Microwave-assisted synthesis and recognition properties of chiral molecular tweezers based on deoxycholic acid

Article abstract of DOI:10.3184/174751913X13700971595393

Ten novel methyl 3α-(4-nitrobenzoylhydrazides)-12α-(L-amino acid carbamates)-cholan-24-oate chiral molecular tweezers based on deoxycholic acid have been easily constructed using microwave irradiation. Their structures were characterised by IR, ¹

Full text of DOI:10.3184/174751913X13700971595393

394 RESEARCH PAPER
JULY, 394–397
JOURNAL OF CHEMICAL RESEARCH 2013
Microwave-assisted synthesis and recognition properties of chiral
molecular tweezers based on deoxycholic acid
Min Liu, Xiaohong Wang, Qingwei Bi and Zhigang Zhao*
College of Chemistry and Environmental Protection Engineering, Southwest University for Nationalities, Chengdu 610041, P. R. China
Ten novel methyl 3α-(4-nitrobenzoylhydrazides)-12α-(L-amino acid carbamates)-cholan-24-oate chiral molecular
tweezers based on deoxycholic acid have been easily constructed using microwave irradiation. Their structures were
1
characterised by IR, H NMR, MS spectra and elemental analysis and their molecular recognition properties were
investigated by UV-Vis spectral titration. The preliminary study indicated that these target compounds possess good
selectivity for D/L amino acid methyl esters.
Keywords: molecular tweezers, microwave irradiation, deoxycholic acid, molecular recognition
During the past decade, molecular recognition by synthetic
receptors has grown to be a large research field, developing
into a distinct branch of supramolecular chemistry.1–6 The
design and synthesis of molecular tweezers has been a subject
of considerable research interest because of their extensive
applications as an artificial receptor.7–9
Bile acids have been widely used as building blocks for the
construction of receptors because of their rigid backbone,
amphiphilicity, and the 3- and 12-hydroxyl groups which they
possess.10,11 Such studies have not only advanced our know-
ledge in understanding fundamental molecular interactions but
have also led to the design of novel molecular tweezers based
on bile acids.
Microwave-assisted synthesis is an eco-friendly green
approach which is widely used in organic research.12–17 The
method is valuable in reducing reaction times, enhancing con-
versions, simplifying work-up and lessening by-products.18,19
We now report a novel and efficient microwave-assisted syn-
thesis method that was developed to synthesise molecular
tweezers from deoxycholic acid methyl ester, 4-nitrobenzoyl-
hydrazide and different L-amino acid methyl esters using
triphosgene as a bridge. The synthetic route is shown in
Scheme 1.
Reagents and conditions: (i) CH3OH, CH3COCl, ice bath;
(ii) dichloromethane, triphosgene, pyridine, MWI; (iii) 4-
nitrobenzoylhydrazide, pyridine, MWI; (iv) dichloromethane,
triphosgene, pyridine, MWI; and (v) L-amino acid methyl
esters hydrochloride, pyridine, MWI.
determined by adding the guest to fixed concentrations of the
hosts and after they were fully coordinated to each other to
form the host–guest complexes (total adding volume of guest
should less than 100 µL so that we can ignore influence of the
volume change). The UV-Vis plot of 6a for D-Phe-OMe is
shown in Fig. 1, it shows that the absorbance value of hosts
had risen in a regular fashion.
The titration data were analysed by using the Hildebrand–
Benesi equation. The plot with 1/∆A versus the 1/[G]0 gave a
straight line (Fig. 2) supporting a stoichiometry of 1:1 host–
guest complexes. The association constants of complexes were
obtained using linear fitting method. The final results show
that molecular tweezers have good ability to form complexes
with guests.
As shown in Table 3, the molecular tweezers 6a, 6e and 6i
not only recognised all the amino acid methyl esters but also
exhibited good selectivity for D-amino acid methyl esters.
The maximum KD /KL of molecular tweeter 6i reached 3.89 for
D/L-Phe-OMe. The details of the molecular recognition of
these molecular tweezers are under further study.
