A facile and efficient approach to the synthesis of novel chiral molecular tweezers based on deoxycholic acid under microwave irradiation

Article abstract of DOI:10.2174/157017811795038421

A rapid, safe and efficient method for the synthesis of novel molecular tweezers with one chiral arm based on deoxycholic acid was reported. Ten new molecular tweezers have been synthesized in good yields. The structures of these new molecular tweezers were characterized by ¹H NMR, IR, MS spectra and elemental analysis. These chiral molecular tweezers showed good enantioselectivity for D-amino acid methyl esters.

Full text of DOI:10.2174/157017811795038421

210
Letters in Organic Chemistry, 2011, 8, 210-215
A Facile and Efficient Approach to the Synthesis of Novel Chiral
Molecular Tweezers Based on Deoxycholic Acid under Microwave
Irradiation
Yu Chen, Zhi-Gang Zhao*, Xing-Li Liu and Zhi-Chuan Shi
College of Chemistry and Environmental Protection Engineering, Southwest University for Nationalities, Chengdu
610041, P. R. China
Received June 08, 2010: Revised September 13, 2010: Accepted October 13, 2010
Abstract: A rapid, safe and efficient method for the synthesis of novel molecular tweezers with one chiral arm based on
deoxycholic acid was reported. Ten new molecular tweezers have been synthesized in good yields. The structures of these
1
new molecular tweezers were characterized by H NMR, IR, MS spectra and elemental analysis. These chiral molecular
tweezers showed good enantioselectivity for D-amino acid methyl esters.
Keywords: Molecular tweezer, deoxycholic acid, synthesis, microwave irradiation, molecular recognition.
1. INTRODUCTION
green synthesis of molecular tweezers [10-13], herein, we
report a simple, green, safe and rapid method to obtain new
deoxycholic acid molecular tweezer artificial receptors
containing naphthoyloxy arm, which are expected to form ꢀ-
As an essential feature of biochemical systems,
molecular recognition plays pivotal role in life processes.
The design and synthesis of model receptor to recognize
substrates of biochemical significance to mimic biological
events are of keen interest in molecular recognition research
[1, 2]. In recent years, many interesting receptors have been
developed. Among the various types of artificial receptors
designed so far, a special class of receptors called molecular
tweezers, which are particularly effective in regard to
complementarities with substrates since functional groups
attached to the interior of the tweezer converge on substrates
held inside [3] has attracted more and more attention in
molecular recognition, mimic enzyme catalysis, self-
assembly of molecular structure, the resolution of race mates
as well as molecular devices [4-6].
ꢀ
stacking interaction with substrates in molecular
recognition. The synthetic route is shown in Scheme 1.
2. RESULTS AND DISCUSSION
In order to make a quantitative comparison in synthesis
molecular tweezers 5a-5j between microwave irradiation and
conventional heating, a series of experiments were carried
out. As indicated in Table 1, the reaction times were
considerably shorter, only 18-21 minutes, however, the
synthesis of these molecular tweezers in conventional
heating required 35-39 h in dichloromethane and yields of
reaction increased (38%-71%) relative to (84%-92%).
Moreover, the recent development in so called “green
chemistry” shows that alternative methods of carrying out
chemical transformation can minimize the environmental
harmfulness of classical reactions. One of the most popular
and interesting approach in this field is the application of
microwave techniques for organic synthesis. This technology
can enhance the selectivity and reactivity, improve product
yields along with several eco-friendly advantages in green
chemistry [7-9]. For this reason, the application of
microwave irradiation for activation of reaction, in general
and under solvent-free conditions in particular, has gained
popularity over the usual homogeneous and heterogeneous
reactions.
In searching for the best reaction results of this reaction,
we took the synthesis of 5a for example and carried out
several experimental works in different conditions: such as
microwave irradiation power, time and solvent (as shown in
Table 2). From Table 2, we found that 19 min was the
optimum reaction time when the yield was the highest under
the same power (200 W). However, more byproducts could
be afforded when lengthening the reaction time; In addition,
we irradiated the reaction using different powers under the
same reaction time (19 min). As a result, 200 W was the
optimum power; Finally, dichloromethane, chloroform and
tetrahydrofuran were compared to evaluate the solvent effect
on the reaction. Different solvents were employed under the
similar reaction conditions, but the results were much
different as shown in Table 2.
