Total synthesis of a lignanamide from Aptenia cordifolia

Article abstract of DOI:10.3184/174751915X14402591178530

(E,E)-N,N-Dityramin-4,4'-dihydroxy-3,5'-dimethoxy-ss,3'-bicinnamamide, a lignanamide isolated from Aptenia cordifolia, was synthesised from vanillin and tyramine. The key 8-5'-neolignan intermediate diacid was formed efficiently using oxidative coupling of the ferulic acid derivatives and the ring-opening reaction of a dihydrobenzofuran.

Full text of DOI:10.3184/174751915X14402591178530

JOURNAL OF CHEMICAL RESEARCH 2015
VOL. 39 SEPTEMBER, 535–538
RESEARCH PAPER 535
Total synthesis of a lignanamide from Aptenia cordifolia
a,
a
a
a
b
Yamu Xia *, Chenchen Li , Huaizheng Zhang , Jiao Lin and Chen Chai
a
College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao 266042,P.R.China
The First Affiliated Hospital of Lanzhou University, Gansu 730000, P.R.China
b
(
E,E)-N,N-Dityramin-4,4’-dihydroxy-3,5’-dimethoxy-ß,3’-bicinnamamide, a lignanamide isolated from Aptenia cordifolia, was synthesised
from vanillin and tyramine. The key 8-5′-neolignan intermediate diacid was formed efficiently using oxidative coupling of the ferulic acid
derivatives and the ring-opening reaction of a dihydrobenzofuran.
Keywords: lignanamide, vanillin, tyramine, oxidative coupling, ring-opening reaction
Lignanamides are widely distributed in plants, and have been
isolated from Cannabis sativa, Mitrephora thorelii, Porcelia
the final product has the skeleton of lignanamide (E,E)-N,N-
1
–3
4
dityramin-4,4’-dihydroxy-3,5’-dimethoxy-ß,3’-bicinnamamide
5
6
7
6
macrocarpa, Aptenia cordifolia, Commelina communis,
(1, Fig. 2), which was first isolated by Marina et al. in 2005
8
9
Solanum melongena L., Piper wallichii, etc. Within this
general class, aryl-naphthalene and acyclic bis-phenylpropane
derivatives have been identified. Because of the wide range
from the leaves of Aptenia cordifolia, possessing a roots
-4
elongation inhibitory activity against Lactuca sativa at 10 M.
We now report full details of the total synthesis of the
lignanamide (E,E)-N,N-dityramin-4,4’-dihydroxy-3,5’-dimeth-
oxy-ß,3’-bicinnamamide. The ring-opening reaction of the
dihydrobenzofuran was studied in various conditions in a series
of experiments, such as the use of diverse bases and solvents
at different temperatures and we studied the different products.
The skeleton of lignanamide 1 was synthesised in alkaline
media through this short route. It relies on the synthesis of the
dihydrobenzofuran lignan from a ferulic acid derivative with
10
8–16
of structures as well as biological activities,
such as anti-
8
16
8
inflammatory, antitumour and insecticide properties, the
total synthesis of several members of the lignanamide family
attracted considerable attention. However, not many synthetic
approaches to the lignanamides have been reported. In 2010, we
reported the first total synthesis of lignanamide Cannabisin G
by Stobbe reaction to construct the skeleton of lignan (C6–C4–
1
7
18
C6), followed by condensation with tyramine, and Hou et al.
1
8
successfully employed oxidative coupling. After that, Uwe’s
group reported a reaction using the laccase/O catalyst system
19
Ag O as the oxidant. This leads to the skeleton of lignanamide
2
2
1
in high yield in the presence of NaOH and alcohol. Finally,
to synthesise a number of lignanamide skeletons.
We have discovered that, in an alkaline media, the
dihydrobenzofuran ring could be opened in high yield, leading
to a 8-5′-neolignan as outlined in Fig. 1. Furthermore, we found
we obtained the desired lignanamide efficiently following a
condensation reaction with tyramine. Compared with the earlier
route, the strategy is novel and concise.
RO
O
OH
OCH3
H CO
3
OCH3
O
OH base
O
OR
H CO
3
O
OR
OH
8-5′-neolignan
O
OR
Dihydrobenzofuran compound
Fig. 1 The opening of the dihydrobenzofuran ring.
