Complete NMR data of methoxylated cis- and trans-stilbenes as well as 1,2-diphenylethanes

Article abstract of DOI:10.1002/mrc.2754

Resveratrol is a polyphenol isolated from many natural sources including grapes, mulberries, eucalyptus, spruce, lilies, and peanuts. The hydroxyl groups in polyphenols can be substituted with various functional groups, allowing production of multiple derivatives. NMR spectroscopy is used to identify new derivatives. Since the complete NMR data of the known derivatives can be useful for identification of the newly isolated derivatives, here, we report the synthesis of 14 methoxylated stilbenes and four 1,2-diphenylethanes and their NMR data.

Full text of DOI:10.1002/mrc.2754

MRC Letters
Received: 10 November 2010
Revised: 14 February 2011
Accepted: 15 February 2011
Published online in Wiley Online Library: 31 March 2011
(wileyonlinelibrary.com) DOI 10.1002/mrc.2754
Complete NMR data of methoxylated
cis- and trans-stilbenes as well
as 1,2-diphenylethanes
Geunhyeong Jo,a Jiye Hyun,a Doseok Hwang,a Young Han Lee,b
Dongsoo Kohc∗ and Yoongho Lima∗
Resveratrol is a polyphenol isolated from many natural sources including grapes, mulberries, eucalyptus, spruce, lilies, and
peanuts. Thehydroxylgroupsinpolyphenolscanbesubstitutedwithvariousfunctionalgroups, allowingproductionofmultiple
derivatives. NMR spectroscopy is used to identify new derivatives. Since the complete NMR data of the known derivatives can
be useful for identification of the newly isolated derivatives, here, we report the synthesis of 14 methoxylated stilbenes and
c
four 1,2-diphenylethanes and their NMR data. Copyright ꢀ 2011 John Wiley & Sons, Ltd.
Keywords: 1H NMR; 13C NMR; 2D NMR; flavonoids; stilbenes
Introduction
hydrogenated using a palladium catalyst to produce the reduced
products (VI).
Polyphenols such as stilbenes (C6–C2–C6) are classified based on
their carbon skeleton. Resveratrol (trans-3,5,4ꢁ-trihydroxystilbene),
a stilbene found in many natural sources, including grapes,
mulberries, eucalyptus, spruce, lilies, and peanuts,[1] is produced
byplantsasadefensemechanism. Inhumans, itactsasatreatment
for cardiovascular diseases and as an anti-oxidative and anticancer
agent.[2] After the discovery of its target proteins, research into
resveratrol derivatives gained considerable interest.[3] However,
their application is limited because of poor oral bioavailability,
which results in rapid excretion from the body. Methoxylation can
overcome low bioavailability and increase metabolic stability.[4]
In addition, because small structural changes can cause a
large change in biological activity, various derivatives are being
prepared still.[5]
NMR spectra
All synthetic derivatives were dissolved in CDCl3. Their concen-
trations were adjusted to approximately 50 mM, and they were
transferred to a 5-mm NMR tube. All NMR data were collected on a
Bruker Avance 400 spectrometer system (9.4 T; Bruker, Karlsruhe,
Germany) at a temperature of 298 K. For the 1H NMR experiment,
the relaxation delay and 90◦ pulse were 1 s and 10.2 µs, respec◦-
tively. For the 13C NMR experiments, the relaxation delay and 90
pulse were 3 s and 10.3 µs, respectively. Two-dimensional experi-
ments, such as COSY, TOCSY, HMQC, and HMBC, were performed
by acquiring 2048 data points for t2 and 256 data points for t1. The
long-range coupling time for HMBC was 70 ms. Prior to Fourier
transformation, zero-filling of 2 K and the sine-squared bell win-
dow function were applied using XWin-NMR (Bruker).[7] Analysis
of the NMR data was carried out using SPARKY.[8]
The complete NMR data of the known derivatives can be useful
for identification of the newly isolated derivatives. Therefore,
we report the synthesis of 14 methoxylated stilbenes and four
1,2-diphenylethanes and their complete NMR data.
Experimental
∗
Correspondence to: Yoongho Lim, Department of Bioscience and Biotechnol-
ogy, Konkuk University, Hwayang-Dong 1, Kwangjin-Ku, Seoul 143-701, Korea.
E-mail: yoongho@konkuk.ac.kr.
