Substituent effects of cis-cinnamic acid analogues as plant growh inhibitors

Article abstract of DOI:10.1016/j.phytochem.2013.08.013

1-O-cis-Cinnamoyl-β-d-glucopyranose is one of the most potent allelochemicals that has been isolated from Spiraea thunbergii Sieb by Hiradate et al. It derives its strong inhibitory activity from cis-cinnamic acid (cis-CA), which is crucial for phytotoxicity. By preparing and assaying a series of cis-CA analogues, it was previously found that the key features of cis-CA for lettuce root growth inhibition are a phenyl ring, cis-configuration of the alkene moiety, and carboxylic acid. On the basis of a structure-activity relationship study, the substituent effects on the aromatic ring of cis-CA were examined by systematic synthesis and the lettuce root growth inhibition assay of a series of cis-CA analogues having substituents on the aromatic ring. While ortho- and para-substituted analogues exhibited low potency in most cases, meta-substitution was not critical for potency, and analogues having a hydrophobic and sterically small substituent were more likely to be potent. Finally, several cis-CA analogues were found to be more potent root growth inhibitors than cis-CA.

Full text of DOI:10.1016/j.phytochem.2013.08.013

Phytochemistry 96 (2013) 132–147
Contents lists available at ScienceDirect
Phytochemistry
journal homepage: www.elsevier.com/locate/phytochem
Substituent effects of cis-cinnamic acid analogues as plant growh
inhibitors
Keisuke Nishikawa a, Hiroshi Fukuda b, Masato Abe a, Kazunari Nakanishi b, Tomoya Taniguchi b,
Takashi Nomura d, Chihiro Yamaguchi d, Syuntaro Hiradate c, Yoshiharu Fujii d, Katsuhiro Okuda a,
Mitsuru Shindo a,
⇑
a Institute for Materials Chemistry and Engineering, Kyushu University, Kasuga-koen, Kasuga 816-8580, Japan
b Interdisciplinary Graduate School of Engineering Sciences, Kyushu University, Kasuga-koen, Kasuga 816-8580, Japan
c Biodiversity Division, National Institute for Agro-Environmental Sciences, 3-1-3 Kan-nondai, Tsukuba, Ibaraki 305-8604, Japan
d International Environmental and Agricultural Sciences, Tokyo University of Agriculture and Technology, 3-5-8, Saiwai-cho, Fuchu, Tokyo 183-8509, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 7 March 2013
Received in revised form 18 July 2013
Available online 23 September 2013
1-O-cis-Cinnamoyl-b-D-glucopyranose is one of the most potent allelochemicals that has been isolated
from Spiraea thunbergii Sieb by Hiradate et al. It derives its strong inhibitory activity from cis-cinnamic
acid (cis-CA), which is crucial for phytotoxicity. By preparing and assaying a series of cis-CA analogues,
it was previously found that the key features of cis-CA for lettuce root growth inhibition are a phenyl ring,
cis-configuration of the alkene moiety, and carboxylic acid. On the basis of a structure–activity relation-
ship study, the substituent effects on the aromatic ring of cis-CA were examined by systematic synthesis
and the lettuce root growth inhibition assay of a series of cis-CA analogues having substituents on the
aromatic ring. While ortho- and para-substituted analogues exhibited low potency in most cases, meta-
substitution was not critical for potency, and analogues having a hydrophobic and sterically small sub-
stituent were more likely to be potent. Finally, several cis-CA analogues were found to be more potent
root growth inhibitors than cis-CA.
Keywords:
Lettuice
Lactuca sativa
Asteraceae
cis-Cinnamic acid
Allelochemicals
Plant growth inhibitors
SAR
Ó 2013 Elsevier Ltd. All rights reserved.
Substituent effects
1. Introduction
it is widely considered to be an auxin agonist. Although mechanis-
tic studies based on molecular biology have been reported (Chen
1-O-cis-Cinnamoyl-b-
D
-glucopyranose (1) (Fig. 1) was isolated
et al., 2005; Guo et al., 2011), the molecular mechanisms of these
activities have not yet been described. Nevertheless the first chem-
ical synthesis of the glycosyl ester 1 was previously achieved,
which confirmed its proposed structure and determined its optical
rotation (Matsuo et al., 2011). A structure activity relationship
study of cis-2 was reported, this establishing the which revealed
that essential structural features for its bioactivity being the cis-
configuration of the alkene or cyclopropane, a carboxylic acid or
its esters, and a planar ring including a phenyl group (Abe et al.,
2012). If additional units can be introduced in the cis-2 isomer
without a loss in activity, stronger bioactive compounds or func-
tional analogues such as molecular probes for mechanistic investi-
gations can be developed. Based on our previous reports, additional
units on the cis-alkene moiety caused a significant loss in bioactiv-
ity, while the introduction of substituents on the aromatic ring
core may be possible without a loss in bioactivity.
from Spiraea thunbergii (Hiradate et al., 2004) as a potent allelo-
chemical and was found in 56 species of woody plants grown in Ja-
pan by a bioassay of growth-inhibitory activity on root elongation
of the germinated seedlings of lettuce (Lactuca sativa L.) (Morita
et al., 2001). An essential structure for the bioactivity of cis-cin-
namic acid (cis-CA) (cis-2) is thought to be the aglycone of the gly-
cosyl ester 1 because cis-CA inhibited lettuce root growth as
effectively as 1, while trans-cinnamic acid (trans-CA) (trans-2)
inhibited growth much less than the cis-isomer (Hiradate et al.,
2005). Generally, the trans-2 isomer is considered to be physiolog-
ically inactive and a weak antagonist of auxin, a plant hormone
that regulates growth in the roots and stem (Koepfli et al., 1938;
van Overbeek et al., 1951; Ferro et al., 2010). On the other hand,
since the cis-2 isomer inhibits the root growth of Avena sativa, Trit-
icum aestivum, and Arabidopsis thaliana, and also induces epinastic
curvature in Solanum lycopersicum seedlings (Koepfli et al., 1938;
van Overbeek et al., 1951; Yang et al., 1999; Wong et al., 2005),
Describe herein are the synthesis and evaluation of the cis-CA
analogues 3–58 having substituent(s) on the aromatic ring, the
purpose of which was to identify substituent effects to clarify
structure–activity relationship. These will be useful in the prepara-
tion of chemical probes (Fig. 2) as well as more active compounds,
⇑
Corresponding author. Tel.: +81 92 583 7802; fax: +81 92 583 7875.
E-mail address: shindo@cm.kyushu-u.ac.jp (M. Shindo).
0031-9422/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.phytochem.2013.08.013

K. Nishikawa et al. / Phytochemistry 96 (2013) 132–147
133
ever, the meta-methylated analogue cis-4 and para-methylated
cis-5 were slightly less active. The analogues cis-6ꢀcis-13 having
larger alkyl and aryl substituents, such as ethyl and phenyl groups,
were markedly less active (entries 5–12). Meta-alkylation may
have less of an effect on bioactivity than ortho- and para-alkylation,
and sterically hindered substituents were more likely to reduce the
activity. While the meta-methoxy analogue cis-15 was more po-
tent, the para-methoxy and meta-ethoxy analogues cis-16 and
cis-17 were slightly less active and the ortho-methoxy one cis-14
was much less active (entries 13–16). The presence of a larger alk-
oxyl group at the meta position led to inactive compounds (entries
17–19).
Fig. 1. Structures of 1-O-cis-cinnamoyl-b-
cinnamic acids (cis- and trans-2).
D-glucopyranose (1) and cis- and trans-
2.2.2. Effects of halogenation of the aromatic ring
Halogenated analogues (Table 1, entries 20–31) showed a sim-
ilar level of activity to cis-2, although cis-21 and cis-32 were
slightly less active. It was found that meta-substituted ones were
preferred, providing compounds with EC50 values in the range of
Fig. 2. An overview of this research.
1.0–2.5 lM, in which the order of activity was F < Cl < Br < I (en-
tries 20–31). As a result, the meta-iodo analogue cis-31 was found
to be more active than cis-CA.
leading to novel agrochemicals. To assay the bioactivity of the cis-
CA analogues, inhibitory activity of these compounds against let-
tuce root growth were tested as described previously (Hiradate
et al., 2005; Abe et al., 2012).
2.2.3. Effects of trifluoromethylation and nitration of the aromatic ring
While ortho-nitrated cis-33 and para-nitrated cis-35 were
inactive, meta-nitrated cis-34 was slightly less active than cis-CA
2 (Table 1, entries 32–34). It is noteworthy that meta-trifluorome-
thylated cis-37 improved the activity, while ortho-substituted
cis-36 and para-substituted cis-38 reduced it (entries 35–37). These
results indicated that strong electron-withdrawing groups may
markedly affect the activity.
In total, for mono-substituted cis-CAs, the meta-substitution of
sterically small alkyl, alkoxy, and halogeno groups was more likely
to maintain strong bioactivity, in which hydrophobic substituents
were somewhat preferred. Steric factors were more important than
inductive and electronic effects. On the other hand, inhibitory
activity was very sensitive to para- and ortho-substitutions, and
sterically bulky and strong electron withdrawing substituents
2. Results and discussion
2.1. Design and synthesis of cis-cinnamic acid analogues
A variety of cis-CA analogues bearing a substituent on the phe-
nyl group at the ortho, meta, and para positions were systemati-
cally designed and synthesized. As a substituent, one of the alkyl,
aromatic, alkoxy, halogeno, nitro, and trifluoromethyl groups were
selected. Furthermore, a few multi-substituted analogues and
polycyclic aromatic analogues including heteroaromatics, in place
of the phenyl group, were also synthesized.
Their syntheses were mainly performed via cis-selective olefin-
ation of the corresponding aldehydes 59–114 with the modified
Horner–Wadsworth–Emmons reaction (Ando, 1997; Ando et al.,
2000), followed by hydrolysis of the ester of cis-olefins 115–170,
as depicted in Scheme 1.
showing a low Hammett
duced the activity.
r value at these positions significantly re-
The commercially unavailable starting aldehydes 63, 68, 74–76,
100, 108 and 109 were prepared as shown in Scheme 2 (Wang
et al., 2009; Li et al., 1998; Zhou and Zhao, 2009; Saitoh et al.,
2009; Tasker et al., 1997).
