Chemical determination of the absolute structures of resveratrol dimers, ampelopsins A, B, D and F

Article abstract of DOI:10.1016/S0040-4020(02)00785-8

The absolute configurations of four stilbenedimers, (+)-ampelopsins A, (+)-ampelopsins B, (-)-ampelopsins D and (+)-ampelopsins F were respectively determined on the basis of chemical evidence.

Full text of DOI:10.1016/S0040-4020(02)00785-8

Tetrahedron 58 (2002) 7259–7265
Chemical determination of the absolute structures of resveratrol
dimers, ampelopsins A, B, D and F
†
Yoshiaki Takaya, Ke-Xu Yan, Kenji Terashima, Junko Ito and Masatake Niwa
*
Faculty of Pharmacy, Meijo University, Tempaku, Nagoya 468-8503, Japan
Received 11 June 2002; accepted 28 June 2002
Abstract—The absolute configurations of four stilbenedimers, (þ)-ampelopsins A, (þ)-ampelopsins B, (2)-ampelopsins D and (þ)-
ampelopsins F were respectively determined on the basis of chemical evidence. q 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
In the course of the structural determination of stilbene-
oligomers, we reported the absolute structure of a
stilbenedimer, (þ)-ampelopsin A (1),1 on the basis of
spectral evidence.2 Namely, based on the evidence that the
CD spectrum of the methylated ketone (2) derived from
(þ)-ampelopsin A (1)1 showed a positive Cotton effect at
357 nm, the absolute structure of (þ)-ampelopsin A was
determined to be 1. The absolute structure of (þ)-
ampelopsin B was also characterized to be 3, because of
the similarity of the CD spectrum to that of (þ)-ampelopsin
A (1).1,2 Thereafter, we received some inquiries about the
validity of the assignment at the wavelength. So, we
undertook to confirm chemically the absolute structures of
(þ)-ampelopsin A (1) and (þ)-ampelopsin B (3). (þ)-1-
Viniferin (4), of which the absolute structure is known,3 is
regarded as an important biogenetic precursor of many
stilbenedimers from Vitaceaeous plants including (þ)-
ampelopsin A (1) and (þ)-ampelopsin B (3). In the present
paper, we describe the regiospecific and stereospecific
transformation of (þ)-1-viniferin (4) to (þ)-ampelopsin A
(1), (þ)-ampelopsin B (3), (2)-ampelopsin D (5),4 and (þ)-
ampelopsin F (6).5 These chemical results gave the absolute
structures of these compounds. Furthermore, the transform-
ation of (þ)-1-viniferin (4) to (2)-ampelopsin D (5) clearly
as raised by Adesanya et al.1,6
2. Results and discussion
resolves any doubt about the structure of (2)-ampelopsin D
2.1. Acid-catalyzed reactions of (1)-1-viniferin
(þ)-1-Viniferin (4) seems to be the biogenetically important
precursor of (þ)-ampelopsin A (1), (þ)-ampelopsin B (3),
(2)-ampelopsin D (5) and (þ)-ampelopsin F (6), as shown
in Scheme 1. The difference of the products apparently is
Keywords: (þ)-ampelopsin A; (þ)-ampelopsin B; (2)-ampelopsin D; (þ)-
due to the difference of the position of protonation at the
initial stage of the reaction. In the case of path a, the reaction
ampelopsin F; oligostilbene; resveratrol dimer; biogenetic reaction.
*
Corresponding author. Tel.: þ81-52-832-1781; fax: þ81-52-834-8090;
starts with the protonation of the double bond, followed by
cyclization to form a seven-membered ring to give (þ)-
e-mail: masa@ccmfs.meijo-u.ac.jp
On leave from Institute of Materia Medica, Chinese Academy of Medical
†
ampelopsin A (1). In the cases of both paths b and c, an acid
protonates the oxygen atom on the dihydrofuran ring,
Sciences and Peking Union Medical College, Beijing 100050, People’s
Republic of China.
0040–4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)00785-8

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Y. Takaya et al. / Tetrahedron 58 (2002) 7259–7265
Scheme 1. Plausible biogenetic pathways of (þ)-ampelopsin B (2), (2)-ampelopsin D (5) and (þ)-ampelopsin F (6) from (þ)-1-viniferin (4).
followed by nucleophilic attack of the double bond; then, a
five-membered ring intermediate is formed. In the case of
path b, the subsequent deprotonation of the intermediate
gives (2)-ampelopsin D (5). In the case of path c, the
second nucleophilic attack of the double bond against the
intermediate and the subsequent deprotonation gives (þ)-
ampelopsin F (6). All reactions above should be carried out
concertedly.
of 4 with sulfuric acid in methanol under reflux for 5 days
afforded a mixture of four compounds, 3, 5, 6 and 7 in 13, 6,
19, and 10% yields, respectively.