The natural rigid concave structure and inherent
asymmetry of cholic acid pose it as ideal building blocks for
the construction of molecular tweezers. With our continuous
investigation on the methodology of microwave-assisted
Considering dichloromethane is less toxic than
chloroform and easily removed than the other two solvents,
we conclude that dichloromethane is the best solvent in this
reaction. For comparison purpose, the best yield (up to 89%)
is obtained in the condition of irradiating 19 min at 200W
using dichloromethane as solvent.
*Address correspondence to this author at the College of Chemistry and
Environmental Protection Engineering, Southwest University for
Nationalities, Chengdu 610041, P. R. China; Tel: +86-28-85522315;
Fax: +86-28-85524382; E-mail: zzg63129@yahoo.com.cn
1570-1786/11 $58.00+.00
© 2011 Bentham Science Publishers Ltd.

A Facile and Efficient Approach to the Synthesis
Letters in Organic Chemistry, 2011, Vol. 8, No. 3
211
COOCH3
COOR1
1-naphthoyl chloride
MWI
OH
OH
OH
O
O
R1= H
1
2
CH3OH,CH3COCl
R1= CH3
3
COOCH3
O
O
L-amino acid methyl esters hydrochloride,pyridine
MWI
dichloromethane,triphosgene,pyridine
MWI
O
Cl
O
4
COOCH3
5a R = CH3
5b R = CH2CH(CH3)2
O
O
O
5c R = CH2OH
5e R = CH2Ph
5d R = CH(CH3)(CH2CH3)
5f R = Ph
HN
O
COOCH3
R
5g R = CH(CH3)2
5h R = CH2CH2SCH3
H
5j R =
H2C
5i R =
H2C
OH
5
N
H
Scheme 1. Synthesis of chiral molecular tweezers 5a-5j.
Table 1. Synthetic Comparison of Molecular Tweezers 5a-5j Between Microwave Irradiation and Conventional Heating
Compd
5a
Conventional method
T/min
Microwave method
T/min
Solvent(mL)
Yield/%
Solvent(mL)
Yield/%
5a
5b
5c
5d
5e
5f
20
20
20
20
20
20
20
20
20
20
2160
2160
2340
2160
2280
2220
2340
2100
2280
2100
67
60
52
64
71
43
40
62
50
38
10
10
10
10
10
10
10
10
10
10
19
19
21
19
21
18
21
19
20
21
89
88
87
90
92
85
86
90
88
84
5g
5h
5i
5j

212 Letters in Organic Chemistry, 2011, Vol. 8, No. 3
Chen et al.
Table 2. Synthetic Comparison of Molecular Tweezers 5a in Different Conditions
Material
Solvent
T/min
Product
Power/W
Yield/%
intermediate 3
intermediate 3
intermediate 3
intermediate 3
intermediate 3
intermediate 3
intermediate 3
intermediate 3
intermediate 3
intermediate 3
intermediate 3
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
THF
12
19
20
25
19
19
19
19
25
19
25
5a
5a
5a
5a
5a
5a
5a
5a
5a
5a
5a
200
200
200
200
50
50
89
84
82
45
80
79
70
73
84
81
150
250
200
200
200
200
THF
CHCl3
CHCl3
It is important to note that in the process of obtaining
product 5a-5j from intermediate 3. Triphosgene was added
to a solution of intermediate 3 in dry dichloromethane at
room temperature. After irradiating the reaction mixture for
9 min at 200 W, intermediate 4 was formed, then L-amino
acid methyl esters hydrochloride and dry pyridine were
added directly to the mixture bypassing the separation of
acyl chloride (intermediate 4). Our methodology has shown
that under microwave irradiation novel chiral molecular
tweezers receptors can be synthesized in one-pot.
modified from domestic microwave oven and tested to
conform to the performance index before use. Optical
rotation was measured on a Wzz-2B polarimeter. Solvents
were dried and distilled according to established procedures.
Reactions were monitored by thin layer chromatography
(TLC), Column chromatography purifications were carried
out using silica gel. All reagents were purchased from
commercial corporations. Deoxycholic acid was converted to
methyl 3ꢀ, 12ꢀ-dihydroxy-7-deoxy-5ꢀ -cholan-24-oate (2)
following a reported procedure [15]. Intermediate（3）was
prepared by known procedures [16]. All the L-amino acid
methyl esters hydrochloride were obtained from the
esterification of corresponding L -amino acids and methanol
in the presence of thionyl chloride.