2.2.4. Effects of disubstitution of the aromatic ring
Disubstituted analogues were subjected to the inhibitory activ-
ity test (Table 1, entries 38–44). Additional para-methylated cis-3
analogue cis-39 and para-methoxylated cis-3 analogue cis-40
exhibited similar activity to cis-3 (entries 38 and 39). However,
the polymethoxylated cis-2 analogues (cis-41 and cis-42) signifi-
cantly diminished the activity (entries 40 and 41). The o,p-dichloro
analogue (cis-43) slightly improved activity, maybe due to higher
hydrophobicity (entry 42).
2.2. Bioassay and discussion
The growth inhibitory activity of the cis-CA analogues against
the root-growth of lettuce (Lactuca sativa cv.) was measured as
described previously (Hiradate et al., 2005). EC50 values, which
indicate the effective concentration required to induce a half-
maximum effect, are shown in the Tables.
If functional moieties were introduced in cis-2 without a loss in
inhibitory activity, a hydrophobic and relatively small substituent
at the meta-position was preferred, regardless of its electronic
properties such as the Hammet
r value.
2.2.1. Effects of alkylation or alkoxylation of the aromatic ring
The ortho-methylated cis-CA analogue cis-3 showed a more pro-
nounced inhibitory activity than cis-CA 2 (Table 1, entry 2). How-
2.2.5. Effects of the ring structure
The fused aromatic ring analogues cis-46-cis-58 were examined
as shown in Table 2. The 1-naphthyl, 9-phenanthryl-, 9-anthranyl-,
and dibenzofuranyl analogues cis-46ꢀcis-49 markedly reduced the
activity (entries 1–4). In contrast, the 2-naphthyl-, 5-benzofuranyl-
,
5-(2,3-dihydro)benzofuranyl, 6-benzofuranyl, and benzothio-
phene-5-yl cis-2 analogues cis-50ꢀcis-54 retained more potent
inhibitory activity than cis-2 (entries 5–9). The 5-benzofuranyl
analogue cis-52 also improved the activity. The potency of the
1-naphthyl analogue cis-46 was markedly lower than that of the
2-naphthyl analogue cis-50. These results indicate that the ‘‘ortho,
meta-disubstituted’’ type cis-CA analogues cis-46ꢀcis-49 were
Scheme 1. Synthesis of the substituted cis-CA analogues 3–58: (a) ethyl 2-[bis(2-
isopropylphenoxy)phosphoryl]acetate, Triton B, THF, ꢀ78 °C, 45–99%, (b) 10% NaOH
aq., EtOH, rt, 53–99%.

134
K. Nishikawa et al. / Phytochemistry 96 (2013) 132–147
Scheme 2. Preparation of commercially unavailable starting aldehydes 63, 68, 74–76, 100, 108, and 109: (a) triethylborane, Pd(dppf)Cl2, CsOAc, THF, reflux, 46%, (b) ethyl 2-
[bis(2-isopropylphenoxy)phosphoryl]acetate, Triton B, THF, ꢀ78 °C, (c) 10% NaOH aq., EtOH, rt, (d) nBuLi, DMF, THF, ꢀ78 °C to 0 °C, 79%, (e) K2CO3, 1-bromopropane, acetone,
reflux, 51%, (f) K2CO3, 1-iodobutane, acetone, reflux, 62%, (g) K2CO3, 2-iodopropane, acetone, reflux, 62%, (h) Li et al. (1998), 23% (4 steps), (i) NBS, AIBN, chlorobenzene, 80 °C,
75%, (j) bromoacetaldehyde diethyl acetal, K2CO3, DMSO, 160 °C, 86%, (k) polyphosphoric acid (PPA), toluene, reflux, 176: 46%, 177: 41%, (l) tBuLi, DMF, Et2O, ꢀ78 °C to 0 °C,
54%.
much less active than the ‘‘meta, para-disubstituted’’ type ana-
logues cis-50ꢀcis-54. The finding that the former type analogues
cis-46ꢀcis-49 had lower potency and the latter type ones cis-
50ꢀcis-54 had higher potency support this hypothesis. The finding
that a meta-substituent did not decrease the activity is consistent
with that of the substituent effect described in the previous
section.
logues having m-iodo, m-methoxy, and m-trifluoromethyl groups
were more potent than cis-CA (2).
This structure–activity relationship study on cis-CA (2) will be
very useful design and synthesize molecular probes for mechanis-
tic investigations in furan and also to obtain strong inhibitors tar-
geting new types of agrochemicals.
The 2-pyridyl analogue cis-55 and 6-methoxy-2-pyridyl ana-
logue cis-56 exhibited a similar level of potency to cis-2, while
the 6-methyl-2-pyridyl analogue cis-57 was much less active than
the corresponding analogue cis-56. The 3-pyridyl analogue cis-58
was less active, which suggests critical electronic interaction be-
tween the nitrogen atom and the biomolecules.
4. Experimental section
4.1. Materials
Optical rotations were obtained on a Horiba SEPA-300. Melting
points were measured on the Yazawa micromelting point BY-1. 1H-
and 13C-NMR spectra were recorded using JNM EX-270 (270 and
67.5 MHz), JEOL JNM AL-400 (400 and 100 MHz) and a JNM ECA-
600 spectrometer (600 and 150 MHz). Chemical shifts were re-
ported in ppm downfield from the peak of Me4Si (TMS) used as
internal standard. Splitting patterns are designed as ‘‘s, d, t, q,
and m,’’ indicating ‘‘singlet, doublet, triplet, quartet, and multi-
plet,’’ respectively. IR spectra were recorded on a Shimadzu FT/
IR-8300 spectrometer using a KBr disk or a NaCl cell. Mass spectra
were obtained on JEOL JMS-700 or JEOL JMS-T100CS. High-resolu-
tion mass spectra were obtained on a JEOL JMS-700 or a JEOL JMS-
3. Conclusion
Substituent effects on the aromatic ring of cis-cinnamic acid
(cis-CA), a potent allelochemical was demonstrated. Although
para- and ortho-substitution were critical for potency as an allelo-
chemical, meta-substituted cis-CA analogues, especially those hav-
ing a hydrophobic group, but not so sterically hindered substituent,
were more likely to be potent. Finally, it was found that cis-CA ana-

K. Nishikawa et al. / Phytochemistry 96 (2013) 132–147
135
Table 1
Table 2
The growth inhibitory activities of the cis-CA analogues 3–45
The growth inhibitory activities of the cis-CA analogues 46–58
Entry
1
(No)
R
EC50
234
(lM)
cis-46
Entry
(No)
R1 (o-)
R2 (m-)
R3 (p-)
R4 (m’-)
EC50 (lM)
1
2
3
4
5
6
7
8
9
cis-2
cis-3
cis-4
cis-5
cis-6
cis-7
cis-8
cis-9
H
Me
H
H
Et
H
H
H
H
Ph
H
H
MeO
H
H
H
H
H
H
F
H
H
Cl
H
H
Br
H
H
I
H
H
NO2
H
H
CF3
H
H
H
Me
H
H
Et
H
H
H
H
Ph
H
H
MeO
H
EtO
nPrO
nBuO
iPrO
H
F
H
H
Cl
H
H
Br
H
H
I
H
H
NO2
H
H
CF3
H
H
H
H
H
H
Me
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
MeO
H
H
I
2.2
1.4
4.1
23
30
10
2
cis-47
169
H
Et
i-Pr
t-Bu
H
H
Ph
H
H
MeO
H
H
H
H
H
H
F
H
H
Cl
H
H
82
218
>500
>500
164
245
64
cis-10
cis-11
cis-12
cis-13
cis-14
cis-15
cis-16
cis-17
cis-18
cis-19
cis-20
cis-21
cis-22
cis-23
cis-24
cis-25
cis-26
cis-27
cis-28
cis-29
cis-30
cis-31
cis-32
cis-33
cis-34
cis-35
cis-36
cis-37
cis-38
cis-39
cis-40
cis-41
cis-42
cis-43
cis-44
cis-45
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
3
cis-48
>500
1.1
2.9
9.3
>500
ꢁ270
ꢁ260
29
3.2
6.2
6.9
3.0
2.2
4.7
2.0
4.1
2.9
1.8
4
cis-49
224
Br
H
H
I
H
H
NO2
H
5
6
cis-50
cis-51
7.7
2.7
17
>500
27
>500
241
0.6
77
5.3
2.0
210
123
1.6
H
H
CF3
Me
MeO
H
MeO
Cl
H
Me
Me
H
MeO
Cl
H
7
8
cis-52
cis-53
cis-54
cis-55
cis-56
1.1
11.2
12
MeO
MeO
H
I
8.3
7.0
H
CF3
H
CF3
T100CS. Column chromatography (CC) was performed on silica gel
(Kanto Chemical Co.). Thin-layer chromatography (TLC) was per-
formed on pre-coated plates (0.25 mm, silica gel Merck 60 F254).
Reaction mixtures were stirred magnetically. Stereochemistry
was determined by NOE experiments, unless otherwise noted.
9
10
11
2.7
4.2. Synthesis
4.2.1. (Z)-3-(o-Tolyl)acrylic acid (cis-3) (Ando, 1997; Ando et al.,
2000)
8.7
Triton B (40% in MeOH, 7.30 mL, 17.5 mmol) was added dropwise
to a solution of ethyl 2-[bis(2-isopropylphenoxy) phosphoryl]
acetate (5.30 g, 13.1 mmol) in THF (150 mL) at ꢀ78 °C under Ar.
After 15 min of stirring, a solution of 2-methylbenzaldehyde (59)
(1.50 g, 12.5 mmol) in THF (50 mL) was added dropwise to the solu-
tion. After 10 h of stirring, the mixture was quenched with satd. aq.
(continued on next page)

136
K. Nishikawa et al. / Phytochemistry 96 (2013) 132–147
–CH3), 2.36 (s, 3H, Ar-CH3), 4.18 (q, J = 7.1 Hz, 2H, –CH2–), 5.90
Table 2 (continued)
(d, J = 12.7 Hz, 1H, @CH–CO2–), 6.91 (d, J = 12.7 Hz, 1H, Ar–CH@),
7.18, 7.52 (d, J = 7.3 Hz, each 2H, Ar–H). The spectroscopic data
were in agreement with those in the literature (Walter and
Oestreich, 2008; Miura et al., 2009).