Experimental
Melting points were determined on a micro-melting point apparatus
and the thermometer was uncorrected. IR spectra were obtained on
1
1700 Perkin-Elmer FTIR using KBr disks. H NMR spectra were
recorded on a Varian INOVA 400 MHz spectrometer using TMS as
internal standard. Mass spectra were determined on Finnigan LCQDECA
instrument. Elemental analysis was performed on a Carlo-Erba-1106
autoanalyser. Optical rotation was measured on a Wzz-2B polari-
meter. All reactions were performed in a commercial microwave
reaction (XH-100A, 100–1000W, Beijing XiangHu Science and Tech-
nology Development Co. Ltd, Beijing, P.R.China). All the solvents
were purified before use. Intermediate 2 was prepared following a
reported procedure.20
Results and discussion
A series of experiments were carried out in order to make a
quantitative comparison between microwave irradiation (MWI)
and conventional heating in the synthesis of molecular
tweezers 6a–j. The results are shown in Tables 1–3.
We took the synthesis of 6a as an example and a series of
reaction conditions influencing yields have been optimised,
such as microwave irradiation (MWI) power, time and solvent.
We conclude (see Table 1) that CH2Cl2, 20 min and 250 W
were the optimum reaction conditions.
As shown in Table 2, reaction times decreased from 2100–
2460 min to 18–21 min, but yields increased from 40–70% to
82–90%. The superiority of microwave-assisted method is
obvious.
Compounds 6a, 6e and 6i were selected to investigate their
recognition of the guests D/L-Phe-OMe and D/L-Tyr-OMe by
UV-Vis spectra titration in CHCl3 at 25 °C. The association
constants were determined.
In tests of UV-Vis spectra titration, concentrations of host
solution 6a, 6e and 6i were been prepared as 1.0×10–5–10×10–5
mol L−1 in 10 mL volumetric flask. Absorbance values were
Microwave synthesis of intermediate 4
Dry pyridine (0.1 mL) was added to a mixed solution of compound 2
(0.5 mmol) and triphosgene (0.17 mmol) in dry dichloromethane
(10 mL) at room temperature. After irradiating the mixture for 6 min
at 250 W, compound 3 was formed, then 4-nitrobenzoylhydrazide
(1 mmol) and dry pyridine (0.2 mL) were added directly to the mixture
which was irradiated continually for 9 min at the same power. The
solvent was removed and the residue was diluted with ethyl acetate
(20 mL) and washed with 1% HCl (10 mL×3), brine (10 mL×3),
finally dried over anhydrous Na2SO4. The crude product was purified
by column chromatography on silica gel H with dichloromethane/
acetone as eluant to give the product as a pale yellow solid, yield 90%,
m.p.116–117 °C; [α]2D0+113.9 (c 0.11, CH2Cl2); IR (KBr) (cm−1): 3287,
2941, 2869, 1727, 1603, 1529, 1452, 1348, 1251, 1039, 853; 1H NMR
(400 MHz, CDCl3) δ 8.55 (s, 1H, NO2-PhCONH), 8.29 (d, J = 8.4 Hz,
2H, ArH), 8.00 (d, J = 8.4 Hz, 2H, ArH), 7.10 (s, 1H, 3α-OCONH),
4.73–4.67 (m, 1H, 3β-H), 4.00 (s, 1H, 12β-H), 3.67 (s, 3H, COOCH3),
0.98 (d, J = 6.0 Hz, 3H, 21-CH3), 0.92 (s, 3H, 19-CH3), 0.68 (s, 3H,
18-CH3); ESI-MS m/z (%): 636.32 ([M+Na]+, 100). Anal. Calcd for
C33H47N3O8: C, 64.58; H, 7.72; N, 6.85. Found: C, 64.50; H, 7.74; N,
6.83%.
* Correspondent. E-mail: zzg63129@yahoo.com.cn

JOURNAL OF CHEMICAL RESEARCH 2013 395
Scheme 1 The synthetic route of molecular tweezers 6a–j.