2.2. Confirmation of the structure of (2)-ampelopsin D
Oshima et al. reported the isolation and structure of
(2)-ampelopsin D (5) from the root of Ampelopsis
brevpedunculata var. hancei (Vitaceae) in 1993,4 and
Adesanya et al. reported the isolation and structure of
(2)-quadrangularin A (8) from the stem of Cissus
quadrangularis (Vitaceae) in 1999.6 The latter authors
described that the reported structure of ampelopsin D is
probably erroneous and should be 8 on the basis of the
similarity of the NMR data in their paper.6 Their claim was
based only on a comparison of their NMR data. But our
product (5) from (þ)-1-viniferin was completely identical
with the natural (2)-ampelopsin D by comparison of the IR,
1H NMR, and 13C NMR spectra and the sign of the
optical rotation7 with those reported by Oshima et al.4
Furthermore, according to the reaction mechanism in
(þ)-1-Viniferin (4) ([a ]2D2¼þ49.18) was treated with
hydrochloric acid in H2O at room temperature for 50 h to
give a mixture of (þ)-ampelopsin B (3) ([a ]D¼þ176.48)1
and (þ)-ampelopsin F (6) ([a]D¼þ19.08)5 in 38 and 8%
yields, respectively. Next, treatment of (þ)-1-viniferin (4)
with trifluoromethanesulfonic acid in nitromethane at room
temperature for 10 h gave a single product, (þ)-ampelopsin
F (6) in 38% yield. Trifluoromethanesulfonic acid in
methanol transformed (þ)-1-viniferin (4) to a mixture of
(2)-ampelopsin D (5) ([a]D¼258),4 its regioisomer (7)
([a]D¼2227.08),7 and (þ)-ampelopsin F (6) in 14, 8 and
21% yields, respectively, under reflux for 7 days. Treatment

Y. Takaya et al. / Tetrahedron 58 (2002) 7259–7265
7261
Scheme 2. Formation of (þ)-ampelopsin A (1) from (þ)-1-viniferin (4) via its (þ)-b-epoxide (9).
Scheme 1, (þ)-1-viniferin would give (2)-ampelopsin D
(5) and would not, in any event, give (2)-quadrangularin A
(8). From the above evidence, we have concluded that the
structure of (2)-ampelopsin D (5) as reported by Oshima
et al. is correct, and (2)-ampelopsin D (5) is a different
compound from (2)-quadrangularin (8), though the 1H and
13C NMR data of both compounds are very similar.4,6,7
2.3. Base-promoted reactions of (1)-b-epoxy-1-viniferin
As shown in Scheme 2, (þ)-b-epoxy-1-viniferin (9) seems
to be the important precursor of (þ)-ampelopsin A (1). So
we tried to transform (þ)-1-viniferin (4) to 9. Any trials of
epoxidation of (þ)-1-viniferin (4) to (þ)-b-epoxy-1-vini-
ferin (9) gave no good results. Therefore, (þ)-1-viniferin
Scheme 3. Transformation of (þ)-1-viniferin (4) by the biomimic pathways.

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Y. Takaya et al. / Tetrahedron 58 (2002) 7259–7265
pentaacetate (10) derived from 4 with acetic anhydride in
pyridine was epoxidated with m-chloroperbenzoic acid to
afford two epoxides 11 and 12 in 49 and 23% yields,
respectively. Both epoxides (11 and 12) were respectively
treated with hydrochloric acid or trifluoroacetic acid in a
mixture of methanol and H2O to give no cyclized product
but the corresponding epoxide-ring cleaved products 13 and
14. As shown in Scheme 3, epoxide 11 was treated with
potassium hydroxide in methanol to give (þ)-ampelopsin A
(1) together with a methyl ether product (15) in 55 and 31%
yields, respectively. On the other hand, epoxide 12 was
treated under the same conditions to give a cyclized product
(16) and a methyl ether (17) in 41 and 52% yields,
respectively. The stereochemistry osf compound 16 was
of the solvent, the residue was subjected to preparative
HPLC [YMC-C8 (B 20£250 mm), MeOH–H2O (6:4), flow
rate: 3.0 ml/min] to give (þ)-ampelopsin B (3) (4.2 mg,
38%), (þ)-ampelopsin F (6) (0.8 mg, 8%), and the starting
material (4) (0.9 mg).