Entry
12
(No)
R
EC50
155
(lM)
cis-57
Hydrolysis of cis-117 was performed using the procedure de-
scribed above to afford cis-5 (91%) as colorless needles: mp 77–
79 °C (Toluene); 1H-NMR (CDCl3, 400 MHz) d: 2.37 (s, 3H, –CH3),
5.92 (d, J = 12.8 Hz, 1H, @CH–CO2–), 7.02 (d, J = 12.8 Hz, 1H, Ar–
CH@), 7.17, 7.55 (d, J = 8.4 Hz, each 2H, Ar–H); 13C-NMR (CDCl3,
100 MHz) d: 21.4 (q, –CH3), 117.7 (d, @CH–CO2–), 128.8 (d, Ar),
130.2 (d, Ar), 131.5 (s, Ar), 139.8 (s, Ar), 146.0 (d, Ar–CH@), 171.9
(s, C@O); IR (KBr) 1693 cmꢀ1; ESI-MS m/z 161 (M+ꢀH); Anal. calcd
for C10H10O2: C, 74.06; H, 6.21. found: C, 74.06; H, 6.21.
13
cis-58
88
NH4Cl (30 mL) and extracted with EtOAc (3 x 30 mL). The organic
layer was washed successively with H2O, satd. aq. (20 mL) NaHCO3
(20 mL) and brine (20 mL), then dried (MgSO4), filtered and concen-
trated in vacuo. The crude product was purified by silica gel flash CC
(EtOAc/hexane, 10:90) to afford (Z)-ethyl 3-(o-tolyl)acrylate
(cis-115) (2.03 g, 10.7 mmol, 85%, Z only, determined by 1H-NMR
spectrum) as a colorless oil: 1H-NMR (CDCl3, 270 MHz) d: 1.15 (t,
J = 7.0 Hz, 3H, –CH3), 2.28 (s, 3H, Ar–CH3), 4.09 (q, J = 7.0 Hz, 2H,
–CH2–), 6.02 (d, J = 12.2 Hz, 1H, @CH–CO2–), 7.12 (d, J = 12.2 Hz,
1H, Ar–CH@), 7.14–7.22 (m, 3H, Ar–H), 7.31 (d, J = 7.3 Hz, 1H, Ar–H).
0.52 M NaOH (10 mL) was added to a solution of cis-115 (1.50 g,
9.26 mmol) in EtOH (6.0 mL) at room temperature. The mixture
was stirred for 4 h, diluted with H2O (10 mL), and the acidity of
the solution was adjusted with 1 M HCl to pH 1.0. The mixture
was extracted with EtOAc (3 x 20 mL), washed with brine
(20 mL), dried (MgSO4), and filtered. After the solvent was removed
in vacuo, the crude product was purified by recrystallization to give
cis-3 (1.35 g, 8.30 mmol, 90%) as colorless needles.: mp 96–97 °C
(Toluene); 1H-NMR (CDCl3, 400 MHz) d: 2.28 (s, 3H, –CH3), 6.01
(d, J = 12.2 Hz, 1H, @CH–CO2–), 7.12–7.25 (m, 3H, Ar–H), 7.21 (d,
J = 12.2 Hz, 1H, Ar–CH@), 7.32 (d, J = 7.6 Hz, 1H, Ar–H); 13C-NMR
(CDCl3, 100 MHz) d: 19.9 (q, –CH3), 120.0 (d, @CH–CO2–), 125.4
(d, Ar), 128.8 (d, Ar), 128.9 (d, Ar), 129.7 (d, Ar), 134.4 (s, Ar),
135.9 (s, Ar), 145.5 (d, Ar–CH@), 170.9 (s, C@O); IR (KBr)
1699 cmꢀ1; ESI-MS m/z 161 (M+ꢀH); Anal. calcd for C10H10O2: C,
74.06; H, 6.21. Found: C, 74.02; H, 6.21.
4.2.4. (Z)-3-(2-Ethylphenyl)acrylic acid (cis-6)
Z-selective olefination of 2-ethylbenzaldehyde (62) was per-
formed using the procedure described above to provide (Z)-ethyl
3-(2-ethylphenyl)acrylate (cis-118) (72%, Z:E = 98:2, determined
by 1H-NMR spectrum) (silica gel CC, EtOAc/hexane, 3:97) as a
colorless oil: 1H-NMR (CDCl3, 270 MHz) d: 1.12 (t, J = 7.0 Hz, 3H,
–CH3), 1.19 (t, J = 7.3 Hz, 3H, Ar–CH2–CH3), 2.63 (q, J = 7.3 Hz, 2H,
Ar–CH2–), 4.07 (q, J = 7.0 Hz, 2H, –CO2–CH2–), 6.03 (d, J = 11.9 Hz,
1H, @CH–CO2–), 7.15–7.30 (m, 5H, Ar–CH@ and Ar–H).
Hydrolysis of cis-118 was performed using the procedure de-
scribed above to afford cis-6 (99%) as colorless needles: mp 68–
69 °C (Hexane); 1H-NMR (CDCl3, 400 MHz) d: 1.18 (t, J = 8.0 Hz,
3H, –CH3), 2.62 (q, J = 8.0 Hz, 2H, –CH2–), 6.03 (d, J = 12.0 Hz, 1H,
@CH–CO2–), 7.13–7.22 (m, 2H, Ar–H and Ar–CH@), 7.28–7.31 (m,
3H, Ar–H); 13C-NMR (CDCl3, 100 MHz) d: 14.8 (q, –CH3), 26.6 (t,
–CH2–), 120.2 (d, @CH–CO2–), 125.3 (d, Ar), 127.9 (d, Ar), 128.9
(d, Ar), 129.2 (d, Ar), 133.8 (s, Ar), 141.8 (s, Ar), 145.5 (d, Ar–CH@),
171.5 (s, C@O); IR (KBr) 1699 cmꢀ1; ESI-MS m/z 175 (M+ꢀH); Anal.
calcd for C11H12O2: C, 74.98; H, 6.86. found: C, 75.01; H, 6.92.
4.2.5. (Z)-3-(3-Ethylphenyl)acrylic acid (cis-7) (Wang et al., 2009)
Triethylborane (1.00 M in THF, 2.00 mL, 2.00 mmol) was added
to
a
suspension of 3-bromobenzaldehyde (84) (0.370 g,
mol), and CsOAc
2.00 mmol), Pd(dppf)Cl2 (14.6 mg, 20.0
l
4.2.2. (Z)-3-(m-Tolyl)acrylic acid (cis-4)
(0.384 g, 2.00 mmol) in THF (3.0 mL) under Ar., and the mixture
was heated until reflux began this being maintained for 6 h. After
cooling to room temperature, the mixture was diluted with Et2O,
washed with saturated aqueous NaHCO3 and brine, dried (Na2SO4),
filtered and concentrated in vacuo. The residue was purified by sil-
ica gel flash CC to afford 3-ethylbenzaldehyde (63) (0.123 g,
0.920 mmol, 46%) as a colorless oil; 1H-NMR (CDCl3, 400 MHz) d:
1.28 (t, J = 7.2 Hz, 3H, –CH3), 2.74 (q, J = 7.2 Hz, 2H, –CH2–), 7.42–
7.48, 7.69–7.72 (m, each 2H, Ar–H), 10.0 (s, 1H, –CHO); spectral
data were in agreement with those in the literature (Wang et al.,
2009).
The Z-selective olefination of 63 was performed using the pro-
cedure described above to provide (Z)-ethyl 3-(2-ethylphe-
nyl)acrylate (cis-119) (72%, Z:E = 98:2, determined by 1H-NMR
spectrum) (silica gel CC, EtOAc/hexane, 3:97) as a colorless oil:
1H-NMR (CDCl3, 400 MHz) d: 1.24 (t, J = 7.2 Hz, 6H, –CH3), 2.65
(q, J = 7.2 Hz, 2H, Ar–CH2–), 4.17 (q, J = 7.2 Hz, 2H, –CO2–CH2–),
5.93 (d, J = 12.6 Hz, 1H, @CH–CO2–), 6.92 (d, J = 12.6 Hz, 1H, Ar–
CH@), 7.16 (d, J = 7.6 Hz, 1H, Ar–H), 7.26 (t, J = 7.6 Hz, 1H, Ar–H),
7.39–7.42 (m, 2H, Ar–H).
The Z-selective olefination of 3-methylbenzaldehyde (60) was
performed using the procedure described above to provide (Z)-
ethyl 3-(m-tolyl)acrylate (cis-116) (94%, Z:E = 98:2, determined
by 1H-NMR spectrum) (silica gel CC, EtOAc/hexane, 3:97) as a
colorless oil: 1H-NMR (CDCl3, 270 MHz) d: 1.24 (t, J = 7.0 Hz, 3H,
–CH3), 2.36 (s, 3H, Ar–CH3), 4.18 (q, J = 7.0 Hz, 2H, –CH2–), 5.92
(d, J = 12.7 Hz, 1H, @CH–CO2–), 6.91 (d, J = 12.7 Hz, 1H, Ar–CH@),
7.14 (d, J = 7.3 Hz, 1H, Ar–H), 7.24 (t, J = 7.3 Hz, 1H, Ar–H), 7.37–
7.40 (m, 2H, Ar–H).
Hydrolysis of cis-116 was performed using the procedure de-
scribed above to afford cis-4 (91%) as colorless needles: mp 36–
38 °C (Toluene); 1H-NMR (CDCl3, 400 MHz) d: 2.36 (s, 3H, –CH3),
5.95 (d, J = 12.8 Hz, 1H, @CH–CO2–), 7.04 (d, J = 12.8 Hz, 1H, Ar–
CH@), 7.16 (d, J = 7.6 Hz, 1H, Ar–H), 7.25 (t, J = 7.6 Hz, 1H, Ar–H),
7.38 (s, 1H, Ar–H), 7.42 (d, J = 7.6 Hz, 1H, Ar–H); 13C-NMR (CDCl3,
100 MHz) d: 21.3 (q, –CH3), 118.5 (d, @CH–CO2–), 127.0 (d, Ar),
130.1 (d, Ar), 134.3 (s, Ar), 137.6 (s, Ar), 146.0 (d, Ar–CH@), 171.7
(s, C@O); IR (KBr) 1697 cmꢀ1; ESI-MS m/z 161 (M+ꢀH); Anal. calcd
for C10H10O2: C, 74.06; H, 6.21. found: C, 74.20; H, 6.10.