Microwave synthesis of molecular tweezers 6a–j
methyl esters hydrochloride (1 mmol) and dry pyridine (0.2 mL) were
added directly to the mixture, and irradiated continually for 9–12 min
at the same power. The solvent was removed and the residue was
diluted with ethyl acetate (20 mL) and washed with 1% HCl
(10 mL×3), brine (10 mL×3), and finally dried over anhydrous
Dry pyridine (0.1 mL) was added to a mixed solution of compound 4
(0.5 mmol) and triphosgene (0.17 mmol) in dry dichloromethane
(10 mL) at room temperature. After irradiating the reaction mixture
for 9 min at 250 W, compound 5 was formed, then the L-amino acid
Table 1 Optimising microwave-assisited reaction conditions
of receptor 6a
Table 2 Synthetic comparison of molecular tweezers 6a–j
between microwave irradiation and conventional heating
Compd.
Solvent
T/min
Power/W
Yield/%
a
Compd. Conventional method Microwave method tC/tMW
6a
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
THF
15
18
20
25
20
20
20
18
20
25
18
20
25
250
250
250
250
100
200
300
250
250
250
250
250
250
55
70
88
80
50
75
72
67
76
71
64
80
73
t/min
Yield/%
t/min
Yield/%
6a
6b
6c
6d
6e
6f
2100
2100
2400
2100
2280
2340
2160
2340
2400
2460
68
50
62
48
70
69
55
58
65
40
20
19
19
20
18
18
20
20
19
21
88
84
86
82
90
88
85
86
85
83
105
110
126
105
127
130
108
117
126
117
THF
6g
6h
6i
THF
CHCl3
CHCl3
CHCl3
6j
a tC, Conventional method time; tMW, microwave method time.

396 JOURNAL OF CHEMICAL RESEARCH 2013
1
Table3 Associationconstants(Ka)fortheinclusioncomplexes
of molecular tweezers 6a, 6e and 6i with amino acid methyl
esters in CHCl3 at 25 °C
1529, 1447, 1347, 1248, 1033, 850; H NMR (400 MHz, CDCl3)
δ 8.54 (s, 1H, NO2-PhCONH), 8.29 (d, J = 8.4 Hz, 2H, ArH), 8.01 (d,
J = 8.4 Hz, 2H, ArH), 7.11 (s, 1H, 3α-OCONH), 5.27 (s, 1H, 12α-
OCONH), 4.96 (s, 1H, 12β-H), 4.71 (s, 1H, 3β-H), 4.35–4.31 (m, 1H,
NCH), 3.76 (s, 3H, COOCH3), 3.66 (s, 3H, COOCH3), 0.90 (s, 3H,
19-CH3), 0.86 (d, J = 6.0 Hz, 3H, 21-CH3), 0.73 (s, 3H, 18-CH3);
ESI-MS m/z (%): 793.31 ([M+Na]+,100).Anal. Calcd for C40H58N4O11:
C, 62.32; H, 7.58; N, 7.27. Found: C, 62.43; H, 7.56; N, 7.26%.
6b: Pale yellow solid, yield 84%, m.p. 102–103 °C; [α]2D0+116.8
(c 0.12, CH2Cl2); IR (KBr)(cm−1): 3329, 2952, 2870, 1728, 1640,
Host
Guest
Ka /L·mol−1
KD /KL
6a
D-Phe-OMe
L-Phe-OMe
D-Tyr-OMe
L-Tyr-OMe
128.68
48.52
104.98
36.70
2.65
2.86
6e
6i
D-Phe-OMe
L-Phe-OMe
D-Tyr-OMe
L-Tyr-OMe
272.50
123.51
136.80
57.91
2.21
2.36
1
1529, 1466, 1347, 1245, 1040, 851; H NMR (400 MHz, CDCl3)
δ 8.81 (s, 1H, NO2-PhCONH), 8.28 (d, J = 8.0 Hz, 2H, ArH), 8.01 (d,
J = 8.0 Hz, 2H, ArH), 7.14 (s, 1H, 3α-OCONH), 5.17 (s, 1H, 12α-
OCONH), 4.96 (s, 1H, 12β-H), 4.69 (s, 1H, 3β-H), 4.44 (s, 1H, NCH),
3.74 (s, 3H, COOCH3), 3.66 (s, 3H, COOCH3), 0.90 (s, 3H, 19-CH3),
0.85 (d, J = 6.0 Hz, 3H, 21-CH3), 0.72 (s, 3H, 18-CH3); ESI-MS m/z
(%): 807.24 ([M+Na]+, 100). Anal. Calcd for C41H60N4O11: C, 62.74;
H, 7.70; N, 7.14. Found: C, 62.69; H, 7.69; N, 7.17%.
