Synthesis of the aglycon of scorzodihydrostilbenes B and D

Article abstract of DOI:10.3762/bjoc.15.56

Benzyl- and methyl-protected 2,4-dihydroxyacetophenones are added under ruthenium catalysis to 4-methoxy- and 3,4-dimethoxystyrene in a completely regioselective manner. Thus, oxygenated dihydrostilbenes are obtained that feature the skeleton of scorzodihydrostilbenes – antioxidative agents that were recently isolated from Scorzonera radiata. Selective deprotection liberates the corresponding phenols, among them the aglycon of scorzodihydrostilbenes B and D.

Full text of DOI:10.3762/bjoc.15.56

Synthesis of the aglycon of scorzodihydrostilbenes B and D
Katja Weimann and Manfred Braun*
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2019, 15, 610–616.
Institute of Organic and Macromolecular Chemistry,
Heinrich-Heine-University Düsseldorf, Universitätsstr. 1, D-40225
Düsseldorf, Germany
doi:10.3762/bjoc.15.56
Received: 09 December 2018
Accepted: 15 February 2019
Published: 06 March 2019
Email:
Manfred Braun* - braunm@hhu.de
Associate Editor: L. Ackermann
* Corresponding author
© 2019 Weimann and Braun; licensee Beilstein-Institut.
License and terms: see end of document.
Keywords:
C–H activation; hydroarylation; phenols; regioselectivity; ruthenium
Abstract
Benzyl- and methyl-protected 2,4-dihydroxyacetophenones are added under ruthenium catalysis to 4-methoxy- and 3,4-
dimethoxystyrene in a completely regioselective manner. Thus, oxygenated dihydrostilbenes are obtained that feature the skeleton
of scorzodihydrostilbenes – antioxidative agents that were recently isolated from Scorzonera radiata. Selective deprotection liber-
ates the corresponding phenols, among them the aglycon of scorzodihydrostilbenes B and D.
Introduction
Among phytochemicals with strong allelopathic effects, various ity that was partly stronger than that of the well-known natu-
natural products are found that feature the structural motif of rally occurring antioxidant resveratrol [5]. In this article, we
dihydrostilbene with multiple phenolic functionality. These describe a synthetic approach that takes advantage of a regiose-
natural products that form as secondary metabolites on a branch lective, ruthenium-catalyzed C–H activation [6] and makes
of flavonoid biosynthesis found wide interest for their various accessible not only the skeleton of dihydrostilbenes with
biological effects like anti-oxidative and biofouling-preventing multiple phenolic ether functionality but also the aglycon of
activity [1]. From crude extracts of the Mongolian medicinal scorzodihydrostilbenes B and D (2 and 4, R1 = R2 = H, instead
plant Scorzonera radiata, that is used in folk medicine for the of β-glycosyl, respectively).
treatment of poisonous ulcers, fever, and various other diseases
[2-4], five new dihydrostilbenes, named scorzodihydrostilbenes Results and Discussion
A–E (1–5), were isolated in 2009 and their structures were de- Most syntheses of dihydrostilbenes rely on a carbonyl olefina-
termined (Scheme 1) [5]. They all are β-glucosides with highly tion followed by hydrogenation of the stilbene [7-9]. However,
oxygenated aryl rings. Scorzodihydrostilbene E (5) features a this route appeared not attractive, particularly as our attempts to
dimeric skeleton that originates from an oxidative coupling of hydrogenate highly substituted stilbenes that would serve as the
compound 1. The natural products exhibited antioxidative activ- precursors of scorzodihydrostilbenes had failed, presumably
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Beilstein J. Org. Chem. 2019, 15, 610–616.
