Asymmetric synthesis and cytotoxicity of (-)-saframycin A analogues

Article abstract of DOI:10.1016/j.ejmech.2012.01.017

(-)-Saframycin A and its nineteen analogues were prepared from l-tyrosine in 24 steps, and their structures were confirmed through NMR and HRMS. The cytotoxicities of these compounds were tested against HCT-8, BEL-7402, Ketr3, A2780, MCF-7, A549, BGC-803,

Full text of DOI:10.1016/j.ejmech.2012.01.017

European Journal of Medicinal Chemistry 49 (2012) 239e244
Contents lists available at SciVerse ScienceDirect
European Journal of Medicinal Chemistry
journal homepage: http://www.elsevier.com/locate/ejmech
Original article
Asymmetric synthesis and cytotoxicity of (ꢀ)-saframycin A analogues
,b,
Wenfang Dong a, Wei Liu a, Zheng Yan a, Xiangwei Liao b, Baohe Guan b, Nan Wang b, Zhanzhu Liu a
*
a State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical
Sciences, Beijing 100050, PR China
b Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical
Sciences, Beijing 100050, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
(ꢀ)-Saframycin A and its nineteen analogues were prepared from
L-tyrosine in 24 steps, and their
Received 24 November 2011
Received in revised form
9 January 2012
Accepted 9 January 2012
Available online 15 January 2012
structures were confirmed through NMR and HRMS. The cytotoxicities of these compounds were tested
against HCT-8, BEL-7402, Ketr3, A2780, MCF-7, A549, BGC-803, Hela, HELF and KB cell lines. The IC50
values of the cytotoxicity of most compounds were at the level of nM. Compound 7d with 2-furan amide
side chain showed the most potent cytotoxicity of all these compounds with an average IC50 value of
6.06 nM.
Ó 2012 Elsevier Masson SAS. All rights reserved.
Keywords:
Tetrahydroisoquinoline
(ꢀ)-Saframycin A
Cytotoxicity
Synthesis
1. Introduction
structureeactivity relationship of the related tetrahydoisoquino-
line alkaloids have also been reported [16e22]. However, the
The tetrahydroisoquinoline family includes a number of natural
products that display a range of biological properties such as
antitumour and antimicrobial activities [1]. As the typical member
of this family, Et-743 has a unique antitumour mechanism of action
and has been launched in Europe for treating soft tissue sarcoma
[2e6]. The remarkable clinical results of Et-743 have stimulated
further research and resulted in the discovery of several simplified
analogues of this family, such as Zalypsis [7,8] and QAD [9].
(ꢀ)-Saframycin A, a member of the tetrahydroisoquinoline
antibiotics with very potent antitumour activity, was isolated from
Streptomyces lavendulae in 1977 by Arai et al [10,11] (Fig. 1). There
have been several reports on the investigation of the mechanism of
action of (ꢀ)-saframycin A [12e14]. Generally, it is believed that the
guanine residues of doubleestranded DNA in the minor groove of
the tumour cell are alkylated by an iminium ion generated from the
amino nitrile function of (ꢀ)-saframycin A in the presence of
reducing cofactors [12]. Myers et al reported the study on the
structureeactivity relationship of a series of the bishydroquinone
structureeactivity relationship of the bisquinone analogues of
(ꢀ)-saframycin A has not been studied so far.
In this paper, nineteen C-22 amide analogues of (ꢀ)-saframycin
A were synthesized in 24 steps employing the synthetic route we
established before, which featured the use of
L-tyrosine as the
starting material [23]. All analogues were evaluated in contrast to
(ꢀ)-saframycin A for their in vitro cytotoxicity against a panel of
human tumour cell lines, including HCT-8, BEL-7402, Ketr3, A2780,
MCF-7, A549, BGC-803, Hela, HELF and KB cells.
2. Chemistry
The preparation of compound 2 basically followed the synthetic
route we had built previously [23]. Compound 3 was prepared by
acylation of compound 2 with different acids using EDC as the
condensation agent. Synthesis of the amide analogues at C-22 of
(ꢀ)-saframycin A was accomplished by oxidation of compound 3
with air in the presence of salcomine at room temperature in
60e80% yield. Totally twenty compounds were synthesized,
including cinnamic acid analogues 4aef, hippuric acid analogue 5a,
tert-butyl carbamate analogue 5b, substituted aromatic acid
analogues 6aed, heterocyclic aromatic acid analogues 7aeg, as
well as (ꢀ)-saframycin A. All these compounds were characterized
by their HRMS, 1H NMR and 13C NMR (Scheme 1).
analogues of (ꢀ)-saframycin
A [15]. Other studies on the
* Corresponding author. Peking Union Medical College and Chinese Academy of
Medical Sciences, Institute of Materia Medica, State Key Laboratory of Bioactive
Substances and Functions of Natural Medicines, 1 Xian Nong Tan Street, Beijing
100050, PR China. Tel.: þ86 10 63165253; fax: þ86 10 63017757.
E-mail address: liuzhanzhu@imm.ac.cn (Z. Liu).
0223-5234/$ e see front matter Ó 2012 Elsevier Masson SAS. All rights reserved.
doi:10.1016/j.ejmech.2012.01.017

240
W. Dong et al. / European Journal of Medicinal Chemistry 49 (2012) 239e244
OMe
against A549. Four compounds (4c, 4e, 6a, and 7f), all of which had
O
Me
O
electronerich aromatic rings, showed higher antitumour activity
than (ꢀ)-saframycin A against BGC-803. Compound 1, the reductive
form of 5b, showed decreased antitumour activity against most cell
lines in comparison with 5b. Although a general structureeactivity
relationship of the amide analogues at C-22 of (ꢀ)-saframycin A
could not be summarized from these data, these data showed that
the side chain of the amide group appeared to be closely related to
the antitumour activity.
HO
O
O
OMe
4
NH
HO
Me
MeO
Me
11 N Me
O
3
AcO
S
N
21
14
13
MeO
O
1
Me
N
Me
CN
22 NH
N
O
O
O
O
OH
CH3
(-)-Saframycin A
Et-743
1
5. Conclusions
(ꢀ)-saframycin A and its nineteen analogues were prepared
OMe
Me
OMe
Me
from L-tyrosine employing the synthetic route we had established
HO
Me
HO
Me
previously. The cytotoxicity of these compounds was tested against
HCT-8, BEL-7402, Ketr3, A2780, MCF-7, A549, BGC-803, Hela, HELF
and KB cell lines by MTT assay. Most of the compounds showed
potent antitumour activity with the IC50 values at the nM level.
