Efficient Synthesis of Several Natural Oligostilbenes from the Biomimetic Oxidation of Brominated Isorhapontigenin

Article abstract of DOI:10.1055/s-0037-1611713

This study extensively investigated the regioselective oxidative coupling reactions of 5-bromoisorhapontigenin catalyzed by FeCl ₃ ·6H ₂ O or HRP/H ₂ O ₂ in different solvent systems and the distinct reductive debromination of the isolated dimeric coupling intermediates. Natural (±)-bisisorhapontigenin A and (±)-lehmbachol A and B were efficiently prepared. (±)-Gnetuhainin I, (±)-gnemontanin E, (±)-7- O -ethylgnetuhainin I, and (±)-gnemontanin F were synthesized for the first time.

Full text of DOI:10.1055/s-0037-1611713

SYNTHESIS
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
©
Georg Thieme Verlag Stuttgart · New York
2019, 51, A–G
paper
A
de
Synthesis
X. Guan et al.
Paper
Efficient Synthesis of Several Natural Oligostilbenes from the
Biomimetic Oxidation of Brominated Isorhapontigenin
Xingchao Guan
Meijie Liu
OH
Br
OMe
Zhibo Shao
Hongpeng Li
Lu Ran
1) FeCl3·6H2O oxidation
2) LiAlH4 debromination
1) HRP-H2O2 oxidation
OMe
2) Pd/C, H2 debromination OH
HO
HO
7
8
OMe
OH
O
OH
RO
8
Wenling Li*
HO
OH
8
10'
HO
8'
School of Chemical and Biological Engineering, Lanzhou
Jiaotong University, Lanzhou 730070, China
liwl@mail.lzjtu.cn
OH
OMe
OH
OH
R = H, Me, or Et
MeO
OH
OH
Received: 30.10.2018
Accepted after revision: 06.12.2018
Published online: 23.01.2019
tions. We successfully produced several dimeric intermedi-
ates with different skeletons. Nevertheless, the expected
5
DOI: 10.1055/s-0037-1611713; Art ID: ss-2018-f0730-op
natural products such as 4 and 6 were difficult to obtain be-
cause of their structural instability under strongly acidic
conditions required for the removal of tert-butyl groups
from the obtained coupling intermediates. Relatively stable
architectures 5, 7, and 8 were finally synthesized in moder-
ate yields. Thus, the efficient synthesis of natural products 4
and 6 remains an important part of our future research
work.
Abstract This study extensively investigated the regioselective oxida-
tive coupling reactions of 5-bromoisorhapontigenin catalyzed by
FeCl ·6H O or HRP/H O in different solvent systems and the distinct
3
2
2
2
reductive debromination of the isolated dimeric coupling intermedi-
ates. Natural (±)-bisisorhapontigenin A and (±)-lehmbachol A and B
were efficiently prepared. (±)-Gnetuhainin I, (±)-gnemontanin E, (±)-7-
O-ethylgnetuhainin I, and (±)-gnemontanin F were synthesized for the
first time.
Inspired by our recent success in concise synthesis of
some natural oligostilbenes by using the regioselective oxi-
dative coupling reactions of 3,5-dibromoresveratrol (10)
Key words isorhapontigenin, oligostilbenes, regioselectivity, biomi-
metic synthesis, oxidative coupling, debromination
6
under different catalytic conditions, we intended to apply
Isorhapontigenin (2), an important natural stilbene in
addition to resveratrol (1), is used to form a number of
complex oligostilbenes, such as natural dimers 3–8,
through enzyme-induced single-electron oxidation in
this synthetic strategy to prepare several isorhapontigenin
dimers, including natural 4 and 6.
Prior to synthesis, coupling precursor, namely, 5-bro-
moisorhapontigenin (14), was prepared (Scheme 1). The
key Wittig reaction of phosphonium salt 11 with 5-bromo-
1
plants (Figure 1). Traditional biomimetic oxidation meth-
ods and well-designed chemical routes toward the synthe-
sis of resveratrol oligomers have been extensively studied
2
in the past four decades. However, few studies have report-
OH
ed on the preparation of oligomeric isorhapontigenins,3
thereby limiting further investigation on their structure-
bioactivity relationship.
BnO
OBn
Br
OMe
n-BuLi, toluene
reflux
+
PPh3Cl
CHO
Previous studies on the construction of diverse skele-
tons of isorhapontigenin dimers mainly focused on the di-
rect oxidative coupling reactions of 2 catalyzed by inorganic
metallic oxidants and enzyme systems. The 8–5-coupled
dimer 3 was predominant in the complex coupling product
mixture when Ag O, AgOAc, FeCl ·6H O, or horseradish per-
76%
1
1
12
OH
OH
Br
OMe
Br
OMe
PhNMe , AlCl
2
3
2
3
2
4
CH2Cl2, r.t.
oxidase (HRP)/H O were used as catalyst. To impede the
2
2
8
2%
formation of 8–5-coupled product 3 and improve the possi-
bility of other coupling modes, our group systematically in-
vestigated the regioselective coupling reactions of 5-tert-
butyl-isorhapontigenin (9) under various oxidative condi-
BnO
OBn
HO
OH
1
3
14
Scheme 1 Preparation of trans-stilbene 14
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–G

B
Synthesis
X. Guan et al.
Paper
OMe
MeO
OMe
OH
OH
HO
HO
R
HO
HO
OMe
O
OH
OH
O
OH
HO
OH
OH
OH
OH
OH
HO
OH
MeO
OH
OH
OH
MeO
R = H, resveratrol (1)
R = OMe, isorhapontigenin (2)
shegansu B (3)
bisisorhapontigenin A (4)
gnetulin (5)
OH
OMe
OMe
OH
MeO
HO
R1
R2
OH
HO
OH
HO
OMe
OH
H
HO
HO
OH
OMe
HO
OH
H
OH
OMe
OH
HO
OH
OH
HO
OH
OH
1
1
= OMe, R2 = t-Bu, 9
= R2 = Br, 10
7
7
S, gnetuhainin I (6a)
R, gnemontanins E (6b)
R
R
gneafricanin F (7)
gnemonol M (8)
Figure 1 Several stilbenes and representative isorhapontigenin dimers
vanillin (12) generated trans-stilbene 13 in 76% yield. The
product was then subjected to the debenzylation reaction
to obtain target precursor 14 in 82% yield.
to 20 equivalents of LiAlH in THF at room temperature for
18 hours to obtain racemic bisisorhapontigenin A (4) in 85%
yield.