3.3.1. Compound 3. [a ]2D2¼þ176.48 (c 0.10, MeOH),
FABMS m/z: 455 (MHþ; C28H23O6); 1H NMR (acetone-d6)
dH 7.08 (2H, d, J¼8.8 Hz; H-2a,6a), 6.92 (2H, d, J¼8.8 Hz;
H-2b,6b), 6.75 (2H, d, J¼8.8 Hz; H-3a,5a), 6.63 (1H, d,
J¼8.8 Hz; H-3b,5b), 6.42 (1H, d, J¼1.8 Hz; H-12a), 6.31
(1H, d, J¼2.2 Hz; H-14b), 6.21 (1H, d, J¼1.8 Hz; H-14a),
6.04 (1H, d, J¼2.2 Hz; H-12b), 5.71 (1H, d, J¼11.4 Hz;
H-7a), 5.20 (1H, t, J¼4.0 Hz; H-7b), 4.16 (1H, d,
J¼11.4 Hz; H-8a), 3.58 (1H, dd, J¼17.6, 4.0 Hz; H-8b),
3.17 (1H, brd, J¼17.6 Hz; H-8b); 13C NMR (acetone-d6) dC
160.4p (s; C-11b), 158.7p (s; C-11a), 158.4p (s; C-13b),
157.1p (s; C-4a), 156.5 (s; C-13a), 156.0 (s; C-4b), 142.5 (s;
C-9a), 138.1 (s; C-9b), 134.7 (s; C-1b), 131.0 (s; C-1a), 130.0
(2C, d; C-2a,6a), 128.5 (2C, d; C-2b,6b), 122.8 (s; C-10a),
118.9 (s; C-10b), 115.9 (2C, d; C-3a,5a), 115.5 (2C, d; C-
3b,5b), 108.9 (d; C-14b), 105.4 (d; C-14a), 101.4 (d; C-12a),
95.6 (d; C-12b), 88.3 (d; C-7a), 49.2 (d; C-8a), 35.8 (d; C-7b),
33.7 (t; C-8b), (p data can be interchanged within the group).
1
characterized on the basis of H NMR data. The chemical
shift value dH-8a 5.37 indicated the anti-configuration
between H-8a and 4-hydroxyphenyl group at the C-7b
position,8 as is observed in isohopeaphenol.9
2.4. Absolute configurations
On the basis of the absolute configuration of (þ)-1-viniferin
(4)3 and the reaction mechanisms of the isomerization of
(þ)-1-viniferin (4) shown above, the absolute configur-
ations of (þ)-ampelopsin A, (þ)-ampelopsin B, (2)-
ampelopsin D and (þ)-ampelopsin F were determined as
1, 3, 5 and 6, respectively.
3.3.2. Compound 6. [a ]2D2¼þ19.08 (c 0.30, MeOH),
1
FABMS m/z: 455 (MHþ; C28H23O6); H NMR (acetone-
d6) dH 7.08 (2H, d, J¼8.1 Hz; H-2a,6a), 6.78 (2H, d,
J¼8.8 Hz; H-2b,6b), 6.75 (2H, d, J¼8.1 Hz; H-3a,5a), 6.56
(2H, d, J¼8.8 Hz; H-3b,5b), 6.51 (1H, d, J¼2.2 Hz; H-14a),
6.44 (1H, d, J¼2.2 Hz; H-14b), 6.15 (1H, d, J¼2.2 Hz;
H-12b), 6.06 (1H, d, J¼2.2 Hz; H-12a), 4.19 (1H, d,
J¼1.5 Hz; H-7a), 4.12 (1H, brs; H-8b), 3.64 (1H, brs; H-7b),
3.36 (1H, brs; H-8a); 13C NMR (acetone-d6) dC 158.6 (s;
C-13a), 157.8 (s; C-11b), 157.1 (s; C-13b), 156.2p (s; C-4a),
156.1p (s; C-4b), 153.1 (s; C-11a), 147.6 (s; C-9b), 147.3 (s;
C-9a), 138.4 (s; C-1a), 135.4 (s; C-1b), 129.9 (2C, d;
C-2a,6a), 129.2 (2C, d; C-2b,6b), 127.8 (s; C-10a), 115.6
(2C, d; C-3a,5a), 115.5 (2C, d; C-3b,5b), 113.3 (s; C-10b),
105.7 (d; C-14b), 104.2 (d; C-14a), 101.9pp (d; C-12a),
101.8pp (d; C-12b), 58.1 (d; C-8a), 50.4 (d; C-7b), 49.7 (d;
C-8b), 47.1 (d; C-7a) (p, pp data can be interchanged within
the group).
3. Experimental
3.1. General
UV and IR spectra were recorded on JASCO Ubest V-560
(cell length 10 mm) and FT/IR-410 spectrometers,
respectively. Optical rotations were measured with a
JASCO P-1020 polarimeter (cell length 100 mm). H and
13C NMR spectra were recorded on JEOL ALPHA-600 (1H:
600 MHz and 13C: 150 MHz). Chemical shifts for H and
13C NMR are given in parts per million (d ) relative to TMS
or solvent signal (methanol-d4: dH 3.30 and dC 49.0,
acetone-d6: dH 2.04 and dC 24.9) as internal standards,
respectively. LR and HR FAB-MS were obtained with
JEOL JMS HX-110 using m-nitrobenzylalcohol as matrix.
Analytical TLC was performed on silica gel 60 F254
(Merck). Column chromatography was carried out on silica
gel BW-820 MH (Fuji Silysia Chemicals, Co. Ltd.).