Hydrolysis of cis-119 was performed using the procedure de-
scribed above to afford cis-7 (90%) as colorless oil; 1H-NMR (CDCl3,
400 MHz) d: 1.23 (t, J = 7.5 Hz 3H, –CH3), 2.65 (q, J = 7.5 Hz, 2H,
–CH2–), 5.95 (d, J = 12.8 Hz, @CH–CO2–), 7.04 (d, J = 12.8 Hz,
1H, Ar–CH@), 7.18 (d, J = 7.6 Hz, 1H, Ar–H), 7.25 (t, J = 7.6 Hz, 1H,
Ar–H), 7.42 (s, 1H, Ar–H), 7.43 (d, J = 7.6 Hz, 1H, Ar–H); 13C-NMR
(CDCl3, 100 MHz) d: 15.4 (q, –CH3), 28.7 (t, –CH2–), 118.4
4.2.3. (Z)-3-(p-Tolyl)acrylic acid (cis-5)
Z-selective olefination of 4-methylbenzaldehyde (61) was per-
formed using the procedure described above to provide (Z)-ethyl
3-(p-tolyl)acrylate (cis-117) (99%, Z:E = 98:2 determined by
1H-NMR spectrum) (silica gel CC, EtOAc/hexane, 3:97) as a color-
less oil: 1H-NMR (CDCl3, 270 MHz) d: 1.26 (t, J = 7.1 Hz, 3H,

K. Nishikawa et al. / Phytochemistry 96 (2013) 132–147
137
(d, @CH–CO2–), 127.3 (d, Ar), 128.0 (d, Ar), 129.0 (d, Ar), 129.5 (d,
Ar), 134.4 (s, Ar), 143.9 (s, Ar), 145.9 (d, Ar–CH@), 171.3
(s, C@O); IR (KBr) 1697 cmꢀ1; ESI-MS m/z 175 (M+ꢀH); HR EI-MS
m/z 176.0837 (M+, calcd for C11H12O2 176.0837).
4.2.9. (Z)-3-[(1,1’-Biphenyl)-2-yl]acrylic acid (cis-11)
Z-selective olefination of [1,10-biphenyl]-2-carbaldehyde (67)
was performed using the procedure described above to provide
(Z)-ethyl
3-[(1,10-biphenyl)-2-yl]acrylate
(cis-123)
(92%,
Z:E = 99:1, determined by 1H-NMR spectrum) (silica gel CC,
EtOAc/hexane, 1:99) as a colorless oil: 1H-NMR (CDCl3, 400 MHz)
d: 1.20 (t, J = 7.2 Hz, 3H, .CH3), 4.15 (q, J = 7.2 Hz, 2H, –CH2–),
5.92 (d, J = 12.0 Hz, 1H, @CH–CO2–), 6.85 (d, J = 12.0 Hz, 1H, Ar–
CH@), 7.32–7.40 (m, 8H, Ar–H), 7.55 (d, J = 7.6 Hz, 1H, Ar–H).
Hydrolysis of cis-123 was performed using the procedure de-
scribed above to afford cis-11 (96%) as colorless needles: mp 91–
93 °C (Toluene); 1H-NMR (CDCl3, 400 MHz) d: 5.91 (d, J = 12.4 Hz,
1H, @CH–CO2–), 6.94 (d, J = 12.4 Hz, 1H, Ar–CH@), 7.30–7.42 (m,
8H), 7.59 (d, J = 7.6 Hz, 1H, Ar–H); 13C-NMR (CDCl3, 100 MHz) d:
119.2 (d, @CH–CO2–), 126.8 (d, Ar), 127.5 (d, Ar), 128.1 (d, Ar),
129.1 (d, Ar), 129.4 (d, Ar), 129.8 (d, Ar), 130.2 (d, Ar), 133.3 (s,
Ar), 140.4 (s, Ar), 141.4 (s, Ar), 146.8 (d, Ar–CH@), 171.8 (s, C@O);
IR (KBr) 1699 cmꢀ1; ESI-MS m/z 223 (M+ꢀH); Anal. calcd for
C15H12O2: C, 80.34; H, 5.39. found: C, 80.42; H, 5.26.
4.2.6. (Z)-3-(4-Ethylphenyl)acrylic acid (cis-8)
Z-selective olefination of 4-ethylbenzaldehyde (64) was per-
formed using the procedure described above to provide (Z)-ethyl
3-(4-ethylphenyl)acrylate (cis-120) (83%, Z:E = 98:2, determined
by 1H-NMR spectrum) (silica gel CC, EtOAc/hexane, 3:97) as a col-
orless oil: 1H-NMR (CDCl3, 270 MHz) d: 1.22–1.28 (m, 6H, –CH3),
2.65 (q, J = 7.6 Hz, 2H, Ar–CH2–), 4.18 (q, J = 7.6 Hz, 2H, –CO2–
CH2–), 5.89 (d, J = 12.8 Hz, 1H, @CH–CO2–), 6.90 (d, J = 12.8 Hz,
1H, Ar–CH@), 7.18, 7.55 (d, J = 8.4 Hz, each 2H, Ar–H).
Hydrolysis of cis-120 was performed using the procedure de-
scribed above to afford cis-8 (99%) as colorless needles: mp 61–
63 °C (Et2O/hexane); 1H-NMR (CDCl3, 400 MHz) d: 1.24 (t,
J = 7.6 Hz, 3H, –CH3), 2.67 (q, J = 7.6 Hz, 2H, –CH2–), 5.92 (d,
J = 12.4 Hz, 1H, @CH–CO2–), 7.02 (d, J = 12.4 Hz, 1H, Ar–CH@),
7.20, 7.58 (d, J = 8.4 Hz, each 2H, Ar–H); 13C-NMR (CDCl3,
100 MHz) d: 15.2 (q, –CH3), 28.7 (t, –CH2–), 117.6 (d, @CH–CO2–),
127.6 (d, Ar), 130.4 (d, Ar), 131.7 (s, Ar), 146.0 (d, Ar–CH@),
146.0 (s, Ar), 171.9 (s, C@O); IR (KBr) 1695 cmꢀ1; ESI-MS m/z 175
(M+ꢀH); Anal. calcd for C11H12O2: C, 74.98; H, 6.86. found: C,
74.96; H, 6.89.
4.2.10. (Z)-3-[(1,10-Biphenyl)-3-yl]acrylic acid (cis-12)
n-BuLi (2.53 mL, 1.54 M in hexane, 3.90 mmol) was added to a
solution of 3-bromo-1,1’-biphenyl (171) (0.50 mL, 3.00 mmol) in
THF (8.0 mL) at ꢀ78 °C Ar., and the mixture was stirred for
20 min. DMF (0.350 mL, 4.50 mmol) was then added to the reac-
tion mixture, and the temperature was gradually warmed to 0 °C.
The reaction was quenched with H2O and extracted with EtOAc.
The organic layers were washed with brine, dried (MgSO4), filtered
and concentrated in vacuo. The crude product was purified by silica
gel CC (EtOAc/hexane, 10:90) to afford (1,10-biphenyl)-3-carbalde-
hyde (68) (0.443 g, 2.43 mmol, 79%) as a colorless oil: 1H-NMR
(CDCl3, 400 MHz) d: 7.39 (t, J = 7.2 Hz, 1H, Ar–H), 7.47 (t,
J = 7.2 Hz, 2H, Ar–H), 7.58–7.63 (m, 3H, Ar–H), 7.86 (dd, J = 2.0,
7.6 Hz, 2H, Ar–H), 8.10 (s, 1H, Ar–H), 10.08 (s, 1H, –CHO).
Z-selective olefination of 68 was performed using the procedure
described above to provide (Z)-ethyl 3-[(1,10-biphenyl)-3-yl]acry-
late (cis-124) (92%, Z:E = 95:5, determined by 1H-NMR spectrum)
(silica gel CC, EtOAc/hexane, 1:99) as a colorless oil: 1H-NMR
(CDCl3, 400 MHz) d: 1.23 (t, J = 7.2 Hz, 3H, –CH3), 4.12 (q,
J = 7.2 Hz, 2H, –CH2–), 5.88 (d, J = 12.8 Hz, 1H, @CH–CO2–), 7.15
(d, J = 12.8 Hz, 1H, Ar–CH@), 7.34 (t, J = 7.6 Hz, 1H, Ar–H), 7.43
(m, 3H, Ar–H), 7.58–7.62 (m, 4H, Ar–H), 7.84 (s, 1H, Ar–H).
Hydrolysis of cis-124 was performed using the procedure de-
scribed above to afford cis-12 (96%) as colorless prisms: mp 105–
106 °C (Toluene); 1H-NMR (CDCl3, 400 MHz) d: 6.03 (d,
J = 12.8 Hz, 1H, @CH–CO2–), 7.14 (d, J = 12.8 Hz, 1H, Ar–CH@),
7.35 (t, J = 7.6 Hz, 1H, Ar–H), 7.43 (t, J = 7.6 Hz, 3H, Ar–H), 7.58–
7.62 (m, 4H, Ar–H), 7.84 (s, 1H, Ar–H); 13C-NMR (CDCl3,
100 MHz) d: 119.0 (d, @CH–CO2–), 127.2 (d, Ar), 127.4 (d, Ar),
128.1 (d, Ar), 128.5 (d, Ar), 128.7 (d, Ar), 128.8 (d, Ar), 128.9 (d,
Ar), 134.8 (s, Ar), 140.7 (s, Ar), 141.1 (s, Ar), 145.7 (d, Ar–CH@),
171.1 (s, C@O); IR (KBr) 1721 cmꢀ1; ESI-MS m/z 223 (M+ꢀH); Anal.
calcd for C15H12O2: C, 80.34; H, 5.39. found: C, 80.08; H, 5.39.