4
We first explored the FeCl ·6H O-promoted oxidation of
We next investigated the enzyme-mediated oxidative
dimerizations of stilbene 14 in three different solvent sys-
tems according to our previous work (Scheme 3 and Table
3
2
stilbene 14 on the basis of our recent research on the cou-
5a
pling dimerizations of 10. As illustrated in Scheme 2 and
Table 1, the 8–10-coupled dimeric intermediate 15 as the
predominant coupling product was found when the precur-
sor 14 was treated with 3.0 equimolar amounts of
FeCl ·6H O in various solvent systems for 8 hours (Table 1,
5b
2). As predicted, the coupling of two M8 semi-quinone
radicals was predominant under the HRP–H O2 catalytic
2
condition. The initially formed bisquinone methide was nu-
cleophilically attacked by the H O, MeOH, or EtOH molecule
3
2
2
entries 1–4). The solvent effects on the coupling reactions
of 14 were largely reflected by differences in the isolated
yields of dimer 15. The 42% yield of 15 in acetone solvent
was relatively higher than that in acetone–benzene (37%) or
from the solvent systems and subjected to intramolecular
Friedel–Crafts alkylation to obtain dimeric mixtures
16a/16b, 17a/17b, or 18a/18b with varied molar ratio. No
other oligomers, such as the predicted pallidol-type struc-
ture like dimer 7, were found in the coupling product. Final-
ly, the reductive debromination reaction of the isomeric in-
acetone–H O (33%) and in dichloromethane–methanol sys-
2
tem (27%). The dihydrobenzofuran 15 was then subjected
Table 2 Coupling Products from the Enzyme-Oxidation of 14 in Differ-
ent Solvent Systems
Table 1 Coupling Products of 14 in Different Catalytic Systems
Entry Catalysta
Solvents
(volume ratio)
Time
(h)
Coupling products
(molar ratio, yield)
b
Entry
FeCl
3
·6H
2
O
Solvents
(volume ratio)
Time
(h)
Product 15
(yield %)
(
equiv)
1
2
3
HRP-H
HRP-H
HRP-H
2
2
2
O
O
O
2
2
2
acetone–H
MeOH–H O (3:1)
EtOH–H O (3:1)
2
O (3:1)
14
24
12
16a:16b (1.4:1, 50%)
17a:17b (1:1, 53%)
18a:18b (1.5:1, 49%)
1
2
3
4
3.0
3.0
3.0
3.0
acetone
8
8
8
8
42
37
33
27
2
acetone–benzene (3:1)
2
acetone–H
2
O (3:1)
a
HRP [RZ (Reinheitszahl): >3; activity: ≥300 U/mg].
Determined by H NMR spectrum of the crude product.
b
1
CH Cl –MeOH (4:1)
2
2
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–G

C
Synthesis
X. Guan et al.
Paper
O
OMe
Br
OMe
O
O
OH
O
OH
Br
FeCl3·6H2O
solvent, r.t.
10
HO
8
14
H
HO
OH
MeO
OH
Br
OH
MeO
Br
M8
M10
OH
OMe
OMe
HO
HO
HO
O
OH
Br
O
OH
HO
LiAlH4
THF, r.t.
OH
OH
15
Br
OMe
(±)-4
OMe
OH
OH
Scheme 2 Synthesis of (±)-4 from the oxidation of 14 and the debromination of 15
dane mixtures 16a and 16b under the Pd-C/Et N-catalyzed
instrument in a solvent as indicated. HRMS spectra were measured
on an Autostec-3090 mass spectrometer. All solvents were freshly pu-
rified and dried by standard techniques prior to use. Purification of
products was performed by column chromatography on silica gel
3
hydrogenation condition easily formed natural (±)-gnetu-
hainin I (6a) and (±)-gnemontanins E (6b) in 73% yield. The
dimeric mixtures 17a/17b or 18a/18b were treated with
(200–300 mush), purchased from Qingdao Marine Chemical Co.
Qingdao, China).
the same Pd-C/Et N-mediated debromination to obtain nat-
3
(
ural products (±)-lehmbachol A (19a) and (±)-lehmbachol B
(
19b) or (±)-7-O-ethylgnetuhainin I (20a) and (±)-gnemont-
Stilbene 13
anin F (20b) in 87% or 77% yield, respectively. The spectral
data of natural products 6, 19, and 20 that we synthesized
were consistent with those in the literature.
In conclusion, the biomimetic oxidative coupling reac-
tions of brominated isorhapontigenin 14 under different
catalytic conditions were extensively investigated. The
introduction of bromine atom as positional protection for
the stilbene precursor efficiently hampered the undesired
A stirred solution of phosphonium salt 11 (3.14 g, 5.0 mmol) in anhyd
toluene (80 mL) under argon atmosphere was added to a solution of
n-BuLi (2.5 mL, 13.6 mmol) in n-hexane. After stirring for 30 min, al-
dehyde 12 (1.0 g, 4.0 mmol) was added and then stirred for an addi-
tional 5 h under reflux at 110 °C, after which MeOH (6 mL) was added.
The reaction mixture was concentrated and extracted with EtOAc (3 ×
1d,e
8
0 mL). The combined organic extracts were washed with H O and
2
brine, and dried (anhyd MgSO ). The solvent was removed under re-
4
duced pressure and the residue purified by silica gel column chroma-
tography (PE–EtOAc 8:1) to give stilbene 13 as a pale white solid;
8–5-coupling mode, which was predominant in the typical
oxidative coupling reaction of isorhapontigenin. The
yield: 1.76 g (79%); mp 132–134 °C; R = 0.42 (PE–EtOAc 4:1).
f
FeCl ·6H O-promoted coupling reaction of 14 in various
1
H NMR (400 MHz, CD Cl): δ = 3.96 (s, 3 H), 5.07 (s, 4 H), 5.96 (br s, 1
3
3
2
solvent systems invariably formed 8–10-coupled dihydro-
H), 6.56 (t, J = 2.0 Hz, 1 H), 6.74 (d, J = 2.0 Hz, 2 H), 6.87 (d, J = 16 Hz, 1
H), 6.93 (d, J = 16 Hz, 1 H), 6.95 (br s, 1 H), 7.23–7.46 (m, 10 H).
benzofuran structure 15. By contrast, the HRP-H O -medi-
2
2
13
ated oxidations of 14 in aqueous acetone, methanol, or
ethanol generated the corresponding 8–8-coupled dimeric
isomers, namely, 16a/16b, 17a/17b, and 18a/18b, which
contain indane skeletons. The dimeric coupling intermedi-
ates 15 and 16–18 were subjected to the distinct debromi-
nation reactions to finally accomplish the efficient prepara-
tion of isorhapontigenin dimers (±)-4 and (±)-19a/19b, and
the first synthesis of natural (±)-6a/6b, (±)-20a/20b.