Synthesis
All the methoxylated stilbene and 1,2-diphenylethane derivatives
(1–18) were synthesized as shown in Scheme 1. 3,5-Dimeth-
oxybenzaldehyde (I) was reduced to 3,5-dimethoxybenzylalcohol
(II), which was chlorinated to 3,5-dimethoxybenzylchloride (III)
as described in the literature.[6] 3,5-Dimethoxybenzylchloride (III)
was treated with triphenylphosphine to produce phosphonium
salt (IV), which was used in the Wittig reaction along with
methoxybenzaldehydes under basic conditions to produce a
mixture of cis and trans isomers of stilbene derivatives (V).
The cis and trans isomers were separated by flash column
chromatography. The mixture of cis and trans isomers (V) was
Dongsoo Koh,DepartmentofAppliedChemistry,DongdukWomen’sUniversity,
Hawolgok-Dong, Seongbuk-Ku, Seoul 136-714, Korea.
E-mail: dskoh@dongduk.ac.kr
a
b
c
Division of Bioscience and Biotechnology, BMIC, Konkuk University, Seoul
143-701, Korea
Department of Biomedical Science and Technology, Research Center for
Transcription Control, Konkuk University, Seoul 143-701, Korea
DepartmentofAppliedChemistry,DongdukWomen’sUniversity,Seoul136-714,
Korea
c
Magn. Reson. Chem. 2011, 49, 374–377
Copyright ꢀ 2011 John Wiley & Sons, Ltd.

NMR data of methoxylated stilbenes and 1,2-diphenylethanes
Table 1. 1H NMR chemical shifts of the methoxylated stilbene and 1,2-diphenylethane derivatives 1–18 (ppm) in CDCl3 and values in parentheses
are 1H,1H coupling constants J (in Hz)a
Position
1
2
3
4
5
6
7
8
9
2
6.47 (d, 2.2) 6.65 (d, 2.2) 6.39 (d, 2.3) 6.66 (d, 2.2)
6.34 (t, 2.2) 6.38 (d, 2.2) 6.27 (t, 2.3) 6.37 (t, 2.2)
6.43 (d, 2.3)
6.33 (t, 2.3)
6.43 (d, 2.3)
6.61 (d, 12.3)
6.77 (d, 12.3)
–
6.70 (d, 2.2)
6.40 (t, 2.2)
6.70 (d, 2.2)
7.06 (d, 16.3)
7.43 (d, 16.3)
–
6.48 (d, 2.3) 6.69 (d, 2.3) 6.47 (d, 2.3)
6.35 (t, 2.3) 6.42 (t, 2.3) 6.36 (t, 2.3)
4
6
6.47 (d, 2.2) 6.65 (d, 2.2) 6.39 (d, 2.3) 6.66 (d, 2.2)
6.51 (d, 12.2) 6.88 (d, 16.1) 6.49 (d, 12.2) 6.95 (d, 16.5)
6.42 (d, 12.2) 7.02 (d, 16.1) 6.61 (d, 12.2) 7.30 (d, 16.5)
6.48 (d, 2.3) 6.69 (d, 2.3) 6.47 (d, 2.3)
6.47 (d, 12.2) 7.07 (d, 16.3) 6.61 (d, 12.3)
6.55 (d, 12.2) 6.93 (d, 16.3) 6.56 (d, 12.3)
7.24 (d, 8.7) 7.46 (d, 8.7) 6.87 (t, 2.5)
7
8
2ꢁ
3ꢁ
4ꢁ
7.15 (d, 8.5) 7.38 (d, 8.6)
6.78 (d, 8.5) 6.87 (d, 8.6)
–
–
–
–
–
–
–
–
6.79 (d, 8.7) 6.91 (d, 8.7)
–
–
–
6.82
6.84
–
–
6.77
(dd, 1.8, 11.3)
6.90 (t, 7.8)
(dd, 1.3, 8.0)
7.05 (d, 8.0)
(dd, 2.5, 7.9)
5ꢁ
6ꢁ
