CH2Cl2. The organic phase was
dried over Na2SO4 and evaporated. The crude product was
purified by column chromatography (petroleum ether:ethyl
acetate = 3:1) to give pure product (2.6 g) as a colourless
needle. Yield 53%. m.p. 163–165 °C (Ref. [30]: m.p.
Experimental
25
163–164 °C), ½aꢂD ? 33.1 (c 1.50, EtOH); 1H NMR
General information
(CDCl3, 500 MHz) d 0.59 (s, 3H, CH3-22), 0.92–0.98
(m, 1H, H-1), 0.99 (d, J = 6.7 Hz, 3H, CH3-18), 1.00
(d, J = 6.7 Hz, 3H, CH3-19), 1.07–1.15(m, 5H, H-2, H-11
and CH3–20), 1.35–1.55 (m, 7H, H-1, H-3, H-5, CH2-6, H-7
and H-9), 1.62–1.73 (m, 3H, H-2, H-3 and H-11), 1.84 (dt,
J = 9.8, 2.7 Hz, 1H, H-15), 1.98 (m, 1H, H-7), 2.20 (m, 2H,
H-16, H-17), 2.37 (s, 1H, H-12), 3.43 (t, J = 10.4 Hz, 1H,
H-23), 3.49–3.60 (m, 2H, H-23, H-24), 3.67 (s, 3H, OCH3),
3.71–3.81 (m, 2H, H-24, OH-23 or OH-24), 5.33 (s, 1H,
H-14). 13C NMR (CDCl3, 125 MHz) d 15.78 (C-22), 16.86
(C-20), 17.17(C-2), 20.48 (C-18), 21.16 (C-19), 22.34 (C-6),
30.13(C-11), 33.21 (C-17), 36.14 (C-3), 36.88 (C-7), 37.69
(C-4), 38.16 (C-12), 38.24 (C-10), 40.26 (C-1), 45.84 (C-8),
47.22(C-16), 49.41 (C-5), 51.96 (OCH3), 54.08 (C-15), 55.20
(C-9), 61.10(C-23), 65.50 (C-24), 124.81 (C-14), 148.10
(C-13), 179.58(C-21); IR (KBr, m, cm-1): 3224(OH), 2928,
2867(CH2), 1719(C=O); MS (APCI) m/z: 405(M ? H?).
Optical pure primary amines and amino acid methyl ester
salts and 2, 20-dihydroxy-1, 10-binaphthyl were purchased
from Sigma-Aldrich Chemicals (St. Louis, MO, USA).
Gum rosin was purchased from Wuzhou Pine Chemicals
(Wuzhou, China). All the other chemicals and organic sol-
vents used in this work were of analytical grade unless
otherwise specified. Optical rotations were measured using a
Perkin Elmer Model 341polarimeter at ambient temperature
and [a]D-values were given in units of 10-1 deg cm2 g-1
.
NMR spectra were measured in CDCl3 on a BRUKER
AVANCE AV500 spectrometer using TMS as the internal
standard. IR spectra were recorded on a Nicolet ESP
360 FT-IR instrument. The mass spectra were obtained on a
BRUKER ESQUIRE HCT spectrometer. Elemental analy-
ses were performed on a Carlo Erba model 1106 elemental
analyzer. HR–ESI–MS was recorded in Agilent 6210LC/
MSD TOF. UV–vis absorption spectra were recorded with a
CARY 100 spectrophotometer.