C NMR (100 MHz, CD Cl): δ = 56.5, 70.3 (2 C), 101.8, 105.8 (2 C),
3
1
1
07.8, 108.7, 123.6, 127.7 (4 C), 127.9, 128.0, 128.2 (2 C), 128.8 (5 C),
30.6, 137.0, 139.3, 143.0, 147.4, 160.3 (2 C).
HRMS (ESI): m/z calcd for C29H25BrO4 + H: 517.10090; found:
17.10034.
5
Coupling Precursor 14
N,N-Dimethylaniline (32 mL, 0.41 mol) was added to a well-stirred
solution of stilbene 13 (2.77 g, 8.0 mmol) in anhyd CH Cl (60 mL) at 0
2
2
°
C. After 5 min, anhyd AlCl (6.4 g, 48.0 mmol) was added to the reac-
3
Structural determinations of the isolated compounds were based on
H, C NMR, NOESY, H- H COSY, HMBC spectra, and HRMS analysis.
All NMR spectra were recorded on a Varian Mercury 400 or 600 MHz
tion mixture. After stirring for an additional 3 h at r.t., the mixture
was quenched with H O at 0 °C and poured into aq 2.0 M HCl (30 mL).
The resulting mixture was extracted with EtOAc (3 × 50 mL), and the
1
13
1
1
2
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–G

D
Synthesis
X. Guan et al.
Paper
HO
OH
O
OMe
Br
Br
OMe
O
R
H
O
O
8
'
OMe
ROH Br
HO
HRP
7
'
14
7
OH
H2O2
8
8'
8
MeO
Br
O
OH
OH
HO
OH
M8
M8
OMe
Br
HO
OH
Br
HO
RO
OMe
OH
OR
OH
OH
HO
ROH
+
OH
OH
OH
OMe
OMe
Br
Br
OH
OH
1
1
1
6b, R = H
7b, R = Me
8b, R = Et
1
1
1
6a, R = H
7a, R = Me
8a, R = Et
OH
OMe
HO
RO
OMe
OH
OR
HO
OH
HO
Pd/C, H2
Et3N, MeOH
OH
OH
+
OH
OMe
OH
OMe
OH
a, R = H
9a, R = Me
0a, R = Et
OH
6
1
2
6
1
2
b, R = H
9b, R = Me
0b, R = Et
Scheme 3 Synthesis of 6 and 19–20 from the oxidation of 14 and the debromination of 16–18
combined organic extracts were washed with brine and dried (anhyd
der argon atmosphere for 8 h. After the removal of the solvent under
reduced pressure, the resulting residue was extracted with EtOAc (3
×). The combined organic layers were washed with brine, dried (an-
MgSO ). The solvent was removed under reduced pressure and the
4
residue was purified by silica gel column chromatography (PE–EtOAc
3
1
1
:1) to give the coupling precursor 14 as a pale yellow solid; yield:
hyd MgSO ), and evaporated in vacuo. The crude products was sub-
4
.55 g (86%); mp 118–120 °C; R = 0.20 (PE–EtOAc 2:1).
jected to silica gel column chromatography (CH Cl –MeOH 30:1) to
f
2
2
give the unreacted 14, and the dimer 15 as a yellow amorphous pow-
der; R = 0.25 (CH Cl –MeOH 20:1). For yields, see Table 1.
H NMR (600 MHz, acetone-d ): δ = 3.92 (s, 3 H), 6.29 (t, J = 2.0 Hz, 1
6
H), 6.55 (d, J = 2.0 Hz, 2 H), 6.97 (d, J = 16.2 Hz, 1 H), 7.00 (d, J = 16.2
Hz, 1 H), 7.22 (d, J = 2.4 Hz, 1 H), 7.28 (d, J = 2.4 Hz, 1 H), 8.36 (br s, 2
H), 8.44 (br s, 1H).
f
2
2
1
H NMR (400 MHz, acetone-d ): δ = 3.83 (s, 3 H), 3.86 (s, 3 H), 4.55 (d,
6
J = 6.4 Hz, 1 H), 5.44 (d, J = 6.4 Hz, 1 H), 6.27 (t, J = 2.0 Hz, 1 H), 6.29 (d,
J = 2.0 Hz, 2 H), 6.37 (d, J = 2.0 Hz, 1 H), 6.72 (d, J = 16.2 Hz, 1 H), 6.75
13
C NMR (100 MHz, acetone-d ): δ = 56.7, 103.1, 105.8 (2 C), 109.1,
6
(d, J = 2.0 Hz, 1 H), 6.81 (d, J = 2.0 Hz, 1 H), 6.88 (d, J = 16.2 Hz, 1 H),
109.6, 124.1, 127.9, 128.6, 131.2, 140.4, 144.7, 149.2, 159.6 (2 C).
7.00 (d, J = 2.0 Hz, 1 H), 7.04 (d, J = 2.0 Hz, 1 H), 7.09 (d, J = 2.0 Hz, 1 H),
HRMS (ESI): m/z calcd for C15H13BrO4 + H: 337.00709; found:
37.00708.
8.26 (br s, 2 H), 8.34 (br s, 1 H), 8.36 (br s, 1 H), 8.48 (br s, 1 H).
3
13
C NMR (150 MHz, acetone-d ): δ = 56.6, 56.7, 57.3, 93.3, 97.2, 102.2,
6
1
1
1
04.4, 107.2 (2 C), 107.7, 109.3 (2 C), 120.1, 122.6 (2 C), 124.8 (2 C),
25.1, 128.7 (2 C), 131.1, 134.7, 135.8, 146.9 (2 C), 159.7, 159.9 (2 C),
62.2 (2 C).
FeCl ·6H O-Catalyzed Coupling Reaction of 14 in Different Sol-
vents
3
2
FeCl ·6H O (121 mg, 0.45 mmol) was slowly added to a solution of
3
2
HRMS (ESI): m/z calcd for C30H24Br O + H: 670.99107; found:
2
8
stilbene 14 (50 mg, 0.15 mmol) in varied solvent system (6.0 mL) (Ta-
ble 1). The reaction mixture was kept out of sun and stirred at r.t. un-
670.99116.
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–G

E
Synthesis
X. Guan et al.
Paper
13
Debromination of 15 for the Synthesis of (±)-4
C NMR (150 MHz, acetone-d ): δ = 56.6, 56.7, 56.9, 101.3, 102.6,
6
1
1
1
05.3, 106.3 (2 C), 108.5, 108.7, 110.9, 122.6, 123.9, 124.2, 124.3,
36.9, 139.7, 142.9, 143.9, 147.2 (2 C), 148.5, 148.8 (2 C), 150.7, 155.1,
59.1, 159.4 (3 C).