1
1
3.4. Reaction of (1)-1-viniferin (4) with CF3SO3H in
nitromethane
A mixture of (þ)-1-viniferin (4) (11.0 mg) and trifluoro-
methanesulfonic acid (2.2 ml) in nitromethane (1.0 ml) was
stirred under nitrogen atmosphere at room temperature for
10 h. The reaction mixture was diluted by water (5 ml), and
then extracted with ethyl acetate (5 ml£2). The extract was
washed with brine and then dried over anhydrous sodium
sulfate. After evaporation of the solvent, the residue was
subjected to preparative HPLC [YMC-C8 (B 20£250 mm),
MeOH–H2O (6:4), flow rate: 3.0 ml/min] to give (þ)-
ampelopsin F (6) (4.2 mg, 38%) and the starting material (4)
(2.5 mg).
3.2. Material
(þ)-1-Viniferin (4) was obtained from corks of Vitis
vinifera ‘Kyohou’.10
3.2.1. Compound 4. [a]D¼þ49.18 (c 1.9, MeOH). Other
spectral and physical data were identical with those reported.3
3.3. Reaction of (1)-1-viniferin (4) with 1 M HCl
A mixture of (þ)-1-viniferin (4) (11.1 mg) in 1 M HCl
(1.5 ml) was stirred under nitrogen atmosphere at room
temperature for 50 h. The reaction mixture was extracted
twice with ethyl acetate (10 ml each), washed with brine and
then dried over anhydrous sodium sulfate. After evaporation
3.5. Reaction of (1)-1-viniferin (4) with CF3SO3H in
methanol
A mixture of (þ)-1-viniferin (4) (10.3 mg) and trifluoro-

Y. Takaya et al. / Tetrahedron 58 (2002) 7259–7265
7263
methanesulfonic acid (2.2 ml) in methanol (1.0 ml) was
stirred under nitrogen atmosphere under reflux for 7 days. The
reaction mixture was diluted with water (5 ml), and then
passed through Sep-Pak C18 (Waters). The absorbed product
was eluted by methanol, and the eluate was concentrated in
vacuo.TheresiduewassubjectedtopreparativeHPLC[YMC-
C8 (B 20£250 mm), MeOH–H2O (6:4), flow rate:
3.0 ml/min] to give (2)-ampelopsin D (5) (1.4 mg, 14%),
(þ)-ampelopsin F (6) (2.1 mg, 20%), compound 7 (0.8 mg,
8%), and the starting material (4) (0.3 mg).
anhydride (2 ml) in pyridine (4 ml) was stirred at
room temperature for 16 h. The reaction mixture was
evaporated to dryness, and the residue was subjected to
silica-gel column chromatography using chloroform as
eluant to give (þ)-1-viniferin pentaacetate (10) (253 mg,
83%).
3.7.1. Compound 10. [a ]2D5¼þ4.68 (c 0.54, CHCl3),
FABMS m/z: 665.2010 (MHþ; 665.2023 for C38H33O11);
IR nmax (film) cm21: 1768, 1198; 1H NMR (CDCl3) d 7.32
(2H, d, J¼8.8 Hz; H-2a,6a), 7.16 (2H, d, J¼8.8 Hz;
H-2b,6b), 7.08 (2H, d, J¼8.8 Hz; H-3a,5a), 6.96 (2H, d,
J¼8.8 Hz; H-3b,5b), 6.93 (1H, d, J¼2.2 Hz; H-14b), 6.88
(1H, t, J¼2.2 Hz; H-12a), 6.86 (1H, d, J¼16.1 Hz; H-8b),
6.84 (2H, d, J¼2.2 Hz; H-10a,14a), 6.63 (1H, d, J¼2.2 Hz;
H-12b), 6.52 (1H, d, J¼16.1 Hz; H-7b), 5.59 (1H, d,
J¼6.6 Hz; H-7a), 4.58 (1H, d, J¼6.6 Hz; H-8a), 2.32, 2.28,
2.25 (each 3H, s; CH3CO), 2.24 (6H, s; CH3CO); 13C NMR
(CDCl3) d 161.0 (s; C-11b), 152.2 (s; C-13b), 151.7 (2C, s;
C-11a,13a), 150.7 (s; C-4a), 150.4 (s; C-4b), 144.4 (s; C-9a),
138.1 (s; C-1a), 135.4 (s; C-9b), 134.5 (s; C-1b), 130.4 (d;
C-8b), 127.8 (2C, d; C-2b,6b), 126.8 (2C, d; C-2a,6a), 124.1
(d; C-7b), 123.9 (s; C-10b), 122.0 (2C, d; C-3a,5a), 121.8
(2C, d; C-3b,5b), 118.6 (2C, d; C-10a,14a), 114.9 (d;
C-12a), 110.7 (d; C-14b), 102.9 (d; C-12b), 92.8 (d; C-7a),
56.7 (d; C-8a), 169.5, 169.42, 169.39 (each s; CH3CO),
168.8 (2C, s; CH3CO), 21.3 (q; C H3CO), 21.2, 21.1 (each
2C, q; CH3CO).