General experimental procedure for the preparation
of chiral 22-crown-6 derivatives (5a–b)
UV spectral measurements
Compound 3 (1.26 g, 3 mmol), dissolved in anhydrous
THF (80 mL) was treated with NaH (60% dispersion in
paraffin oil, 0.96 g, 24 mmol); after 10 min, (S)- or (R)- 1
(2.4 g, 3 mmol) in dry THF (80 mL) was added and the
reaction mixture was left under stirring at room tempera-
ture within 2 h. Then the suspension was stirred for another
The abilities of crown ethers to coordinate to amines and
amino acid methyl ester hydrochlorides salts were
1
See in the Supplementary Data for the calculated structure of 5a
and 5b by MMFF94 Minimization
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J Incl Phenom Macrocycl Chem (2012) 73:177–183
181
48 h at refluxing temperature. After cooling to room tem-
petature, 10 mL water was add to the mixture in order to
deactivate the excess NaH and the mixture was filtered
and concentrated in vacuo. Water (20 mL) was added to
the residue, and then extracted with dichloromethane
(20 mL 9 3). The combined organic layer was dried over
MgSO4 and the dichloromethane was evaporated off. The
residue was purified by chromatography over silica
(petroleum ether:acetone = 12:1) to give 4a or 4b as a
colourless powder.
(m, 1H, H-7), 2.09 (dt, J = 9.9, 4.9 Hz, 1H, H-16), 2.22 (sept.
d, J = 6.5, 1.2 Hz, 1H, H-17), 2.62 (s, 1H, H-12), 2.88
(t, J = 9.4 Hz, 1H, H-23), 3.04 (t, J = 9.6 Hz, 1H, H-24),
3.16–3.66 (m, 17H, H-23, H-24, OCH3, CH2-10, CH2-100,
CH2-20, CH2-200, CH2-30, CH2-300), 3.97–4.16 (m, 4H, CH2-
40 and CH2-400), 5.31 (s, 1H, H-14), 7.11 (t, J = 8.9 Hz,
2H, H-h or H-h0), 7.20(dd, J = 8.3, 6.9 Hz, 2H, H-g
and H-g0), 7.27–7.36 (m, 2H, H-f and H-f0), 7.42
(d, J = 8.9 Hz, 1H, H-c or H-c0), 7.47 (d, J = 8.8 Hz, 1H,
H-c or H-c0), 7.85(t, J = 6.9 Hz, 2H, H-e and H-e0), 7.92
(d, J = 9.0 Hz, 1H, H-d or H-d0), 7.94 (d, J = 8.9 Hz, 1H,
H-d or H-d0); 13C NMR (CDCl3, 125 MHz) d 15.81 (C-22),
16.82 (C-20), 17.15 (C-2), 20.19 (C-19), 21.04 (C-18),
22.30 (C-6), 29.23 (C-11), 33.23 (C-17), 35.87 (C-12),
35.87 (C-7), 36.80 (C-3), 37.72 (C-10), 38.22 (C-1), 40.08
(C-8), 42.15 (C-16), 47.25 (C-4), 49.51 (C-5), 50.74 (C-
15), 51.82 (OCH3), 55.92 (C-9), 69.44 (C-400), 69.69 (C-40),
69.74(C-300), 69.74 (C-23), 69.87 (C-30), 70.02 (C-200),
70.17 (C-20), 70.47 (C-100), 70.96 (C-10), 71.47 (C-24),
115.83, 116.78 (C-c and C-c0), 120.63, 120.87 (H-a and
H-a0), 123.62, 123.67 (C-h and C-h0), 124.65 (C-14),
125.45, 125.50 (C-f and C-f0), 126.17, 126.23 (C-g and
C-g0), 127.79, 127.85 (C-e and C-e0), 129.19, 129.32 (C-d
and C-d0), 129.40, 129.57 (C-j and C-j0), 134.10, 134.15
(C-i and C-i0), 147.89 (C-13), 154.42, 154.69 (C-b and
