A novel, convenient synthesis of the 3-O-β-D- and 4′-O-β -D-glucopyranosides of trans-resveratrol

Article abstract of DOI:10.1081/SCC-120030744

trans-Resveratrol-3-O-β-D-glucupyranoside (trans-piceid, 2) and trans-resveratrol-4′-O-β-D-glucupyranoside (trans-resveratroloside 3) are the naturally occurring O-glucoside conjugates of the polyphenolic stilbenoid trans-resveratrol 1. Recently, attention has been drawn towards the interesting biological properties of the glucoside conjugates 2 and 3 as well as those of the aglycone 1. The fact that only limited quantities can be obtained by extraction from natural sources has prompted the development of novel syntheses of 2 and 3, based on a convergent Heck-coupling strategy, which now conveniently allows for the preparation of multi-milligram to gram quantities of each.

Full text of DOI:10.1081/SCC-120030744

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A Novel, Convenient Synthesis of the 3‐O‐β‐D‐ and
4′‐O‐β‐D‐Glucopyranosides of trans‐Resveratrol
David A. Learmonth a
a Laboratory of Chemical Research, Department of Research and Development , BIAL,
4745‐457, S. Mamede do Coronado, Portugal
Published online: 16 Aug 2006.
To cite this article: David A. Learmonth (2004) A Novel, Convenient Synthesis of the 3‐O‐β‐D‐ and
4′‐O‐β‐D‐Glucopyranosides of trans‐Resveratrol, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 34:9, 1565-1575, DOI: 10.1081/SCC-120030744
To link to this article: http://dx.doi.org/10.1081/SCC-120030744
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SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 9, pp. 1565–1575, 2004
A Novel, Convenient Synthesis of the
3-O-b-D- and 40-O-b-D-Glucopyranosides
of trans-Resveratrol
*
David A. Learmonth
Laboratory of Chemical Research, Department of Research and
Development, BIAL, S. Mamede do Coronado, Portugal
ABSTRACT
trans-Resveratrol-3-O-b-D-glucupyranoside (trans-piceid, 2) and
trans-resveratrol-40-O-b-D-glucupyranoside (trans-resveratroloside 3)
are the naturally occurring O-glucoside conjugates of the polyphenolic
stilbenoid trans-resveratrol 1. Recently, attention has been drawn towards
the interesting biological properties of the glucoside conjugates 2 and 3 as
well as those of the aglycone 1. The fact that only limited quantities can
be obtained by extraction from natural sources has prompted the develop-
ment of novel syntheses of 2 and 3, based on a convergent Heck-coupling
strategy, which now conveniently allows for the preparation of multi-
milligram to gram quantities of each.
Key Words: trans-Resveratrol; Glucupyranoside; Glucosidation; Heck
reaction.
*
Correspondence: David A. Learmonth, Laboratory of Chemical Research, Department
of Research and Development, BIAL, 4745-457 S. Mamede do Coronado, Portugal;
Fax: þ351-22-9866192; E-mail: david.learmonth@bial.com.
1565
DOI: 10.1081/SCC-120030744
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