3.5.1. Compound 5. [a ]2D2¼25.08 (c 0.27, MeOH);
HRFABMS m/z 455.1498 (calcd for C28H23O6, 455.1495);
1H NMR (acetone-d6) d 7.17 (2H, d, J¼8.8 Hz; H-2b,6b),
7.11 (2H, d, J¼8.8 Hz; H-2a,6a), 7.03 (1H, d, J¼2.2 Hz;
H-7b), 6.79 (1H, d, J¼2.2 Hz; H-14b), 6.74 (2H, d, J¼8.8 Hz;
H-3a,5a), 6.65 (2H, d, J¼8.8 Hz; H-3b,5b), 6.29 (1H, d,
J¼2.2 Hz;H-12b), 6.11(1H, t, J¼2.2 Hz; H-12a), 6.10(2H, d,
J¼2.2 Hz; H-10a,14a), 4.27 (1H, brs; H-7a), 4.14 (1H, brs;
H-8a); 13C NMR (acetone-d6) d 159.7 (s; C-13b), 159.3 (s;
C-11a,13a), 157.3 (s; C-4b), 156.7 (s; C-4a), 156.1 (s; C-11b),
149.9 (s; C-9a), 147.5 (s; C-9b), 143.1 (s; C-8b), 137.3 (s;
C-1a), 131.0 (d; C-2b,6b), 129.7 (s; C-1b), 128.8 (d; C-2a,6a),
123.8 (s; C-10b), 122.6 (d; C-7b), 116.3 (d; C-3a,5a), 116.0 (d;
C-3b,5b), 106.4 (d; C-10a,14a), 103.8 (d; C-12b), 101.3 (d;
C-12a), 98.4 (d; C-14b), 59.5 (d; C-7a), 58.7 (d; C-8a).
3.5.2. Compound 7. [a ]2D2¼2227.08 (c 0.39, MeOH);
HRFABMS m/z 455.1499 (calcd for C28H23O6, 455.1495);
1H NMR (methanol-d4) d 3.81 (1H, d, J¼16.1 Hz; H-7b), 3.86
(1H, d, J¼16.1 Hz; H-7b0), 4.79 (1H, s, H-8a), 5.98 (1H, t,
J¼2.2 Hz;H-12a), 6.06(3H, d, J¼2.2 Hz; H-10a,14a, H-12b),
6.17 (1H, d, J¼2.2 Hz; H-14b), 6.65 (2H, d, J¼8.5 Hz;
H-3a,5a), 6.72 (2H, d, J¼8.5 Hz; H-3b,5b), 7.06 (2H, d,
J¼8.5 Hz; H-2a,6a), 7.10 (2H, d, J¼8.5 Hz; H-2b,6b); 13C
NMR (methanol-d4) d 158.9 (s, C-13b), 158.8 (s, C-11a,13a),
157.5 (d, C-4a), 156.5 (s, C-4b), 154.0 (s, C-11b), 150.4 (s,
C-7a), 149.9 (s, C-9b), 144.0 (s, C-9a), 136.6 (s, C-8b), 132.1
(s, C-1b), 131.1 (d, 2a,6a), 130.2 (d, 2b,6b), 128.9 (s, C-1a),
125.4 (s, C-10b), 116.3 (d, C-3b,5b), 115.8 (s, C-3a,5a), 108.2
(d, C-10a,14a), 101.5 (d, C-12a), 101.1 (d, C-12b), 100.8 (d,
C-14b), 56.8 (d, C-8a), 32.2 (t, C-7b).
3.8. Reaction of (1)-1-viniferin pentaacetate (4) with
m-chloroperbenzoic acid in dichloromethane
A mixture of (þ)-1-viniferin pentaacetate (10) (150 mg) and
m-chloroperbenzoic acid (118 mg) in dichloromethane
(5 ml) was stirred at room temperature for 16 h. A saturated
sodium bicarbonate aqueous solution (20 ml) was added to
the reaction solution, and the mixture was extracted with
chloroform (10 ml£2). The extract was washed with water
and brine, and then dried over sodium sulfate. After
evaporation of the solvent, the residue was subjected to
preparative silica-gel TLC using chloroform–acetone
(99:1) as solvent to give b-epoxide (11) (75 mg, 49%),
a-epoxide (12) (36 mg, 23%) and recovered starting
material (10) (17 mg).
3.6. Reaction of (1)-1-viniferin (4) with H2SO4 in
methanol
3.8.1. Compound 11. [a]2D5¼þ40.38 (c 0.74, CHCl3);
To a mixture of (þ)-1-viniferin (4) (54 mg) and methanol
(5.0 ml) was added H2SO4 (7.2 ml), and the solution was
refluxed under nitrogen atmosphere for 5 days. The reaction
mixture was diluted by water (12 ml), and then passed
through Sep-Pak C18. The absorbed product was eluted by
methanol, and the eluate was concentrated in vacuo. The
residue was subjected to preparative HPLC [YMC-C8 (B
20£250 mm), MeOH–H2O (6:4), flow rate: 3.0 ml/min] to
give (þ)-ampelopsin B (3) (7.0 mg, 13%), (2)-ampelopsin
D (5) (3.5 mg, 6%), (þ)-ampelopsin F (6) (10 mg, 19%),
compound 7 (5.4 mg, 10%), and the starting material (4)
(1.4 mg), respectively.