Scheme 1: Structures of scorzodihydrostilbenes A–E (1–5) and resveratrol.
due to steric hindrance caused by the accumulation of substitu- times of 7 to 10 days turned out to be necessary. Thus, dihy-
ents at the acetophenone moiety [10]. We felt that a straightfor- drostilbenes 8a–c were obtained in fair yields in a single step,
ward access to the scorzodihydrostilbene aglycons would be whereas in the case of the tetramethoxy-substituted derivative
possible by using the transition metal-mediated, regioselective, 8d, the yield was lower (Scheme 2).
chelation-directed activation of an aryl–hydrogen bond. A
promising approach was seen in an application of Murai’s In order to bring about the cleavage of the benzyl protecting
elegant ruthenium-catalyzed ortho-functionalization of aryl groups in the ketones 8a and 8b by hydrogenolysis [17,18],
alkyl ketones and their addition to olefins [11-15]. This route various metal catalysts were tested. It turned out that palladium
appeared particularly attractive as it leads in an atom-economic on charcoal was the only catalytic system that provided satis-
manner directly to the carbon skeleton of scorzodihydrostil- fying results. Ethyl acetate was found to be the appropriate sol-
benes, starting from suitably substituted acetophenone and vent, whereas the starting materials did not dissolve in metha-
styrene derivatives. Furthermore, Murai’s protocol offers nol or ethanol. The reaction required a hydrogen overpressure
another advantage: the regioselective formation of the anti- of 3 bar for one to three days at room temperature, but even
Markovnikov product. Here, a modified version based upon an then, the deprotection was not completed in all cases. On the
in situ generation of the ruthenium complex described by Genet other hand, partial hydrogenation of the aromatic rings had to
and Darses [16] was applied.
be suppressed. Nevertheless, the aglycon 9 of scorzodihydrostil-
benes B and D (2 and 4) was obtained in good yield from 8a.
Thus, O-protected 2,5-dihydroxyacetophenones 6 were Hydrogenolysis of ketone 8b led to hydroquinone 10, however,
submitted to a hydroarylation reaction with two equivalents of along with a minor amount of mono-deprotected phenol 11. The
styrenes 7 in the presence of [Ru(p-cymene)Cl2]2 and main product 10 was isolated in pure form by column chroma-
P(4-CF3C6H4)3. The reactions were performed with sodium tography, whereas the fraction containing the phenol 11 was
formate in toluene in a sealed tube at 140–150 °C. Reaction still contaminated with hydroquinone 10 (Scheme 3).
Scheme 2: Synthesis of dihydrostilbenes 8a–d by ruthenium-catalyzed addition of ketones 6 to styrenes 7. Yields: 8a: 65%; 8b: 68%; 8c: 73%;
8d: 40%.
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Beilstein J. Org. Chem. 2019, 15, 610–616.
Scheme 3: Cleavage of benzyl protecting groups in ketones 8a and 8b. Synthesis of scorzodihydrostilbene aglycon 9.
Finally, the glycosylation of the aglycon 9 was briefly studied Information File 1). Attempts aimed at synthesizing the natural
using Helferich’s method [19]. It turned out that, upon treat- β-anomeric scorzodihydrostilbenes A–D are pursued.
ment of 9 with β-D-glucose pentaacetate in the presence of an
excess of boron trifluoride etherate [20], a regioselective reac- Conclusion
tion occurred at the phenolic group in ortho-position to the alkyl In summary, a straightforward procedure for the synthesis of
side chain to give mono-glycosylated product 12. Chelation of dihydrostilbenes with multiple phenolic substitutions was
the carbonyl and the neighboring phenolic group by the Lewis opened based upon Murai’s ruthenium-catalyzed hydroaryl-
acid is assumed to be responsible for this regiochemical ation of olefins. Thus, the aglycon of scorzodihydrostilbene D
outcome. The 1H NMR spectrum of 12 clearly indicates – by became accessible in two steps from readily available starting
the low-field shift of the phenolic hydrogen chelated with the materials.
carbonyl group – that glycosylation had not occurred at this po-
sition. Unfortunately, however, the α-anomer 12 formed exclu- Experimental
sively, so that, after cleavage of the ester groups, epi-scorzodi- General: Melting points (uncorrected) were determined with a
hydrostilbene D (13) was obtained as single stereoisomer Büchi 540 melting point apparatus. NMR spectra were re-
(Scheme 4).
corded with Bruker DXR 600 and DXR 300 spectrometers.