ORDER
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1566
Learmonth
INTRODUCTION
trans-Resveratrol [(E)-3,40,5-trihydroxystilbene, 1] (Fig. 1) is a poly-
phenolic stilbenoid derivative produced by certain plants as a natural
antibiotic to protect against fungal attack.[1] 1 has been detected in pharmaco-
logically significant quantities in foodstuffs such as peanuts[2] and in red
wines.[3] A number of independent studies attest to the ability of 1 to exert
an impressively wide array of biological activities. For example, 1 has been
observed to display anti-platelet aggregation activity,[4] anti-leukemic[5] and
anti-fungal activity,[6] and vasorelaxant action.[7] Indeed, 1 has probably
been most famously implicated in the so-called “French Paradox.”[8] Regular
ingestion of 1 by the red wine-drinking population is believed to contribute to
lower rates of coronary heart disease in some regions of France than would be
expected due to the typical diet rich in fat and alcohol.[9]
Although pharmacological attention has centered mainly on the aglycone 1,
red wine also contains trans-resveratrol-3-O-b-D-glucopyranoside 2[10] (also
known as trans-piceid or polydatin, Fig. 1) which is endowed with anti-platelet
aggregation[11] and anti-cancer activity.[12] Appreciable quantities of 2 have
been found in the roots of Polygonum cuspidatum,[13] an Asian plant that
has been used in traditional Chinese herbal medicines for the treatment of
hypertension and cancer. The regioisomeric trans-resveratrol-40-O-b-D-gluco-
pyranoside 3 (also known as trans-resveratroloside, Fig. 1) has also been
identified in extracts from certain varieties of Polygonum cuspidatum[14] and
in Vitis vinifera cell cultures.[15,16] Kinase[17] and endopeptidase[18] inhibitory
properties have been ascribed to 3.
Although increasing interest in the biological properties of such polyphe-
nolic stilbenoids has recently led to a number of elegant new syntheses[19–23]
of the aglycone 1, it is rather surprising to find that comparatively few methods
Figure 1. Chemical structures of trans-resveratrol 1, trans-resveratrol-3-O-b-D-
glucupyranoside 2, and trans-resveratrol-40-O-b-D-glucupyranoside 3.

ORDER
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Synthesis of 3-O-b-D- and 40-O-b-D-Glucopyranosides
1567
exist for the chemical synthesis of 2, and to the best of the author’s knowledge,
no synthesis of 3 has been yet disclosed. Orsini et al. reported[11,24] a synthesis
of 2 based on a Wittig olefination strategy to form the core stilbenic skeleton,
which requires chromatographic separation of the cis- and trans-olefinic iso-
mers. Brandolini et al. described a direct glucosidation of 1, although the con-
version of 1 to 2 is quite low.[25] From this laboratory there was recently
reported a novel method for the preparation of the corresponding 3-O-b-D-
and 40-O-b-D-glucuronide conjugates of 1 based on a novel Heck coupling
of iodoaryl-O-b-D-glucuronate esters with appropriately substituted styr-
enes.[26] In the present study, it is shown that a similar convergent strategy
can now be conveniently applied to the synthesis of the corresponding gluco-
sides 2 and 3.
The present synthesis of trans-resveratrol-3-O-b-D-glucopyranoside 2 is
outlined in Sch. 1.
The aryl iodide was preferred due to the generally greater reactivity over
the corresponding aryl bromides in the palladium-catalyzed Heck coupling
reaction, which was employed as the key step in forming the fully functiona-
lized stilbenoid. Accordingly, 3,5-dihydroxyiodobenzene 4 was prepared from
commercially available 3,5-dimethoxyaniline via Sandmeyer reaction (59%
yield) and demethylation (57% HI, 90% yield) as previously described by
Deboves et al.[27] Reaction of 4 with commercially available acetobromo-a-
D-glucose 5 in acetonitrile in the presence of silver carbonate afforded the
Scheme 1. Synthesis of trans-resveratrol-3-O-b-D-glucupyranoside 2. Reagents:
(a) Ag2CO3, CH3CN, rt; (b) Ac2O, py, DMAP, CH2Cl2, rt; (c) Pd(OAc)2, BnEt3NþCl2,
Bu3N, CH3CN, 858C; and (d) 0.2 M NaOCH3/CH3OH, rt.