FABMS m/z: 681.2009 (MHþ; 681.1972 for C38H33O12); IR
1
nmax (film) cm21: 1767, 1201; H NMR (CDCl3) d 7.28
(2H, d, J¼8.8 Hz; H-2a,6a), 7.06 (2H, d, J¼8.8 Hz; H-3a
(5a)), 6.89 (2H, brs; H-3b,5b), 6.89 (2H, brs; H-2b,6b), 6.69
(1H, d, J¼2.2 Hz; H-12b), 6.66 (1H, t, J¼2.2 Hz; H-12a),
6.64 (2H, d, J¼2.2 Hz; H-10a,14a), 6.61 (1H, d, J¼2.2 Hz;
H-14b), 5.59 (1H, d, J¼6.6 Hz; H-7a), 4.51 (1H, d,
J¼6.6 Hz; H-8a), 3.43 (1H, d, J¼1.8 Hz; H-8b), 3.40 (1H,
d, J¼1.8 Hz; H-7b), 2.29, 2.27, 2.26 (each 3H, s; CH3CO),
2.23 (6H, s; CH3CO); 13C NMR (CDCl3) d 160.4 (s; C-11b),
152.4 (s; C-13b), 151.5 (2C, s; C-11a,13a), 150.63p (s;
C-4a), 150.58p (s; C-4b), 143.9 (s; C-9a), 137.9 (s; C-1a),
135.3 (s; C-9b), 133.4 (s; C-1b), 126.5 (2C, d; C-2a,6a),
126.5 (2C, d; C-2b,6b), 124.2 (d; C-10b), 122.0 (2C, d;
C-3a,5a), 121.5 (2C, d; C-3b,5b), 117.9 (2C, d; C-10a,14a),
114.4 (d; C-12a), 109.9 (d; C-14b), 103.6 (d; C-12b), 93.0
(d; C-7a), 61.6 (d; C-7b), 60.0 (d; C-8b), 56.2 (d; C-8a),
3.7. Reaction of (1)-1-viniferin (4) with acetic anhydride
in pyridine
A mixture of (þ)-1-viniferin (4) (209 mg) and acetic

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Y. Takaya et al. / Tetrahedron 58 (2002) 7259–7265
169.3, 169.5 (each 2C, s; CH3CO), 169.1 (s; CH3CO),
21.07, 21.12 (each 2C, q; CH3CO), 25.7 (q; C H3CO).
3.9.2. Compound 15. [a ]2D5¼þ61.98 (c 0.11, MeOH),
FABMS m/z: 502.1644 (Mþ; 502.1628 for C28H23O7); IR
1
nmax (film) cm21: 3363, 1600; H NMR (methanol-d4) d
3.8.2. Compound 12. [a]2D5¼þ24.08 (c 0.51, CHCl3);
7.07 (2H, d, J¼8.8 Hz; H-2a,6a), 6.71 (2H, d, J¼8.8 Hz;
H-3a,5a), 6.66 (2H, d, J¼8.8 Hz; H-2b,6b), 6.60 (1H, d,
J¼2.2 Hz; H-14b), 6.58 (2H, d, J¼8.8 Hz; H-3b,5b), 6.26
(1H, d, J¼2.2 Hz; H-12b), 6.22 (1H, t, J¼2.2 Hz; H-12a),
6.07 (2H, d, J¼2.2 Hz; H-10a,14a), 5.31 (1H, d, J¼4.8 Hz;
H-7a), 4.43 (1H, d, J¼4.0 Hz; H-8b), 4.27 (1H, d,
J¼4.8 Hz; H-8a), 3.86 (1H, d, J¼4.0 Hz; H-7b), 3.04 (3H,
s, OMe); 13C NMR (methanol-d4) d 162.3 (s; C-11b), 160.7
(2C, s; C-11a,13a), 159.8 (s; C-13b), 158.6 (s; C-4a), 157.8
(s; C-4b), 148.4 (s; C-9a), 141.2 (s; C-9b), 134.4 (s; C-1a),
131.0 (s; C-1b), 130.0 (2C, d; C-2b,6b), 127.6 (2C, d;
C-2a,6a), 120.1 (d; C-10b), 116.4 (2C, d; C-3a,5a), 115.8 (2C,
d; C-3b,5b), 108.8 (d; C-14b), 107.4 (2C, d; C-10a,14a), 102.4
(d; C-12a), 97.2(d; C-12b), 89.1(d; C-7a), 86.0(d; C-7b), 74.4
(d; C-8b), 57.8 (d; C-8a), 57.1 (q; OMe).