D-Phe-OMe
L-Phe-OMe
D-Tyr-OMe
L-Tyr-OMe
168.81
41.6
497.32
186.76
3.89
2.66
6c: Pale yellow solid, yield 86%, m.p. 106–107 °C; [α]2D0+118.9
(c 0.12, CH2Cl2); IR (KBr)(cm−1): 3314, 2950, 2870, 1730, 1603,
1
1529, 1447, 1347, 1249, 1047, 850; H NMR (400 MHz, CDCl3)
δ 9.05 (s, 1H, NO2-PhCONH), 8.28 (d, J = 8.4 Hz, 2H, ArH), 8.03 (d,
J = 8.4 Hz, 2H, ArH), 7.61 (s, 1H, 3α-OCONH), 6.04 (s, 1H, 12α-
OCONH), 5.00 (s, 1H, 12β-H), 4.69 (s, 1H, 3β-H), 4.43 (s, 1H, NCH),
4.10 (d, J = 9.2 Hz, 1H, OCH), 3.96 (d, J = 9.2 Hz, 1H, OCH), 3.80
(s, 3H, COOCH3), 3.66 (s, 3H, COOCH3), 0.90 (s, 3H, 19-CH3), 0.86
(d, J = 6.0 Hz, 3H, 21-CH3), 0.73 (s, 3H, 18-CH3); ESI-MS m/z (%):
781.30 ([M+Na]+, 100). Anal. Calcd for C38H54N4O12: C, 60.14; H,
7.17; N, 7.38. Found: C, 60.18; H, 7.15; N, 7.36%.
6d: Pale yellow solid, yield 82%, m.p. 104–105 °C; [α]2D0+59.7
(c 0.13, CH2Cl2); IR (KBr)(cm−1): 3311, 2956, 2872, 1734, 1602,
1
1529, 1454, 1346, 1247, 1040, 853; H NMR (400 MHz, CDCl3)
δ 8.73 (s, 1H, NO2-PhCONH), 8.30 (d, J = 8.4 Hz, 2H, ArH), 8.00
(d, J = 8.4 Hz, 2H, ArH), 7.07 (s, 1H, 3α-OCONH), 5.29 (s, 1H, 12α-
OCONH), 4.96 (s, 1H, 12β-H), 4.71 (s, 1H, 3β-H), 4.38 (d, J = 8.8 Hz,
1H, NCH), 3.75 (s, 3H, COOCH3), 3.66 (s, 3H, COOCH3), 0.90 (s,
3H, 19-CH3), 0.86 (d, J = 6.0 Hz, 3H, 21-CH3), 0.72 (s, 3H, 18-CH3);
ESI-MS m/z (%): 807.32 ([M+Na]+,100).Anal. Calcd for C41H60N4O11:
C, 62.74; H, 7.70; N, 7.14. Found: C, 62.70; H, 7.72; N, 7.12%.
6e: Pale yellow solid, yield 90%, m.p. 88–89 °C; [α]2D0-46.6 (c 0.14,
CH2Cl2); IR (KBr)(cm−1): 3348, 2948, 2868, 1732, 1604, 1528, 1446,
Fig. 1 UV-Vis spectra of molecular tweezers 6a (8×10–5mol L–1)
in the presence of D-Phe-OMe (a) 0 mol L–1, (b) 0.38×10–3 mol L–1,
(c) 0.76×10–3 mol L–1, (d) 1.14×10–3 mol L–1, (e) 1.52×10–3 mol L–1,
(f) 1.90×10–3 mol L–1, (g) 2.28×10–3 mol L–1, (h) 2.66×10–3 mol L–1,
(i) 3.04×10–3 mol L–1, (j) 3.42×10–3 mol L–1 with λmax at 261.0 nm.