4.2.7. (Z)-3-(4-Isopropylphenyl)acrylic acid (cis-9)
Z-selective olefination of 4-isopropylbenzaldehyde (65) was
performed using the procedure described above to provide (Z)-
ethyl 3-(4-isopropylphenyl)acrylate (cis-121) (85%, Z only, deter-
mined by 1H-NMR spectrum) (silica gel CC, EtOAc/hexane, 3:97)
as a colorless oil: 1H-NMR (CDCl3, 270 MHz) d: 1.24 (d, J = 6.8 Hz,
6H, –CH–(CH3)2), 1.26 (t, J = 7.0 Hz, 3H, –CH3), 2.91 (heptet,
J = 6.8 Hz, 1H, –CH–(CH3)2), 4.19 (q, J = 7.0 Hz, 2H, –CH2–), 5.89
(d, J = 12.4 Hz, 1H, @CH–CO2–), 6.90 (d, J = 12.4 Hz, 1H, Ar–CH@),
7.21, 7.57 (d, J = 8.1 Hz, each 2H, Ar–H).
Hydrolysis of cis-121 was performed using the procedure de-
scribed above to afford cis-9 (99%) as colorless needles: mp 42–
43 °C (Toluene); 1H-NMR (CDCl3, 400 MHz) d: 1.25 (d, J = 7.2 Hz,
6H, –CH3), 2.92 (heptet, J = 7.2 Hz, 1H, –CH–(CH3)2), 5.92 (d,
J = 12.8 Hz, 1H, @CH–CO2–), 7.02 (d, J = 12.8 Hz, 1H, Ar–CH@),
7.23, 7.60 (d, J = 8.4 Hz, each 2H, Ar–H); 13C-NMR (CDCl3,
100 MHz) d: 23.7 (q, –CH3), 34.0 (d, –CH–(CH3)2), 117.6 (d, @CH–
CO2–), 130.4 (d, Ar), 131.8 (s, Ar), 146.0 (d, Ar–CH@), 150.6 (s,
Ar), 172.0 (s, C@O); IR (KBr) 1695 cmꢀ1; ESI-MS m/z 189 (M+ꢀH);
Anal. calcd for C12H14O2: C, 75.76; H, 7.42. found: C, 75.81; H, 7.46.
4.2.8. (Z)-3-[4-(tert-Butyl)phenyl]acrylic acid (cis-10)
Z-selective olefination of 4-(tert-butyl)benzaldehyde (66) was
performed using the procedure described above to provide (Z)-
ethyl 3-[4-(tert-butyl)phenyl]acrylate (cis-122) (94%, Z:E = 98:2,
determined by 1H-NMR spectrum) (silica gel CC, EtOAc/hexane,
3:97) as a colorless oil: 1H-NMR (CDCl3, 270 MHz) d: 1.26 (t,
J = 7.0 Hz, 3H, –CH3), 1.31 (s, 9H, –C–(CH3)3), 4.18 (q, J = 7.0 Hz,
2H, –CH2–), 5.89 (d, J = 12.4 Hz, 1H, @CH–CO2–), 6.90 (d,
J = 12.4 Hz, 1H, Ar–CH@), 7.37, 7.58 (d, J = 7.8 Hz, each 2H, Ar–H).
Hydrolysis of cis-122 was performed using the procedure de-
scribed above to afford cis-10 (90%) as colorless needles: mp 89–
90 °C (Toluene); 1H-NMR (CDCl3, 400 MHz) d: 1.32 (s, 9H, –CH3),
5.91 (d, J = 12.8 Hz, 1H, @CH–CO2–), 7.02 (d, J = 12.8 Hz, 1H, Ar–
CH@), 7.38, 7.61 (d, J = 8.4 Hz, each 2H, Ar–H); 13C-NMR (CDCl3,
100 MHz) d: 31.2 (q, CH3), 34.8 (s, –C–(CH3)3), 117.6 (d, @CH–
CO2–), 125.1 (d, Ar), 130.2 (d, Ar), 131.4 (d, Ar), 145.9 (d, Ar–
CH@), 171.7 (s, C@O); IR (KBr) 1693 cmꢀ1; ESI-MS m/z 203
(M+ꢀH); Anal. calcd for C13H16O2: C, 76.44; H, 7.90. found: C,
76.56; H, 7.91.
4.2.11. (Z)-3-[(1,10-Biphenyl)-4-yl]acrylic acid (cis-13)
Z-selective olefination of (1,10-biphenyl)-4-carbaldehyde (69)
was performed using the procedure described above to provide
(Z)-ethyl
3-[(1,10-biphenyl)-4-yl]acrylate
(cis-125)
(86%,
Z:E = 95:5, determined by 1H-NMR spectrum) (silica gel CC,
EtOAc/hexane, 5:95) as a colorless oil: 1H-NMR (CDCl3, 270 MHz)
d: 1.28 (t, J = 7.3 Hz, 3H, –CH3), 4.20 (q, J = 7.3 Hz, 2H, –CH2–),
5.97 (d, J = 12.7 Hz, 1H, @CH–CO2–), 6.97 (d, J = 12.7 Hz, 1H,
Ar–CH@), 7.26 (t, J = 7.6 Hz, 1H, Ar–H), 7.33–7.48 (m, 2H, Ar–H),
7.57–7.62 (m, 4H, Ar–H), 7.70 (d, J = 6.2 Hz, 2H, Ar–H).
Hydrolysis of cis-125 was performed using the procedure de-
scribed above to afford cis-13 (96%) as colorless needles: mp

138
K. Nishikawa et al. / Phytochemistry 96 (2013) 132–147
145–146 °C (Toluene); 1H-NMR (CDCl3, 400 MHz) d: 6.00 (d,
J = 13.2 Hz, 1H, @CH–CO2–), 7.09 (d, J = 13.2 Hz, 1H, Ar–CH@),
7.36 (t, J = 7.6 Hz, 1H, Ar–H), 7.45 (t, J = 7.6 Hz, 2H, Ar–H), 7.59–
7.62 (m, 4H, Ar–H), 7.73 (d, J = 8.8 Hz, 2H, Ar–H); 13C-NMR (CDCl3,
100 MHz) d: 118.4 (d, @CH–CO2–), 126.8 (d, Ar), 127.1 (d, Ar), 127.7
(d, Ar), 128.8 (d, Ar), 130.8 (d, Ar), 133.2 (s, Ar), 140.3 (s, Ar), 142.2
(s, Ar), 145.6 (d, Ar–CH@), 171.7 (s, C@O); IR (KBr) 1697 cmꢀ1; ESI-
MS m/z 223 (M+ꢀH); Anal. calcd for C15H12O2: C, 80.34; H, 5.39.
found: C, 80.34; H, 5.39.
scopic data were in agreement with those in the literature (Walter
and Oestreich, 2008; Miura et al., 2009).
Hydrolysis of cis-128 was performed using the procedure
described above to afford cis-16 (85%) as colorless needles: mp
77–79 °C (Toluene); 1H-NMR (CDCl3, 400 MHz) d: 3.84 (s, 3H,
–OCH3), 5.85 (d, J = 12.8 Hz, 1H, @CH–CO2–), 6.89 (d, J = 8.8 Hz,
2H, Ar–H), 6.97 (d, J = 12.8 Hz, 1H, Ar–CH@), 7.72 (d, J = 8.8 Hz,
2H, Ar–H); 13C-NMR (CDCl3, 100 MHz) d: 55.2 (q, –OCH3), 113.5
(d, Ar), 115.9 (d, @CH–CO2–), 126.9 (s, Ar), 132.6 (d, Ar), 145.9 (d,
Ar–CH@), 160.6 (s, Ar), 172.1 (s, C = O); IR (KBr) 1693 cmꢀ1; ESI-
MS m/z 177 (M+ꢀH); Anal. calcd for C10H10O3: C, 67.41; H, 5.66.
found: C, 67.41; H, 5.67.
4.2.12. (Z)-3-(2-Methoxyphenyl)acrylic acid (cis-14)
Z-selective olefination of 2-methoxybenzaldehyde (70) was
performed using the procedure described above to provide (Z)-
ethyl 3-(2-methoxyphenyl)acrylate (cis-126) (99%, Z only, deter-
mined by 1H-NMR spectrum) (silica gel CC, EtOAc/hexane, 10:90)
as a colorless oil: 1H-NMR (CDCl3, 270 MHz) d: 1.20 (t, J = 7.0 Hz,
3H, –CH3), 3.83 (s, 3H, –OCH3), 4.13 (q, J = 7.0 Hz, 2H, –CH2–),
5.97 (d, J = 12.6 Hz, 1H, @CH–CO2–), 6.87 (d, J = 7.6 Hz, 1H, Ar–H),
6.92 (t, J = 7.6 Hz, 1H, Ar–H), 7.16 (d, J = 12.6 Hz, 1H, Ar–CH@),
7.26–7.33 (m, 1H, Ar–H), 7.54 (d, J = 7.6 Hz, 1H, Ar–H); The spectro-
scopic data were in agreement with those in the literature (Byrne
and Gilheany, 2012).
Hydrolysis of cis-126 was performed using the procedure de-
scribed above to afford cis-14 (85%) as colorless needles: mp 90–
93 °C (toluene); 1H-NMR (CDCl3, 400 MHz) d: 3.75 (s, 3H, –OCH3),
5.93 (d, J = 12.6 Hz, 1H, @CH–CO2–), 6.81 (d, J = 8.8 Hz, 1H, Ar–H),
6.87 (m, 1H, Ar–H), 7.22 (d, J = 12.6 Hz, 1H, Ar–CH@), 7.27 (m,
1H, Ar–H), 7.52 (d, J = 7.6 Hz, 1H, Ar–H); 13C-NMR (CDCl3,
100 MHz) d: 55.1 (q, –OCH3), 110.2 (d, Ar), 118.8 (d, Ar), 119.8
(d, @CH–CO2–), 123.4 (s, Ar), 130.6 (d, Ar), 141.4 (d, Ar–CH@),
157.0 (s, Ar), 172.1 (s, C@O); IR (KBr) 1697 cmꢀ1; ESI-MS m/z 177
(M+ꢀH); Anal. calcd for C10H10O3: C, 67.41; H, 5.66. found: C,
67.54; H, 5.62.