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Learmonth
3-O-b-D-glycosylated iodophenol 6 in moderate yield (38%) exclusively as
the b-anomer. Unreacted 4 could be recovered (20%) by chromatographic
separation and recycled. Protection of the phenol as the O-acetate proceeded
uneventfully to provide 7, which was then successfully coupled with commer-
cially available 4-acetoxystyrene 8 (Pd(OAc)2, BnEt3NþCl2, Bu3N) in warm
acetonitrile to give the fully protected glucoside 9 in moderate yield (40%).
Deprotection of the acetyl protecting groups of 9 proceeded smoothly with
dilute methanolic sodium methoxide solution at room temperature to provide
trans-resveratrol-3-O-b-D-glucopyranoside 2 in 94% yield. HPLC analysis
showed that this product was ꢀ98% homogenous.
Accordingly, preparation of trans-resveratrol-40-O-b-D-glucopyranoside
3 followed along similar lines (Sch. 2).
3,5-Diacetoxystyrene 10 was prepared as previously reported by Guiso
et al. from commercially available 3,5-dihydroxybenzaldehyde.[19] The iodo-
4-O-b-D-glucosidated phenol 12 was obtained exclusively as the b-anomer
by reaction of commercially available 4-iodophenol 11 with acetobromo-a-D-
glucose 5 and silver carbonate in acetonitrile (30% yield). 12 subsequently
underwent smooth palladium-catalyzed coupling with styrene 10 under very
slightly different conditions previously used to give the fully O-acetyl protected
40-O-b-D-glycoside 13 in quite respectable (61% yield). Basic hydrolysis of
the protecting groups afforded trans-resveratrol-40-O-b-D-glucopyranoside 3
(97% yield) and HPLC analysis again revealed homogeneity ꢀ98%.
Scheme 2. Synthesis of trans-resveratrol-40-O-b-D-glucopyranoside 2. Reagents:
(a) Ag2CO3, CH3CN, rt; (b) Ac2O, py, DMAP, CH2Cl2, rt; (c) Pd(OAc)2, BnEt3NþCl2,
Bu3N, CH3CN, 1008C; and (d) 0.2 M NaOCH3/CH3OH, rt.

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Synthesis of 3-O-b-D- and 40-O-b-D-Glucopyranosides
1569
CONCLUSIONS
Novel, convenient syntheses are described for trans-resveratrol-3-O-b-D-
glucupyranoside (trans-piceid, 2) and trans-resveratrol-40-O-b-D-glucupyra-
noside (trans-resveratroloside 3), which allow for convenient preparation of
pure, multi-milligram to gram quantities of either glucoside.
EXPERIMENTAL SECTION
Melting points were measured in open capillary tubes on an Electrother-
mal Model 9100 hot stage apparatus and are uncorrected. NMR spectra were
recorded on a Bruker Avance DPX (400 MHz) spectrometer with solvent used
as internal standard, and data are reported in the order: chemical shift (ppm),
number of protons, approximate coupling constant in Hertz, multiplicity
(s, singlet; d, doublet; t, triplet; m, multiplet; dd, double doublet; br, broad),
and assignment of the signal. IR spectra were measured with a Bomem Hart-
mann & Braun MB Series FTIR spectrometer using KBr discs. Analytical
HPLC was performed on an automated Agilent 1100 Series HPLC, using
LiChrospher 100 RP-18 (5 mm) LiChroCart 250-4 Cartridges (Merck) in com-
bination with acetonitrile/water (1% formic acid) mixtures. Analytical TLC
was performed on pre-coated silica gel plates (either Merck 60 Kieselgel
F254 or Merck RP-18 F254s) and visualized with UV light. Preparative chroma-
tography was done on Merck 60 Kieselgel (0.063–0.2 mm). Optical rotation
determinations were performed on a Jasco DIP-1000 digital polarimeter at
the sodium d line (589 nm), at 258C using a 50 mm path length cell. Elemental
analyses were performed on a Fisons EA 1110 CHNS instrument and all
analyses are consistent with theoretical values to within +0.4% unless
otherwise indicated. 4-Acetoxystyrene 8 was purchased from Aldrich and
acetobromo-a-D-glucose 5 from Lancaster and these were used as received.
3-Hydroxy-5-iodophenyl-2,3,4,6-tetra-O-acetyl-b-D-glucopyrano-
side 6. To a stirred solution of 4 (2.0 g, 8.47 mmol) and acetobromo-a-D-
glucose 5 (3.48 g, 8.47 mmol) in acetonitrile (20 cm3) at room temperature
was added silver carbonate (2.34 g, 8.47 mmol) in portions. The resulting
suspension was stirred for 8 hr and then filtered through a short Celite pad.
The filtrate was evaporated (408C, water-aspirator pressure) to leave a
dark brown gum. Chromatography over silica gel (petroleum ether/ethyl
acetate, 2/1) afforded the major product as a slightly hygroscopic white
foam (1.82 g, 38%). [a]2D5 ¼ 239.68 (c 0.32, MeOH); (Found: C, 42.49;
H, 4.09. C20H23IO11 requires C, 42.42; H, 4.09%); nmax (KBr disc)/cm21
3359 (OH) and 1755 (CO); dH (400 MHz, DMSO-d6) 7.0 (1H, s, H-2), 6.9
(1H, s, H-6), 6.5 (1H, s, H-4), 5.9 (1H, s, phenolic OH), 5.32–5.21 (2H, m,