FABMS m/z: 681.1994 (MHþ; 681.1972 for C38H33O12); IR
1
nmax (film) cm21: 1768, 1215; H NMR (CDCl3) d 7.28
(2H, d, J¼8.8 Hz; H-2a,6a), 7.10 (2H, d, J¼8.8 Hz;
H-2b,6b), 7.05 (2H, d, J¼8.8 Hz; H-3a,5a), 6.98 (2H, d,
J¼8.8 Hz; H-3b,5b), 6.89 (1H, t, J¼2.2 Hz; H-12a), 6.72
(2H, d, J¼2.2 Hz; H-10a,14a), 6.71 (1H, d, J¼2.2 Hz;
H-12b), 6.61 (1H, d, J¼2.2 Hz; H-14b), 5.61 (1H, d,
J¼6.2 Hz; H-7a), 4.47 (1H, d, J¼6.2 Hz; H-8a), 3.54 (1H, d,
J¼1.8 Hz; H-7b), 3.41 (1H, d, J¼1.8 Hz; H-8b), 2.29, 2.27,
2.26 (each 3H, s; CH3CO), 2.23 (6H, s; CH3CO); 13C NMR
(CDCl3) d 160.7 (s; C-11b), 152.3 (s; C-13b), 151.6 (2C, s;
C-11a,13a), 150.7p (s; C-4a), 150.6p (s; C-4b), 143.8 (s;
C-9a), 138.0 (s; C-1a), 135.5 (s; C-9b), 133.7 (s; C-1b),
126.9 (2C, d; C-2b,6b), 126.4 (2C, d; C-2a,6a), 123.9 (d;
C-10b), 122.0 (2C, d; C-3a,5a), 121.7 (2C, d; C-3b,5b),
118.3 (2C, d; C-10a,14a), 114.9 (d; C-12a), 110.7 (d;
C-14b), 103.7 (d; C-12b), 92.7 (d; C-7a), 61.2 (d; C-7b),
59.3 (d; C-8b), 56.9 (d; C-8a), 168.7 (2C, s; CH3CO),
169.34, 169.29, 169.26 (each s; CH3CO), 21.0, 21.1 (each
2C, q; C H3CO), 29.2 (q; C H3CO), ( p data can be
interchanged within the group).
3.9.3. Compound 16. [a ]2D5¼þ4.58 (c 0.14, MeOH),
FABMS m/z: 471.1425 (MHþ; 471.1444 for C28H23O7);
IR nmax (film) cm21: 3359, 1614; 1H NMR (methanol-d4) d
7.45 (2H, d, J¼8.8 Hz; H-2a,6a), 6.88 (2H, d, J¼8.8 Hz;
H-3a,5a), 6.65 (2H, d, J¼8.8 Hz; H-2b,6b), 6.43 (2H, d,
J¼8.8 Hz; H-3b,5b), 6.16 (1H, d, J¼2.2 Hz; H-14a), 6.14
(1H, d, J¼2.2 Hz; H-12a), 6.00 (1H, d, J¼2.2 Hz; H-14b),
5.72 (1H, d, J¼9.6 Hz; H-7a), 5.67 (1H, d, J¼2.2 Hz;
H-12b), 5.37 (1H, d, J¼9.6 Hz; H-8a), 5.03 (1H, d,
J¼5.6 Hz; H-7b), 4.69 (1H, d, J¼5.6 Hz; H-8b); 13C
NMR (methanol-d4) d 161.0 (s; C-11b), 159.7 (s; C-4a),
159.1 (s; C-11a), 159.0 (s; C-13b), 157.0 (s; C-13a), 155.8
(s; C-4b), 141.8 (s; C-9a), 140.6 (s; C-9b), 135.7 (s; C-1b),
133.6 (s; C-1a), 130.8 (2C, d; C-2b,6b), 130.7 (2C, d;
C-2a,6a), 118.6 (d; C-10a), 118.5 (d; C-10b), 116.9 (2C, d;
C-3a,5a), 115.2 (2C, d; C-3b,5b), 108.9 (d; C-14b), 106.8 (d;
C-14a), 102.2 (d; C-12a), 96.2 (d; C-12b), 94.4 (d; C-7a),
79.1 (d; C-8b), 53.3 (d; C-8a), 49.6 (d; C-7b).
3.9. Reaction of (1)-epoxy-1-viniferin pentaacetate (11
and 12) with potassium hydroxide in methanol
A mixture of compound 11 (18 mg) and potassium
hydroxide (8.9 mg) in methanol (2 ml) was stirred in an
ice bath for 30 min. Then the mixture was acidified with
2 M hydrochloric acid aqueous solution and extracted with
ethyl acetate (5 ml£2). The extract was washed with water
and brine, and dried over anhydrous sodium sulfate. The
solvent was removed by evaporation, and the residue was
subjected to preparative silica-gel TLC using chloroform–
methanol–H2O (40:10:1) as solvent to give (þ)-ampelopsin
A (1) (9.7 mg, 55%) and 8b-hydroxy-7b-methoxy-1-vini-
ferin (15) (5.8 mg, 31%).
3.9.4. Compound 17. [a ]2D5¼þ46.78 (c 0.12, MeOH),
FABMS m/z: 503.1700 (MHþ; 503.1706 for C28H23O7); IR
1
nmax (film) cm21: 3356, 1613; H NMR (methanol-d4) d
In almost the same manner, compound 12 (8.9 mg) was
treated to give compound 16 (2.5 mg, 41%) and compound
17 (3.4 mg, 52%).