Mass spectra were recorded on ion-trap API mass spectrometer
Obviously, the conditions required in the glycosylation reaction Finnigan LCQ Deca (ESI), triple-quadrupole-mass spectrome-
– excess of the Lewis acid and elongated reaction time – ter Finnigan TSQ 7000, and sector field mass spectrometer
resulted in the formation of the thermodynamically favored Finnigan MAT 8200 (EI, 70 eV), Thermo Finnigan TraceGC
α-anomer (for details, see Experimental Part and Supporting Ultra (GC–MS). Column chromatography was performed with
Scheme 4: Synthesis of glycoside 12 and deprotected epi-scorzodihydrostilbene D (13). Yields of isolated products: 12: 14%; 13: 17%.
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Fluka silica gel 60 (230–400 mesh) and thin-layer chromatogra- 140 to 150 °C. After cooling to 25 °C, deionized water (2 mL)
phy was carried out by using Merck TLC Silicagel 60F254 alu- was added and the mixture was extracted with five 20 mL
minium sheets. Tetrahydrofuran (THF) and toluene were re- portions of ethyl acetate. The combined organic layers were
fluxed under nitrogen over sodium wire and a small amount of washed with brine and dried with MgSO4. The solvent was re-
benzophenone until the dark blue color of the solution persisted. moved in a rotary evaporator and the residue was purified by
Then, the solvents were distilled under nitrogen and taken from column chromatography. According to this procedure, the
the distillation flask, which was closed by a septum, by syringes following compounds were obtained:
or cannulas. 2,5-Dimethoxyacetophenone (6c) and 4-methoxy-
styrene (7b) were purchased from Sigma-Aldrich. 2,5-Di- 1-[3,6-Bis(benzyloxy)-2-(3,4-dimethoxypheneth-
benzyloxyacetophenone (6a) was prepared from commercially yl)phenyl)]ethan-1-one (8a): Prepared from 2,4-bis(benzyl-
available 2,5-dihydroxyacetophenone according to [21].
oxy)acetophenone (6a, 760 mg, 2.3 mmol) and 3,4-
dimethoxystyrene (7a, 860 mg, 5.2 mmol) in 2 mL of toluene at
1-(5-Benzyloxy-2-methoxyphenyl)ethan-1-one (6b): A mix- 150 °C for 7 d. The crude product was purified by column chro-
ture of commercially available 5-hydroxy-2-methoxyacetophe- matography (silica gel; ethyl acetate/n-hexane, 1:7) and 8a was
none (1.0 g, 6.0 mmol), K2CO3 (1.24 g, 9.0 mmol), benzyl bro- obtained as a greenish syrup in 65% yield (741 mg). Rf 0.1;
mide (2.05 g, 12.0 mmol) and DMF (14 mL) was stirred at 1H NMR (CDCl3, 600 MHz) δ 2.40 (s, 3H), 2.80 (s, 4H), 3.73
25 °C for 5 h. After acidification with 5% hydrochloric acid, the (s, 3H), 3.84 (s, 3H), 5.03 (s, 2H), 5.04 (s, 2H), 6.60 (d, J = 1.8
mixture was extracted with three 15 mL portions of ethyl Hz, 1H), 6.67–6.69 (dd, J = 8.1, 2.0 Hz, 1H), 6.74 (d, J = 8.1
acetate. The combined organic layers were washed with brine, Hz, 1H), 6.77 (d, J = 8.9 Hz, 1H), 6.85 (d, J = 8.9 Hz, 1H),
the solvent was removed in a rotary evaporator and the residue 7.31–7.41 (m, 8H), 7.45 (m, 2H); 13C NMR (CDCl3, 150 MHz)
was purified by column chromatography (silica gel; ethyl δ 30.8, 32.6, 36.3, 55.9, 56.1, 70.3, 70.1, 110.8, 111.3, 112.0,
acetate/n-hexane, 1:9) to give white, crystalline product 6b in 112.7, 120.5, 127.3, 127.3, 127.5, 127.5, 128.1, 128.1, 128.5,
99% yield (1.518 g). The spectroscopic data agree with those 128.7, 128.7, 133.7, 135.2, 137.0, 137.4, 147.3, 148.9, 149.2,
described in the literature [21].