ORDER
REPRINTS
1570
Learmonth
H-200, H-300), 5.13 (1H, m, H-400), 5.03 (1H, d, J 7.6, anomeric H-100), 4.25–
4.13 (2H, m, H-600A, H-600B), 3.91–3.87 (1H, m, H-500), and 2.14–2.03
(12H, 4 ꢁ s, 4 ꢁ CH3); dC (100 MHz, DMSO-d6) 171.5 (CO), 170.9 (CO),
170.1 (CO), 170.0 (CO), 158.6 (C-5), 157.9 (C-3), 120.5 (C-2), 118.8 (C-6),
105.3 (C-4), 99.3 (anomeric C-100), 94.3 (C-1), 73.2 (C-200), 72.7 (C-500),
71.6 (C-300), 68.9 (C-400), 62.6 (C-600), 21.4 (CH3), and 21.2 (3 ꢁ CH3).
3-Acetoxy-5-iodophenyl-2,3,4,6-tetra-O-acetyl-b-D-glucopyrano-
side 7. To a stirred solution of phenol 6 (1.60 g, 2.83 mmol) in dichloro-
methane (10cm3) at room temperature was added pyridine (0.28g,
3.53mmol), 4-dimethylaminopyridine (0.02 g) followed by acetic anhydride
(0.36 g, 3.53 mmol) dropwise. The resulting mixture was stirred for 30 min,
whereupon ice/water (10 cm3) was added. The organic phase was separated
and washed with dilute hydrochloric acid (10 cm3), water (10 cm3), and
brine (10 cm3), then dried over anhydrous magnesium sulfate, filtered, and
evaporated (408C, water-aspirator pressure). Toluene (10 cm3) was added to
the residue and re-evaporated to leave a colorless gum (1.68 g, 98%) which
was used without further purification. [a]2D5 ¼ 243.68 (c 0.3, MeOH);
(Found: C, 43.61; H, 4.00. C22H25O12 requires C, 43.43; H, 4.14%); nmax
(KBr disc)/cm21 1750 (CO); dH (400 MHz, DMSO-d6) 7.22 (1H, s, H-2),
7.19 (1H, s, H-6), 6.74 (1H, s, H-4), 5.32–5.23 (2H, m, H-200, H-300), 5.16–
5.11 (1H, m, H-400), 5.07 (1H, d, J 7, anomeric H-100), 4.25–4.18 (2H, m,
H-600A, H-600B), 3.93–3.88 (1H, m, H-500), 2.24 (3H, s, CH3), 2.13 (3H, s,
CH3), 2.08 (3H, s, CH3), 2.07 (3H, s, CH3), and 2.02 (3H, s, CH3); dC
(100 MHz, DMSO-d6) 171.2 (CO), 170.7 (CO), 170.0 (CO), 169.8 (CO),
169.3 (CO), 158.0 (C-5), 152.0 (C-3), 125.8 (C-2), 123.4 (C-6), 111.4 (C-
4), 99.2 (anomeric C-100), 93.6 (C-1), 73.1 (C-200), 72.8 (C-500), 71.5 (C-300),
68.7 (C-400), 62.7 (C-600), 22.02 (CH3), 21.5 (CH3), 21.4 (CH3), 21.2 (CH3),
and 21.1 (CH3).
(E)-1-(3-Acetoxy-5-O-2,3,4,6-tetraacetyl-b-D-glucopyranosidophenyl)-
2-(40-acetoxyphenyl)ethene 9. A mixture of 7 (1.63 g, 2.69 mmol), 4-
acetoxystyrene
8 (0.44 g, 2.69 mmol), palladium(II) acetate (0.03 g,
0.13 mmol), benzyltriethylammonium chloride (0.61 g, 2.69 mmol), and tribu-
tylamine (1.31 g, 7.06 mmol) in acetonitrile (20 cm3) was stirred at 858C for
one and a half hours under argon, and then allowed to cool to room tempera-
ture. The mixture was filtered through a short Celite path and evaporated to
dryness (408C, water-aspirator pressure). The residue was dissolved in
dichloromethane (20 cm3) and washed with dilute hydrochloric acid
(10 cm3), water (10 cm3), and brine (10 cm3), then dried over anhydrous
magnesium sulfate, filtered, and evaporated (408C, water-aspirator pressure).
The residue was chromatographed over silica gel (petroleum ether/ethyl acet-
ate, 3/2) to give a pale yellow foam that was recrystallized from diethyl ether
to give a white powder (0.69 g, 40%) of m.p. 109–1108C; [a]2D5 ¼ 268.78