1
1348, 1246, 1041, 851; H NMR (400 MHz, CDCl3) δ 8.62 (s, 1H,
NO2-PhCONH), 8.26 (d, J = 8.4 Hz, 2H, ArH), 7.97 (d, J = 8.4 Hz,
2H, ArH), 7.33–7.28 (m, 4H, ArH), 7.20–7.07 (m, 2H, ArH+3α-
OCONH), 5.24 (s, 1H, 12α-OCONH), 4.94 (s, 1H, 12β-H), 4.74–4.68
(m, 2H, NCH+3β-H), 3.75 (s, 3H, COOCH3), 3.69 (s, 3H, COOCH3),
3.20–3.02 (m, 2H, PhCH2), 0.90 (s, 3H, 19-CH3), 0.79 (d, J = 6.0 Hz,
3H, 21-CH3), 0.71 (s, 3H, 18-CH3); ESI-MS m/z (%): 841.34
([M+Na]+,100). Anal. Calcd for C44H58N4O11: C, 64.53; H, 7.14; N,
6.84. Found: C, 64.48; H, 7.16; N, 6.83%.
6f: Pale yellow solid, yield 88%, m.p. 109–110 °C; [α]2D0-22.1
(c 0.12, CH2Cl2); IR (KBr)(cm−1): 3312, 2949, 2869, 1734, 1603,
1
1528, 1449, 1347, 1250, 1045, 851; H NMR (400 MHz, CDCl3)
δ 8.84 (s, 1H, NO2-PhCONH), 8.25 (d, J = 8.8 Hz, 2H, ArH), 7.99 (d,
J = 8.8 Hz, 2H, ArH), 7.37 (brs, 5H, ArH), 7.12 (s, 1H, 3α-OCONH),
5.87 (s, 1H, 12α-OCONH), 5.42 (d, J = 6.8 Hz, 1H, NCH), 4.94 (s,
1H, 12β-H), 4.70 (s, 1H, 3β-H), 3.74 (s, 3H, COOCH3), 3.67 (s, 3H,
COOCH3), 0.90 (s, 3H, 19-CH3), 0.64 (d, J = 6.0 Hz, 3H, 21-CH3),
0.62 (s, 3H, 18-CH3); ESI-MS m/z (%): 827.29 ([M+Na]+,100). Anal.
Calcd for C43H56N4O11: C, 64.16; H, 7.01; N, 6.96. Found: C, 64.12; H,
7.03; N, 6.98%.
6g: Pale yellow solid, yield 85%, m.p. 100–101 °C; [α]2D0+32.6
(c 0.13, CH2Cl2); IR (KBr)(cm−1): 3331, 2948, 2869, 1734, 1604,
1
1529, 1451, 1347, 1247, 1040, 852; H NMR (400 MHz, CDCl3)
δ 8.65 (s, 1H, NO2-PhCONH), 8.29 (d, J = 8.0 Hz, 2H, ArH), 8.00 (d,
J = 8.0 Hz, 2H, ArH), 7.07 (s, 1H, 3α-OCONH), 5.34 (s, 1H, 12α-
OCONH), 4.97 (s, 1H, 12β-H), 4.70 (s, 1H, 3β-H), 4.44–4.41 (m, 1H,
NCH), 3.77 (s, 3H, COOCH3), 3.66 (s, 3H, COOCH3), 0.91 (s, 3H,
19-CH3), 0.86 (d, J = 6.0 Hz, 3H, 21-CH3), 0.72 (s, 3H, 18-CH3); ESI-
MS m/z (%): 765.33 ([M+Na]+, 100). Anal. Calcd for C38H54N4O11: C,
61.44; H, 7.33; N, 7.54. Found: C, 61.46; H, 7.30; N, 7.52%.