Excess LiAlH (0.055 g, 1.44 mmol) was added to a stirred solution of
4
dimer 15 (48.6 mg, 0.072 mmol) in anhyd THF (10 mL) at ice-bath
temperature under argon atmosphere and the stirring of the mixture
was continued at room tempreature for 18 h. Ice-water was added
slowly to quench the reaction and the resulting mixture was extract-
ed with EtOAc (3 × 10 mL). The combined organic layers were washed
HRMS (ESI): m/z calcd for C30H26Br O + Na: 710.98358; found:
710.98425.
2
9
with brine, dried (anhyd MgSO ), and evaporated in vacuo. The crude
4
Enzyme-Mediated Coupling Reaction of 14 in Aqueous Methanol
product was subjected to silica gel column chromatography (CH Cl –
2
2
A solution of compound 14 (0.25 g, 0.74 mmol) and horseradish per-
MeOH 15:1) to give (±)-bisisorhapontigenin A (4) as a yellowish oil;
yield: 52.3 mg (85%); R = 0.22 (CH Cl –MeOH 10:1).
oxidase (25 mg, RZ >3, activity ≥300 U/mg) in MeOH (9 mL) and H O
2
f
2
2
(
3 mL) was treated with H O (3%, 2.5 mL) at r.t. under argon atmo-
2 2
1
H NMR (600 MHz, acetone-d ): δ = 3.80 (s, 3 H), 3.82 (s, 3 H), 4.51 (d,
6
sphere and continuously stirred for 24 h. MeOH was removed and the
aqueous reaction mixture was extracted with EtOAc (50 mL). The
J = 7.2 Hz, 1 H), 5.42 (d, J = 7.2 Hz, 1 H), 6.26 (t, J = 2.4 Hz, 1 H), 6.28 (d,
J = 2.4 Hz, 2 H), 6.33 (d, J = 2.4 Hz, 1 H), 6.68 (d, J = 16.2 Hz, 1 H), 6.71
EtOAc layer washed with brine and dried (anhyd MgSO ). The solvent
4
(dd, J = 8.4, 1.8 Hz, 1 H), 6.73 (d, J = 1.8 Hz, 1 H), 6.77 (dd, J = 8.4, 1.8
was removed under reduced pressure and the residue was puried by
silica gel column chromatography (CH Cl –MeOH 25:1) to give the
Hz, 1 H), 6.81 (d, J = 2.0 Hz, 2 H), 6.90 (d, J = 16.2 Hz, 1 H), 7.00 (d, J =
2
2
1.8 Hz, 1 H), 7.66 (br s, 2 H), 8.22 (br s, 2 H), 8.37 (br s, 1 H).
unreacted 14 (71 mg), and a mixture of the dimer 17a and 17b in a
1:1 molar ratio as yellowish amorphous powder; yield: 98 mg (53%).
13
C NMR (150 MHz, acetone-d ): δ = 56.1, 56.3, 57.4, 94.3, 96.9, 102.2,
6
104.0, 107.3, 108.8, 110.4 (2 C), 115.7, 119.6 (2 C), 120.2, 121.8 (2 C),
123.4, 130.0, 130.4, 133.9 (2 C), 136.2 (2 C), 147.2 (2 C), 159.9 (2 C),
161.5 (2 C).
17a
R = 0.30 (CH Cl –MeOH 15:1).
f
2
2
HRMS (ESI): m/z calcd for C30H27O8
15.17004.
+
H: 515.17004; found:
1
H NMR (600 MHz, acetone-d ): δ = 2.81 (t, J = 3.6 Hz, 1 H), 3.06 (s, 3
6
5
H), 3.35 (dd, J = 3.6, 8.4 Hz, 1 H), 3.76 (s, 3 H), 3.68 (s, 3 H), 3.98 (d, J =
.4 Hz, 1 H), 4.20 (d, J = 3.6 Hz, 1 H), 5.83 (d, J = 2.4 Hz, 2 H), 6.01 (d,
8
Enzyme-Mediated Coupling Reactions of 14 in Aqueous Acetone
J = 2.4 Hz, 1 H), 6.11 (t, J = 2.4 Hz, 1 H), 6.36 (d, J = 1.8 Hz, 1 H), 6.59 (d,
J = 1.8 Hz, 1 H), 6.66 (d, J = 1.8 Hz, 1 H), 6.70 (d, J = 2.4 Hz, 1 H), 6.92 (d,
J = 2.4 Hz, 1 H).
A solution of compound 14 (0.10 g, 0.296 mmol) and horseradish per-
oxidase (10 mg, RZ >3, activity ≥300 U/mg) in acetone (12 mL) and
H O (4.0 mL) was treated with H O (3%, 1 mL) at r.t. under argon at-
mosphere and continuously stirred for 12 h. Acetone was removed
and the aqueous reaction mixture was extracted with EtOAc (20 mL),
13
2
2
2
C NMR (150 MHz, acetone-d ): δ = 55.9, 56.6, 56.7, 56.9, 59.3, 60.7,
6
8
1
8.0, 101.3, 105.5, 106.3, 108.7, 110.6, 111.3, 115.2, 122.7, 123.9 (2 C),
25.0 (2 C), 132.0, 133.1, 139.0, 143.1, 144.5, 148.7, 148.8, 150.1,
the organic layer washed with brine, and dried (anhyd MgSO ). The
4
155.2, 159.1, 159.4 (2 C).
solvent was removed under reduced pressure and the residue was pu-
ried by silica gel column chromatography (CH Cl –MeOH 25:1) to give
HRMS (ESI): m/z calcd for C31H29Br O + H: 703.01728; found:
2
9
2
2
703.01624.
the unreacted 14 (20 mg) and a mixture of the dimer 16a and 16b in a
1.4:1 molar ratio as yellowish amorphous powder; yield: 40 mg (50%).
17b
R = 0.30 (CH Cl –MeOH 15:1).
1
6a
f
2
2
1
H NMR (600 MHz, acetone-d ): δ = 3.10 (s, 3 H), 3.32 (t, J = 4.2 Hz, 1
R = 0.28 (CH Cl –MeOH 15:1).