Some compounds showed better antitumour activity than
(ꢀ)-saframycin A against A549 and BGC-803. Compound 7d with 2-
furan amide side chain showed the most potent cytotoxicity of all
these compounds with an average IC50 value of 6.06 nM. This study
shows that the side chain of the amide group plays an important
role for the antitumour activity of these analogues.
OAc
OMe
OH
Me
O
Me
OMe
N
N
N
N
MeO
O
OH
CN
NH
NH
N
O
O
CF3
Zalypsis
QAD
Fig. 1. Structures of tetrahydroisoquinoline compounds.
6. Experimental protocols
6.1. General
3. Cytotoxicity
Melting points were obtained on Yanaco MP-500D melting
point apparatus and were uncorrected. Optical rotations were
measured on a PerkinElmer Polarimeter 341LC using 10 cm cells
and the sodium D line (589 nm) at 20 ꢁC and concentration indi-
cated. HRMS were carried out by Agilent LC/MSD TOF. 1H and 13C
NMR spectra were recorded on a Varian Mercury 400 spectrometer
(400 MHz, 1H; 100 MHz, 13C) or a Bruker AV 500 spectrometer
(500 MHz, 1H; 125 MHz, 13C) or a Varian INOVA 600 spectrometer
(600 MHz, 1H; 150 MHz, 13C) in CDCl3, using tetramethylsilane
Cytotoxicity of (ꢀ)-saframycin A analogues was evaluated
against ten human cell lines: HCT-8 (human colon cancer cell line),
BEL-7402 (human hepatic carcinoma cell line), Ketr3 (human renal
cell carcinoma cell line), A2780 (human ovarian cancer cell line),
MCF-7 (human breast cancer cell line), A549 (human lung cancer
cell line), BGC-803 (human gastric adenocarcinoma cell line), Hela
(human cervical cancer cell line), HELF (human embryonic lung
fibroblast cell line) and KB (human oral epidermoid carcinoma cell
line) by the standard MTT assay. The results are shown in Table 1.
(TMS) as an internal standard. Chemical shifts (d) are expressed in
parts per million (ppm), and the following abbreviations are used:
singlet (s), doublet (d), triplet (t), doubled doublet (dd), multiplet
(m), etc. All common reagents and solvents were purchased from
commercial suppliers and purified before use.
4. Results and discussion
Among the six cinnamic acid derivatives (4aef), 4a, 4b, 4c and
4e showed potent cytotoxicity similar to (ꢀ)-saframycin A against
MCF-7 (IC50 value 2.23e5.44 nM) and Hela (3.85e8.33 nM). In
contrast, the IC50 values of these compounds against other cell lines
were at the level of 10ꢀ8 M, which implied that cinnamamide side
chain derivatives appeared to have better selectivity towards MCF-
7 and Hela. Compound 5a, the hippuric acid derivative with the IC50
values at the level of 10ꢀ8 M against most cell lines, showed
decreased cytotoxicity. The tert-butyl carbamate side chain deriv-
ative 5b exhibited potent inhibitory activity against MCF-7 and
Hela with the IC50 values of 8.89 nM and 7.41 nM. Among the four
substituted aromatic acid derivatives (6aed), compound 6a, which
had three electronedonating methoxy groups on the benzene ring,
showed similar cytotoxicity to (ꢀ)-saframycin A against most cell
lines, and even higher cytotoxicity against BGC-803 than
(ꢀ)-saframycin A. Compound 6d with two electronewithdrawing
groups showed the least cytotoxic activity with the IC50 values
greater than 100 nM against most cell lines. Among the seven
heterocyclic aromatic acid derivatives (7aeg), compound 7d with
2-furan amide side chain showed the most potent inhibitory
activity among all the twenty analogues with the average IC50 value
of 6.06 nM. 2-Pyrazinamide derivative 7c also exhibited 20-fold
increase cytotoxic activity in comparison with (ꢀ)-saframycin A
6.2. General procedure for the synthesis of compounds 4ae7g
To a solution of compound 2 (1.0 eq) in CH2Cl2 was added the
corresponding carboxylic acid (1.5 eq), DMAP (1.0 eq) and EDC (1.5
eq), then the mixture was stirred at room temperature for 10 h. The
mixture was diluted with CH2Cl2, washed with saturated aq.
NaHCO3 and brine, dried over anhydrous Na2SO4, concentrated
under reduced pressure to give the crude product. Purification by
column chromatography (PE/EtOAc ¼ 1:1) afforded the amide 3 as
a white solid (yield 75e85%).
To a solution of compound 3 (1.0 eq) in CH3CN was added sal-
comine (1.0 eq) at room temperature, and the dark suspension was
stirred in air for 2 h. The mixture was purified by column chro-
matography (PE/EtOAc ¼ 1:1) and pTLC (PE/EtOAc ¼ 1:1) to afford
compounds 4aef, 5aeb, 6aed, and 7aeg. The preparation and data
of compound 1 and (ꢀ)-saframycin A were the same as reported
before [23].
6.2.1. Data of compound 4a
Yellow solid, yield 80%, mp: 117e119 ꢁC ½aD20ꢂ: ꢀ208 (c 0.10,
CH2Cl2). HRMS calcd for C36H34F3N4O7 [M þ H]þ 691.2374, found

W. Dong et al. / European Journal of Medicinal Chemistry 49 (2012) 239e244
241
OMe
Me
OMe
HO
Me
HO
Me
COOH
ref.23
TFA,rt
90%
Me
Me
N
N
Me
NH2
HO
N
N
MeO
MeO
OH
CN
NH2
OH
CN
NHBoc
L-Tyrosine
2
1
OMe
Me
OMe
O
Me
O
HO
Me
O
Me
Me
N
N
Me
Salcomine
RCOOH
N
N
CH3CN, rt,
60%-80%
EDC, DMAP,
rt, 80%
MeO
MeO
O
CN
NHCOR
OH
CN
NHCOR
4a-f, 5a-b,
3
6a-d, 7a-g
O
O
N
O
O
O
O
O
RCO=
OCH3
OCH3
N
H
O
CF3
OCH3
OCH3
4a
4b
4c
4d
4e
4f
5a
O
O
O
O
O
O
Cl
O
O
O
O
N
CF3
Br
O
O
5b
6a
6b
6c
6d
7a
O
O
O
O
N
O
N
O
S
N
O
N
H
N
7b
7c
7d
7e
7f
7g
Scheme 1. Synthesis of (ꢀ)-saframycin A analogues.