The enantioselective recognition of molecular tweezers
5e, 5f for some amino acid methyl esters have been
investigated by UV-Visible spectra titration in chloroform at
25ꢀ. The titration data were analyzed by using the
Hildebrand-Benesi equation [14]. The preliminary results, as
expected, showed that all these molecular tweezers posses
the ability to complex with amino acid methyl esters
examined. The association constants (Ka) and Gibbs free
energy changes (- △ G0) for inclusion complexation of
molecular tweezers 5e, 5f with all D–amino acid methyl
esters are higher than with all L–amino acid methyl esters.
The enantioselectivity KD/KL for 5e, for example, is 5.3 for
Phe-OMe. It shows fairly good enantioselective recognition
which could be obtained practical application in chiral
resolution. The details of complexing experiments are under
further studies.
3.2. General Procedure for the Synthesis of Molecular
Tweezers 5a-5j under Microwave Irradiation
Triphosgene (0.2 mmol) was added to a solution of
compound 3 (0.5 mmol) in 10 mL dry dichloromethane and
0.1 mL dry pyridine at room temperature. After irradiating
the reaction mixture for 9 min at 200 W, compound 4 was
formed, then L-amino acid methyl esters hydrochloride (1
mmol) and 0.2 mL dry pyridine were added directly to the
mixture, irradiated continually for 9-12 min at the same
power. The solvent was removed and the residue was diluted
with 20 mL ethyl acetate and washed with 10% NaHCO3 (10
mLꢀ3), brine (10 mLꢀ3), and finally dried over anhydrous
Na2SO4. The crude product was purified by column
chromatography on silica gel H with dichloromethane/ethyl
acetate as eluant.
3. EXPERIMENTAL
3.1. General
Melting points were determined on a micro-melting point
apparatus and the thermometer was uncorrected. Infrared
spectra were obtained on 1700 Perkin-Elmer FTIR using
KBr disks. 1H NMR spectra were recorded on a Varian
INOVA 400 MHz spectrometer using CDCl3 as solvent and
TMS as internal standard. Mass spectra were determined on
Finnigan LCQDECA instrument. Elemental analysis was
performed on a Carlo-Erba-1106 autoanalyzer. Microwave
irradiation was carried out with a MCL-3 microwave oven
(very safe, reliable) at full power (700 W), which was
3.2.1. Molecular Tweezer 5a
Prepared according to the general procedure to afford the
product 5a as a white crystals; yield 89%; Mp
: 41–42ꢀ.
= +62.17°(c 0.15, CH2Cl2). 1H NMR (400 MHz,
[ꢀ]2D0
CDCl3) ꢁ 0.74 (s, 3H, 18-CH3), 0.86 (d, 3H, J = 6.0 Hz, 21-
CH3), 0.96 (s, 3H, 19-CH3), 3.56 (s, 3H, COOCH3), 3.66 (s,
3H, COOCH3), 4.34-4.41 (m, 1H, 3ꢀ-H), 4.97 (s, 1H, 12ꢀ-
H), 5.05-5.11 (m, 1H, NCH), 5.30 (d, 1H, J = 8.4 Hz,
CONH), 7.47-7.62 (m, 3H, ArH), 7.88 (d, 1H, J = 8.0 Hz,

A Facile and Efficient Approach to the Synthesis
Letters in Organic Chemistry, 2011, Vol. 8, No. 3
213
ArH), 8.01 (d, 1H, J = 8.0 Hz, ArH), 8.21 (d, 1H, J = 7.2 Hz,
ArH), 8.87 (d, 1H, J = 8.4 Hz, ArH); IR (KBr, cm-1): 3432,
2942, 2869, 1719, 1654, 1515, 1449, 1247; ESI–MS m/z
(%): 712.7 [(M+23)+, 100]; Elemental analysis: Found (%):
C, 71.56; H, 8.02; N, 2.04 Calcd. For C41H55NO8: C, 71.38;
H, 8.04; N, 2.03.