H
N
O
OH
8
2''
OCH3
'
HO
7
3
2
1'
4''' OH
5
7'
H CO
8'
3
OH
O
N
H
1
Fig. 2 The lignanamide 1.
*
Correspondent. E-mail: xiaym@qust.edu.cn

536 JOURNAL OF CHEMICAL RESEARCH 2015
Result and discussion
compound 8 was determined to be a threo-racemic compound.
Then, by the opening of the dihydrobenzofuran ring using an
alkaline catalytic system in the key step in this synthesis, we
obtained compound 9 efficiently. The protection of the hydroxyl
group and subsequent hydrolysis of these ester groups afforded
through 10 the key intermediate compound 11. According to
literature spectral data, the configuration of compounds 9, 10,
11 and 12 was determined to be E,E. In our short synthetic route,
we took advantage of the opening of the dihydrobenzofuran
ring to obtain the lignanamide skeleton simply and efficiently.
As shown in Scheme 3, compound 12 was successfully
prepared from diacid 11 with tyramine using CDI as the
reagent. Finally, the removal of the protecting groups using
TFA at ambient temperature afforded the desired (E,E)-N,N-
dityramin-4,4’-dihydroxy-3,5’-dimethoxy-ß,3’-bicinnamamide.
As shown in Scheme 1, the synthesis of the required tyramine
intermediate began from compound 2. Because both hydroxyl
and amino groups of tyramine can react with the diacid, it is
necessary to protect the hydroxyl group before the condensation
reaction. First, the amino group of tyramine was protected
to afford the product 3. Then, the hydroxyl group of 3 was
protected with MOMCl to give the intermediate 4. Finally,
selective removal of the formyl group afforded the desired key
intermediate 5.
As shown in Scheme 2, the required ferulic acid ethyl ester 7
could easily be prepared by Knoevenagel condensation between
vanillin and the corresponding monoethyl malonate with yields
ranging from 80 to 95%. The skeleton of the dihydrobenzofuran
lignan 8 was obtained from the ferulic acid ethyl ester 7
2
5
through oxidative coupling by using Ag O. By comparison of
the spectral data reported elsewhere,
2
3,24
2
the configuration of
NH2
NHCHO
C O
NH H
NH2
HCOOCH3
MOM-Cl,K CO
30%N OH
a
2
3
DMSO, rt
acetone, rt
acetone,reflux
HO
HO
O O
M M
O O
M M
2
5
3
4
Scheme 1 Synthesis of tyramine ligand (5).
OH
COOH
OH
OCH3
OCH
3
H
3CO
OCH3
COOCH CH
Ag
2
O, rt
O
2
3
NaOH, alcohol, rt
OH
0.5 mol/L HCl aq
toluene/acetone
O
C H N/C H11N, reflux
5
5
5
CHO
2
OCH CH3
O
OCH CH3
O
OCH CH3
2
2
6
7
8
H CH CO
O
HO
O
H CH CO
O
3
2
3
2
OMOM
OMOM
OH
OCH3
OCH3
OCH3
MOM-Cl,K CO
20%NaOH aq
2
3
acetone, rt
0.5 mol/L HCl aq
H CO
H CO
3
H CO
3
3
OMOM
OMOM
OH
O
OCH CH3
O
OH
O
OCH CH
2
2
3
9
10
11
Scheme 2 Synthesis of 8-5′-neolignan diacid (11).
H
N
O
OMOM
OCH3
MOMO
TFA
rt
CDI
CH Cl , rt
+
5
11
1
2
2
OMOM
H CO
3
OMOM
O
N
H
12
Scheme 3 Synthesis of lignanamide (1).

JOURNAL OF CHEMICAL RESEARCH 2015 537
Conclusions
170.2 (C=O). HRMS calcd. for C H O 442.1628, found 442.1632.
The spectral data are consistent with the literature.