691.2351. 1H NMR (600 MHz, CDCl3):
d
7.69 (s, 1H), 7.62 (d, 1H,
4.02 (s, 3H), 3.92 (s, 1H), 3.87 (s, 3H), 3.66 (s, 1H), 3.64 (s, 1H), 3.43
(d, J ¼ 7.2 Hz, 1H), 3.13e3.10 (m, 1H), 2.90 (d, J ¼ 15.6 Hz, 1H), 2.78
(dd, J ¼ 20.8, 7.6 Hz,1H), 2.48 (d, J ¼ 21.2 Hz,1H), 2.28 (s, 3H),1.92 (s,
3H), 1.72e1.69 (m, 1H), 1.61 (s, 3H), 1.43e1.40 (m, 1H). 13C NMR
J ¼ 8.4 Hz), 7.60 (d, 1H, J ¼ 9.0 Hz), 7.50 (t, 1H, J ¼ 7.8 Hz), 7.45 (d, 1H,
J ¼ 15.6 Hz), 6.15 (d, 1H, J ¼ 15.6 Hz), 5.60 (t, 1H, J ¼ 6.6 Hz), 4.29 (s,
1H), 4.04 (s, 3H), 4.03 (s,1H), 3.91 (s, 3H), 3.89 (s,1H), 3.66e3.58 (m,
2H), 3.43 (d, 1H, J ¼ 7.2 Hz), 3.11 (dt, 1H, J ¼ 10.8, 2.4 Hz), 2.89 (dd,
1H, J ¼ 17.4, 2.4 Hz), 2.78 (dd, 1H, J ¼ 21.0, 7.2 Hz), 2.50 (d, 1H,
J ¼ 21.0 Hz), 2.29 (s, 3H), 1.96 (s, 3H), 1.71 (s, 3H), 1.37 (ddd, 1H,
(100 MHz, CDCl3):
d 186.3, 185.6, 182.4, 181.4, 167.7, 164.7, 155.8,
155.1, 149.8, 148.6, 142.3, 141.2, 140.2, 136.6, 135.1, 132.3, 130.0,
129.9, 128.5, 128.4, 127.4, 126.0, 125.9, 123.5, 117.7, 117.0, 61.1, 61.0,
58.3, 57.6, 54.5, 54.2, 54.1, 41.9, 25.6, 21.2, 8.8, 8.5.
J ¼ 17.4, 11.4, 2.4 Hz). 13C NMR (150 MHz, CDCl3):
d 186.2, 185.6,
182.4,181.4,165.1,155.9, 155.2, 142.2, 141.2,140.6, 136.6, 135.2,135.1,
131.4, 129.4, 128.6, 128.4, 126.4, 124.0, 121.1, 116.9, 61.2, 61.0, 58.1,
57.7, 54.5, 54.2, 53.9, 41.5, 41.4, 25.7, 21.1, 8.8, 8.4.
6.2.3. Data of compound 4c
ꢁ
a20
Yellow solid, yield 78%, mp: 140e142 C ½
ꢂ: ꢀ175 (c 0.20,
CH2Cl2). HRMS calcd for C36H37N4O8 [M þ H]þD 653.2606, found
6.2.2. Data of compound 4b
653.2596. 1H NMR (400 MHz, CDCl3):
d
7.35 (d, 2H, J ¼ 8.0 Hz), 7.32
Yellow solid, yield 75%, mp: 123e125 ꢁC ½aD20ꢂ: ꢀ115 (c 0.50,
(d, 1H, J ¼ 14.8 Hz), 6.86 (d, 2H, J ¼ 8.4 Hz), 5.93 (d, 1H, J ¼ 15.6 Hz),
5.53 (t, 1H, J ¼ 6.0 Hz), 4.26 (s, 1H), 4.03 (s, 3H), 4.02 (s, 1H), 3.89 (s,
1H), 3.87 (s, 3H), 3.83 (s, 3H), 3.62e3.58 (m, 2H), 3.41 (d, 1H,
J ¼ 7.2 Hz), 3.09 (d,1H, J ¼ 11.6 Hz), 2.87 (d,1H, J ¼ 17.2 Hz), 2.78 (dd,
1H, J ¼ 21.2, 7.6 Hz), 2.49 (d,1H, J ¼ 21.2 Hz), 2.28 (s, 3H),1.94 (s, 3H),
CH2Cl2). HRMS calcd for C38H36N5O7 [M þ H]þ 674.2609, found
674.2606. 1H NMR (400 MHz, CDCl3):
d
8.86 (d, 1H, J ¼ 4.4 Hz), 8.15
(d, 1H, J ¼ 15.6 Hz), 7.75 (t, 1H, J ¼ 8.0 Hz), 7.70 (dd, 1H, J ¼ 5.6,
3.6 Hz), 7.63 (t, 1H, J ¼ 8.0 Hz), 7.51 (dd, 1H, J ¼ 5.6, 3.6 Hz), 7.35 (d,
1H, J ¼ 4.8 Hz), 6.32 (d, 1H, J ¼ 15.6 Hz), 6.05 (s, 1H), 4.02 (s, 1H),
1.74 (s, 3H), 1.39e1.32 (m, 1H). 13C NMR (100 MHz, CDCl3):
d 186.2,

242
W. Dong et al. / European Journal of Medicinal Chemistry 49 (2012) 239e244
Table 1
Cytotoxicity of (ꢀ)-saframycin A analogues against ten cell lines.