C-b0), 179.53 (C-21); IR (KBr, m, cm-1): 2929 (CH2),
1593, 1507, 1464 (Ar), 1723 (C=O), 1622 (C = C), 1107
(C–O-C); MS (APCI) m/z: 832 [M]?. HRMS (ESI) m/z
calcd for C53H66O8Na: 853.4656 found: 853.4662 [M–
2H ? Na]?. Anal. Calcd for C53H68O8: C 76.41 H 8.23
found: C 76.36 H 8.68
25
Compound 5a. Yield: 10.3%, ½aꢂD -84.8 (c 1.12,
CH2Cl2); 1H NMR (CDCl3, 500 MHz) d 0.58 (s, 3H, CH3-
22), 0.85–0.93 (m, 1H, H-1), 1.00 (d, J = 6.8 Hz, 3H, CH3-
18), 1.03 (d, J = 6.9 Hz, 3H, CH3-19), 1.08–1.14 (m, 4H,
H-11, CH3-20), 1.34–1.59 (m, 9H, H-1, CH2-2, H-10, H-5,
CH2-6, H-7 and H-9), 1.67–1.77 (m, 3H, H-3, H-11, and
H-15), 1.90–1.93 (m, 1H, H-7), 2.10–2.14 (m, 1H, H-16),
2.19 (sept. d, J = 6.5, 1.2 Hz, 1H, H-17), 2.66 (s, 1H,
H-12), 2.86 (t, J = 9.3 Hz, 1H, H-23), 2.95 (t, J = 9.1 Hz,
1H, H-24), 3.11–3.73 (m, 17H, H-23, H-24, OCH3, CH2-10,
CH2-100, CH2-20, CH2-200, CH2-300, CH2-30), 3.98–4.22 (m,
4H, CH2-40 and CH2-400), 5.31 (s, 1H, H-14), 7.13 (d,
J = 8.5 Hz, 2H, H-h or H-h0), 7.20(t, J = 7.6 Hz, 2H, H-g
and H-g0), 7.32 (dd, J = 11.5, 7.2 Hz, 2H, H-f and H-f0),
7.42 (d, J = 9.0 Hz, 1H, H-c or H-c0), 7.46 (d, J = 9.0 Hz,
1H, H-c or H-c0), 7.85(t, J = 9.2 Hz, 2H, H-e and H-e0),
7.90 (d, J = 9.0 Hz, 1H, H-d or H-d0), 7.95 (d, J = 9.0 Hz,
1H, H-d or H-d0); 13C NMR (CDCl3, 125 MHz) d 15.81
(C-22), 16.80 (C-20), 17.14 (C-2), 19.55 (C-19), 20.26 (C-18),
20.97 (C-6), 29.03 (C-11), 33.37 (C-17), 35.82 (C-12),
35.90 (C-7), 36.83 (C-3), 37.71 (C-9), 38.18 (C-1), 40.08
(C-8), 42.38 (C-16), 47.26 (C-4), 49.46 (C-5), 49.55 (C-15),
51.85 (OCH3), 55.94 (C-9), 69.57(C-400), 69.63 (C-40),
69.63 (C-300), 70.00 (C-23), 70.19 (C-30), 70.19 (C-200),
70.35 (C-20), 70.70 (C-100), 70.87 (C-10), 71.42 (C-24),
115.17, 117.72(C-c and C-c0), 120.15, 121.44(C-a and
C-a0), 123.58, 123.79(C-h and C-h0), 124.89(C-14), 125.42,
125.55(C-f and C-f0), 126.15, 126.29 (C-g and C-g0),
127.78, 127.87(C-e and C-e0), 129.13, 129.38(C-d and
C-d0), 129.30, 129.71(C-j and C-j0), 134.08, 134.11(C-i
and C-i0), 147.52(C-12), 154.27, 154.93(C-b and C-b0),
179.54(C-21); IR (KBr, m, cm-1): 2923, 2870(CH2), 1593,
1508, 1464 (Ar), 1724 (C=O), 1622 (C = C), 1107 (C–O-
C); MS (APCI) m/z: 831 [M-H] ?. Anal. Calcd for
C53H68O8: C 76.41 H 8.23 found: C 76.38 H 8.61
Conclusions
We have synthesized two 22-crown-6 ethers possessing
methoxycarbonyl side groups comprising 1, 10-binaphthyl
and rosin acid moieties in the crown ring. These receptors
showed strong affinity and different complementarity to
various amines salts, and exhibit excellent enantiodis-
criminating abilities toward protonated primary amines and
amino acid methyl ester salts isomers in chiral recognition.