CDCl3) ꢀ 0.72 (s, 3H, 18-CH3), 0.79 (d, 3H, J = 6.0 Hz, 21-
CH3), 0.95 (s, 3H, 19-CH3), 3.00-3.17 (m, 2H, PhCH2), 3.49
(s, 3H, COOCH3), 3.68 (s, 3H, COOCH3), 4.64-4.70 (m, 1H,
3ꢁ-H), 4.94 (s, 1H, 12ꢁ-H), 5.03-5.09 (m, 1H, NCH), 5.22
(d, 1H, J = 8.4 Hz, CONH), 7.06-7.29 (m, 5H, ArH), 7.46-
7.61 (m, 3H, ArH), 7.88 (d, 1H, J = 8.0 Hz, ArH), 8.00 (d,
1H, J = 8.0 Hz, ArH), 8.18 (d, 1H, J = 7.2 Hz, ArH), 8.87 (d,
1H, J = 8.8 Hz, ArH); IR (KBr, cm-1): 3430, 2943, 2868,
1716, 1509, 1447, 1246, 1201; ESI–MS m/z (%): 788.6
[(M+23)+, 100]; Elemental analysis: Found (%): C, 73.68; H,
7.70; N, 1.81 Calcd. For C47H59NO8: C, 73.70; H, 7.76; N,
1.83.
3.2.2. Molecular Tweezer 5b
Prepared according to the general procedure to afford the
product 5b as a white crystals; yield 88%; Mp: 57–58ꢀ.
1
[ꢀ]2D0
= +35.72ꢁ(c 0.092, CH2Cl2). H NMR (400 MHz,
CDCl3) ꢀ 0.73 (s, 3H, 18-CH3), 0.94 (d, 3H, J = 6.0 Hz, 21-
CH3), 0.96 (s, 3H, 19-CH3), 3.52 (s, 3H, COOCH3), 3.66 (s,
3H, COOCH3), 4.35-4.41 (m, 1H, 3ꢁ-H), 4.97 (s, 1H, 12ꢁ-
H), 5.05-5.08 (m, 1H, NCH), 5.14 (d, 1H, J = 9.2 Hz,
CONH), 7.47-7.62 (m, 3H, ArH), 7.88 (d, 1H, J = 8.0 Hz,
ArH), 8.00 (d, 1H, J = 8.0 Hz, ArH), 8.22 (d, 1H, J = 7.2 Hz,
ArH), 8.88 (d, 1H, J = 8.8 Hz, ArH); IR (KBr, cm-1): 3400,
2949, 2868, 1713, 1450, 1384, 1246, 1199; ESI–MS m/z
(%): 1485.7 [(2M+23)+, 100]; Elemental analysis: Found
(%): C, 72.09; H, 8.38; N, 1.89 Calcd. For C44H61NO8: C,
72.20; H, 8.40; N, 1.91.
3.2.6. Molecular Tweezer 5f
Prepared according to the general procedure to afford the
product 5f as a white crystals; yield 85%; Mp: 113–114ꢀ.
1
[ꢀ]2D0
= +44.04ꢁ(c 0.14, CH2Cl2). H NMR (400 MHz,
CDCl3) ꢀ 0.65 (d, 3H, J = 6.0 Hz, 21-CH3), 0.70 (s, 3H, 18-
CH3), 0.97 (s, 3H, 19-CH3), 3.58 (s, 3H, COOCH3), 3.66 (s,
3H, COOCH3), 4.95 (s, 1H, 12ꢁ-H), 5.07-5.12 (m, 1H, 3ꢁ-
H), 5.36 (d, 1H, J = 8.0 Hz, NCH), 5.84 (d, 1H, J = 8.0 Hz,
CONH), 7.00-7.35 (m, 5H, ArH), 7.48-7.63 (m, 3H, ArH),
7.89 (d, 1H, J = 8.0 Hz, ArH), 8.02 (d, 1H, J = 7.6 Hz, ArH),
8.24 (d, 1H, J = 7.2 Hz, ArH), 8.90 (d, 1H, J = 8.8 Hz, ArH);
IR (KBr, cm-1): 3432, 2946, 2869, 1717, 1501, 1447, 1382,
1200; ESI–MS m/z (%): 774.8 [(M+23)+, 100]; Elemental
analysis: Found (%): C, 73.50; H, 7.59; N, 1.84 Calcd. For
C46H57NO8: C, 73.47; H, 7.64; N, 1.86.