Compound
Cytotoxicity IC50 (nM)a
HCT-8
BEL-7402
Ketr3
9.56
28.88
11.49
11.01
52.09
15.47
A2780
MCF-7
A549
40.44
77.08
35.74
23.77
96.65
81.82
BGC-803
Hela
HELF
2.54
>100
23.42
4.88
>100
>100
>100
16.69
18.43
3.38
25.72
2.18
KB
2.23
11.70
5.70
9.04
28.41
9.85
26.28
16.91
29.44
1.27
53.88
3.94
Saframycin A
2.49
1.83
29.68
18.16
6.23
24.34
11.43
>100
22.39
5.38
2.75
39.79
17.46
14.42
25.46
33.74
6.39
4.20b
2.23
5.35
18.51
5.44
25.57
39.47
8.89
1.13
26.06
4.79
10.98
22.34
17.09
6.91
21.23
6.27
31.02
27.68
66.25
4.19
58.53
20.03
66.25
21.50
26.27
12.11
16.04
32.08
4.19
1.06
7.90
8.33
7.77
8.68
3.85
31.18
10.70
7.41
2.52
43.22
3.34
4a
4b
4c
4d
4e
4f
5a
5b
6a
6b
6c
6d
7a
7b
7c
7d
7e
7f
43.29
18.21
46.66
>100
27.36
>100
58.55
>100
14.94
>100
21.10
>100
43.36
90.51
10.53
12.41
22.08
>100
>100
63.80
>100
>100
23.60
12.94
3.63
30.56
6.88
43.93
22.69
3.67
47.14
5.11
10.01
34.27
18.75
>100
69.01
3.03
21.01
2.02
>100
23.74
11.49
1.87
1.22
3.80
16.45
84.73
32.36
69.90
19.68
1.61
3.01
15.07
37.29
29.63
11.15
7.17
14.86
22.85
3.06
15.31
15.61
45.22
24.22
17.31
65.26
34.95
1.89
0.95
30.03
>100
88.62
26.82
9.51
5.29
1.89
2.58
7.27
17.40
26.64
92.71
19.84
17.48
1.53
1.68
6.57
27.22
85.37
19.50
16.59
14.89
1.85
3.55
9.17
17.48
74.95
31.44
3.87
11.95
27.36
98.05
45.03
7g
1
>100
23.70
58.53
32.08
a
The IC50 values represent the inhibitory concentration of 50% of cell growth.
Boldface: IC50ꢃ (ꢀ)-saframycin A.
b
185.6, 182.4, 181.3, 166.0, 161.1, 155.9, 155.2, 142.2, 141.6, 141.0, 136.7,
135.1, 129.4, 128.6, 128.4, 127.0, 117.0, 116.9, 114.2 (2C), 61.1, 60.9,
58.1, 57.6, 55.4, 54.5, 54.2, 53.9, 41.5, 41.1, 25.6, 21.1, 8.8, 8.6.
J ¼ 7.2 Hz), 3.10 (d, 1H, J ¼ 11.2 Hz), 2.88 (d, 1H, J ¼ 17.6 Hz), 2.79 (dd,
1H, J ¼ 21.2, 7.2 Hz), 2.48 (d,1H, J ¼ 21.2 Hz), 2.28 (s, 3H),1.94 (s, 3H),
1.74 (s, 3H), 1.39e1.35 (m, 1H), 1.32 (s, 9H). 13C NMR (100 MHz,
CDCl3):
d 186.1, 185.6, 182.4, 181.3, 165.9, 155.9, 155.2, 153.6, 142.2,
6.2.4. Data of compound 4d
141.8, 141.0, 136.7, 135.1, 131.5, 128.6, 128.4, 127.7 (2C), 125.7 (2C),
118.5, 117.0, 61.1, 60.9, 58.1, 57.6, 54.5, 54.2, 53.9, 41.5, 41.3, 34.8, 31.1
(3C), 25.6, 21.2, 8.8, 8.5.
ꢁ
a20
Yellow solid, yield 80%, mp: 124e126 C ½
ꢂ: ꢀ177 (c 0.20,
D
CH2Cl2). HRMS calcd for C37H39N4O7 [M þ H]þ 651.2813, found
651.2800. 1H NMR (400 MHz, CDCl3):
d
7.35 (d, 1H, J ¼ 15.2 Hz), 7.32
(d, 2H, J ¼ 7.6 Hz), 7.17 (d, 2H, J ¼ 8.0 Hz), 6.02 (d, 1H, J ¼ 15.6 Hz),
5.60 (t, 1H, J ¼ 6.4 Hz), 4.26 (s, 1H), 4.04 (s, 3H), 4.02 (s, 1H), 3.89 (s,
1H), 3.86 (s, 3H), 3.61e3.59 (m, 2H), 3.41 (d, 1H, J ¼ 7.6 Hz), 3.09 (d,
1H, J ¼ 11.2 Hz), 2.87 (d, 1H, J ¼ 17.6 Hz), 2.78 (dd, 1H, J ¼ 21.2,
7.6 Hz), 2.66 (q, 2H, J ¼ 7.6 Hz), 2.48 (d, 1H, J ¼ 21.2 Hz), 2.28 (s, 3H),
1.94 (s, 3H), 1.74 (s, 3H), 1.36 (ddd, 1H, J ¼ 17.2, 11.6, 2.0 Hz). 13C NMR
6.2.7. Data of compound 5a
Yellow solid, yield 70%, mp: 126e128 ꢁC ½aD20ꢂ: ꢀ94 (c 0.20,
CH2Cl2). HRMS calcd for C35H36N5O8 [M þ H]þ 654.2558, found
654.2536. 1H NMR (500 MHz, CDCl3):
d
7.70 (d, 2H, J ¼ 7.5 Hz), 7.52
(t, 1H, J ¼ 7.5 Hz), 7.44 (t, 2H, J ¼ 7.5 Hz), 6.97 (t, 1H, J ¼ 5.0 Hz), 6.58
(t, 1H, J ¼ 6.0 Hz), 4.15 (s, 1H), 4.04 (s, 1H), 4.00 (s, 3H), 3.93 (s, 3H),
3.88 (s, 1H), 3.82 (dd, 1H, J ¼ 16.0, 6.0 Hz), 3.65 (dd, 1H, J ¼ 16.0,
5.0 Hz), 3.49e3.47 (m, 2H), 3.41 (d, 1H, J ¼ 7.5 Hz), 3.07 (d, 1H,
J ¼ 11.5 Hz), 2.87 (dd, 1H, J ¼ 17.5, 2.0 Hz), 2.77 (dd, 1H, J ¼ 21.0,
7.5 Hz), 2.40 (d,1H, J ¼ 20.5 Hz), 2.30 (s, 3H),1.86 (s, 3H),1.80 (s, 3H),
(100 MHz, CDCl3):
d 186.2, 185.6, 182.4, 181.3, 165.9, 155.9, 155.2,
146.7, 142.2, 141.9, 141.0, 136.7, 135.1, 131.8, 128.6, 128.3 (3C), 127.9
(2C), 118.4, 117.0, 61.1, 60.9, 58.1, 57.6, 54.5, 54.2, 53.9, 41.5, 41.2,
28.8, 25.6, 21.1, 15.4, 8.8, 8.5.