6.78 (2H, d, J¼8.7 Hz; H-2a,6a), 6.76 (2H, d, J¼8.7 Hz;
H-2b,6b), 6.73 (2H, d, J¼8.7 Hz; H-3a,5a), 6.64 (2H, d,
J¼8.7 Hz; H-3b,5b), 6.56 (1H, d, J¼2.3 Hz; H-14b), 6.13
(1H, d, J¼2.3 Hz; H-12b), 6.12 (1H, t, J¼2.3 Hz; H-12a),
5.94 (2H, d, J¼2.3 Hz; H-10a,14a), 4.95 (1H, d, J¼7.8 Hz;
H-7a), 4.33 (1H, d, J¼9.2 Hz; H-7b), 3.93 (1H, d,
J¼9.2 Hz; H-8b), 3.18 (1H, d, J¼7.8 Hz; H-8a), 3.14 (3H,
s; OMe); 13C NMR (methanol-d4) d 163.2 (s; C-11b), 161.2
(2C, s; C-11a,13a), 161.0 (s; C-13b), 160.1 (s; C-4a), 160.0
(s; C-4b), 147.9 (s; C-9a), 141.4 (s; C-9b), 133.9 (s; C-1a),
131.6 (2C, d; C-2b,6b), 130.8 (s; C-1b), 130.7 (2C, d;
C-2a,6a), 122.1 (s; C-10b), 117.7 (2C, d; C-3a,5a), 117.1
(2C, d; C-3b,5b), 108.9 (2C, d; C-10a,14a), 108.7 (d;
C-14b), 103.6 (d; C-12a), 98.4 (d; C-12b), 96.8 (d; C-7a),
91.5 (d; C-7b), 76.5 (d; C-8b), 58.1 (q; OMe), 58.0 (d;
C-8a).
3.9.1. Compound 1. [a ]2D5¼þ191.98 (c 0.96, MeOH);
FABMS m/z: 471.1479 (MHþ; 471.1444 for C28H23O7); IR
nmax (film) cm21: 3333, 1613, 1515, 1455; 1H NMR
(acetone-d6) dH 7.10 (2H, d, J¼8.4 Hz; H-2a,6a), 6.88
(2H, d, J¼8.8 Hz; H-2b,6b), 6.77 (2H, d, J¼8.4 Hz;
H-3a,5a), 6.63 (2H, d, J¼8.4 Hz; H-3b,5b), 6.60 (1H, d,
J¼2.2 Hz; H-14b), 6.42 (1H, d, J¼2.2 Hz; H-12a), 6.22
(1H, brs; H-14a), 6.14 (1H, d, J¼2.2 Hz; H-12b), 5.75 (1H,
d, J¼11.4 Hz; H-7a), 5.44 (1H, d, J¼4.8 Hz; H-7b), 5.40
(1H, d, J¼4.8 Hz; H-8b), 4.15 (1H, d, J¼11.4 Hz; H-8a);
13C NMR (acetone-d6) d 159.8 (s; C-13a), 159.8 (s; C-11b),
158.5 (s; C-13b), 158.1 (s; C-4b), 156.9 (s; C-4a), 155.7 (s;
C-11a), 142.7 (s; C-9a), 140.1 (s; C-9b), 132.3 (s; C-1a),
130.6 (s; C-1b), 129.6 (2C, d; C-2a,6a), 128.3 (2C, d;
C-2b,6b), 118.5 (d; C-10a), 118.0 (s; C-10b), 115.6 (2C, d;
C-3a,5a), 115.0 (2C, d; C-3b,5b), 110.1 (d; C-14b), 105.1 (d;
C-14a), 101.1 (d; C-12a), 97.0 (d; C-12b), 88.1 (d; C-7a),
70.7 (d; C-8b), 49.2 (d; C-8a), 43.5 (d; C-7b).
Acknowledgments
This research was financially supported by a Grant-in-Aid
for Scientific Research and for High-Tech Research Center

Y. Takaya et al. / Tetrahedron 58 (2002) 7259–7265
7265
4. Oshima, Y.; Ueno, Y. Phytochemistry 1993, 33, 179–182.
5. Oshima, Y.; Ueno, Y.; Hisamichi, K.; Takeshita, M.
Tetrahedron 1993, 49, 5801–5804.
Project from the Ministry of Education, Science, Sports and
Culture of Japan, and specially promoted research from
Meijo University, and Pfizer Inc., which are gratefully
acknowledged.
6. Adesanya, S. A.; Nia, R.; Martin, M.-T.; Boukamcha, N.;
Montagnac, A.; Pais, M. J. Nat. Prod. 1999, 62, 1694–1695.
7. Niwa, M.; Ito, J.; Terashima, K.; Takaya, Y.; Yan, K.-X.
Heterocycles 2000, 53, 1475–1478.
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