3.2.3. Molecular Tweezer 5c
Prepared according to the general procedure to afford the
product 5c as a yellow crystals; yield 87%; Mp: 77–78ꢀ.
1
[ꢀ]2D0
= +61.32ꢁ(c 0.082, CH2Cl2). H NMR (400 MHz,
CDCl3) ꢀ 0.74 (s, 3H, 18-CH3), 0.87 (d, 3H, J = 6.0 Hz, 21-
CH3), 0.96 (s, 3H, 19-CH3), 3.59 (s, 3H, COOCH3), 3.65 (s,
3H, COOCH3), 3.75-3.99 (m, 3H, OH+OCH2), 4.44-4.46 (m,
1H, 3ꢁ-H), 5.04-5.12 (m, 1H, NCH), 4.99 (s, 1H, 12ꢁ-H),
5.70 (d, 1H, J = 8.0 Hz, CONH), 7.47-7.63 (m, 3H, ArH),
7.88 (d, 1H, J = 8.0 Hz, ArH), 8.00 (d, 1H, J = 8.0 Hz, ArH),
8.20 (d, 1H, J = 7.2 Hz, ArH), 8.87 (d, 1H, J = 8.8 Hz, ArH);
IR (KBr, cm-1): 3438, 2946, 2869, 1715, 1511, 1449, 1244,
1201; ESI–MS m/z (%): 706.6 [(M+1)+, 100]; Elemental
analysis: Found (%): C, 69.80; H, 7.89; N, 2.01 Calcd. For
C41H55NO9: C, 69.76; H, 7.85; N, 1.98.
3.2.7. Molecular Tweezer 5g
Prepared according to the general procedure to afford the
product 5g as a yellow crystals; yield 86%; Mp: 64–65ꢀ.
= +38.46ꢁ(c 0.16, CH2Cl2). 1H NMR (400 MHz,
[ꢀ]2D0
CDCl3) ꢀ 0.74 (s, 3H, 18-CH3), 0.87 (d, 3H, J = 6.8 Hz, 21-
CH3), 0.96 (s, 3H, 19-CH3), 3.49 (s, 3H, COOCH3), 3.65 (s,
3H, COOCH3), 4.28-4.31 (m, 1H, 3ꢁ-H), 4.98 (s, 1H, 12ꢁ-
H), 5.03-5.11 (m, 1H, NCH), 5.27 (d, 1H, J = 9.6 Hz,
CONH), 7.47-7.62 (m, 3H, ArH), 7.88 (d, 1H, J = 8.4 Hz,
ArH), 8.00 (d, 1H, J = 8.0 Hz, ArH), 8.24 (d, 1H, J = 7.2 Hz,
ArH), 8.89 (d, 1H, J = 8.8 Hz, ArH); IR (KBr, cm-1): 3435,
2948, 2870, 1717, 1629, 1450, 1385, 1199; ESI–MS m/z
(%): 740.8 [(M+23)+, 100]; Elemental analysis: Found (%):
C, 71.53; H, 8.30; N, 1.98 Calcd. For C43H59NO8: C, 71.94;
H, 8.28; N, 1.95.
3.2.4. Molecular Tweezer 5d
Prepared according to the general procedure to afford the
product 5d as a colorless crystals; yield 90%; Mp: 62–63ꢀ.
= +34.63ꢁ(c 0.14, CH2Cl2). 1H NMR (400 MHz,
[ꢀ]2D0
CDCl3) ꢀ 0.74 (s, 3H, 18-CH3), 0.92 (d, 3H, J = 6.8 Hz, 21-
CH3), 0.96 (s, 3H, 19-CH3), 3.49 (s, 3H, COOCH3), 3.66 (s,
3H, COOCH3), 4.31-4.35 (m, 1H, 3ꢁ-H), 4.98 (s, 1H, 12ꢁ-
H), 5.03-5.10 (m, 1H, NCH), 5.27 (d, 1H, J = 9.6 Hz,
CONH), 7.47-7.62 (m, 3H, ArH), 7.88 (d, 1H, J = 8.0 Hz,
ArH), 8.00 (d, 1H, J = 8.0 Hz, ArH), 8.23 (d, 1H, J = 7.2 Hz,
ArH), 8.88 (d, 1H, J = 9.2 Hz, ArH); IR (KBr, cm-1): 3377,
2950, 2870, 1716, 1510, 1450, 1246, 1200; ESI–MS m/z
(%): 753.2 [(M+23)+, 100]; Elemental analysis: Found (%):
C, 72.24; H, 8.38; N, 1.89 Calcd. For C44H61NO8: C, 72.20;
H, 8.40; N, 1.91.