1.68e1.62 (m, 1H). 13C NMR (125 MHz, CDCl3):
d 186.8, 185.2, 182.7,
6.2.5. Data of compound 4e
181.2, 169.3, 167.8, 155.6, 155.4, 142.1, 141.9, 135.8, 135.2, 132.7, 132.1,
128.6 (2C), 128.5, 127.2 (2C), 117.1, 61.1, 61.0, 58.4, 56.8, 54.6, 54.3
(2C), 44.0, 41.5, 40.8, 25.3, 21.2, 8.7 (2C).
Yellowsolid, yield 76%, mp: 81e83 ꢁC ½aD20ꢂ: ꢀ122 (c 0.20, CH2Cl2).
HRMS calcd for C38H41N4O10 [M þ H]þ 713.2817, found 713.2795. 1H
NMR (400 MHz, CDCl3):
d
7.50 (d, 1H, J ¼ 16.0 Hz), 7.10 (d, 1H,
J ¼ 8.8 Hz), 6.65 (d,1H, J ¼ 8.4 Hz), 6.11 (d,1H, J ¼ 15.6 Hz), 5.55 (t,1H,
J ¼ 6.4 Hz), 4.32 (s, 1H), 4.26 (s, 1H), 4.04 (s, 3H), 4.02 (s, 1H), 3.89 (s,
6H), 3.86 (s, 6H), 3.59e3.57 (m, 2H), 3.41 (d, 1H, J ¼ 7.2 Hz), 3.10 (d,
1H, J ¼ 11.2 Hz), 2.88 (d,1H, J ¼ 17.2 Hz), 2.78 (dd,1H, J ¼ 21.2, 7.6 Hz),
2.48 (d, 1H, J ¼ 21.2 Hz), 2.28 (s, 3H), 1.94 (s, 3H), 1.76 (s, 3H),
6.2.8. Data of compound 5b
Yellow solid, yield 80%, mp: 116e118 ꢁC ½aD20ꢂ: ꢀ32 (c 0.20,
CH2Cl2). HRMS calcd for C31H37N4O8 [M þ H]þ 593.2606, found
593.2612. 1H NMR (600 MHz, CDCl3):
d
4.28 (d, 1H, J ¼ 8.4 Hz), 4.08
(s, 1H), 4.04 (s, 3H), 4.03 (s, 3H), 3.96 (s, 1H), 3.85 (s, 1H), 3.60 (dd,
1H, J ¼ 13.8, 9.6 Hz), 3.43e3.41 (m, 1H), 3.14 (d, 1H, J ¼ 9.0 Hz), 2.93
(d, 1H, J ¼ 14.4 Hz), 2.88 (dd, 1H, J ¼ 17.4, 2.4 Hz), 2.83 (dd, 1H,
J ¼ 21.0, 7.2 Hz), 2.32 (s, 3H), 2.19 (d, 1H, J ¼ 21.0 Hz), 1.95 (s, 3H),
1.88 (s, 3H), 1.35e1.30 (m, 1H), 1.18 (s, 9H). 13C NMR (150 MHz,
1.38e1.33 (m, 1H). 13C NMR (100 MHz, CDCl3):
d 186.1, 185.6, 182.5,
181.4,166.4,155.9,155.2,153.1,142.2,140.9,136.9,135.1,130.9,128.8,
128.6,128.4,123.3,121.4,118.8,117.0,107.4, 65.6, 61.1, 60.9, 58.2, 57.8,
56.1, 54.5, 54.2, 54.0, 41.5, 30.6, 25.6, 21.2, 19.2, 13.7, 8.8, 8.5.
CDCl3):
d 186.2, 185.6, 182.3, 180.8, 155.8, 155.4, 141.2, 139.8, 136.6,
6.2.6. Data of compound 4f
136.1, 128.2, 127.5, 116.6, 79.6, 61.1, 60.9, 58.1, 57.0, 54.4, 54.2, 53.6,
42.3, 41.6, 28.4, 28.2, 28.0, 27.9, 25.2, 21.5, 8.6, 8.5.
Yellow solid, yield 77%, mp: 115e117 ꢁC ½aD20ꢂ: ꢀ105 (c 0.50,
CH2Cl2). HRMS calcd for C39H43N4O7 [M þ H]þ 679.3126, found
679.3125. 1H NMR (400 MHz, CDCl3):
d
7.43e7.34 (m, 5H), 6.04 (d,
6.2.9. Data of compound 6a
1H, J ¼ 15.6 Hz), 5.60 (t,1H, J ¼ 6.4 Hz), 4.26 (s,1H), 4.04 (s, 3H), 4.03
Yellow solid, yield 76%, mp: 130e132 ꢁC ½aD20ꢂ: ꢀ143 (c 0.20,
(s, 1H), 3.90 (s, 1H), 3.85 (s, 3H), 3.61e3.59 (m, 2H), 3.42 (d, 1H,
CH2Cl2). HRMS calcd for C36H39N4O10 [M þ H]þ 687.2661, found

W. Dong et al. / European Journal of Medicinal Chemistry 49 (2012) 239e244
243
687.2678. 1H NMR (600 MHz, CDCl3):
d
6.61 (s, 2H), 5.91 (t, 1H,
(m, 1H). 13C NMR (125 MHz, CDCl3):
d
185.7, 185.6, 182.1, 181.0,
J ¼ 6.6 Hz), 4.20 (s, 1H), 4.05 (s, 3H), 3.97 (s, 1H), 3.95 (s, 1H), 3.87 (s,
3H), 3.84 (s, 3H), 3.81 (s, 6H), 3.78e3.74 (m, 1H), 3.51 (dd, 1H,
J ¼ 12.6, 6.6 Hz), 3.41 (d, 1H, J ¼ 7.2 Hz), 3.10 (d, 1H, J ¼ 11.4 Hz), 2.90
(d, 1H, J ¼ 17.4 Hz), 2.74 (dd, 1H, J ¼ 21.0, 7.8 Hz), 2.48 (d, 1H,
J ¼ 21.0 Hz), 2.25 (s, 3H), 2.04 (s, 3H), 1.73 (s, 3H), 1.41 (ddd, 1H,
164.6, 155.9, 154.6, 149.3, 146.2, 142.7, 142.1, 137.5, 136.0, 134.5,
130.4, 129.6, 129.2, 128.4, 128.2, 127.7, 127.3, 119.0, 117.2, 61.2, 60.2,
58.4, 57.3, 54.6, 54.2, 54.1, 41.4, 40.1, 25.7, 21.0, 8.8, 8.6.