6
f
2
2
H), 3.47 (dd, J = 4.8, 7.2 Hz, 1 H), 3. 75 (s, 3 H), 3.77 (s, 3 H), 4.03 (d, J =
1
H NMR (600 MHz, acetone-d ): δ = 2.97 (t, J = 4.2 Hz, 1 H), 3.45 (d, J =
6
7.2 Hz, 1 H), 4.21 (d, J = 4.2 Hz, 1 H), 6.13 (d, J = 2.4 Hz, 2 H), 6.18 (d, J =
2.4 Hz, 1 H), 6.26 (d, J = 1.8 Hz, 1 H), 6.50 (d, J = 1.8 Hz, 1 H), 6.59 (d, J =
1.8 Hz, 1 H), 6.62 (d, J = 1.8 Hz, 1 H), 6.69 (d, J = 1.8 Hz, 1 H), 6.82 (d, J =
1.8 Hz, 1 H).
6.0 Hz, 1 H), 4.21 (d, J = 3.6 Hz, 1 H), 4.38 (d, J = 4.8 Hz, 1 H), 4.54 (dd,
J = 7.2, 4.8 Hz, 1 H), 5.95 (d, J = 2.4 Hz, 2 H), 6.14 (t, J = 2.4 Hz, 1 H),
6
6
.20 (d, J = 2.4 Hz, 1 H), 6.33 (d, J = 2.4 Hz, 1 H), 6.61 (d, J = 2.0 Hz, 1 H),
.65 (d, J = 2.4 Hz, 1 H), 6.73 (d, J = 2.4 Hz, 1 H), 6.75 (d, J = 2.4 Hz, 1 H).
13
C NMR (150 MHz, acetone-d ): δ = 56.2, 56.6, 56.7, 56.9, 59.0, 60.3,
13
6
C NMR (150 MHz, acetone-d ): δ = 56.0, 56.4, 56.5, 101.4, 102.6,
6
87.0, 101.4, 102.7, 105.9, 111.0, 111.2, 124.2 (2 C), 125.3 (2 C), 129.6,
133.4, 139.5, 143.2, 144.5, 146.7 (2 C), 148.7, 148.8, 149.1, 150.1,
155.2, 159.2, 159.5 (2 C).
106.0, 106.2 (2 C), 108.4, 108.7, 108.9, 110.2, 110.9, 111.3, 121.8,
123.8, 123,9, 134.9, 137.4, 138.8, 139.0, 143.1, 143.8, 148.6, 148.7,
150.0, 155.2, 158.8, 159.2 (2 C).
HRMS (ESI): m/z calcd for C31H29Br O + H: 703.01728; found:
2
9
HRMS (ESI): m/z calcd for C30H26Br O + Na: 710.98358; found:
2
9
703.01624.
710.98425.
Enzyme-Mediated Coupling Reaction of 14 in Aqueous Ethanol
1
6b
A solution of compound 14 (201 mg, 0.57 mmol) and horseradish per-
oxidase (20 mg, RZ >3, activity ≥300 U/mg) in EtOH (6.0 mL) and H O
R = 0.28 (CH Cl –MeOH 15:1).
f
2
2
2
1
H NMR (600 MHz, acetone-d ): δ = 3.43 (t, J = 4.2 Hz, 1 H), 3.85 (dd,
6
(2.0 mL) was treated with H O (3%, 2.0 mL) at r.t. under argon atmo-
2
2
J = 4.8, 8.4 Hz, 1 H), 4.22 (d, J = 3.0 Hz, 1 H), 4.42 (d, J = 4.8 Hz, 1 H),
sphere and continuously stirred for 12 h. EtOH was removed and the
aqueous reaction mixture was extracted with EtOAc (50 mL). The
4.61 (dd, J = 8.4, 4.8 Hz, 1 H), 5.98 (d, J = 2.4 Hz, 1 H), 6.10 (d, J = 2.4 Hz,
2 H), 6.16 (d, J = 2.4 Hz, 1 H), 6.26 (d, J = 2.4 Hz, 1 H), 6.69 (d, J = 2.4 Hz,
1 H), 6.74 (d, J = 2.4 Hz, 1 H), 6.84 (d, J = 2.4 Hz, 1 H), 6.98 (d, J = 2.4 Hz,
1 H).
EtOAc layer washed with brine and dried (anhyd MgSO ). The solvent
4
was removed under reduced pressure and the residue was purified by
silica gel column chromatography (CH Cl –MeOH 25:1) to give the
2
2
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–G

F
Synthesis
X. Guan et al.
Paper
1
3
unreacted 14 (68 mg), and a mixture of the dimer 18a and 18b in a
.5:1 molar ratio as yellowish amorphous powder; yield: 65.2 mg
49%).
C NMR (125 MHz, acetone-d ): δ = 56.0 (2 C), 56.3, 59.4, 61.9, 77.4,
6
1
(
101.2, 102.4, 106.1 (2 C), 106.4, 111.3, 112.3, 115.1, 115.3, 120.4,
120.8, 122.4, 136.6, 138.1, 145.7, 146.4, 147.7, 148.1, 149.0, 150.7,
155.1, 158.7, 159.1 (2 C).
1
18a
H NMR (500 MHz, CD OD): δ = 2.80 (dd, J = 3.5, 3.5 Hz, 1 H), 3.35(dd,
3
R = 0.32 (CH Cl –MeOH 15:1).
J = 3.5, 8.0 Hz, 1 H), 3.64 (s, 3 H), 3.73 (s, 3 H), 4.19 (d, J = 3.5 Hz, 1 H),
4.41 (d, J = 8.0 Hz, 1 H), 5.81 (d, J = 2.0 Hz, 2 H), 6.02 (t, J = 2.0 Hz, 1 H),
f
2
2
1
H NMR (400 MHz, acetone-d ): δ = 1.10 (t, J = 7.2 Hz, 3 H), 2.82 (t, J =
6
6.25 (d, J = 2.0 Hz, 1 H), 6.41 (dd, J = 2.0, 8.0 Hz, 1 H), 6.43 (d, J = 2.0 Hz,
1 H), 6.45 (dd, J = 2.0, 8.0 Hz, 1 H), 6.55 (d, J = 2.0 Hz, 1 H), 6.63 (d, J =
8.0 Hz, 1 H), 6.64 (d, J = 2.0 Hz, 1 H), 6.67 (d, J = 8.0 Hz, 1 H).
3.6 Hz, 1 H), 3.18 (dd, J = 6.8, 9.2 Hz, 1 H), 3.40 (q, J = 7.2 Hz, 2 H), 4.07
(
(
(
(
1
d, J = 8.8 Hz, 1 H), 4.21 (d, J = 3.2 Hz, 1 H), 5.84 (d, J = 2.0 Hz, 2 H), 6.11
t, J = 2.0 Hz, 1 H), 6.36 (d, J = 2.0 Hz, 1 H), 6.51 (d, J = 2.0 Hz, 1 H), 6.62
d, J = 2.0 Hz, 1 H), 6.71 (d, J = 2.0 Hz, 1 H), 6.91 (d, J = 2.0 Hz, 1 H), 7.83
s, 1 H), 7.98 (s, 1 H), 8.04 (s, 1 H), 8.10 (s, 2 H), 8.19 (s, 1 H).