Practically, through a short-step synthesis, the methoxy-
carbonyl side groups in the resulted host molecular will
facilitate the crown ether covalently bound to silica gel in
the preparing chiral stationary phases.
25
Compound 5b. Yield: 10.7%, ½aꢂD ?56.2 (c 1.12,
CH2Cl2); 1H NMR (CDCl3, 500 MHz) d 0.58 (s, 3H, CH3-
22), 0.92–0.98 (m, 1H, H-1), 1.00 (d, J = 6.8 Hz, 3H,
CH3-18), 1.01 (d, J = 6.9 Hz, 3H, CH3-19), 1.08–1.15 (m,
4H, H-11, CH3-20), 1.34–1.55 (m, 9H, H-1, CH2-2, H-10,
H-5, CH2-6, H-7 and H-9), 1.67–1.75 (m, 2H, H-10 and
H-11), 1.82 (dt, J = 9.7, 2.7 Hz, 1H, H-15), 1.89–1.90
Acknowledgements This study was supported by the National
Natural Science Foundation of China (No. 20762001), the Project of
Ten, Hundred, Thousand Distinguished Talents in New Century of
Guangxi (No. 2007228), 973 project (No. 2011CB512005) and
Guangxi Natural Science Foundation of China (2010GXNSFF013001;
2011GXNSFD018010).
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182
J Incl Phenom Macrocycl Chem (2012) 73:177–183
16. Hyun, M.H., Jin, J.S., Lee, W.: Liquid chromatographic resolu-
tion of racemic amino acids and their derivatives on a new chiral
stationary phase based on crown ether. J. Chromatogr. A 822(1),
155–161 (1998). doi:10.1016/s0021-9673(98)00606-2
17. Hirose, K., Jin, Y.Z., Nakamura, T., Nishioka, R., Ueshige, T.,
Tobe, Y.: Chiral stationary phase covalently bound with a chiral
pseudo-18-crown-6 ether for enantiomer separation of amino
compounds using a normal mobile phase. Chirality 17(3),
142–148 (2005). doi:10.1002/chir.20138
References
1. Zhang, X.X., Bradshaw, J.S., Izatt, R.M.: Enantiomeric recog-
nition of amine compounds by chiral macrocyclic receptors.
Chem. Rev. 97(8), 3313–3362 (1997). doi:10.1021/cr960144p
2. Wenzel, T.J., Wilcox, J.D.: Chiral reagents for the determination
of enantiomeric excess and absolute configuration using NMR
spectroscopy. Chirality 15(3), 256–270 (2003). doi:10.1002/chir.
10190
18. Gao, M.-Z., Yang, Y.-Q., Xu, Z.-L.: Development of chiral crown
ethers. Chin. J. Org. Chem. 21(7), 477–484 (2001)
¨
3. Karakaplan, M., Turgut, Y.ı., Aral, T., Hos¸goren, H.: The syn-
thesis and formation of complexes between derivatives of chiral
aza-18-crown-6 ethers and chiral primary organic ammonium
salts. J. Incl. Phenom. Macrocycl. Chem. 54(3), 315–319 (2006)
4. Ema, T., Tanida, D., Sakai, T.: Versatile and practical macrocyclic
reagent with multiple hydrogen-bonding sites for chiral discrimi-
nation in NMR. J. Am. Chem. Soc. 129(34), 10591–10596 (2007).