6.2.14. Data of compound 7b
J ¼ 17.4, 11.4, 2.4 Hz). 13C NMR (150 MHz, CDCl3):
d
186.1, 185.7,
Yellow solid, yield 62%, mp: 127e129 ꢁC ½aD20ꢂ: ꢀ149 (c 0.20,
182.5, 181.3, 167.4, 156.0, 154.8, 153.2 (2C), 142.2, 141.4, 136.7, 134.6,
129.5, 128.6, 128.4, 117.1, 103.8 (3C), 61.2, 61.8, 58.3, 57.7, 56.1 (3C),
54.5, 54.1, 54.0, 41.5, 41.3, 26.0, 21.1, 8.8, 8.4.
CH2Cl2). HRMS calcd for C35H34N5O7 [M þ H]þ 636.2453, found
636.2468. 1H NMR (500 MHz, CDCl3):
d 9.00 (s, 1H), 7.48 (d, 1H,
J ¼ 8.0 Hz), 7.40 (d, 1H, J ¼ 8.0 Hz), 7.28 (t, 1H, J ¼ 8.0 Hz), 7.12 (t, 1H,
J ¼ 8.0 Hz), 6.31 (s, 1H), 5.93 (t, 1H, J ¼ 6.5 Hz), 4.15 (s, 1H), 4.06 (s,
3H), 4.00 (s, 1H), 3.99 (s, 1H), 3.84e3.80 (m, 1H), 3.64e3.61 (m, 1H),
3.61 (s, 3H), 3.40 (d, 1H, J ¼ 7.5 Hz), 3.09 (d, 1H, J ¼ 11.0 Hz), 2.88 (d,
1H, J ¼ 17.0 Hz), 2.73 (dd, 1H, J ¼ 21.0, 7.5 Hz), 2.50 (d, 1H,
J ¼ 21.0 Hz), 2.25 (s, 3H), 1.96 (s, 3H), 1.64 (s, 3H), 1.32 (ddd, 1H,
6.2.10. Data of compound 6b
Yellow solid, yield 74%, mp: 117e119 ꢁC ½aD20ꢂ: ꢀ89 (c 0.20,
CH2Cl2). HRMS calcd for C34H32F3N4O7 [M þ H]þ 665.2218, found
665.2232. 1H NMR (600 MHz, CDCl3):
d 7.84 (s, 1H), 7.74 (d, 1H,
J ¼ 7.2 Hz), 7.55 (d, 1H, J ¼ 7.8 Hz), 7.48 (t, 1H, J ¼ 7.8 Hz), 6.22 (t, 1H,
J ¼ 6.6 Hz), 4.26 (s, 1H), 4.04 (s, 3H), 4.02 (s, 1H), 3.95 (s, 1H), 3.90 (s,
3H), 3.77 (dd,1H, J ¼ 14.4, 7.2 Hz), 3.55 (dt, 1H, J ¼ 14.4, 4.8 Hz), 3.44
(d, 1H, J ¼ 7.2 Hz), 3.12 (dt, 1H, J ¼ 10.8, 2.4 Hz), 2.90 (d, 1H,
J ¼ 17.4 Hz), 2.79 (dd, 1H, J ¼ 20.4, 7.2 Hz), 2.42 (d, 1H, J ¼ 21.0 Hz),
2.28 (s, 3H), 1.94 (s, 3H), 1.80 (s, 3H), 1.30 (ddd, 1H, J ¼ 17.4, 11.4,
J ¼ 17.5, 11.5, 2.5 Hz). 13C NMR (125 MHz, CDCl3):
d 186.3, 185.4,
182.2, 181.1, 161.3, 155.9, 155.2, 142.1, 141.6, 136.2, 136.1, 135.0, 129.8,
128.5, 128.2, 127.3, 124.9, 121.8, 121.0, 117.0, 112.2, 101.4, 61.2, 60.7,
58.2, 57.4, 54.6, 54.1, 54.1, 41.4, 40.1, 25.6, 21.1, 8.8, 8.5.
6.2.15. Data of compound 7c
2.4 Hz). 13C NMR (150 MHz, CDCl3):
d
186.1,185.4,182.3,181.5,166.0,
Yellow solid, yield 64%, mp: 120e122 C ½
ꢂ: ꢀ75 (c 0.20,
ꢁ
a20
156.0, 155.1, 142.0, 140.9, 136.6, 135.1, 134.6, 129.2 (2C), 128.5, 128.4,
128.3, 124.2, 116.8, 61.1, 60.9, 58.3, 57.7, 54.5, 54.1, 54.0, 42.1, 41.5,
25.6, 21.3, 8.8, 8.6.
CH2Cl2). HRMS calcd for C31H31N6O7 [M þ H]þ D599.2249, found
599.2238. 1H NMR (500 MHz, CDCl3):
d 9.14 (s, 1H), 8.70 (s, 1H), 8.24
(s, 1H), 7.46 (t, 1H, J ¼ 6.5 Hz), 4.08 (s, 1H), 4.07 (s, 3H), 4.05 (s, 1H),
3.99 (s, 1H), 3.94 (s, 3H), 3.86e3.82 (m, 1H), 3.58e3.53 (m, 1H), 3.44
(d, 1H, J ¼ 7.5 Hz), 3.12 (d, 1H, J ¼ 11.5 Hz), 2.87 (d, 1H, J ¼ 17.5 Hz),
2.82 (dd, 1H, J ¼ 21.0, 7.5 Hz), 2.39 (d, 1H, J ¼ 21.0 Hz), 2.32 (s, 3H),
1.91 (s, 3H), 1.90 (s, 3H), 1.35e1.32 (m, 1H). 13C NMR (125 MHz,
6.2.11. Data of compound 6c
Yellow solid, yield 74%, mp: 125e127 ꢁC ½aD20ꢂ: ꢀ133 (c 0.20,
CH2Cl2). HRMS calcd for C34H33N4O9 [M þ H]þ 641.2242, found
641.2247. 1H NMR (600 MHz, CDCl3):
d
6.93 (s, 1H), 6.83 (d, 1H,
CDCl3): d 186.1, 185.4, 182.3, 180.8, 163.0, 156.0, 155.1, 147.5, 144.6,
J ¼ 8.4 Hz), 6.68 (d, 1H, J ¼ 8.4 Hz), 6.00 (s, 2H), 5.87 (t, 1H,
J ¼ 6.6 Hz), 4.16 (s, 1H), 4.06 (s, 3H), 4.01 (s, 1H), 3.95 (s, 1H), 3.89 (s,
3H), 3.74 (dd, 1H, J ¼ 14.4, 7.2 Hz), 3.53 (dt, 1H, J ¼ 14.4, 4.8 Hz), 3.43
(d, 1H, J ¼ 7.2 Hz), 3.10 (dt, 1H, J ¼ 11.4, 2.4 Hz), 2.86 (dd, 1H, J ¼ 17.4,
2.4 Hz), 2.79 (dd, 1H, J ¼ 20.4, 7.2 Hz), 2.42 (d, 1H, J ¼ 20.4 Hz), 2.28
(s, 3H), 1.94 (s, 3H), 1.80 (s, 3H), 1.28e1.22 (m, 1H). 13C NMR
143.7, 142.4, 142.1, 141.5, 135.8, 135.2, 128.3, 128.1, 116.8, 61.2, 61.1,
58.5, 57.0, 54.5, 54.3, 54.2, 41.6, 40.6, 25.2, 21.4, 8.8, 8.6.