3
13C NMR (125 MHz, CD
OD): δ = 56.1, 56.3, 56.4, 60.2, 62.1, 78.7,
3
101.2, 102.6, 106.3 (3 C), 111.9, 112.4, 115.7 (2 C), 120.9 (2 C), 123.0,
136.5, 138.8, 145.6. 146.7, 148.5, 148,7, 149.5, 151.3, 155.5, 159.2,
C NMR (150 MHz, acetone-d ): δ = 15.5, 55.8, 56.6, 56.7, 59.2, 60.4,
6
159.3 (2 C).
64.7, 85.8, 101.3, 105.9 (2 C), 106.1, 108.6, 108.9, 110.5, 111.2, 121.5,
123.9, 124.8, 134.2, 139.0, 143.1, 144.3, 148.7 (2 C), 148.9, 149.2,
150.2, 155.1, 159.3 (2 C), 159.4.
HRMS (ESI): m/z calcd for
C H O + H: 533.18061; found:
30 28 9
533.18036.
HRMS (ESI): m/z calcd for C32H30Br O + Na: 739.01488; found:
2
9
(±)-6b
739.01471.
R = 0.26 (CH Cl –MeOH 8:1).
f
2
2
1
18b
H NMR (500 MHz, acetone-d ): δ = 3.43 (dd, J = 4.5, 4.0 Hz, 1 H), 3.46
6
R = 0.32 (CH Cl –MeOH 15:1).
(dd, J = 4.5, 8.0 Hz, 1 H), 3.71 (s, 3 H), 3.73 (s, 3 H), 4.22 (d, J = 4.0 Hz, 1
H), 4.56 (d, J = 8.0 Hz, 1 H), 5.95 (d, J = 2.0 Hz, 1 H), 6.13 (d, J = 2.0 Hz,
f
2
2
1
H NMR (400 MHz, acetone-d ): δ = 1.02 (t, J = 7.2 Hz, 3 H), 3.08 (dd,
6
2
8
H), 6.16 (d, J = 2.0 Hz, 1 H), 6.22 (d, J = 2.0 Hz, 1 H), 6.46 (dd, J = 2.0,
.0 Hz, 1 H), 6.61 (d, J = 2.0 Hz, 1 H), 6.64 (dd, J = 2.0, 8.0 Hz, 1 H), 6.67
J = 6.8, 9.6 Hz, 1 H), 3.30 (q, J = 7.2 Hz, 2 H), 3.81 (t, J = 5.6 Hz, 1 H),
4.11 (d, J = 7.6 Hz, 1 H), 4.24 (d, J = 3.6 Hz, 1 H), 5.95 (d, J = 2.0 Hz, 1 H),
6.15 (d, J = 2.0 Hz, 2 H), 6.18 (d, J = 2.0 Hz, 1 H), 6.27 (d, J = 2.0 Hz, 1 H),
6.62 (d, J = 2.0 Hz, 1 H), 6.71 (d, J = 2.0 Hz, 2 H), 6.83 (d, J = 2.0 Hz, 1 H),
7.76 (s, 1 H), 8.01 (s, 1 H), 8.09 (s, 2 H), 8.10 (s, 1 H), 8.17 (s, 1 H).
(d, J = 8.0 Hz, 1 H), 6.68 (d, J = 8.0 Hz, 1 H), 6.92 (d, J = 2.0 Hz, 1 H).
13C NMR (125 MHz, acetone-d
): δ = 56.1, 56.2, 56.6, 59.0, 62.3, 77.3,
6
101.0, 102.2, 105.7, 106.3 (2 C), 111.9 (2 C), 114.8, 115.3, 120.9, 121.4,
130.6, 136.2, 138.6, 145.7, 146.6, 147.4, 147.8, 148.1, 151.1, 154.9,
13
C NMR (150 MHz, acetone-d ): δ = 15.5, 55.9, 56.6, 56.7, 59.1, 60.9,
6
1
58.7, 159.3 (2 C).
1H NMR (500 MHz, CD
J = 5.0, 8.0 Hz, 1 H), 3.67 (s, 3 H), 3.71 (s, 3 H), 4.14 (d, J = 5.0 Hz, 1 H),
64.6, 84.8, 101.4, 105.7, 106.3 (2 C), 108.6, 108.8, 111.1, 111.3, 122.6,
124.2, 125.2, 133.8, 139.5, 143.0, 144.4, 146.7, 148.8 (2 C), 150.3,
155.2, 159.0, 159.4 (3 C).
OD): δ = 3.23 (dd, J = 5.0, 5.0 Hz, 1 H), 3.55 (dd,
3
4
6
1
8
.54 (d, J = 8.0 Hz, 1 H), 6.08 (t, J = 2.0 Hz, 1 H), 6.09 (d, J = 2.0 Hz, 2 H),
.13 (d, J = 2.0 Hz, 1 H), 6.14 (d, J = 2.0 Hz, 1 H), 6.35 (dd, J = 2.0, 8.0 Hz,
H), 6.43 (d, J = 2.0 Hz, 1 H), 6.61 (d, J = 8.0 Hz, 1 H), 6.62 (dd, J = 2.0,
.0 Hz, 1 H), 6.65 (d, J = 8.0 Hz, 1 H), 6.88 (d, J = 2.0 Hz, 1 H).
HRMS (ESI): m/z calcd for C31H29Br O + Na: 739.01488; found:
2
9
739.01471.
Debromination of 16a/16b for the Preparation of 6a/6b
13
C NMR (125 MHz, CD OD): δ = 56.2, 56.3, 57.4, 60.0, 61.8, 78.0,
3
After two vacuum/H2 cycles to remove air from a round-bottomed
flask, a suspension of the mixture of 16a and 16b (56 mg, 0.081
101.3, 102.6, 106.0, 106.9 (2 C), 112.0, 112.4, 115.3, 115.6, 121.1,
122.0, 123.9, 135.5, 139.0, 145.5, 146.9, 147.4, 148.5, 148,7, 150.7,
155.4, 158.8, 159.4 (2 C).
mmol), 10% Pd/C (26 mg), and Et N (0.3 mL) in anhyd MeOH (3 mL)
3
was vigorously stirred using a stir bar under H atmosphere at r.t. Af-
2
HRMS (ESI): m/z calcd for C30H28O9
33.18036.