151.5, 205.4; HRMS (ESI): [M + H]+ calcd for C32H33O5,
497.2328; found, 497.2321.
1,2-Dimethoxy-4-vinylbenzene (7a): A 100 mL two-necked
flask was equipped with a reflux condenser, a magnetic stirrer 1-[3,6-Bis(benzyloxy)-2-(4-methoxyphenethyl)phenyl]ethan-
and a connection to a combined nitrogen-vacuum line, charged 1-one (8b): Prepared from 2,5-bis(benzyloxy)acetophenone
with sodium hydride (1.6 g; 60% in mineral oil, 40 mmol) and (6a, 665 mg, 2.0 mmol) and commercially available 4-methoxy-
closed with a septum. n-Hexane (20 mL) was injected by styrene (7b, 537 mg, 4.0 mmol) in 1.5 mL of toluene at 145 °C
syringe and the suspension was stirred for 10 min. Then, stir- for 10 d. The crude product was purified by column chromatog-
ring was interrupted and the supernatant liquid was removed by raphy (silica gel; ethyl acetate/n-hexane, 1:18) and 8b was ob-
syringe. THF (30 mL) and 3,4-dimethoxybenzaldehyde (3.32 g, tained as a yellowish syrup in 68% yield (633 mg); Rf 0.4;
20.0 mmol), and methyltriphenylphosphonium bromide (10 g, 1H NMR (CDCl3, 600 MHz) δ 2.40 (s, 3H), 2.80 (s, 4H), 3.73
28 mmol) were added and the mixture was refluxed for 24 h. (s, 3H), 5.03 (s, 2H), 5.04 (s, 2H), 6.60 (s, 1H), 6.67–6.69 (m,
After cooling in an ice bath, deionized water (5 mL) was added 1H), 6.73–6.78 (m, 2H), 6.85 (d, J = 8.9 Hz, 1H), 7.31–7.41 (m,
and the mixture was extracted with three 30 mL portions of 8H), 7.45 (m, 2H); 13C NMR (CDCl3, 150 MHz) δ 30.8, 32.6,
ethyl acetate. The combined organic layers were washed with 36.3, 55.9, 70.3, 70.1, 110.8, 111.3, 112.0, 112.7, 120.5, 127.3,
brine, dried with sodium sulfate and concentrated under reduced 127.3, 127.5, 127.5, 128.1, 128.1, 128.5, 128.7, 128.7, 128.7,
pressure. The crude product was purified by column chromatog- 128.7, 133.7, 135.2, 137.0, 137.4, 147.3, 148.9, 149.2, 151.5,
raphy (ethyl acetate/n-hexane, 1:9) to give 2.01 g (61%) of 205.4; HRMS (ESI): [M + H]+ calcd for C31H31O4, 467.2222;
styrene 7a as a colorless liquid. The spectroscopic data agree found, 467.2216.
with those described in the literature [22].