3.2.8. Molecular Tweezer 5h
Prepared according to the general procedure to afford the
product 5h as a yellow crystals; yield 90%; Mp:72–73ꢀ.
= +57.91ꢁ(c 0.11, CH2Cl2). 1H NMR (400 MHz,
[ꢀ]2D0
CDCl3) ꢀ 0.74 (s, 3H, 18-CH3), 0.86 (d, 3H, J = 6.4 Hz, 21-
CH3), 0.96 (s, 3H, 19-CH3), 3.54 (s, 3H, COOCH3), 3.66 (s,
3H, COOCH3), 4.45-4.50 (m, 1H, 3ꢁ-H), 4.98 (s, 1H, 12ꢁ-
H), 5.03-5.10 (m, 1H, NCH), 5.37 (d, 1H, J = 8.4 Hz,
CONH), 7.48-7.62 (m, 3H, ArH), 7.88 (d, 1H, J = 8.0 Hz,
ArH), 8.01 (d, 1H, J = 8.4 Hz, ArH), 8.21 (d, 1H, J = 7.2 Hz,
ArH), 8.87 (d, 1H, J = 8.4 Hz, ArH); IR (KBr, cm-1): 3397,
2923, 2863, 1715, 1516, 1446, 1383, 1198; ESI–MS m/z
(%): 1521.5 [(2M+23)+, 100]; Elemental analysis: Found
(%): C, 68.90; H, 7.89; N, 1.85 Calcd. For C43H59NO8S: C,
68.86; H, 7.93; N, 1.87.
3.2.5. Molecular Tweezer 5e
Prepared according to the general procedure to afford the
product 5e as a white crystals; yield 92%; Mp: 59–61ꢀ.
= +32.77ꢁ(c 0.10, CH2Cl2). 1H NMR (400 MHz,
[ꢀ]2D0

214 Letters in Organic Chemistry, 2011, Vol. 8, No. 3
Chen et al.
3.2.9. Molecular Tweezer 5i
phosgene, triphosgene was used in the synthetic process of
these tweezers, which provided a convenient and safe
procedure for the synthesis of molecular tweezers.
Prepared according to the general procedure to afford the
product 5i as a yellow crystals; yield 88%; Mp: 86–87ꢀ.
= +37.87ꢁ(c 0.068, CH2Cl2). 1H NMR (400 MHz,
[ꢀ]2D0
ACKNOWLEDGEMENT
CDCl3) ꢀ 0.61 (d, 3H, J = 6.0 Hz, 21-CH3), 0.68 (s, 3H, 18-
CH3), 0.93 (s, 3H, 19-CH3), 2.32-2.40 (m, 1H, OH), 2.69-
3.23 (m, 2H, PhCH2), 3.52 (s, 3H, COOCH3), 3.71 (s, 3H,
COOCH3), 4.58-4.64 (m, 1H, 3ꢁ-H), 4.87 (s, 1H, 12ꢁ-H),
5.03-5.09 (m, 1H, NCH), 5.14 (d, 1H, J = 9.2 Hz, CONH),
6.77 (d, 2H, J = 8.4 Hz, ArH), 6.99 (d, 2H, J = 8.4 Hz, ArH),
7.48-7.62 (m, 3H, ArH), 7.88 (d, 1H, J = 8.0 Hz, ArH), 8.01
(d, 1H, J = 8.4 Hz, ArH), 8.21 (d, 1H, J = 8.4 Hz, ArH), 8.87
(d, 1H, J = 8.8 Hz, ArH); IR (KBr, cm-1): 3432, 2943, 2868,
1712, 1515, 1445, 1247, 1201; ESI–MS m/z (%): 1586.7
[(2M+23)+, 100]; Elemental analysis: Found (%): C, 72.23;
H, 7.57; N, 1.81 Calcd. For C47H59NO9: C, 72.19; H, 7.60;
N, 1.79.
We are grateful to the State Ethnic Affairs Commission
of P.R. China (Project No.09XN08) for providing financial
support for this project.