Ethyl (E,E)-4,4’-dihydroxy-3,5’-dimethoxy-ß,3’-bicinnamate (9):
Compound 8 (5.68 g, 12.85 mmol) was suspended in ethyl alcohol
2
4
26
8
2
4
In summary, a new and concise strategic approach toward
synthesising the natural product lignanamide (E,E)-N,N-
dityramin-4,4’-dihydroxy-3,5’-dimethoxy-ß,3’-bicinnamamide
(50 mL), and NaOH (0.62 g, 15.5 mmol) was added. The mixture
(1, Fig. 2) has been developed. The synthesis of diferulic acid
was stirred vigorously for 4 h at room temperature. The solution was
acidified with HCl (1 M) and evaporated under reduced pressure to
remove EtOH. The residue was extracted with EtOAc (2×20 mL) and
the organic layer washed with saturated NaCl aq. (2×20 mL) followed
11 from precursor 6 was achieved in an overall yield of 30% in
five steps involving Knoevenagel reaction, oxidative coupling,
the opening of the dihydrobenzofuran ring, MOMCl protection
and hydrolysis. The lignanamide was finally prepared in good
yield by condensing the diferulic acid 11 with a derivative of
tyramine. We are continuing to examine the bioactivity of
lignanamide 1 and the synthesis of related derivatives in our
laboratory.
by drying over MgSO . The filtrate was concentrated and purified by
4
column chromatography (petroleum/ ethyl acetate = 5: 3) to afford
compound 9: yellow solid; m.p. 138–139°C; yield 5.40 g (95 %).
1
H NMR (CDCl ), δ 1.21 (t, J = 7.5 Hz, 3H, CH CH ), 1.23 (t, J = 7.5
3
2
3
Hz, 3H, CH CH ), 3.42 (s, 3H, OCH ), 3.89 (s, 3H, OCH ), 4.17 (q, J =
2
3
3
3
1
2.0 Hz, 2H, OCH CH ), 4.20(q, J = 12.0 Hz, 2H, OCH CH ), 5.84 (s,
2
3
2
3
Experimental
1H, OH), 6.06 (s, 1H, OH), 6.19 (d, J = 16.0 Hz, 1H, H-8’), 6.51–7.00
All reagents and the solvents used in this study were of analytical
grade and were used as-received. Dry solvents were prepared by
literature methods and stored over molecular sieves. Flash column
chromatography and TLC were performed on silica gel (200–300
(m, 5H, ArH), 7.51 (d, J = 16.0 Hz, 1H, H-7’), 7.76 (s, 1H, H-7).
13
C NMR (CDCl ), δ 14.3, 55.3, 56.2, 60.4, 61.1, 108.7, 111.6, 114.3,
3
116.1, 123.3, 124.8, 125.8, 126.9, 127.0, 141.5, 144.3, 145.9, 146.0, 147.1,
147.3, 167.1 (C=O), 167.4 (C=O). HRMS calcd for C H O 442.1628,
2
4
26
8
1
mesh) and silica gel GF254 plates, respectively. The H NMR (500
found 442.1634. The data are consistent with that reported in ref. 25.
Ethyl (E,E)-4,4’-dimethoxymethyl-3,5’-dimethoxy-ß,3’-bicinnamate
(10): Compound 9 (5.40 g, 12.2 mmol) was dissolved in dry acetone
(30 mL), and potassium carbonate (8.43 g, 61.1 mmol) was added at
room temperature. After 10 h of vigorous stirring, MOMCl (2.36 g,
29.3 mmol) was added dropwise. Stirring was continued for 3 h. The
mixture was extracted with ethyl acetate and the organic layer was
13
MHz) and C NMR (125 MHz) spectra were recorded on a Bruker
AM-500 MHz spectrometer. HRMS spectra were obtained on a Bruker
Daltonics APEXII47e spectrometer. Melting points were taken on a
Gallenkamp melting point apparatus and are uncorrected.
N-[2-(4-Hydroxyphenyl) ethyl] formamide (3), N-{2-[4-(meth-
oxymethoxy) phenyl] ethyl} formamide (4), 2-[4-(methoxymethoxy)
phenyl] ethan-1-amine (5) and (E)-ferulic acid ethyl ester (7) were
synthesised according to procedures that have been described previously.
dried over MgSO . Then, it was concentrated under reduced pressure.
4
The residual oil was purified by column chromatography (petroleum/
21
N-[2-(4-Hydroxyphenyl) ethyl] formamide (3): White solid; m.p.
ethyl acetate = 3/1) to give the compound 10: yellow solid; m.p.