6.2.16. Data of compound 7d
Yellow solid, yield 65%, mp: 130e132 ꢁC ½aD20ꢂ: ꢀ75 (c 0.20,
CH2Cl2). HRMS calcd for C31H31N4O8 [M þ H]þ 587.2136, found
(150 MHz, CDCl3):
d
186.1, 185.5, 182.3, 181.1, 166.6, 156.2, 155.1,
587.2120. 1H NMR (500 MHz, CDCl3):
d 7.22 (s, 1H), 6.89 (s, 1H),
150.5, 148.1, 142.0, 140.6, 136.6, 135.2, 128.3, 128.1, 128.0, 120.7,
116.9, 107.9, 107.4, 101.8, 61.1, 60.9, 58.2, 57.6, 54.5, 54.2, 53.9, 41.5,
41.2, 25.5, 21.3, 8.7, 8.6.
6.42 (s, 1H), 6.09 (t, 1H, J ¼ 6.5 Hz), 4.09 (s, 1H), 4.05 (s, 3H), 4.02 (s,
1H), 3.97 (s, 1H), 3.96 (s, 3H), 3.77 (dd, 1H, J ¼ 13.0, 7.5 Hz), 3.48 (dt,
1H, J ¼ 14.5, 5.0 Hz), 3.44 (d, 1H, J ¼ 7.5 Hz), 3.12 (d, 1H, J ¼ 11.0 Hz),
2.88 (dd, 1H, J ¼ 17.5, 2.5 Hz), 2.82 (dd, 1H, J ¼ 21.0, 7.5 Hz), 2.40 (d,
1H, J ¼ 21.5 Hz), 2.30 (s, 3H), 1.94 (s, 3H), 1.92 (s, 3H), 1.34e1.30 (m,
6.2.12. Data of compound 6d
Yellow solid, yield 60%, mp: 132e134 ꢁC ½aD20ꢂ: ꢀ25 (c 0.10,
1H). 13C NMR (125 MHz, CDCl3):
d 186.1, 185.4, 182.3, 180.9, 158.0,
CH2Cl2). HRMS calcd for C33H31BrClN4O7 [M þ H]þ 709.1059, found
156.0, 155.1, 147.3, 144.0, 142.0, 141.1, 136.1, 135.3, 128.3, 128.1, 116.8,
114.8, 112.3, 61.1, 60.4, 58.3, 57.2, 54.5, 54.3, 54.0, 41.5, 40.2, 25.2,
21.4, 8.8, 8.7.
709.1058. 1H NMR (600 MHz, CDCl3):
d 7.64 (s, 1H), 7.45 (d, 1H,
J ¼ 8.4 Hz), 7.14 (d,1H, J ¼ 8.4 Hz), 6.22 (t,1H, J ¼ 7.2 Hz), 4.15 (s,1H),
4.07 (s, 3H), 4.05 (s, 1H), 3.98 (s,1H), 3.94 (s, 3H), 3.98e3.95 (m, 1H),
3.45 (d, 1H, J ¼ 7.8 Hz), 3.41 (dt, 1H, J ¼ 15.0, 4.2 Hz), 3.14 (dt, 1H,
J ¼ 11.4, 3.0 Hz), 2.85 (dd, 1H, J ¼ 17.4, 1.8 Hz), 2.80 (dd, 1H, J ¼ 21.0,
7.8 Hz), 2.32 (d,1H, J ¼ 21.0 Hz), 2.29 (s, 3H),1.94 (s, 3H),1.79 (s, 3H),
1.37 (ddd, 1H, J ¼ 28.8, 13.8, 2.4 Hz). 13C NMR (150 MHz, CDCl3):
6.2.17. Data of compound 7e
Yellow solid, yield 65%, mp: 127e129 ꢁC ½aD20ꢂ: ꢀ93 (c 0.20,
CH2Cl2). HRMS calcd for C32H32N5O7 [M þ H]þ 598.2296, found
598.2272. 1H NMR (500 MHz, CDCl3):
d
8.26 (d, 1H, J ¼ 4.0 Hz), 7.92
d
186.1, 185.5, 182.2, 181.1, 164.6, 156.3, 155.2, 141.6, 140.6, 136.2,
(d, 1H, J ¼ 7.5 Hz), 7.77e7.72 (m, 2H), 7.36 (t, 1H, J ¼ 6.5 Hz), 4.09 (s,
1H), 4.07 (s, 3H), 4.03 (s, 1H), 3.99 (s, 1H), 3.89 (s, 3H), 3.76 (dd, 1H,
J ¼ 12.5, 5.5 Hz), 3.61e3.59 (m, 1H), 3.43 (d, 1H, J ¼ 7.5 Hz), 3.10 (d,
1H, J ¼ 11.0 Hz), 2.84 (d, 1H, J ¼ 16.5 Hz), 2.81 (dd, 1H, J ¼ 21.0,
7.5 Hz), 2.42 (d,1H, J ¼ 21.0 Hz), 2.31 (s, 3H), 1.90 (s, 3H),1.89 (s, 3H),
135.5, 135.0, 134.7, 133.6, 131.5, 128.7, 128.2, 127.9, 121.3, 116.6, 61.1,
61.0, 58.1, 57.4, 54.5, 54.1, 53.9, 41.6, 41.5, 25.5, 21.4, 8.7, 8.6.