doi:10.1021/ja073476s
5. Turgut, Y., Aral, T., Hosgoren, H.: Synthesis of novel C2-sym-
metric chiral crown ethers and investigation of their enantiomeric
recognition properties. Tetrahedron Asymmetr. 20(19), 2293–2298
(2009)
6. Lovely, A.E., Wenzel, T.J.: Chiral NMR discrimination of sec-
ondary amines using (18-crown-6)-2, 3, 11, 12-tetracarboxylic
acid. Org. Lett. 8(13), 2823–2826 (2006). doi:10.1021/ol0609558
7. Nakatsuji, Y., Nakahara, Y., Muramatsu, A., Kida, T., Akashi,
M.: Novel C2-symmetric chiral 18-crown-6 derivatives with two
aromatic sidearms as chiral NMR discriminating agents. Tetra-
hedron Lett. 46(25), 4331–4335 (2005)
19. Nicolas, I., Chevance, S., Maux, P.L., Simonneaux, G.: Chiral
recognition of amines and amino acid derivatives by optically
active ruthenium Halterman porphyrins in organic solvents and
water. Tetrahedron Asymmetr. 21(13–14), 1788–1792 (2010).
doi:10.1016/j.tetasy.2010.05.026
20. Brunet, E., Poveda, A.M., Rabasco, D., Oreja, E., Font, L.M.,
Batra, M.S., Rodriguez-Ubis, J.C.: New chiral crown ethers
derived from camphor and their application to asymmetric
Michael addition. First attempts to rationalize enantioselection by
AM1 and AMBER calculations. Tetrahedron Asymmetr 5(5),
935–948 (1994)
21. Ayer, W.A., Mcdonald, C.E.: The stereochemistry of maleo-
pimaric acid and the long range shielding effect of the olefinic
bond. Can. J. Chem. 41, 1113–1126 (1963)
22. Tolstikov, A.H., Tolstikova, O.V., Khlebnikova, T.B., Karpy-
shev, N.N.: Higer terpenoids in the synthesis of chiral phosphor-
and nitrogen-containing ligands for metal-complex catalysts of
asymmetric reactions. Chem. Comput. Simul. Butl. Commun.
2(7), 1–8 (2002)
23. Ye, F.G., Wang, H.S., Huang, B.J., Zhao, S.L.: Maleopimaric
acid anhydride-bonded silica monolith as chiral stationary phase
for separations of phenylthiocarbamyl amino acids by CEC.
Electrophoresis 31(9), 1488–1492 (2010). doi:10.1002/elps.2009
00716
24. Wang, H., Zhao, S., He, M., Zhao, Z., Pan, Y., Liang, Q.: Sodium
maleopimaric acid as pseudostationary phase for chiral separa-
tions of amino acid derivatives by capillary micellar electroki-
netic chromatography. J. Sep. Sci. 30(16), 2748–2753 (2007)
25. Zhao, S.L., Wang, H.S., Zhang, R.C., Tang, L.D., Liu, Y.M.:
Degradingdehydroabietylisothiocyanate as a chiral derivatizing
reagent for enantiomeric separations by capillary electrophoresis.
Electrophoresis 27(17), 3428–3433 (2006). doi:10.1002/elps.
200600008
26. Zhao, S., Zhang, R., Wang, H., Tang, L., Pan, Y.: Capillary elec-
trophoresis enantioselective separation of vigabatrin enantiomers
by precolumn derivatization with dehydroabietylisothiocyante and
UV-vis detection. J. Chromatogr. B 833(2), 186–190 (2006)
27. Wright, K., Lohier, J.-F., Wakselman, M., Mazaleyrat, J.-P.,
Formaggio, F., Peggion, C., De Zotti, M., Toniolo, C.: Synthesis
of enantiopure, axially chiral, C[alpha]-tetrasubstituted [alpha]-
amino acids with binaphthyl-based crowned side chains and 3D-
structural analysis of their peptides. Tetrahedron 64(10),
2307–2320 (2008)
¨
8. Turgut, Y., Demirel, N., Hos¸goren, H.: Synthesis of novel chiral
C 2-symmetric diaza-18-crown-6 ether derivatives and their
enantioselective recognition of amino acid derivatives. J. Incl.