Fig. 2 Typical plot of 1/∆A versus 1/[G]0 for the inclusion
complex of molecular tweezer 6a with D-Phe-OMe in CHCl3 at
25 °C.
Na2SO4. The crude product was purified by column chromatography
on silica gel H with dichloromethane/acetone as eluant. The physical
and spectra data of the compounds 6a–j are as follows.
6h: Pale yellow solid, yield 86%, m.p. 106–107 °C; [α]2D0+183.9
(c 0.15, CH2Cl2); IR (KBr)(cm−1): 3317, 2948, 2869, 1733, 1604,
6a: Pale yellow solid, yield 88%, m.p. 106–107 °C; [α]2D0+101.8
(c 0.15, CH2Cl2); IR (KBr)(cm−1): 3321, 2953, 2871, 1733, 1604,

JOURNAL OF CHEMICAL RESEARCH 2013 397
1
1528, 1444, 1347, 1248, 1043, 852; H NMR (400 MHz, CDCl3)
The work was financially supported by the Postgraduate
Innovation Project of Southwest University for Nationalities
(No.CX2013SZ26), the Science and Technology Department
of Sichuan Province (No.2012SZ0160) and the Fundamental
Research Funds of the Central University, Southwest Univer-
sity for Nationalities (No.11NZYTH05).
δ 8.76 (s, 1H, NO2-PhCONH), 8.28 (d, J = 7.6 Hz, 2H, ArH), 7.99 (d,
J = 7.6 Hz, 2H, ArH), 7.13 (s, 1H, 3α-OCONH), 5.43 (s, 1H, 12α-
OCONH), 4.97 (s, 1H, 12β-H), 4.70 (s, 1H, 3β-H), 4.52 (d, J = 4.8 Hz,
1H, NCH), 3.77 (s, 3H, COOCH3), 3.66 (s, 3H, COOCH3), 0.90 (s,
3H, 19-CH3), 0.86 (d, J = 6.0 Hz, 3H, 21-CH3), 0.72 (s, 3H, 18-CH3);
ESI-MSm/z(%):825.35([M+Na]+,100).Anal.CalcdforC40H58N4O11S:
C, 59.83; H, 7.28; N, 6.98. Found: C, 59.70; H, 7.26; N, 6.97%.
6i: Pale yellow solid, yield 85%, m.p. 112–113 °C; [α]2D0+100.4
(c 0.16, CH2Cl2); IR (KBr)(cm−1): 3325, 2949, 2869, 1725, 1605,
Received 16 February 2013; accepted 17 April 2013
Paper 1301796 doi: 10.3184/174751913X13700971595393
Published online: 18 July 2013
1
1525, 1445, 1348, 1248, 1045, 850; H NMR (400 MHz, CDCl3)
δ 8.98 (s, 1H, NO2-PhCONH), 8.26 (d, J = 8.4 Hz, 2H, ArH), 8.10 (d,
J = 8.4 Hz, 2H, ArH), 7.50 (s, 1H, 3α-OCONH), 7.01 (d, J = 8.0 Hz,
2H, ArH), 6.80 (d, J = 8.0 Hz, 2H, ArH), 5.19 (s, 1H, 12α-OCONH),
4.89 (s, 1H, 12β-H), 4.68 (s, 1H, 3β-H), 4.53 (d, J = 8.8 Hz, 1H, NCH),
3.78 (s, 3H, COOCH3), 3.72 (s, 3H, COOCH3), 3.66 (s, 1H, OH),
3.24–2.83 (m, 2H, PhCH2), 0.87 (s, 3H, 19-CH3), 0.67 (brs, 6H, 21-
CH3 +18-CH3); ESI-MS m/z (%): 857.33 ([M+Na]+,100). Anal. Calcd
for C44H58N4O12: C, 63.29; H, 7.00; N, 6.71. Found: C, 63.40; H, 7.01;
N, 6.68%.