4.2.15. (Z)-3-(3-Ethoxyphenyl)acrylic acid (cis-17)
Z-selective olefination of 3-ethoxybenzaldehyde (73) was per-
formed using the procedure described above to provide (Z)-ethyl
3-(3-ethoxyphenyl)acrylate (cis-129) (78%, Z:E = 96:4, determined
by 1H-NMR spectrum) (silica gel CC, EtOAc/hexane, 15:85) as a col-
orless oil: 1H-NMR (CDCl3, 400 MHz) d: 1.25 (t, J = 7.2 Hz, 3H,
–CH3), 1.41 (t, J = 6.8 Hz, 3H, –OCH2–CH3), 4.05 (q, J = 6.8 Hz, 2H,
Ar–OCH2–), 4.18 (q, J = 7.2 Hz, 2H, –CO2–CH2–), 5.94 (d,
J = 13.2 Hz, 1H, @CH–CO2–), 6.89–6.91 (m, 2H, Ar–CH@ and Ar–
H), 7.11 (d, J = 7.2 Hz, 1H, Ar–H), 7.21–7.26 (m, 2H, Ar–H).
Hydrolysis of cis-129 was performed using the procedure de-
scribed above to afford cis-17 (93%) as colorless needles: mp 38–
40 °C (Toluene/hexane, 30:70); 1H-NMR (CDCl3, 400 MHz) d: 1.34
(t, J = 7.2 Hz, 3H, –CH3), 4.05 (q, J = 7.2 Hz, 2H, –CH2–), 5.95 (d,
J = 12.6 Hz, 1H, @CH–CO2–), 6.89 (dd, J = 2.8, 7.8 Hz, 1H, Ar–H),
7.02 (d, J = 12.6 Hz, 1H, Ar–CH@), 7.12 (d, J = 7.8 Hz, 1H, Ar–H),
7.23–7.27 (m, 2H, Ar–H); 13C-NMR (CDCl3, 100 MHz) d: 14.8 (q,
–CH3), 63.4 (t, –OCH2–), 115.4 (d, Ar), 116.2 (d, Ar), 118.7 (d,
@CH–CO2–), 122.5 (d, Ar), 129.1 (d, Ar), 135.6 (s, Ar), 145.7 (d,
Ar–CH@), 158.5 (s, Ar), 171.1 (s, C@O); IR (KBr) 1685 cmꢀ1; ESI-
MS m/z 191 (M+ꢀH); HRMS (EI) calcd for C11H12O3 192.0786, found
192.0784.
4.2.13. (Z)-3-(3-Methoxyphenyl)acrylic acid (cis-15)
Z-selective olefination of 3-methoxybenzaldehyde (71) was
performed using the procedure described above to provide (Z)-
ethyl 3-(3-methoxyphenyl)acrylate (cis-127) (88%, Z:E = 98:2,
determined by 1H-NMR spectrum) (silica gel CC, EtOAc/hexane,
10:90) as a colorless oil: 1H-NMR (CDCl3, 270 MHz) d: 1.24 (t,
J = 7.0 Hz, 3H, –CH3), 3.80 (s, 3H, –OCH3), 4.17 (q, J = 7.0 Hz, 2H,
–CH2–), 5.94 (d, J = 12.7 Hz, 1H, @CH–CO2–), 6.88 (d, J = 7.8 Hz, 1H,
Ar–H), 6.89 (d, J = 12.7 Hz, 1H, Ar–CH@), 7.11 (d, J = 7.8 Hz, 1H,
Ar–H), 7.22–7.28 (m, 2H, Ar–H). The spectroscopic data were in
agreement with those in the literature (Mueller and Jennigs, 2007).
Hydrolysis of cis-127 was performed using the procedure de-
scribed above to afford cis-15 (90%) as colorless needles: mp 36–
38 °C (toluene); 1H-NMR (CDCl3, 400 MHz) d: 3.81 (s, 3H, –OCH3),
5.97 (d, J = 12.8 Hz, 1H, @CH–CO2–), 6.91 (d, J = 7.4 Hz, 1H, Ar–H),
7.04 (d, J = 12.8 Hz, 1H, Ar–CH@), 7.14 (d, J = 7.4 Hz, 1H, Ar–H),
7.26–7.30 (m, 2H, Ar–H); 13C-NMR (CDCl3, 100 MHz) d: 54.8 (q,
–OCH3), 114.4 (d, Ar), 115.1 (d, Ar), 122.2 (d, @CH–CO2–), 128.6
(d, Ar), 135.1 (s, Ar), 145.1 (d, Ar–CH@), 158.7 (s, Ar), 171.7 (s,
C@O); IR (KBr) 1699 cmꢀ1; ESI-MS m/z 177 (M+ꢀH); Anal. calcd
for C10H10O3: C, 67.41; H, 5.66. found: C, 67.49; H, 5.66.
4.2.16. (Z)-3-(3-Propoxyphenyl)acrylic acid (cis-18)
3-Hydroxybenzaldehyde (172) (1.47 g, 12.0 mmol) was added
to a solution of K2CO3 (2.49 g, 18.0 mmol) in acetone (30 mL) at
0 °C under Ar, then the mixture was stirred for 15 min. After 1-bro-
mopropane (2.18 mL, 24.0 mmol) was added to the solution, the
resulting mixture was heated until reflux began this being main-
tained for 6 h. The reaction was quenched with saturated aqueous
NH4Cl (10 mL) and extracted with EtOAc (3 x 30 mL). The organic
layers were washed with H2O (20 mL) and brine (20 mL), dried
(MgSO4), filtered and concentrated in vacuo. The residue was
purified by silica gel CC (EtOAc/hexane, 15:85) to afford 3-prop-
oxybenzaldehyde (74) (1.00 g, 6.10 mmol, 51%) as a colorless oil:
1H-NMR (CDCl3, 400 MHz) d: 1.06 (t, J = 7.0 Hz, 3H, –CH3), 1.84
(sextet, J = 7.0 Hz, 2H, –CH2–), 3.99 (t, J = 7.0 Hz, 2H, –OCH2–),
7.15–7.20 (m, 1H, Ar–H), 7.37 (d, J = 2.4 Hz, 1H, Ar–H), 7.43–7.46
(m, 2H, Ar–H), 9.97 (s, 1H, –CHO).
Z-selective olefination of 74 was performed using the procedure
described above to provide (Z)-ethyl 3-(3-propoxyphenyl)acrylate
(cis-130) (92%, Z:E = 95:5, determined by 1H-NMR spectrum) (silica
CC, EtOAc/hexane, 15:85) as a colorless oil: 1H-NMR (CDCl3,
400 MHz) d: 1.04 (t, J = 7.0 Hz, 3H, –CH3), 1.25 (t, J = 7.6 Hz, 3H,
–CO2–CH2–CH3), 1.81 (sextet, J = 7.0 Hz, 2H, –CH2–), 3.93 (t,
J = 7.0 Hz, 2H, –OCH2–), 4.18 (q, J = 7.6 Hz, 2H, –CO2–CH2–), 5.94
(d, J = 12.8 Hz, 1H, @CH–CO2–), 6.87–6.91 (m, 2H, Ar–H and Ar–
CH@), 7.11 (d, J = 7.2 Hz, 1H, Ar–H), 7.21–7.25 (m, 2H, Ar–H).
The hydrolysis of cis-130 was performed using the procedure
described above to afford cis-18 (90%) as colorless oil: 1H-NMR
(CDCl3, 400 MHz) d:1.03 (t, J = 7.0 Hz, 3H, –CH3), 1.80 (sextet,
J = 7.0 Hz, 2H, –CH2), 3.93, (t, J = 7.0 Hz, 2H, –OCH2–), 5.96 (d,
J = 12.8 Hz, 1H, @CH–CO2–), 6.90 (dd, J = 2.4, 8.2 Hz, 1H, Ar–H),
4.2.14. (Z)-3-(4-Methoxyphenyl)acrylic acid (cis-16)
Z-selective olefination of 4-methoxybenzaldehyde (72) was
performed using the procedure described above to provide (Z)-
ethyl 3-(4-methoxyphenyl)acrylate (cis-128) (98%, Z:E = 98:2,
determined by 1H-NMR spectrum) (silica gel CC, EtOAc/hexane,
10:90) as a colorless oil: 1H-NMR (CDCl3, 270 MHz) d: 1.28 (t,
J = 7.2 Hz, 3H, –CH3), 3.83 (s, 3H, –OCH3), 4.19 (q, J = 7.2 Hz, 2H, –
CH2–), 5.82 (d, J = 12.8 Hz, 1H, @CH–CO2–), 6.84 (d, J = 12.8 Hz,
1H, Ar–CH@), 6.87, 7.68 (d, J = 8.6 Hz, each 2H, Ar–H). The spectro-

K. Nishikawa et al. / Phytochemistry 96 (2013) 132–147
139
7.03 (d, J = 12.8 Hz, 1H, Ar–CH@), 7.13 (d, J = 8.2 Hz, 1H, Ar–H),
7.24–7.28 (m, 2H, Ar–H); 13C-NMR (CDCl3, 100 MHz) d: 10.5 (q,
–CH3), 22.5 (t, –CH2–CH3), 69.5 (t, –OCH2–), 115.5 (d, Ar), 116.2
(d, Ar), 118.7 (d, @CH–CO2–), 122.4 (d, Ar), 129.0 (d, Ar), 135.6 (s,
Ar), 145.7 (d, Ar–CH@), 158.7 (s, Ar), 171.1 (s, C@O); IR (KBr)
Z-selective olefination of 76 was performed using the procedure
described above to provide (Z)-ethyl 3-(3-isopropoxyphenyl)acry-
late (cis-132) (82%, Z:E = 96:4, determined by 1H-NMR spectrum)
(silica gel CC, EtOAc/hexane, 10:90) as a colorless oil: 1H-NMR
(CDCl3, 400 MHz) d: 1.25 (t, J = 7.2 Hz, 3H, –CH3), 1.34 (d,
J = 5.6 Hz, 6H, –CH–(CH3)2), 4.18 (q, J = 7.2 Hz, 2H, –CH2–), 4.56
(heptet, J = 5.6 Hz, –CH–(CH3)2), 5.93 (d, J = 12.8 Hz, 1H, @CH–
CO2–), 6.85 (m, 1H, Ar–H), 6.89 (d, J = 12.8 Hz, 1H, Ar–CH@), 7.10
(d, J = 7.6 Hz, 1H, Ar–H), 7.22 (s, 1H, Ar–H), 7.25 (d, J = 8.4 Hz, 1H,
Ar–H).