1-[3-(Benzyloxy)-6-methoxy-2-(4-methoxyphen-ethyl)phe-
General procedure for the synthesis of dihydrostilbenes 8: In nyl]ethan-1-one (8c): Prepared from 5-(benzyloxy)-2-
a glove-box under argon atmosphere, a 20 mL overpressure methoxyacetophenone (6b, 513 mg, 2.0 mmol) and commer-
tube was charged with ketone 6 (4.0 mmol), styrene 7 cially available 4-methoxystyrene (7b, 537 mg, 4.0 mmol). The
(8.0 mmol), [Ru(p-cymene)Cl2]2 (62.0 mg, 0.1 mmol), crude product was purified by column chromatography (silica
P(4-CF3C6H4)3 (190 mg, 0.6 mmol), and sodium formate gel; ethyl acetate/n-hexane, 1:18) and 8c was obtained as a
(82 mg; 1.2 mmol). Freshly distilled toluene (3 mL) was added, greenish syrup in 73% yield (571 mg); Rf 0.3; 1H NMR
and the mixture was kept in the sealed tube for 7 to 10 days at (CDCl3, 600 MHz) δ 2.39 (s, 3H), 2.79 (m, 4H), 3.697 (s, 3H),
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Beilstein J. Org. Chem. 2019, 15, 610–616.
3.698 (s, 3H), 5.06 (s, 2H), 6.73 (d, J = 8.5 Hz, 1H), 6.78 (d, J = 56.1, 111.5, 111.9, 116.3, 120.3, 121.8, 125.2, 127.5, 134.1,
8.5 Hz, 2H), 6.88 (d, J = 8.5 Hz, 1H), 7.03 (d, J = 8.3 Hz, 2H), 147.0, 147.7, 149.1, 152.9, 205.9; HRMS (ESI): [M + H]+ calcd
7.35 (t, J = 7.3 Hz, 1H), 7.41 (t, J = 7.4 Hz, 2H), 7.45 (d, J = for C18H21O5, 317.1389; found, 317.1384.
7.1 Hz, 2H); 13C NMR (CDCl3, 150 MHz) δ 30.8, 32.5, 35.9,
55.4, 56.1, 70.8, 109.1, 112.8, 113.9, 113.9, 127.3, 127.3, 128.0, 1-[3,6-Dihydroxy-2-(4-methoxyphenethyl)phenyl]ethan-1-
128.5, 128.7, 128.7, 129.6, 133.1, 134.7, 137.5, 150.1, 151.2, one (10): Prepared from 8b (510 mg, 1.1 mmol), palladium on
158.0, 205.5; HRMS (ESI): [M + H]+ calcd for C25H27O4, charcoal (135 mg) in ethyl acetate (15 mL) at 3 bar hydrogen
391.1909; found, 391.1905.
pressure for 25 h. The crude product was purified by column
chromatography (silica gel; ethyl acetate/n-hexane, 1:7) to give
1-[2-(3,4-Dimethoxyphenethyl)-3,6-dimethoxyphenyl]ethan- 10 (204 mg, 65%) as a greenish-brownish syrup; Rf 0.12;
1-one (8d): Prepared from 2,5-dimethoxyacetophenone (6c, 1H NMR (CDCl3, 600 MHz) δ 2.64 (s, 3H), 2.85–2.87 (m, 2H),
168 mg, 1.04 mmol) and 3,4-dimethoxystyrene (7a, 348 mg, 3.06–3.09 (m, 2H), 3.79 (s, 3H), 4.45 (br s, 1H), 6.73 (d, J =
2.0 mmol) in 1 mL of toluene at 145 °C for 7 d. The crude prod- 6.73 Hz, 1H), 6.83–6.85 (m, 3H), 7.10 (d, J = 7.1 Hz, 2H);
uct was purified by column chromatography (silica gel; ethyl 13C NMR (CDCl3, 150 MHz) δ 30.8, 32.7, 35.6, 55.5, 114.2,
acetate/n-hexane, 1:9) and 8d was obtained as an orange syrup 114.2, 116.3, 121.8, 125.0, 127.6, 129.4, 129.4, 133.6, 146.0,
in 40% yield (145 mg); Rf 0.35; 1H NMR (CDCl3, 600 MHz) δ 153.1, 158.3, 206.0; HRMS (ESI): [M + H]+ calcd for
2.34 (s, 3H), 2.75 (s, 4H), 3.76 (s, 3H), 3.80 (s, 3H), 3.84 (s, C17H19O4, 287.1283; found, 287.1279.