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6j: Yellow solid, yield 83%, m.p. 114–115 °C; [α]2D0+72.4 (c 0.13,
CH2Cl2); IR (KBr)(cm−1): 3354, 2928, 2867, 1726, 1604, 1528, 1453,
1
1346, 1247, 1045, 851; H NMR (400 MHz, CDCl3) δ 8.83 (s, 1H,
indole-NH), 8.77(s, 1H, NO2-PhCONH), 8.14 (d, J = 8.0 Hz, 2H,
ArH), 7.90 (d, J = 8.0 Hz, 2H, ArH), 7.54 (d, J = 7.2 Hz, 1H, ArH),
7.31 (d, J = 6.8 Hz, 1H, ArH), 7.15–7.09 (m, 3H, ArH+3α-OCONH),
7.02 (s, 1H, indole-CH), 5.30 (d, J = 6.4 Hz, 1H, 12α-OCONH), 4.94
(s, 1H, 12β-H), 4.77 (s, 1H, NCH), 4.65 (s, 1H, 3β-H), 3.74 (d, J =
5.2 Hz, 6H, COOCH3), 3.38–3.27 (m, 2H, indole-CH2), 0.87 (s, 3H,
19-CH3), 0.81 (d, J = 6.0 Hz, 3H, 21-CH3), 0.70 (s, 3H, 18-CH3);
ESI-MS m/z (%): 880.36 ([M+Na]+,100).Anal. Calcd for C46H59N5O11:
C, 64.39; H, 6.93; N, 8.16. Found: C, 64.42; H, 6.91; N, 8.14%.
10 F.L. Devedec, D. Fuentealba, S. Strandman, C. Bohne and X.X. Zhu,
Langmuir, 2012, 28, 13431.
11 R.K. Chhatra, A. Kumar and P.S. Pandey, J. Org. Chem., 2011, 76, 9086.
12 P.S. Vargas, F.A. Rosa, L. Buriol, M. Rotta, D.N. Moreira, C.P. Frizzo,
H.G. Bonacorso, N. Zanatta and M.A.P. Martins, Tetrahedron Lett., 2012,
53, 3131.
13 J.F. Collados, E. Toledano, D. Guijarro and M. Yus, J. Org. Chem., 2012,
77, 5744.
14 X.R. Li, Z.G. Zhao, Y.Y. Cheng and H. Li, J. Chem. Res., 2011, 35, 234.
15 J. Bisceglia, J.E. Díaz, R.A. Torres and L.R. Orelli, Tetrahedron Lett.,
2011, 52, 5238.
16 J. Hu, P.Yu, T.Y. Zhou and Y.H. Xu, J. Chem. Res., 2011, 35, 672.
17 Z.Y. Mei, P. Liu, Z.H. Li, F.G. Liang and G.L. Jun, J. Chem. Res., 2012, 36,
536.
18 S.R.K. Pingali and B.S. Jursic, Tetrahedron Lett., 2011, 52, 4371.
19 H. Xu, H. Tian, L.Y. Zheng, Q.W. Liu, L.Wang and S.Q. Zhang, Tetrahedron
Lett., 2011, 52, 2873.
Conventional heating method for 6a–j
Dry pyridine (0.1 mL) was added to a mixed solution of compound 4
(0.5 mmol) and triphosgene (0.17 mmol) in dry dichloromethane
(10 mL) at room temperature. The solution was refluxed for 15 h,
and compound 5 was formed. Then L-amino acid methyl esters hydro-
chloride (1 mmol) and dry pyridine (0.2 mL) were added directly to
the mixture which was further refluxed for 20–26 h. The solvent was
removed and the residue was diluted with ethyl acetate (20 mL) and
washed with 1% HCl (10 mL×3), brine (10 mL×3), and finally dried
over anhydrous Na2SO4. The crude product was purified by column
chromatography on silica gel H with dichloromethane/acetone as
eluant, in 40–70% yields.
20 X.L. Liu, Z.G. Zhao and B.T. Zeng, Chin. J. Org. Chem., 2007, 27, 994
(in Chinese).

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