1686 cmꢀ1
;
ESI-MS m/z 205 (M+ꢀH); HRMS (EI) calcd for
C12H14O3 206.0943, found 206.0938.
4.2.17. (Z)-3-(3-Butoxyphenyl)acrylic acid (cis-19)
172 (1.99 g, 16.3 mmol) was added to a solution of K2CO3
(3.39 g, 24.5 mmol) in acetone (40 mL) at 0 °C under Ar, then the
reaction was stirred for 15 min. After 1-iodobutane (3.72 mL,
32.6 mmol) was added to the solution, the resulting mixture was
heated until reflux began this being maintained for 5 h. The reac-
tion was quenched with H2O (20 mL) and extracted with EtOAc
(3 x 30 mL). The organic layers were washed with H2O (20 mL)
and brine (20 mL), dried (MgSO4), filtered and concentrated in va-
cuo. The residue was purified by silica gel CC (EtOAc/hexane, 5:95)
to afford 3-butoxybenzaldehyde (75) (1.80 g, 10.1 mmol, 62%) as a
yellow oil: 1H-NMR (CDCl3, 400 MHz) d: 0.96 (t, J = 7.0 Hz, 3H,
–CH3), 1.47 (m, 2H, –CH2–CH3), 1.75 (m, 2H, –OCH2–CH2–), 3.99
(t, J = 7.0 Hz, 2H, –OCH2–), 7.13–7.16 (m, 2H, Ar–H), 7.36 (s, 1H,
Ar–H), 7.38–7.43 (m, 2H, Ar–H), 9.94 (s, 1H, –CHO); The spectro-
scopic data were in agreement with those in the literature
(Lindgren et al., 2009).
Z-selective olefination of 75 was performed using the procedure
described above to provide (Z)-ethyl 3-(3-butoxyphenyl)acrylate
(cis-131) (79%, Z:E = 94:6, determined by 1H-NMR spectrum) (silica
gel CC, EtOAc/hexane, 3:97) as a colorless oil: 1H-NMR (CDCl3,
400 MHz) d: 0.97 (t, J = 7.2 Hz, 3H, –CH3), 1.25 (t, J = 7.2 Hz, 3H,
–CO2–CH2–CH3), 1.49 (sextet, J = 7.2 Hz, 2H, –CH2–CH3), 1.77 (m,
2H, –OCH2–CH2–), 3.97 (t, J = 6.8 Hz, 2H, –OCH2–), 4.18 (q,
J = 7.2 Hz, 2H, –CO2–CH2–), 5.94 (d, J = 12.8 Hz, 1H, @CH–CO2–),
6.86–6.91 (m, 2H, Ar–H and Ar–CH@), 7.11 (d, J = 7.2 Hz, 1H, Ar–
H), 7.20 (s, 1H, Ar–H), 7.25 (d, J = 7.2 Hz, 1H, Ar–H).
Hydrolysis of cis-131 was performed using the procedure de-
scribed above to afford cis-19 (91%) as colorless needles: mp 41–
42 °C (Hexane); 1H-NMR (CDCl3, 400 MHz) d: 0.96 (t, J = 7.6 Hz,
3H, –CH3), 1.47 (sextet, J = 7.6 Hz, 2H, –CH2–CH3), 1.79–1.72 (m,
2H, –OCH2–CH2–), 3.95 (t, J = 6.8 Hz, 2H, –OCH2–), 5.95 (d,
J = 12.8 Hz, 1H, @CH–CO2–), 6.89 (dd, J = 2.4, 8.4 Hz, 1H, Ar–H),
7.02 (d, J = 12.8 Hz, 1H, Ar–CH@), 7.12 (d, J = 7.2 Hz, 1H, Ar–H),
7.23–7.27 (m, 2H, Ar–H); 13C-NMR (CDCl3, 100 MHz) d: 13.8 (q,
–CH3),19.2 (t, –CH2–CH3), 31.2 (t, –OCH2–CH2–), 67.7 (t, –OCH2–),
115.4 (d, Ar), 116.2 (d, Ar), 118.7 (d, @CH–CO2–), 122.4 (d, Ar),
129.0 (d, Ar), 135.5 (s, Ar), 145.7 (d, Ar–CH@), 158.7 (s, Ar), 171.4
(s, C@O); IR (KBr) 1699 cmꢀ1; ESI-MS m/z 219 (M+ꢀH); Anal. calcd
for C13H16O3: C, 70.98; H, 7.32. found: C, 70.98; H, 7.32.
Hydrolysis of cis-132 was performed using the procedure de-
scribed above to afford cis-20 (99%) as colorless needles: mp 49–
50 °C (hexane); 1H-NMR (CDCl3, 400 MHz) d: 1.32 (d, J = 6.4 Hz,
6H, –CH–(CH3)2), 4.53 (heptet, J = 6.4 Hz, 1H, –CH–(CH3)2), 5.95
(d, J = 12.6 Hz, 1H, @CH–CO2–), 6.88 (dd, J = 2.0, 8.2 Hz, 1H, Ar–
H), 7.02 (d, J = 12.6 Hz, 1H, Ar–CH@), 7.10 (d, J = 8.2 Hz, 1H, Ar–
H), 7.24–7.27 (m, 2H, Ar–H); 13C-NMR (CDCl3, 100 MHz) d: 22.0
(q, –CH3), 70.0 (d, –OCH–(CH3)2), 116.7 (d, Ar), 117.7 (d, Ar),
118.6 (d, @CH–CO2–), 122.5 (d, Ar), 129.1 (d, Ar), 135.6 (s, Ar),
145.8 (d, Ar–CH@), 157.5 (s, Ar), 171.1 (s, C@O); IR (KBr)
1694 cmꢀ1; ESI-MS m/z 205 (M+ꢀH); Anal. calcd for C12H14O3: C,
69.88; H, 6.84. found: C, 69.84; H, 6.86.
4.2.19. (Z)-3-(2-Fluorophenyl)acrylic acid (cis-21)
Z-selective olefination of 2-fluorobenzaldehyde (77) was per-
formed using the procedure described above to provide (Z)-ethyl
3-(2-fluorophenyl)acrylate (cis-133) (94%, Z:E = 98:2, determined
by 1H-NMR spectrum) (silica gel CC, EtOAc/hexane, 3:97) as a
colorless oil: 1H-NMR (CDCl3, 270 MHz) d: 1.29 (t, J = 7.2 Hz, 3H,
–CH3), 4.19 (q, J = 7.2 Hz, 2H, –CH2–), 6.04 (d, J = 12.4 Hz, @CH–
CO2–), 7.03–7.12 (m, 2H, Ar–H), 7.28–7.32 (m, 2H, Ar–H and
Ar–CH@), 7.60 (t, J = 6.8 Hz, 1H, Ar–H); spectrosopic data were in
agreement with those in the literature (Houghton and Voyle,
1983).
Hydrolysis of cis-133 was performed using the procedure de-
scribed above to afford cis-21 (77%) as colorless needles: mp 90–
93 °C (toluene); 1H-NMR (CDCl3, 400 MHz) d: 6.09 (d, J = 12.2 Hz,
1H, @CH–CO2–), 7.04–7.14 (m, 2H, Ar–H), 7.14 (d, J = 12.2 Hz, 1H,
Ar–CH@), 7.33 (m, 1H, Ar–H), 7.60 (t, J = 6.8 Hz, 1H, Ar–H); 13C-
NMR (CDCl3, 100 MHz) d: 115.3 (d, as a doublet, @CH–CO2–),
121.2 (d, as a doublet, Ar), 122.6 (s, as a doublet, Ar), 123.6 (d, as
a doublet, Ar), 138.1 (d, as a doublet, Ar–CH@), 160.2 (s, as a dou-
blet, Ar), 171.3 (s, C@O); IR (KBr) 1701 cmꢀ1; ESI-MS m/z 165
(M+ꢀH); Anal. calcd for C9H7FO2: C, 65.06; H, 4.25. found: C,
65.02; H, 4.29.
4.2.20. (Z)-3-(3-Fluorophenyl)acrylic acid (cis-22)
Z-selective olefination of 3-fluorobenzaldehyde (78) was per-
formed using the procedure described above to provide (Z)-ethyl
3-(3-fluorophenyl)acrylate (cis-134) (94%, Z:E = 98:2, determined
by 1H-NMR spectrum) (silica gel CC, EtOAc/hexane, 2:98) as a
colorless oil: 1H-NMR (CDCl3, 400 MHz) d: 1.25 (t, J = 6.8 Hz, 3H,
–CH3), 4.18 (q, J = 6.8 Hz, 2H, –CH2–), 5.99 (d, J = 12.6 Hz, @CH–
CO2–), 6.90 (d, J = 12.6 Hz, 1H, Ar–CH@), 7.01–7.04 (m, 1H, Ar–H),
7.29–7.34 (m, 3H, Ar–H).
Hydrolysis of cis-134 was performed using the procedure de-
scribed above to afford cis-22 (80%) as colorless needles: mp 40–
41 °C (toluene); 1H-NMR (CDCl3, 400 MHz) d: 6.02 (d, J = 12.8 Hz,
1H, @CH–CO2–), 7.03 (d, J = 12.8 Hz, 1H, Ar–CH@), 7.07 (m, 1H,
Ar–H), 7.31–7.34 (m, 2H, Ar–H), 7.38 (m, 1H, Ar–H); 13C-NMR
(CDCl3, 100 MHz) d: 116.2 (d, as a doublet, Ar), 116.5 (d, as a dou-
blet, Ar), 119.8 (d, @CH–CO2–), 125.7 (d, as a doublet, Ar), 129.5 (d,
as a doublet, Ar), 136.3 (s, as a doublet, Ar), 144.4 (d, as a doublet,
Ar–CH@), 162.3 (d, as a doublet, Ar), 171.7 (s, C@O); IR (KBr)
1697 cmꢀ1; ESI-MS m/z 165 (M+ꢀH); Anal. calcd for C9H7FO2: C,
65.06; H, 4.25. found: C, 65.06; H, 4.25.