SUPPLEMENTARY MATERIAL
Supplementary material is available on the publishers
Web site along with the published article.
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3.2.10. Molecular Tweezer 5j
Prepared according to the general procedure to afford the
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[ꢀ]2D0
[3]
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CDCl3) ꢀ 0.71 (s, 3H, 18-CH3), 0.77 (d, 3H, J = 6.0 Hz, 21-
CH3), 0.94 (s, 3H, 19-CH3), 3.20-3.36 (m, 2H, PhCH2), 3.47
(s, 3H, COOCH3), 3.72 (s, 3H, COOCH3), 4.70-4.75 (m, 1H,
3ꢁ-H), 4.94 (s, 1H, 12ꢁ-H), 5.03-5.09 (m, 1H, NCH), 5.29
(d, 1H, J = 10.0 Hz, CONH), 7.00-7.29 (m, 5H, ArH+indole-
CH), 7.42-7.61 (m, 3H, ArH), 7.88 (d, 1H, J = 8.0 Hz, ArH),
8.00 (d, 1H, J = 8.4 Hz, ArH), 8.16 (d, 1H, J = 7.2 Hz, ArH),
8.60 (s, 1H, indole-NH), 8.85 (d, 1H, J = 8.4 Hz, ArH); IR
(KBr, cm-1): 3397, 2944, 2867, 1714, 1508, 1447, 1245,
1015; ESI–MS m/z (%): 827.7 [(M+23)+, 100]; Elemental
analysis: Found (%): C, 73.07; H, 7.48; N, 3.50 Calcd. For
C49H60N2O8: C, 73.11; H, 7.51; N, 3.48.
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[5]
[6]
[7]
3.3. General Procedure for the Synthesis of Molecular
Tweezers 5a-5j Under Conventional Heating Method
Triphosgene (0.2 mmol) was added to a solution of
compound 3 (0.5 mmol) in 20 mL dry dichloromethane and
0.1 mL dry pyridine at room temperature. The solution was
refluxing for 18 h, and compound 4 was formed, then L-
amino acid methyl esters hydrochloride (1 mmol) and 0.2
mL dry pyridine were added directly to the mixture which
was further refluxed for 17-21 h. The solvent was removed
and the residue was diluted with 20 mL ethyl acetate and
washed with 10% NaHCO3 (10 mLꢀ3), brine (10 mLꢀ3),
and finally dried over anhydrous Na2SO4. The crude product
was purified by column chromatography on silica gel H with
dichloromethane/ethyl acetate as eluant, in 38~71% yields.
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Ramesh, E.; Raghunathan, R. An expedient microwave-assisted,
solvent-free, solid-supported synthesis of pyrrolo[2,3-d]pyrimidine-
pyrano[5,6-c]coumarin/[6,5-c]chromone
derivatives
by
intramolecular hetero Diels–Alder reaction. Tetrahedron Lett.,
2008, 49, 1812-1817.
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Shi, Y.; Zhao, Z.-G.; Liu, X.-L. Synthesis of chiral molecular
tweezers based on o,o'-diphenic acid under microwave irradiation.
Chin. J. Org. Chem., 2007, 27, 898-901 (in chinese).
Zhao, Z.-G.; Liu, X.-L.; Chen, S.-H. Microwave assisted synthesis
of chiral molecular tweezers derived from ꢂ-hyodeoxycholic acid.
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and efficient synthesis of ester-type molecular tweezers derived
from hyodeoxycholic acid in solvent-free conditions under
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Xue, C.-H.; Hu, R.; Mu, Q.-M.; Li, F.; Chen, S.-H.
Enantioselective recognition of amino acid derivatives by chiral
CONCLUSION
In summary, we developed a successful synthetic route to
prepare a novel class of chiral molecular tweezers based on
deoxycholic acid under microwave irradiation in one-pot.
The present method has many advantages comparing to the
conventional method, such as shorter reaction times, good
product yields and finally agreement with the green
chemistry protocols. In addition, avoiding the use of toxic
[13]
[14]

A Facile and Efficient Approach to the Synthesis
Letters in Organic Chemistry, 2011, Vol. 8, No. 3
215
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[15]
Liu, X.-L.; Zhao, Z.-G.; Zeng, B.-T. Solvent-fee synthesis of
molecular tweezer artificial receptors derived from deoxycholic