ORDER
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Synthesis of 3-O-b-D- and 40-O-b-D-Glucopyranosides
1571
(c 0.25, MeOH); (Found: C, 59.63; H, 4.99. C32H34O14 requires C, 59.81; H,
5.33%); nmax (KBr disc)/cm21 1756 (CO); dH (400 MHz, DMSO-d6) 7.51
(2H, d, J 8.4, H-20, H-60), 7.11 (2H, d, J 8.4, H-30, H-50), 7.05–6.94 (4H, m,
H-2, H-4, 2 ꢁ vinylic CH), 6.7 (1H, s, H-6), 5.34–5.27 (2H, m, H-200,
H-300), 5.2–5.13 (2H, m, anomeric H-100, H-400), 4.32–4.27 (1H, m, H-600A),
4.21–4.18 (1H, m, H-600B), 3.94–3.92 (1H, m, H-500), 2.32 (6H, s,
2 ꢁ CH3), 2.09 (3H, s, CH3), 2.07 (6H, s, 2 ꢁ CH3), and 2.05 (3H, s, CH3);
dC (100 MHz, DMSO-d6) 171.1 (CO), 170.8 (CO), 170.0 (CO), 169.9 (CO),
169.8 (CO), 158.1 (C-3), 150.9 (C-40), 150.2 (C-6), 150.0 (C-1), 140.2
(C-2), 135.0 (C-10), 130.1 (vinylic C), 128.2 (vinylic C), 127.9 (C-60), 122.5
(C-50), 99.3 (anomeric C-100), 73.2 (C-300), 72.6 (C-200), 71.6 (C-400), 68.9
(C-500), 62.6 (C-600), 21.7 (CH3), 21.2 (CH3), and 21.1 (CH3).
trans-Resveratrol-3-O-b-D-glucopyranoside 2. To a suspension of 9
(0.55 g, 0.86 mmol) in methanol (30 cm3) at room temperature was added a
0.2 M methanolic solution of sodium methoxide (30 cm3). The resulting mix-
ture was stirred for 1 hr, whereupon sufficient Dowex 50WX8-100 ion
exchange resin was added in portions to maintain pH ꢀ2. The resin was
filtered off and washed with methanol (5 cm3). The combined filtrate was
evaporated (408C, water-aspirator pressure), and the residue was dried at 458C
over phosphorus pentoxide to give the product as a beige solid (0.31 g, 94%)
of m.p. 226–2298C (lit.,[28] 228–2308C); [a]2D5 ¼ 2648 (c 0.32, MeOH)
(lit.,[25] [a]2D5 ¼ 2628); (Found: C, 58.16; H, 6.32. C20H22O81 3H2O requires
.
C, 57.97; H, 6.00%); nmax (KBr disc)/cm21 3367 (OH, very broad) and 1592;
dH (400 MHz, DMSO-d6) 9.59 (1H, s, phenolic OH), 9.46 (1H, s, phenolic
OH), 7.40 (2H, d, J 8.2, H-20, H-60), 7.03 (1H, d, J 16.3, vinylic CH), 6.86
(1H, d, J 16.3, vinylic CH), 6.76 (2H, d, J 8.2, H-30, H-50), 6.7 (1H, s, H-6),
6.6 (1H, s, H-2), 6.3 (1H, s, H-4), 4.80 (1H, d, J 7.3, anomeric H-100), 3.73–
3.71 (1H, m, H-600A), and 3.69–3.14 (5H, m, H-200, H-300, H-400, H-500,
H-600B); dC (100 MHz, DMSO-d6) 159.9 (C-5), 159.3 (C-3), 158.3 (C-40),
140.3 (C-1), 129.5 (vinylic C), 128.9 (C-60), 126.2 (vinylic C), 116.5 (C-50),
108.2 (C-2), 105.7 (C-6), 103.7 (C-4), 101.6 (anomeric C-100), 78.13 (C-500),
77.69 (C-300), 74.29 (C-200), 70.6 (C-400), and 61.7 (C-600).
4-Iodophenyl-2,3,4,6-tetra-O-acetyl-b-D-glucopyranoside 12. To a stir-
red solution of 4-iodophenol (1.0 g, 4.54 mmol) and acetobromo-a-D-glucose
5 (2.80 g, 6.82 mmol) in acetonitrile at room temperature was added silver
carbonate (1.88 g, 6.82 mmol) in portions. The resulting mixture was stirred
in the dark for 48 hr, and then filtered through a short Celite pad. The filtrate
was evaporated to dryness (408C, water-aspirator pressure) to leave an oil that
solidified on standing. Recrystallization from a dichloromethane/isopropanol
mixture afforded the product as a white solid (0.75g, 30%) of m.p. 142–1438C;
[a]2D5 ¼ 251.68 (c 0.29, MeOH); (Found: C, 43.84; H, 4.33. C20H23IO10
requires C, 43.65; H, 4.21%); nmax (KBr disc)/cm21 1747 (CO); dH