6.78 (d, 8.5) 6.87 (d, 8.6) 6.47 (d, 8.7) 6.69 (d, 8.8)
6.79 (d, 8.7) 6.91 (d, 8.7) 7.18 (t, 7.9)
7.15 (d, 8.5) 7.38 (d, 8.6) 6.89 (d, 8.7) 7.29 (d, 8.8) 6.84 (dd, 1.8, 11.3) 7.23 (dd, 1.3, 8.0) 7.24 (d, 8.7) 7.46 (d, 8.7) 6.90 (d, 7.9)
3-OMe
5-OMe
2ꢁ-OMe
3ꢁ-OMe
4ꢁ-OH
4ꢁ-OMe
5ꢁ-OMe
3.66 (s)
3.83 (s)
3.62 (s)
3.62 (s)
3.86 (s)
3.86 (s)
–
3.82 (s)
3.82 (s)
3.89 (s)
3.88 (s)
–
3.66 (s)
3.66 (s)
3.87 (s)
3.89 (s)
–
3.84 (s)
3.84 (s)
3.85 (s)
3.88 (s)
–
3.79 (s)
3.83 (s)
3.66 (s)
3.66 (s)
3.83 (s)
3.79 (s)
3.83 (s)
3.66 (s)
–
–
–
–
–
–
–
–
–
3.69 (s)
4.92 (s)
5.02 (s)
–
3.69 (s)
–
–
3.81 (s)
–
–
–
–
–
–
–
–
3.79 (s)
–
3.87 (s)
–
–
–
–
–
Position
10
11
12
13
14
15
16
17
18
2
6.67 (d, 2.2) 6.43 (d, 2.3) 6.69 (d, 2.3) 6.48 (d, 2.3)
6.40 (t, 2.2) 6.31 (t, 2.3) 6.38 (t, 2.3) 6.35 (t, 2.3)
6.67 (d, 2.2) 6.43 (d, 2.3) 6.69 (d, 2.3) 6.48 (d, 2.3)
6.68 (d, 2.3)
6.42 (t, 2.3)
6.68 (d, 2.3)
7.03 (s)
6.34 (d, 2.2)
6.31 (t, 2.2)
6.34 (d, 2.2)
2.84 (m)
2.84 (m)
7.10 (d, 8.5)
6.84
6.36 (d, 2.3) 6.43 (d, 2.3) 6.35 (d, 2.4)
6.33 (t, 2.3) 6.37 (t, 2.3) 6.31 (t, 2.4)
6.36 (d, 2.3) 6.43 (d, 2.3) 6.35 (d, 2.4)
4
6
7
7.06 (d, 16.4) 6.58 (d, 12.2) 7.04 (d, 16.4)
7.01 (d, 16.4) 6.73 (d, 12.2) 7.45 (d, 16.4)
6.56 (s)
6.56 (s)
6.48 (d, 2.3)
–
2.88 (m)
2.89 (m)
6.76 (m)
–
2.89 (m)
2.84 (s)
2.84 (s)
6.35 (d, 2.4)
–
8
7.03 (s)
2.94 (m)
2ꢁ
3ꢁ
7.04 (d, 2.6)
–
–
–
6.68 (d, 2.3)
–
–
6.90
6.89
6.89
(dd, 0.8, 7.8) (dd, 0.7, 7.8)
7.21 7.24
(d, 8.5)
(dd, 1.0, 7.5)
7.23
4ꢁ
5ꢁ
6ꢁ
6.82
6.35
(t, 2.3)
–
6.42
(t, 2.3)
–
–
6.80
(d, 7.5)
7.21
(d, 7.5)
6.74
(m)
6.31
(t, 2.4)
–
(dd, 2.6, 8.1) (dt, 1.7, 7.8) (dt, 1.7, 7.8)
(dt, 1.7, 7.5)
6.92
7.27
(t, 8.1)
7.10
(m)
6.80
(dt, 0.8, 7.8) (dt, 0.7, 7.8)
7.25 7.58
(dd, 1.7, 7.8) (dd, 1.7, 7.8)
6.96
6.84
(d, 8.5)
7.10
(d, 8.5)
3.76 (s)
3.76 (s)
–
(dt, 1.0, 7.5)
7.15
6.48
(d, 2.3)
3.69 (s)
3.69 (s)
–
6.68
(d, 2.3)
3.85 (s)
3.85 (s)
–
6.35
(d, 2.4)
3.76 (s)
3.76 (s)
–
(dd, 1.7, 7.5)
3.80 (s)
3.80 (s)
3.86 (s)
–
3-OMe
5-OMe
2ꢁ-OMe
3ꢁ-OMe
4ꢁ-OH
4ꢁ-OMe
5ꢁ-OMe
3.82 (s)
3.82 (s)
–
3.62 (s)
3.82 (s)
3.76 (s)
3.76 (s)
–
3.62 (s)
3.82 (s)
3.83 (s)
3.88 (s)
3.84 (s)
–
–
–
–
–
–
–
–
–
3.69 (s)
–
3.85 (s)
–
–
3.78 (s)
–
3.76 (s)
–
–
–
–
–
–
3.78 (s)
–
–
–
–
–
3.69 (s)
3.85 (s)
–
–
3.76 (s)
a Signal multiplicities: s, singlet; d, doublet; t, triplet.
Results and Discussion
at δ = 6.39 ppm and the 13C peak at δ = 99.8 ppm observed
in the HMBC spectrum indicated that the 13C peak was C-4.