6.2.13. Data of compound 7a
Yellow solid, yield 75%, mp: 119e121 ꢁC ½aD20ꢂ: ꢀ121 (c 0.20,
1.42e1.36 (m, 1H). 13C NMR (125 MHz, CDCl3):
d 186.1, 185.4, 182.3,
CH2Cl2). HRMS calcd for C36H34N5O7 [M þ H]þ 648.2453, found
180.8, 164.3, 156.0, 155.1, 149.2, 148.0, 142.0, 141.5, 137.3, 136.1, 135.1,
128.1, 127.9, 126.2, 122.4, 116.9, 61.1, 61.0, 58.4, 57.1, 54.6, 54.3, 54.2,
41.5, 40.5, 25.2, 21.3, 8.9, 8.7.
648.2464. 1H NMR (500 MHz, CDCl3):
d
8.24 (d, 1H, J ¼ 8.5 Hz), 8.00
(d, 1H, J ¼ 8.5 Hz), 7.86 (d, 1H, J ¼ 8.0 Hz), 7.84 (s, 1H), 7.79 (d, 1H,
J ¼ 8.0 Hz), 7.75 (t, 1H, J ¼ 7.5 Hz), 7.63 (t, 1H, J ¼ 7.5 Hz), 4.16 (s, 1H),
4.10 (s,1H), 4.09 (s, 3H), 3.93 (s,1H), 3.44 (d,1H, J ¼ 14.0 Hz), 3.39 (d,
1H, J ¼ 7.0 Hz), 3.30 (s, 3H), 3.09 (d, 1H, J ¼ 11.0 Hz), 2.88 (d, 1H,
J ¼ 17.0 Hz), 2.75 (dd, 1H, J ¼ 21.0, 7.0 Hz), 2.50 (d, 1H, J ¼ 20.5 Hz),
2.20 (s, 3H), 2.04e2.01 (m, 1H), 2.01 (s, 3H), 1.60 (s, 3H), 1.60e1.56
6.2.18. Data of compound 7f
Yellow solid, yield 62%, mp: 125e127 ꢁC ½aD20ꢂ: ꢀ73 (c 0.20,
CH2Cl2). HRMS calcd for C31H31N4O7S [M þ H]þ 603.1908, found
603.1901. 1H NMR (600 MHz, CDCl3):
d
7.36 (d, 1H, J ¼ 4.8 Hz), 7.19

244
W. Dong et al. / European Journal of Medicinal Chemistry 49 (2012) 239e244
(d, 1H, J ¼ 4.8 Hz), 6.98 (t, 1H, J ¼ 4.8 Hz), 5.77 (t, 1H, J ¼ 6.6 Hz), 4.12
(s, 1H), 4.06 (s, 3H), 4.03 (s, 1H), 3.97 (s, 1H), 3.90 (s, 3H), 3.77 (dd,
1H, J ¼ 14.4, 7.8 Hz), 3.50 (dt, 1H, J ¼ 14.4, 5.4 Hz), 3.44 (d, 1H,
J ¼ 7.8 Hz), 3.12 (dt, 1H, J ¼ 10.8, 2.4 Hz), 2.87 (dd, 1H, J ¼ 17.4,
2.4 Hz), 2.82 (dd, 1H, J ¼ 21.0, 7.8 Hz), 2.40 (d, 1H, J ¼ 21.0 Hz), 2.28
(s, 3H), 1.93 (s, 3H), 1.90 (s, 3H), 1.30 (ddd, 1H, J ¼ 17.4, 11.4, 2.4 Hz).
Acknowledgements
We thank Beijing Natural Science Foundation (NO. 7092069),
Specialized Research Fund for the Doctoral Program of Higher
Education (NO. 200800230030) for financial support.
13C NMR (150 MHz, CDCl3):
d 186.1, 185.4, 182.3, 181.0, 161.6, 156.1,
Appendix. Supplementary data
155.3, 141.9, 140.9, 137.5, 136.2, 135.3, 129.6, 128.8, 128.3, 128.1,
127.9, 116.8, 61.1, 61.0, 58.2, 57.4, 54.5, 54.2, 54.0, 41.5, 40.9, 25.5,
21.3, 8.8, 8.7.
Supplementary data related to this article can be found online at
doi:10.1016/j.ejmech.2012.01.017.
6.2.19. Data of compound 7g
Yellow solid, yield 70%, mp: 124e126 ꢁC ½aD20ꢂ: ꢀ120 (c 0.20,
CH2Cl2). HRMS calcd for C36H34N5O7 [M þ H]þ 648.2453, found
References
648.2465. 1H NMR (500 MHz, CDCl3):
d
8.24 (d, 1H, J ¼ 8.5 Hz), 8.00
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(d, 1H, J ¼ 8.5 Hz), 7.87e7.84 (m, 2H), 7.79 (d, 1H, J ¼ 8.0 Hz), 7.75 (t,
1H, J ¼ 8.0 Hz), 7.63 (t, 1H, J ¼ 7.0 Hz), 4.16 (s, 1H), 4.08 (s, 3H), 4.04
(s, 1H), 3.93 (s, 1H), 3.44 (d, 1H, J ¼ 14.5 Hz), 3.39 (d, 1H, J ¼ 7.5 Hz),
3.30 (s, 3H), 3.08 (d, 1H, J ¼ 11.0 Hz), 2.88 (d, 1H, J ¼ 16.5 Hz), 2.75
(dd, 1H, J ¼ 21.0, 7.5 Hz), 2.50 (d, 1H, J ¼ 21.0 Hz), 2.19 (s, 3H),
2.06e2.03 (m, 1H), 2.01 (s, 3H), 1.60 (s, 3H), 1.60e1.56 (m, 1H). 13C
NMR (125 MHz, CDCl3):
d 185.7, 185.6, 182.1, 181.0, 164.6, 155.9,
154.6, 149.3, 146.2, 142.7, 142.1, 137.5, 136.0, 134.5, 130.4, 129.6,
129.2, 128.4, 128.2, 127.7, 127.3, 119.0, 117.2, 61.2, 60.2, 58.4, 57.3,
54.6, 54.2, 54.1, 41.4, 40.1, 25.7, 21.0, 8.8, 8.6.
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,
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