2
0
1
1
9
(
5–97°C (lit. 96–97°C); yield 11.8 g (98 %). H NMR (CDCl ), δ 2.79
55–57°C; yield 5.30 g (81.8 %). H NMR (CDCl ), δ 1.21 (t, J = 7.0 Hz,
3
3
t, J = 7.0 Hz, 2H, ArCH ), 3.55 (t, J = 7.0 Hz, 2H, CH NH), 5.03 (s,
3H, CH CH ), 1.27 (t, J = 7.0 Hz, 3H, CH CH ), 3.38 (s, 3H, OCH ),
2
2
2
3
2
3
3
NH, 1H), 5.65 (s, 1H, OH), 6.79 (d, J = 8.5 Hz, 2H, ArH), 7.08 (d, J =
3.46 (s, 3H, OCH ), 3.48 (s, 3H, OCH ), 3.92 (s, 3H, OCH ), 4.23 (q, J
= 7.5 Hz, 2H, OCH CH ), 4.25(q, J = 7.5 Hz, 2H, OCH CH ), 5.21 (s,
2 3 2 3
3
3
3
13
8
.5 Hz, 2H, ArH), 8.15 (s, 1H, CH=O). C NMR (CDCl ), δ 31.1, 39.5,
3
116.9, 129.8, 156.0, 161.3, 207.2 (CH=O).
2H, OCH OCH ), 5.22 (s, 2H, OCH OCH ), 6.28 (d, J = 16.0 Hz, 1H,
2
3
2
3
2
1
N-{2-[4-(Methoxymethoxy) phenyl] ethyl} formamide (4): Yellowish
H-8’), 6.65-7.10 (s, 5H, ArH), 7.57 (d, J = 16.0 Hz, 1H, H-7’), 7.85 (s,
1
13
liquid; yield 11.2 g (75 %). H NMR (CDCl ), δ 2.62 (t, J = 7.0 Hz,
2
1H, H-7). C NMR (CDCl ), δ 14.3, 55.2, 55.9, 56.3, 57.1, 60.5, 61.9,
3
3
H, ArCH ), 3.29 (s, 3H, CH O), 3.33 (t, J = 7.0 Hz, 2H, CH NH),
95.1, 98.3, 110.9, 113.0, 115.3, 117.7, 123.9, 124.9, 128.6, 131.0, 132.2,
2
3
2
4
.98 (s, 2H, OCH O), 6.83 (d, J = 8.5 Hz, 2H, ArH), 6.97 (d, J = 8.5
140.4, 143.8, 146.3, 147.7, 148.9, 153.1, 167.9 (C=O), 167.5 (C=O).
2
1
3
Hz, 2H,ArH), 7.86 (s, H, CH=O). C NMR (CDCl ), δ 33.9, 38.9,
5
Phenyl] ethan-1-amine (5): Yellowish liquid; yield 9.0 g (94.5
%
CH NH ), 3.41 (s, 3H, CH O), 5.09 (s, 2H, OCH O), 6.84–7.06 (m, 4H,
ArH). C NMR (CDCl ), δ 38.9, 43.5, 55.9, 94.5, 116.3, 129.8, 133.0,
HRMS calcd for C H O 530.2152, found 530.2159.
3
28 34 10
5.1, 93.7, 115.8, 129.1, 131.5, 155.3, 161.2. 2-[4-(Methoxymethoxy)
(E,E)-4,4’-Dimethoxymethyl-3,5’-dimethoxy-ß,3’-bicinnamic acid
(11): 20% NaOH aq. (20 mL) was added to an ethanol solution (5 mL)
of 10 (5.3 g, 10 mmol), and the mixture was stirred at 40°C for 4 h.
The solution was evaporated under reduced pressure to remove EtOH.
Then, the mixture was poured into EtOAc (30 mL). The organic layer
was separated, and the aqueous layer was back-extracted with EtOAc
(3×10 mL). The combined organic extracts were dried over MgSO4
and concentrated under reduced pressure affording the crude product
which was purified by recrystallisation (EtOAc/petroleum ether (3: 1))
to give compound 11: yellow solid; m.p. 138–139°C; yield 4.6 g (97 %).
2
1
1
). H NMR (CDCl ), δ 2.64 (t, J = 7.0 Hz, 2H, ArCH ), 2.87 (t, 2H,
3
2
2
2
3
3
2
1
3
1
7
55.7.
2
2
22
(
E)-Ferulic acid ethyl ester (7): White powder; m.p. 77°C (lit.