Two 13C peaks at δ = 126.0 and 130.0 ppm were attached to
The structures and nomenclature of the methoxylated stilbene
and 1,2-diphenylethane derivatives (1–18) are shown in Fig. 1.
Among the 18 compounds, 3, 4, and 5 are novel. The 13C NMR
spectrum for 3 had 16 peaks because of its symmetrical A ring. The
carbon atoms were identified using DEPT experiments. Among
the four quaternary carbons between δ = 55 and 65 ppm, the 13C
peak at δ = 55.4 ppm was assigned to 3-OMe/5-OMe of A-ring
because of its double intensity. C-3/C-5 and C-2/C6 were assigned
in the same manner. H-2/H-6 were identified using HMQC data
1
two H peaks at δ = 6.61 and 6.49 ppm, respectively, and they
were assigned to the carbons of the double bond, C-7 or C-8.
HMBC data showed that the 13C peak at δ = 130.0 ppm was
long-range coupled to H-2/H-6; thus, it was identified as C-7.
The 13C peak at δ = 139.5 ppm showed long-range coupling
with H-8 at δ = 6.61 ppm; thus, it was identified as C-1. In the
same manner, the 1H peak at δ = 6.89 ppm was identified as
H-6ꢁ of the B-ring because it was long-range coupled to C-8.
Based on the interpretation of the COSY data, the 1H peak at
1
(δ = 6.39 ppm). The long-range coupling between the H peak
c
Magn. Reson. Chem. 2011, 49, 374–377
Copyright ꢀ 2011 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/mrc

G. Jo et al.
Table 2. 13C NMR chemical shifts of methoxylated stilbene and 1,2-diphenylethane derivatives 1–18 (ppm) in CDCl3
Position
1
2
3
4
5
6
7
8
9
1
139.8
106.9
160.9
99.9
160.9
106.9
128.5
130.6
129.1
130.5
115.4
156.0
115.4
130.5
55.4
55.4
–
140.0
104.6
161.2
99.9
161.2
104.6
126.6
129.1
130.0
128.2
116.0
156.0
116.0
128.2
55.6
55.6
–
139.5
107.0
160.7
99.8
140.2
104.7
161.1
99.8
139.0
107.1
160.6
99.9
139.9
105.0
161.2
100.1
161.2
105.0
130.1
123.8
131.6
147.3
153.3
111.7
124.3
118.2
55.6
139.7
106.9
160.8
99.9
160.8
106.9
128.9
130.4
129.8
130.5
113.8
159.0
113.8
130.5
55.4
55.4
–
139.8
104.4
161.1
99.7
161.1
104.4
128.8
126.6
130.0
127.9
114.2
159.5
114.2
127.9
55.4
55.4
–
139.3
107.0
160.8
100.2
160.8
107.0
130.8
130.7
138.8
114.2
159.7
113.5
129.4
121.8
55.4
55.4
–
2
3
4
5
160.7
107.0
130.0
126.0
124.3
152.2
142.4
153.3
107.3
124.9
55.4
161.1
104.7
128.1
124.5
123.7
152.0
142.6
153.6
108.0
121.0
55.5
160.6
107.1
130.9
126.3
131.9
153.0
147.4
111.6
123.7
122.4
55.3
6
7
8
1ꢁ
2ꢁ
3ꢁ
4ꢁ
5ꢁ
6ꢁ
3-OMe
5-OMe
2ꢁ-OMe
3ꢁ-OMe
4ꢁ-OMe
5ꢁ-OMe
55.4
55.5
55.3
55.6
61.3
61.5
60.9
61.3
–
–
61.2
61.1
55.9
56.1
–
–
55.3
–
–
–
56.2
56.2
–
–
55.4
–
55.3
–
–
–
–
–
–
–
–
δ of 13
C
Position
10
11
12
13
14
15
16
17
18
1
139.5
104.8
161.2
100.3
161.2
104.8
129.9
129.3
138.8
113.7
160.1
112.0
129.2
119.5
55.6
139.2
106.8
160.2
99.9
160.2
106.8
130.3
126.5
126.2
157.6
110.7
128.8
120.3
130.4
55.2
55.2
55.6
–
140.2
104.8
161.1
100.0
161.1
104.8
129.3
124.2
126.4
157.21
111.1
129.0
120.9
126.7
55.6
139.1
106.9
160.6
100.0
160.6
106.9
130.7
130.7
139.1
106.9
160.6
100.0
160.6
106.9
55.3
139.3
104.8
161.2
100.3
161.2
104.8
129.4
129.4
139.3
104.8
161.2
100.3
161.2
104.8
55.6
144.5
106.7
160.9
98.1
160.9
106.7
37.0
38.7
134.0
129.5
113.9
158.1
113.9
129.5
55.4
55.4
–
144.3
106.6
160.9
98.1
160.9
106.6
37.9
38.2
143.5
114.5
159.8
121.0
129.4
111.4
55.3
55.3
–
145.0
106.7
160.8
98.0
160.8
106.7
36.6
32.4
130.3
157.6
110.4
127.3
120.5
130.0
55.3
55.3
55.4
–
144.3
106.7
161.0
98.2
161.0
106.7
38.2
38.2
144.3
106.7
161.0
98.2
161.0
106.7
55.5
55.5
–
2
3
4
5
6
7
8
1ꢁ
2ꢁ
3ꢁ
4ꢁ
5ꢁ
6ꢁ
3-OMe
5-OMe
2ꢁ-OMe
3ꢁ-OMe
4ꢁ-OMe
5ꢁ-OMe
55.6
55.6
55.3
55.6
–
55.7
–
–
55.5
–
55.3
55.6
–
55.2
–
55.5
–
–
–
–
–
–
55.4
–
–
–
–
–
55.3
55.6
–
–
55.5
δ = 6.47 ppm was H-5ꢁ. The long-range coupling between the 13
C
completely, and their 1H and 13C NMR data are listed in Tables 1
and 2, respectively.