ORDER
REPRINTS
1572
Learmonth
(400 MHz, DMSO-d6) 7.57 (2H, d, J 8, H-3, H-5), 6.75 (2H, d, J 8, H-2, H-6),
5.30–5.22 (2H, m, H-200, H-300), 5.15 (1H, m, H-400), 5.03 (1H, d, J 8, anomeric
H-100), 4.27 (1H, dd, J 4 and 12, H-600A), 4.15 (1H, dd, J 4 and 12, H-600B),
3.86–3.82 (1H, m, H-500), and 2.08–2.03 (12H, 4 ꢁ s, 4 ꢁ CH3); dC
(100 MHz, DMSO-d6) 170.4 (CO), 170.1 (CO), 169.2 (CO), 169.1 (CO),
156.5 (C-1), 138.4 (C-3), 119.2 (C-2), 99.0 (anomeric C-100), 86.3 (C-4),
78.2 (C-500), 72.7 (C-200), 71.2 (C-300), 68.3 (C-400), 62.0 (C-600), 21.0 (CH3),
20.9 (CH3), and 20.8 (CH3).
(E)-1-(3,5-Diacetoxy)-2-(40-O-2,3,4,6-tetraacetyl-b-D-glucopyrano-
sidophenyl)ethene 13. A mixture of 3,5-diacetoxystyrene 10 (0.20 g,
0.89 mmol), 12 (0.49 g, 0.89 mmol), palladium(II) acetate (0.01 g,
0.044 mmol), benzyltriethylammonium chloride (0.20 g, 0.89 mmol) and tri-
butylamine (0.43 g, 2.34 mmol) in acetonitrile was stirred at 1008C for 2 hr
under argon, and then allowed to cool to room temperature. The mixture
was filtered through a short Celite pad and then evaporated to dryness
(408C, water-aspirator pressure). The residue was taken up in dichloro-
methane (20 cm3) and washed with dilute hydrochloric acid (10 cm3), water
(10 cm3), and brine (10 cm3), then dried over anhydrous magnesium sulfate,
filtered, and evaporated (408C, water-aspirator pressure) to leave an oil that
solidified on standing. Recrystallization from dichloromethane/isopropanol
gave the product as white crystals (0.35 g, 61%) of m.p. 169–1708C;
[a]2D5 ¼ 246.48 (c 0.35, MeOH); (Found: C, 59.75; H, 5.42. C32H34O14
requires C, 59.81; H, 5.33%); nmax (KBr disc)/cm21 1747 (CO); dH
(400 MHz, DMSO-d6) 7.40 (2H, d, J 8, H-20, H-60), 7.10 (2H, m, H-2,
H-6), 7.02 (1H, d, J 16, vinylic H), 6.97 (2H, d, J 8, H30, H50), 6.90 (1H, d,
J 16, vinylic H), 6.79 (1H, m, H-4), 5.30–5.28 (2H, m, H-200, H-300), 5.17
(1H, m, H-400), 5.09 (1H, d, J 8, anomeric H-100), 4.30 (1H, dd, J 4 and 12,
H-600A), 4.17 (1H, dd, J 4 and 12, H-600B), 3.89–3.86 (1H, m, H-500), 2.31
(6H, s, 2 ꢁ CH3), and 2.09–2.04 (12H, 4 ꢁ s, 4 ꢁ CH3); dC (100 MHz,
DMSO-d6) 170.1 (CO), 169.3 (CO), 168.9 (CO), 156.5 (C-40), 139.6 (C-1),
132.0 (C-10), 129.6 (vinylic C), 127.9 (C-20), 126.1 (vinylic C), 117.2 (C-2,
C-6) 116.8 (C-30), 114.2 (C-4), 99.0 (anomeric C-100), 72.8 (C-200), 72.2
(C-500), 71.2 (C-300), 68.4 (C-400), 62.1 (C-600), 21.5 (CH3), 21.0 (CH3), and
20.9 (CH3).
trans-Resveratrol-40-O-b-D-glucopyranoside 3. To a suspension of 13
(0.29 g, 0.45 mmol) in methanol (20 cm3) at room temperature was added a
0.2 M methanolic solution of sodium methoxide (20 cm3). The resulting
mixture was stirred for 1 hr, whereupon sufficient Dowex 50WX8-100 ion
exchange resin was added in portions to maintain pH ꢀ2. The resin was
filtered off and washed with methanol (5 cm3). The combined filtrate was
evaporated (408C, water-aspirator pressure), and the residue was dried at 458C
over phosphorus pentoxide to give the product as a beige solid (0.17 g, 97%)