1
7–78°C). H NMR (CDCl ), δ 1.34 (t, J = 12.0 Hz, 3H, CH CH ), 3.91
3
2
3
(s, 3H, OCH ), 4.25 (q, J = 12.0 Hz, 2H, CH CH ), 5.91 (s, 1H, OH),
3
2
3
6
.29 (d, J = 16.0 Hz, 1H, =CHCO), 6.91–7.06 (m, 3H, ArH), 7.61 (d, J =
13
1
1
6.0 Hz, 1H, ArCH). C NMR (CDCl ), δ 14.4, 55.9, 60.4, 109.4, 114.8,
H NMR (CDCl ), δ 3.39 (s, 3H, OCH ), 3.47 (s, 3H, OCH ), 3.48 (s,
3
3
3
3
115.7, 123.1, 127.1, 144.7, 146.8, 147.9, 167.3(C=O).
3H, OCH ), 3.90 (s, 3H, OCH ), 5.02 (s, 2H, OCH OCH ), 5.21 (s, 2H,
3
3
2
3
Threo(±)-ethyl 5-[(E)-3-ethoxy-3-oxoprop-1-en-1-yl]-2-(4-hydroxy-
-methoxyphenyl)-7-methoxy-2,3-dihydrobenzofuran-3-carboxylate
OCH OCH ), 6.30 (d, J = 16.0 Hz, 1H, H-8’), 6.68–7.26 (m, 5H, ArH),
2 3
13
3
(
(
5
7.64 (d, J = 16.0 Hz, 1H, H-7’), 7.93 (s, 1H, H-7). C NMR (CDCl ), δ
3
8): Fresh Ag O (6.57 g, 28.47 mmol) was added to a dry acetone
55.2, 56.0, 56.3, 57.2, 95.1, 98.4, 111.2, 113.1, 115.3, 116.9, 124.3, 125.5,
126.0, 128.2, 130.8, 131.7, 142.8, 146.1, 146.7, 148.2, 149.0, 153.1, 172.2
(C=O), 172.5 (C=O). HRMS calcd for C H O 474.1526, found
2
30 mL) and toluene (40 mL) solution of compound 7 (12.64 g,
6.93 mmol) under a nitrogen atmosphere at -20℃. The reaction
2
4
26 10
mixture was stirred until complete disappearance of compound 7, and
then it was filtered and evaporated under reduced pressure. The residue
was purified by column chromatography (petroleum/ethyl acetate
474.1528.
( E , E ) - N, N- (4 , 4’- d i m e t h ox y m e t h yl ) - d i t yra m i n - 4 , 4’-
dimethoxymethyl-3,5’-dimethoxy-ß,3’-bicinnamamide (12): Diacid
11 (4.6 g, 9.7 mmol) was dissolved in dry CH Cl (10 mL), and CDI
(3.15 g, 19.4 mmol) was added under a nitrogen atmosphere at room
temperature. After 3h of stirring, the reaction mixture was added
2
3
=
3: 1) to afford the compound 8: white solid; m.p. 151–152°C (lit.
2
2
1
1
52.8-153.1°C); yield 5.68 g (45.2 %). H NMR (CDCl ), δ: 1.34–1.37
3
(
m, 6H, 2×CH ), 3.88 (s, 3H, Ar-OCH ), 3.96(s, 3H, Ar-OCH ),
3
3
3
4
.25–4.30 (m, 4H, 2×OCH ), 4.33 (d, J = 8.0 Hz, 1H, H-3), 6.11 (d,
dropwise to a stirred solution of 5 (3.85 g, 21.3 mmol) in dry CH Cl2
2
2
J = 8.0 Hz, 1H, H-2), 6.32 (d, J = 15.9 Hz, 1H, H-2′), 6.90–7.27 (m, 5H,
(5 mL). The white precipitate, which formed, was filtered off and the
solvent was evaporated under reduced pressure to afford a yellow oil.
The residue was subjected to flash column chromatography (diethyl
ether/petroleum ether (2:1)) to give compound 12: white solid; m.p.