+ H: 533.18061; found:
ter stirring for 15 h, the reaction mixture was filtered. The filtrate was
washed with dil HCl and then extracted with EtOAc (3 × 15 mL). The
combined organic layers were washed with brine and dried (anhyd
5
MgSO ). The solvent was removed under reduced pressure and the
Debromination of 17a/17b for the Synthesis of 19a/19b
4
residue was purified by silica gel column chromatography (CH Cl –
2
2
After two vacuum/H2 cycles to remove air from a round-bottomed
MeOH 15:1) to obtain a mixture of (±)-gnetuhainin I (6a) and (±)-
gnemontanins E (6b) in a 1.3:1 molar ratio as a yellowish oil; yield: 32
mg (73%).
flask, a suspension of the mixture of 17a and 17b (60 mg, 0.085
mmol), 10% Pd/C (60 mg), and Et N (0.6 mL) in MeOH (5.0 mL) was
3
vigorously stirred using a stir bar under H2 atmosphere at r.t. After
stirring for 23 h, the reaction mixture was filtered. The filtrate was
washed with dil HCl and then extracted with EtOAc (3 × 15 mL). The
combined organic layers were washed with brine and dried (anhyd
(±)-6a
R = 0.26 (CH Cl –MeOH 8:1).
f
2
2
1
H NMR (500 MHz, acetone-d ): δ = 2.96 (dd, J = 3.5, 3.5 Hz, 1 H), 3.37
6
MgSO ). The solvent was removed under reduced pressure and the
4
(dd, J = 3.5, 8.0 Hz, 1 H), 3.65 (s, 3 H), 3.72 (s, 3 H), 4.22 (d, J = 3.5 Hz,
residue was separated by silica gel column chromatography (CH Cl –
2
2
1 H), 4.50 (d, J = 8.0 Hz, 1 H), 5.91 (d, J = 2.0 Hz, 2 H), 6.12 (t, J = 2.0 Hz,
1 H), 6.31 (d, J = 2.0 Hz, 1 H), 6.46 (dd, J = 2.0, 8.0 Hz, 1 H), 6.51 (dd, J =
2.0, 8.0 Hz, 1 H), 6.56 (d, J = 2.0 Hz, 1 H), 6.62 (d, J = 2.0 Hz, 1 H), 6.64
MeOH 15:1) to obtain a mixture of (±)-lehmbachol A (19a) and (±)-
lehmbachol B (19b) in a 1:1 molar ratio as a yellowish oil; yield: 40.7
mg (87%).
(d, J = 2.0 Hz, 1 H), 6.67 (d, J = 8.0 Hz, 1 H), 6.71 (d, J = 8.0 Hz, 1 H).
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–G

G
Synthesis
X. Guan et al.
Paper
(±)-19a
(±)-20b
R = 0.30 (CH Cl –MeOH 8:1).
R = 0.30 (CH Cl –MeOH 8:1).
f
2
2
f
2
2
1
1
H NMR (600 MHz, CD OD): δ = 3.12 (s, 3 H), 2.75 (br s, 1 H), 3.38 (dd,
H NMR (600 MHz, CD OD): δ = 1.07 (t, J = 7.2 Hz, 3 H), 3.12 (q, J = 7.2
3
3
J =3.0, 7.2 Hz, 1 H), 3.74 (s, 3 H), 3.76 (s, 3 H), 3.97 (d, J = 3.0 Hz, 1 H),
.21 (br s, 1 H), 5.77 (br s, 2 H), 6.04 (br s, 1 H), 6.18 (br s, 1 H), 6.29 (br
s, 1 H), 6.38 (d, J = 7.8 Hz, 1 H), 6.42 (br s, 1 H), 6.63 (d, J = 7.8 Hz, 1 H),
Hz, 2 H), 3.50 (dd, J = 5.4, 6.6 Hz, 1 H), 3.58 (dd, J = 3.0, 6.0 Hz, 1 H),
3.69 (s, 3 H), 3.73 (s, 3 H), 4.10 (d, J =7.8 Hz, 1 H), 4.17 (d, J = 4.8 Hz, 1
H), 6.12 (d, J = 2.4 Hz, 2 H), 6.16 (d, J = 2.4 Hz, 1 H), 6.28 (d, J = 2.4 Hz,
1 H), 6.33 (d, J = 2.4 Hz, 1 H), 6.38 (d, J = 7.8 Hz, 1 H), 6.44 (br s, 1 H),
6.60 (d, J = 8.4 Hz, 1 H), 6.65 (d, J = 8.4 Hz, 1 H), 6.71 (d, J = 7.8 Hz, 1 H),
4
6.69 (d, J = 8.4 Hz, 1 H), 6.71 (br s, 1 H), 6.73 (d, J = 7.8 Hz, 1 H).
13
C NMR (150 MHz, CD OD): δ = 56.2, 56.3, 56.5, 57.1, 60.0, 60.6, 89.4,
3
6.83 (br s, 1 H).
101.2, 102.6, 106.0, 106.2 (2 C), 112.4, 112.5, 115.4, 115.6, 120.9,
121.2, 122.8, 123.9, 132.2, 138.9, 145.6, 147.3, 148.7, 149.0, 150.7,
155.4, 158.7, 159.2 (2 C).
13
C NMR (150 MHz, CD OD): δ = 15.5, 56.3 (2 C), 56.8, 60.1, 59.5, 60.9,
3
64.9, 85.8, 101.4, 102.6, 106.2, 106.8 (2 C), 112.0, 112.7, 115.3, 115.6,
1
1
21.2, 121.7, 122.9, 133.0, 139.0, 145.5, 147.2, 148.7, 150.6, 151.3,
55.4, 158.7, 159.2 (2 C).
HRMS (ESI): m/z calcd for C31H30O9
47.19568.
+ H: 547.19626; found:
5
HRMS (ESI): m/z calcd for C32H32O9
61.21222.
+ H: 561.21191; found:
5
(±)-19b
R = 0.30 (CH Cl –MeOH 8:1).
f
2
2
1
H NMR (600 MHz, CD OD): δ = 3.13 (s, 3 H), 3.21 (dd, J = 4.8, 5.4 Hz, 1
3
Funding Information
H), 3.58 (dd, J = 3.0, 6.0 Hz, 1 H), 3.65 (s, 3 H), 3.70 (s, 3 H), 4.03 (d, J =
6.6 Hz, 1 H), 4.17 (d, J = 4.8 Hz, 1 H), 6.13 (br s, 2 H), 6.14 (br s, 1 H),
6.15 (br s, 1 H), 6.29 (br s, 1 H), 6.42 (d, J = 7.8 Hz, 1 H), 6.56 (br s, 1 H),
6.64 (dd, J = 1.8, 7.8 Hz, 1 H), 6.65 (d, J = 7.8 Hz, 1 H), 6.72 (d, J = 7.8 Hz,
1 H), 6.85 (br s, 1 H).
This research work was financially supported by the National Natural
Science Foundation of China (No. 21462024).