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Synthesis of 3-O-b-D- and 40-O-b-D-Glucopyranosides
1573
of m.p. 210–2158C; [a]2D5 ¼ 273.98 (c 0.39, MeOH); (Found: C, 60.96; H,
6.22. C20H22O8 H2O requires C, 61.22; H, 6.16%); nmax (KBr disc)/cm21
.
3429 (OH, very broad) and 1600; dH (400 MHz, (CH3)2CO-d6) 9.23 (2H, s,
phenolic OH), 7.48 (2H, d, J 8, H-20, H-60), 7.06–7.02 (3H, vinylic H, H-30,
H-50), 6.94 (1H, d, J 16, vinylic H), 6.54 (2H, s, H-2, H-6), 6.27 (1H, s,
H-4), 4.97 (1H, d, J 7.7, anomeric H-100) 3.89 (1H, dd, J 2.6 and 11.8,
H-600A), 3.70 (1H, dd, J 2.6 and 11.8, H-600B), and 3.55–3.44 (4H, m, H-200,
H-300, H-400, H-500); dC (100 MHz, (CH3)2CO-d6) 159.4 (C-3, C-5), 158.3
(C-40), 140.5 (C-1), 132.3 (C-10), 128.5 (vinylic C), 128.4 (C-20), 128.1
(vinylic C), 117.5 (C-30), 105.7 (C-2), 102.8 (C-4), 101.8 (anomeric C-100),
77.9 (C-200), 74.7 (C-500), 71.3 (C-400), and 62.7 (C-600).
ACKNOWLEDGMENT
The author wishes to thank Dr. Alexandra Antunes for providing 1H and
13C NMR spectra and microanalytical data.
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Received in the UK October 7, 2003

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