1
3
ArH), 7.65 (d, J = 15.9 Hz, 1H, H-1′). C NMR (CDCl ), δ 14.3, 55.5,
3
5
6.3, 56.1, 60.4, 61.8, 87.5, 108.7, 111.7, 114.5, 115.9, 117.9, 119.5,
1
25.8, 128.6, 131.4, 144.5, 144.7, 145.9, 146.6,149.9, 167.2 (C=O),

538 JOURNAL OF CHEMICAL RESEARCH 2015
1
1
2
(
29–130°C; yield 4.8 g (62 %). H NMR (CDCl ), δ 2.72 (t, J = 7.0 Hz,
Received 13 July 2015; accepted 10 August 2015
Paper 1503489 doi: 10.3184/174751915X14402591178530
Published online: 1 September 2015
3
H, ArCH ), 2.82 (t, J = 7.0 Hz, 2H, ArCH ), 3.34 (s, 3H, OCH ), 3.43
2
2
3
s, 3H, CH O), 3.45 (s, 3H, OCH ), 3.47 (s, 3H, OCH ), 3.48 (t, J = 7.0
3
3
3
Hz, 2H, CH NH), 3.51 (s, 3H, OCH ), 3.62 (t, J = 7.0 Hz, 2H, CH NH),
2
3
2
3
.91 (s, 3H, OCH ), 5.00 (s, 2H, OCH O), 5.07 (s, 2H, OCH O), 5.16
3
2
2
References
(s, 2H, OCH O), 5.17 (s, 2H, OCH O), 6.17 (d, J = 16.0 Hz, 1H, H-8’),
2
2
1
2
3
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.57–7.14 (m, 13H, ArH), 7.50 (d, J = 16.0 Hz, 1H, H-7’), 7.81 (s, 1H,
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13
H-7). C NMR (CDCl ), δ 34.6, 34.9, 41.0, 41.3, 55.2, 55.9, 56.3,
3
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4
4
52
2
12
8
00.3520, found 800.3529.
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2
014, 12, 377.
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/
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4,4’-dihydroxy-3,5’-dimethoxy-ß,3’-bicinnamamide (1): amorphous
1
powder; yield 67.2 mg (86.2 %). H NMR (CDCl ), δ 2.66 (t, J = 7.0
Hz, 2H, ArCH ), 2.72 (t, J = 7.0 Hz, 2H, ArCH ), 3.35 (s, 3H, OMe),
3
2
2
3.43 (t, J = 7.0 Hz, 2H, CH NH), 3.50 (t, J = 7.0 Hz, 2H, CH NH), 3.95
2
2
14
C.F. Tseng, A. Mikajiri and M. Shibuya, Chem. Pharm. Bull., 1986, 34,
1380.
S. Iwakami, M. Shibuya, C.F. Tseng, F. Hanaoka and U. Sankawa, Chem.
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(s, 3H, OMe), 6.36 (d, J = 16.0 Hz, 1H, H-8’), 6.55–7.16 (m, 13H, ArH),
13
7.40 (d, J = 16.0 Hz, 1H, H-7’), 7.60 (s, 1H, H-7). C NMR (CDCl ),
3
15
δ 36.1, 36.3, 43.0, 43.3, 56.3, 57.3, 112.2, 113.8, 115.6, 116.4, 116.8,
20.2, 125.3, 126.3, 127.2, 129.1, 131.8, 131.9, 132.1, 138.9, 141.9, 147.1,
1
16
148.2, 149.3, 151.6, 156.8, 168.8, 169.5. HRMS calcd for C H N O
3
6
36
2
8
624.2472, found 624.2477. Physical and spectral data are in accordance
1
7
Y.M. Xia, X.L. Guo and Y.L. Wen, J. Serb. Chem. Soc., 2010, 75, 1617.
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9 C. Mihaela-Anca, C. Jürgen and B. Uwe, Green Chem., 2012, 14, 2375.
6
with those previously reported.
1
8
1
This work was supported by the National Natural Science
Foundation of China (No. 21472105), the Chinese Medicine
Administration Bureau of Gansu Province (No.GZK-2011-62).
20 Y.M. Xia, J. You and C. Chai, Chem. Pap., 2014, 68, 384.
21 N. Tumma, M. Jacolot, M. Jean, S. Chandrasekhar and P.V.D. Weghe,
Synlett, 2012, 23, 2919.
2
2
2
2
3
4
C. Vafiadi, E. Topakas, K.K.Y. Wong, Ian D. Suckling and P.
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Electronic Supplementary Information:
1
13
Copies of the original H (500 MHz) NMR and C (125 MHz)
NMR spectra for compounds 3, 4, 5, 8, 9, 10, 11, 12 and 1 are
available through stl.publisher.ingentaconnect.com/content/stl/
jcr/supp-data
4
6, 2531.
M.A. Constantin, J. Conrad, U. Beifuss, Green Chem., 2012, 14, 2375.
25 F.C. Lu, L.P. Wei, A. Azarpira and J. Ralph, J. Agric. Food Chem., 2012,
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