3H), 3.85 (s, 3H), 6.69 (s, 1H), 6.72–6.74 (d, J = 8.7 Hz, 2H),
6.77–6.78 (d, J = 8.1 Hz, 1H), 6.81 (d, J = 8.9 Hz, 1H); A forerun in the column chromatography contained mono-
13C NMR (CDCl3, 150 MHz) δ 30.1, 32.4, 36.1, 55.9, 56.1, deprotected 1-[3-(benzyloxy)-6-hydroxy-2-(4-methoxyphen-
56.1, 109.1, 111.3, 111.4, 112.1, 120.5, 128.0, 133.0, 135.2, ethyl)phenyl]ethan-1-one (11) that was still contaminated with a
147.3, 148.8, 149.8, 151.1, 205.5; HRMS (ESI): [M + H]+ calcd small amount of hydroquinone 10. Yield: 68 mg (16%); Rf 0.3;
for C20H25O5, 345.1702; found 345.1697; anal. calcd for 1H NMR (CDCl3, 600 MHz) δ 2.65 (s, 3H), 2.82–2.85 (m, 2H),
C20H24O5: C, 69.75; H, 7.02; found: C, 69.56; H, 6.73.
3.04–3.09 (m, 2H), 3.78 (s, 3H), 5.02 (s, 2H), 6.81–6.83 (m,
3H), 6.99 (d, J = 8.2 Hz, 2H), 7.13–7.16 (m, 3H), 7.35–7.37 (m,
General procedure for the synthesis of phenols 9–11 by 1H), 7.44 (d, 2H), 9.31 (br s, 1H); 13C NMR (CDCl3,
hydrogenolytic cleavage of benzyl ether protecting groups: 150 MHz) δ 32.7, 35.4, 35.8, 55.4, 71.6, 114.0, 114.0, 115.9,
An autoclave was equipped with a stirring bar and charged with 118.7, 118.7, 121.4, 126.8, 127.6, 128.2, 128.8, 129.4, 129.8,
O-protected dihydrostilbenes 8a,b (0.8 mmol), palladium on 130.5, 134.0, 137.5, 152.5, 154.6, 158.1, 205.2; ESIMS m/z
charcoal (50 mg) and ethyl acetate (12 mL). The autoclave was (%): 377.2 [M + 1] (100); HRMS (ESI): [M + H]+ calcd for
connected to the hydrogen source and rinsed carefully with C24H25O4, 377.1753; found, 377.1748.
hydrogen. Thereafter, the mixture was stirred at 25 °C and 3 bar
hydrogen pressure for 1–3 d. Then, the mixture was filtered (2R,3R,4S,5R,6R)-2-(Acetoxymethyl)-6-[3-acetyl-2-(3,4-
through a frit filled with silica gel that was rinsed five times dimethoxyphenethyl)-4-hydroxyphenoxy]tetrahydro-2H-
with ethyl acetate. The combined filtrates were concentrated pyran-3,4,5-triyl triacetate (12): A 50 mL two-necked flask
under reduced pressure and the crude product was purified by was equipped with a stirring bar and a connection to the
column chromatography using mixtures of ethyl acetate and combined nitrogen/vacuum line. The flask was charged with
n-hexane. According to this procedure, the following com- dihydrostilbene 9 (330 mg, 1.04 mmol) and β-glucose pentaac-
pounds were obtained:
etate (814 mg, 2.08 mmol) and closed with a septum. The air in
the flask was replaced by nitrogen. Then, dichloromethane
1-[2-(3,4-Dimethoxyphenethyl)-3,6-dihydroxyphenyl)ethan- (4 mL) and boron trifluoride etherate (0.4 mL, 3.12 mmol) were
1-one (9): Prepared from 8a (741 mg, 1.5 mmol), palladium on injected by syringe. The mixture was stirred at 25 °C for 2 d.