Phenom. Macrocycl. Chem. 54(1), 29–33 (2006)
´
9. Lakatos, S., Fetter, J., Bertha, F., Huszthy, P., Toth, T., Farkas,
V., Orosz, G., Hollosi, M.: Preparation of a new chiral acridino-
´
18-crown-6 ether-based stationary phase for enantioseparation of
racemic protonated primary aralkyl amines. Tetrahedron 64(6),
1012–1022 (2008)
10. Choi, H.J., Park, Y.J., Hyun, M.H.: Liquid chromatographic
resolution of secondary amino alcohols on a chiral stationary
phase based on (?)-(18-crown-6)-2, 3, 11, 12-tetracarboxylic
acid: Dependence of temperature effect on analyte structure.
J. Chromatogr. A 1164(1–2), 235–239 (2007)
11. Yongzhu, J., Hirose, K., Nakamura, T., Nishioka, R., Ueshige, T.,
Tobe, Y.: Preparation and evaluation of a chiral stationary phase
covalently bound with a chiral pseudo-18-crown-6 ether having a
phenolic hydroxy group for enantiomer separation of amino
compounds. J. Chromatogr. A 1129(2), 201–207 (2006)
12. Farkas, V., Toth, T., Orosz, G., Huszthy, P., Hollosi, M.: Enan-
tioseparation of protonated primary arylalkylamines and amino
acids containing an aromatic moiety on a pyridino-crown ether
based new chiral stationary phase. Tetrahedron Asymmetr.
17(12), 1883–1889 (2006)
13. Hyun, M.H., Tan, G., Xue, J.Y.: Unusual resolution of N-(3,
5-dinitrobenzoyl)-[alpha]-amino acids on a chiral stationary
phase based on (?)-(18-crown-6)-2, 3, 11, 12-tetracarboxylic
acid. J. Chromatogr. A 1097(1–2), 188–191 (2005)
14. Schlauch, M., Kos, O., Frahm, A.W.: Comparison of three chiral
stationary phases with respect to their enantio- and diastereose-
lectivity for cyclic [beta]-substituted [alpha]-amino acids.
J. Pharm. Biomed 27(3–4), 409–419 (2002)
15. Hirose, K., Yongzhu, J., Nakamura, T., Nishioka, R., Ueshige, T.,
Tobe, Y.: Preparation and evaluation of a chiral stationary phase
covalently bound with chiral pseudo-18-crown-6 ether having
1-phenyl-1, 2-cyclohexanediol as a chiral unit. J. Chromatogr. A
1078(1–2), 35–41 (2005)
´
´
28. Benniston, A.C., Gunning, P., Peacock, R.D.: Synthesis and
binding properties of hybrid cyclophane–azamacrocyclic recep-
tors. J. Org. Chem. 70(1), 115–123 (2004). doi:10.1021/jo04
8621o
29. Hess, S.C., Farah, M.I.S., Eguchib, S.Y., Imamura, P.M.: Syn-
thetic studies with Pinus elliottiis?rosin derivatives. Oxidation of
maleopimaric anhydride methyl ester and trimethyl fumaropim-
arate. J. Brazil. Chem. Soc. 11, 59–63 (2000)
´ ´
30. Gastambide, B., Langlois, N.: Etudes stereochimiques VII Syn-
`
theses dieniques en serie resinique; action des peroxoacides et des
hydrures doubles. Helv. Chim. Acta 51, 2048–2057 (1968)
´
´
´
123

J Incl Phenom Macrocycl Chem (2012) 73:177–183
183
¨
31. Turgut, Y., Hosgoren, H.: Synthesis of chiral monoaza-15-crown-
32. Hirose, K.: A practical guide for the determination of binding
constants. J. Incl. Phenom. Macrocycl. Chem. 39(3), 193–209
(2001). doi:10.1023/a:1011117412693
5 ethers from -valinol and the enantiomeric recognition of chiral
amines and their perchlorates salts. Tetrahedron Asymmetr.
14(23), 3815–3818 (2003)
123