N
ati
o
n
a
l Natural S
c
i
e
n
c
e
F
o
u
n
d
ati
o
n
of
C
h
i
n
a
(2
1
4
6
2
0
2
4)
13
C NMR (150 MHz, CD OD): δ = 56.2, 56.3, 56.7, 56.8, 59.9, 60.8, 87.9,
Supporting Information
3
101.4, 102.7, 106.1, 106.9 (2 C), 112.5, 112.7, 115.6, 115.8, 120.9,
121.2, 121.9, 123.1, 132.8, 138.8, 145.5, 147.3, 148.7, 149.8, 151.2,
155.4, 159.2, 159.4 (2 C).
Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1611713.
S
u
p
p
orit
n
g Inform ati
o
n
S
u
p
p
orit
n
g Inform ati
o
n
HRMS (ESI): m/z calcd for C31H30O9
47.19568.
+ H: 547.19626; found:
5
References
Debromination of 18a/18b for the Synthesis of 20a/20b
(1) (a) Lin, M.; Yao, C. S. Stud. Nat. Prod. Chem. 2006, 33, 601.
(b) Shen, T.; Wang, X. N.; Lou, H. X. Nat. Prod. Rep. 2009, 26, 916.
After two vacuum/H2 cycles to remove air from a round-bottomed
flask, a suspension of the mixture of 18a and 18b (62 mg, 0.087
(c) Kawazoe, K.; Shimogai, N.; Takaishi, Y.; Rao, K. S.; Imakura, Y.
Phytochemistry 1997, 44, 1569. (d) Zhai, Y.-M.; Jiang, K.; Qu, S.-
J.; Luo, H.-F.; Tan, J.-J.; Tan, C.-H. RSC Adv. 2016, 6, 50083.
mmol), 10% Pd/C (62 mg), and Et N (1.5 mL) in MeOH (10 mL) was
3
vigorously stirred using a stir bar under H2 atmosphere at r.t. After
stirring for 9 h, the reaction mixture was filtered. The filtrate was
washed with dil HCl and then extracted with EtOAc (3 × 15 mL). The
combined organic layers were washed with brine and dried (anhyd
(e) Huang, K.-S.; Wang, Y.-H.; Li, R.-L.; Lin, M. Phytochemistry
2000, 54, 875.
(
2) For reviews, see: (a) Velu, S. S.; Thomas, N. F.; Weber, J. F. Curr.
Org. Chem. 2012, 16, 605. (b) Snyder, S. A.; Elsohly, A. M.;
Kontes, F. Nat. Prod. Rep. 2011, 28, 897. (c) Synder, S. A. Recent
Adv. Polyphenol Res. 2012, 3, 311. (d) Li, W. L.; Zang, P.; Li, H. F.;
Yang, S. X. Prog. Chem. 2012, 24, 545. (e) Li, W. L.; Lv, T.; Yang, Y.
H.; Yang, Y. D. Chin. J. Chem. 2013, 33, 2443. (f) Keylor, M. H.;
Matsurra, B. S.; Stephenson, C. R. J. Chem. Rev. 2015, 115, 8976.
3) (a) Li, X.-M.; Huang, K.-S.; Lin, M.; Zhou, L.-X. Tetrahedron 2003,
MgSO ). The solvent was removed under reduced pressure and the
4
residue was purified by silica gel column chromatography (CH Cl –
2
2
MeOH 15:1) to obtain a mixture of (±)-7-O-ethylgnetuhainin I (20a)
and (±)-gnemontanin F (20b) in a 1.3:1 molar ratio as a yellowish oil;
yield: 37.1 mg (77%).
(
(
(±)-20a
59, 4405. (b) Yao, C.-S.; Lin, M. Heterocycles 2006, 68, 983.
R = 0.32 (CH Cl –MeOH 8:1).
f
2
2
4) (a) Zhou, L. X.; Lin, M. Chin. Chem. Lett. 2000, 11, 515. (b) Zhou,
L. X.; Lin, M. Acta Pharm. Sin. 2000, 35, 669. (c) Yao, C. S.; Zhou,
L. X.; Lin, M. Chem. Pharm. Bull. 2004, 52, 238. (d) Li, W. L.; He,
K. K.; Li, Y.; Hou, Z. J. Acta Chim. Sin. 2005, 63, 1607. (e) Wang,
X.-F.; Zhang, Y.; Lin, M.-B.; Yao, C.-S.; Shi, J.-G. J. Asian Nat.
Prod. Res. 2014, 16, 511.
(5) (a) Li, W. L.; Luo, Y. L.; Li, H. F.; Zang, P.; Han, X. Q. Synthesis
2010, 3822. (b) Li, W. L.; Yang, S. X.; Lv, T.; Yang, Y. D. Org.
Biomol. Chem. 2014, 12, 2273.
1
H NMR (600 MHz, CD OD): δ = 1.13 (t, J = 7.2 Hz, 3 H), 2.74 (3.19 (dd,
3
J =3.0, 3.6 Hz, 1 H), 3.19 (q, J = 7.2 Hz, 2 H), 3.26 (dd, J = 4.2, 4.8 Hz, 1
H), 3.63 (s, 3 H), 3.75 (s, 3 H), 4.03 (d, J = 9.0 Hz, 1 H), 4.20 (d, J = 3.0
Hz, 1 H), 5.75 (d, J = 2.4 Hz, 2 H), 6.02 (d, J = 2.4 Hz, 1 H), 6.05 (d, J = 2.4
Hz, 1 H), 6.39 (br s, 1 H), 6.42 (d, J = 8.4 Hz, 1 H), 6.44 (br s, 1 H), 6.56
(
(
1
d, J = 2.4 Hz, 1 H), 6.66 (d, J = 7.8 Hz, 1 H), 6.71 (d, J = 8.4 Hz, 1 H), 6.72
d, J = 8.4 Hz, 1 H).
3
C NMR (150 MHz, CD OD): δ = 15.4, 56.2, 56.3 (2 C), 59.8, 60.8, 65.0,
3
(
6) (a) Li, W. L.; Dong, T.; Chen, P. L.; Liu, X. L.; Liu, M. J.; Han, X. Q.
Tetrahedron 2017, 73, 3056. (b) Liu, M. J.; Guan, X. C.; Shao, Z. B.;
Li, W. L. Tetrahedron 2018, 74, 4013.
87.4, 101.1, 102.6, 106.2 (2 C), 106.3, 112.4, 112.5, 115.6, 115.8, 120.9,
121.2, 123.8, 133.6, 138.8, 145.6, 146.9, 147.1, 148.6, 148.7, 150.0,
155.3, 159.1, 159.4 (2 C).
HRMS (ESI): m/z calcd for C32H32O9
61.21222.
+ H: 561.21191; found:
5
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–G