charcoal (200 mg) in ethyl acetate (15 mL) at 3 bar hydrogen Thereafter, saturated aqueous sodium hydrogen carbonate
pressure for 72 h. The crude product was purified by column (10 mL) was added and the mixture was extracted five times
chromatography (silica gel; ethyl acetate/n-hexane, 1:7) to give with 15 mL portions of dichloromethane. The combined organic
9 as a greenish syrup in 75% yield (356 mg); Rf 0.1; 1H NMR layers were washed with brine and dried with magnesium
(CDCl3, 600 MHz) δ 2.63 (s, 3H), 2.87 (dd, J = 9.0, 6.8 Hz, sulfate. The solvent was removed in a rotary evaporator and the
2H), 3.09 (dd, J = 9.0, 6.8 Hz, 2H), 3.83 (s, 3H), 3.85 (s, 3H), crude product (1.08 g) was purified by column chromatography
4.41 (br s, 1H), 6.64 (d, J = 1.9 Hz, 1H), 6.72–6.75 (m, 2H), (silica gel; ethyl acetate/n-hexane, 1:4 to 1:2) to give 91 mg
6.79 (d, J = 8.00 Hz, 1H), 6.83 (d, J = 8.9 Hz, 1H), 9.35 (br s, (14%) of pure glycoside 12 as a colorless syrup. 1H NMR
1H); 13C NMR (CDCl3, 150 MHz) δ 30.6, 32.7, 36.1, 56.0, (CDCl3, 600 MHz) δ 2.04 (s, 3H), 2.06 (s, 3H), 2.07 (s, 3H),
614

Beilstein J. Org. Chem. 2019, 15, 610–616.
2. Grubov, V. I. Key to the Vascular Plants of Mongolia; Nauka:
Leningrad, 1982; pp 263–264.
2.08 (s, 3H), 2.64 (s, 3H), 2.77–2.82 (m, 1H), 2.92–2.97 (m,
1H), 3.08–3.14 (m, 2H), 3.85 (s, 3H), 3.87 (s, 3H), 4.0–4.14 (m,
2H), 4.26 (dd, J = 12.4, 4.7 Hz, 1H), 5.10 (ddd, J = 10.3, 3.8,
1.1 Hz, 1H), 5.18 (t, J = 5.2 Hz, 1H), 5.59 (d, J = 3.5 Hz, 1H),
5.75 (t, J = 10.2 Hz, 1H), 6.71 (s, 1H), 6.78 (dd, J = 9.0, 1.1 Hz,
1H), 6.82–6.85 (m, 2H), 7.28 (dd, J = 9.1, 1.0 Hz, 1H), 8.99
(brs, 1H); 13C NMR (CDCl3, 150 MHz) δ 20.7, 20.8, 20.8,
20.9, 31.0, 32.7, 36.6, 56.0, 56.1, 60.6, 61.8, 68.2, 68.4, 70.2,
70.4, 95.8, 111.7, 116.2, 120.5, 120.6, 120.8, 124.7, 134.0,
147.7, 149.1, 170.1, 170.7, 205.6, 206.1, 206.2, 210.7, 213.0;
HRMS: [M + H]+ calcd for C32H38NaO14, 669.2159; found,
669.2154.
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plants); Valang: Moscow, 1996; p 106.
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epi-Scorzodihydrostilbene D (13): A mixture of 12 (18 mg,
0.03 mmol), methanol (1 mL) and sodium ethoxide (3 mg,
0.06 mmol) was stirred at 25 °C for 4 h. The mixture was
filtered and the filtrate was concentrated under reduced pres-
sure. The residue was purified by semi-preparative reversed-
phase HPLC (methanol–water gradient) to give 11 mg (17%) of
pure epi-scorzodihydrostilbene D (13) as a colorless syrup.
1H NMR (CD3OD, 600 MHz) δ 2.33 (s, 3H), 2.69–2.99 (m,
8. Zhang, W.-G.; Zhao, R.; Ren, J.; Ren, L.-X.; Lin, J.-G.; Liu, D.-L.;
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