peak at δ = 124.3 ppm and H-7 observed in HMBC identified the
C-1ꢁ carbon. Because the 13C peak at δ = 152.2 ppm was long-
range coupled to H-8 and H-6ꢁ, it was assigned to C-2ꢁ. Likewise,
two 13C peaks at δ = 142.4 and 153.3 ppm showed two long-
range couplings with H-5ꢁ and H-6ꢁ, respectively, and they were
identified as C-3ꢁ and C-4ꢁ, respectively. Based on three long-range
couplings observed in the HMBC spectrum, 2ꢁ-OMe, 3ꢁ-OMe, and
4ꢁ-OMe were identified. The coupling constant between H-7 and
H-8 was 12.2 Hz; thus, this derivative had a cis configuration. The
1H and 13C chemical shifts for all 18 compounds were assigned
Among the 18 compounds, the 1H NMR data of 1, 2, and 13–15
and the 1H and 13C NMR data of 7–12 and 16–18 had been
previously reported, and their literature spectra agreed well with
the NMR data in this study.[9–13] Here, we report the 1H and
13C NMR data of 3–6, including the three novel compounds,
and the 13C NMR data of 1, 2, and 13–15. In conclusion,
the results in this study provide a useful tool for structural
analysis of various methoxylated stilbene and 1,2-diphenylethane
derivatives.
c
wileyonlinelibrary.com/journal/mrc
Copyright ꢀ 2011 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2011, 49, 374–377

NMR data of methoxylated stilbenes and 1,2-diphenylethanes
O
R2
MeO
MeO
MeO
NaBH4
MeOH
Cl
H
OH
CCl4
R1
R3
R4
PPh3
OMe
OMe
OMe
2′
III
II
I
B
7
MeO
O
3
MeO
8
1
H
MeO
PPh3
A
PPh3Cl
H
4
OMe
IV
OMe
MeO
MeO
derivatives C7- C8 configuration
R1
H
R2
H
R4
OH
OH
OMe
OMe
H
R4
H
+
OMe
OMe
OMe
V-cis
1
2
Double
Double
Double
Double
cis
trans
cis
OMe
H
H
H
V-trans
3
OMe
OMe
OMe
H
OMe
OMe
OMe
trans
cis
4
H
MeO
5
H
Double
Double
Pd/C
H2
OMe
6
trans
cis
H
H
OMe
H
OMe
H
7
H
OMe
OMe
Double
Double
Double
Double
VI
8
H
H
H
trans
cis
OMe
H
9
H
H
OMe
Scheme 1. Synthesis of methoxylated stilbene and 1,2-diphenylethane
derivatives 1–18.
10
11
12
13
14
15
16
17
18
H
H
H
H
OMe
H
trans
cis
OMe
H
Double
Double
Double
Double
H
H
H
OMe
H
trans
cis
Acknowledgements
OMe
H
OMe
H
H
OMe
H
OMe
H
trans
–
This work was supported by the Priority Research Centers Program
through NRF and by MEST (2009-0093824), Agenda Program (RDA,
8-20-52), and a Disease Network Research Program Grant (NRF,
20090084183).
Single
Single
Single
Single
H
OMe
H
–
–
–
H
H
OMe
H
H
H
OMe
H
H
OMe
OMe
Figure 1. Structures and nomenclature of methoxylated stilbene and 1,2-
diphenylethane derivatives 1–18.
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