4.2.18. (Z)-3-(3-Isopropoxyphenyl)acrylic acid (cis-20)
172 (1.99 g, 16.3 mmol) was added to a solution of K2CO3
(4.08 g, 29.5 mmol) in acetone (40 mL) at 0 °C under Ar, then the
reaction was stirred for 15 min. After 2-iodopropane (3.32 mL,
32.8 mmol) was added to the solution, the resulting mixture was
heated until reflux began this being maintained for 9 h. The reac-
tion was quenched with H2O (20 mL) and extracted with EtOAc
(3 x 30 mL). The organic layers were washed with H2O (20 mL)
and brine (20 mL), dried (MgSO4), filtered and concentrated in va-
cuo. The residue was purified by silica gel CC (EtOAc/hexane,
10:90) to afford 3-isopropoxybenzaldehyde (76) (1.61 g,
9.78 mmol, 62%) as a yellow oil: 1H-NMR (CDCl3, 400 MHz) d:
1.36 (d, J = 5.6 Hz, 6H, –CH3), 4.63 (heptet, J = 5.6 Hz, 1H, –CH–
(CH3)2), 7.15 (m, 1H, Ar–H), 7.38 (brs, 1H, Ar–H), 7.42–7.43 (m,
2H, Ar–H), 9.97 (s, 1H, –CHO); spectral data were in agreement
with those in the literature (García-Díaz et al., 2011).

140
K. Nishikawa et al. / Phytochemistry 96 (2013) 132–147
4.2.21. (Z)-3-(4-Fluorophenyl)acrylic acid (cis-23)
by 1H-NMR spectrum) (silica gel CC, EtOAc/hexane, 4:96) as a
colorless oil: 1H-NMR (CDCl3, 270 MHz) d: 1.26 (t, J = 7.3 Hz, 3H,
–CH3), 4.18 (q, J = 7.3 Hz, 2H, –CH2–), 5.96 (d, J = 12.6 Hz, 1H,
@CH–CO2–), 6.88 (d, J = 12.6 Hz, 1H, Ar–CH@), 7.32, 7.55 (d,
J = 7.8 Hz, each 2H, Ar–H); The spectroscopic data were in agree-
ment with those in the literature (Walter and Oestreich, 2008).
Hydrolysis of cis-138 was performed using the procedure de-
scribed above to afford cis-26 (89%) as colorless needles: mp
108–110 °C (toluene); 1H-NMR (CDCl3, 400 MHz) d: 5.99 (d,
J = 12.8 Hz, 1H, @CH–CO2–), 7.01 (d, J = 12.8 Hz, 1H, Ar–CH@),
7.33, 7.56 (d, J = 8.6 Hz, each 2H, Ar–H); 13C-NMR (CDCl3,
100 MHz) d: 119.1 (d,@CH–CO2–), 128.3 (d, Ar), 131.4 (d, Ar),
132.7 (s, Ar), 135.3 (s, Ar), 144.8 (d, Ar–CH@), 171.5 (s, C@O); IR
Z-selective olefination of 4-fluorobenzaldehyde (79) was per-
formed using the procedure described above to provide (Z)-ethyl
3-(4-fluorophenyl)acrylate (cis-135) (94%, Z:E = 98:2, determined
by 1H-NMR spectrum) (silica gel CC, EtOAc/hexane, 2:98) as a
colorless oil: 1H-NMR (CDCl3, 400 MHz) d: 1.30 (t, J = 7.2 Hz, 3H,
–CH3), 4.19 (q, J = 7.2 Hz, 2H, –CH2–), 5.96 (d, J = 12.4 Hz, @CH–
CO2–), 6.93 (d, J = 12.4 Hz, 1H, Ar–CH@), 7.07 (m, 2H, Ar–H), 7.68
(dd, J = 2.9, 8.8 Hz, 2H, Ar–H). The spectroscopic data were in
agreement with those in the literature (Mueller and Jennigs, 2007).
Hydrolysis of cis-135 was performed using the procedure de-
scribed above to afford cis-23 (77%) as colorless needles: mp 90–
93 °C (toluene); 1H-NMR (CDCl3, 400 MHz) d: 5.96 (d, J = 12.8 Hz,
1H, @CH–CO2–), 7.00–7.08 (m, 3H, Ar–CH@ and Ar–H), 7.64–7.68
(m, 2H, Ar–H); 13C-NMR (CDCl3, 100 MHz) d: 115.1 (d, as a doublet,
Ar), 118.3 (d, @CH–CO2–), 130.3 (s, Ar), 132.3 (d, as a doublet, Ar),
145.0 (d, Ar–CH@), 163.1 (s, Ar), 171.7 (s, C@O); IR (KBr)
1686 cmꢀ1; ESI-MS m/z 165 (M+ꢀH); Anal. calcd for C9H7FO2: C,
65.06; H, 4.25. found: C, 64.86; H, 4.25.
(KBr) 1699 cmꢀ1
;
ESI-MS m/z 181 (M+ꢀH); Anal. calcd for
C9H7ClO2: C, 59.20; H, 3.86. found: C, 59.33; H, 3.86.
4.2.25. (Z)-3-(2-Bromophenyl)acrylic acid (cis-27)
Z-selective olefination of 2-bromobenzaldehyde (83) was per-
formed using the procedure described above to provide (Z)-ethyl
3-(2-bromophenyl)acrylate (cis-139) (81%, Z only, determined by
4.2.22. (Z)-3-(2-Chlorophenyl)acrylic acid (cis-24)
1H-NMR spectrum) (silica gel CC, EtOAc/hexane, 7:93) as
a
Z-selective olefination of 2-chlorobenzaldehyde (80) was per-
formed using the procedure described above to provide (Z)-ethyl
3-(2-chlorophenyl)acrylate (cis-136) (90%, Z:E = 98:2, determined
by 1H-NMR spectrum) (silica gel CC, EtOAc/hexane, 5:95) as a
colorless oil: 1H-NMR (CDCl3, 270 MHz) d: 1.18 (t, J = 7.3 Hz, 3H,
–CH3), 4.11 (q, J = 7.3 Hz, 2H, –CH2–), 6.08 (d, J = 12.4 Hz, 1H,
@CH–CO2–), 7.14 (d, J = 12.4 Hz, 1H, Ar–CH@), 7.23–7.29 (m, 2H,
Ar–H), 7.38 (dd, J = 2.1, 7.0 Hz, 1H, Ar–H), 7.50 (m, 1H, Ar–H); spec-
troscopic data were in agreement with those in the literature
(Byrne and Gilheany, 2012).
Hydrolysis of cis-136 was performed using the procedure de-
scribed above to afford cis-24 (77%) as colorless needles: mp
136–137 °C (toluene); 1H-NMR (CDCl3, 400 MHz) d: 6.08 (d,
J = 12.8 Hz, 1H, @CH–CO2–), 7.20–7.29 (m, 3H, Ar–H and Ar–
CH@), 7.38, 7.50 (d, J = 7.2 Hz, each 1H, Ar–H); 13C-NMR (CDCl3,
100 MHz) d: 120.9 (d, @CH–CO2–), 126.2 (d, Ar), 129.1 (d, Ar),
130.1 (d, Ar), 130.9 (d, Ar), 133.2 (s, Ar), 133.4 (s, Ar), 143.0 (d,
Ar–CH@), 171.0 (s, C@O); IR (KBr) 1701 cmꢀ1; ESI-MS m/z 181
(M+ꢀH); Anal. calcd for C9H7ClO2: C, 59.20; H, 3.86. found: C,
59.38; H, 3.85
colorless oil: 1H-NMR (CDCl3, 400 MHz) d: 1.17 (t, J = 7.2 Hz, 3H,
–CH3), 4.11 (q, J = 7.2 Hz, 2H, –CH2–), 6.06 (d, J = 12.2 Hz, 1H,
@CH–CO2–), 7.09 (d, J = 12.2 Hz, 1H, Ar–CH@), 7.18 (dt, J = 1.6,
8.0 Hz, 1H, Ar–H), 7.26–7.30 (m, 1H, Ar–H), 7.47, 7.58 (d,
J = 8.0 Hz, each 1H, Ar–H); spectroscopic data were in agreement
with those in the literature (Byrne and Gilheany, 2012).
Hydrolysis of cis-139 was performed using the procedure de-
scribed above to afford cis-27 (92%) as colorless needles: mp
146–147 °C (toluene); 1H-NMR (CDCl3, 600 MHz) d: 6.05 (d,
J = 12.4 Hz, 1H, @CH–CO2–), 7.18 (d, J = 12.4 Hz, 1H, Ar–CH@),
7.19 (m, 1H, Ar–H), 7.27 (t, J = 7.3 Hz, 1H, Ar–H), 7.46 (dd, J = 1.2,
7.3 Hz, 1H, Ar–H), 7.58 (d, J = 7.3 Hz, 1H, Ar–H); 13C-NMR (CDCl3,
150 MHz) d: 120.6 (d, @CH–CO2–), 123.0 (s, Ar), 126.8 (d, Ar),
130.2 (d, Ar), 130.9 (d, Ar), 135.3 (s, Ar), 145.1 (d, Ar–CH@),
170.4 (s, C@O); IR (KBr) 1703 cmꢀ1; ESI-MS m/z 225 (M+ꢀH); Anal.
calcd for C9H7ClO2: C, 47.61; H, 3.11. found: C, 47.76; H, 3.11.
4.2.26. (Z)-3-(3-Bromophenyl)acrylic acid (cis-28)
Z-selective olefination of 3-bromobenzaldehyde (84) was per-
formed using the procedure described above to provide (Z)-ethyl
3-(3-bromophenyl)acrylate (cis-140) (77%, Z:E = 98:2, determined
by 1H-NMR spectrum) (silica gel CC, EtOAc/hexane, 5:95) as a col-
orless oil: 1H-NMR (CDCl3, 270 MHz) d: 1.25 (t, J = 7.3 Hz, 3H,
–CH3), 4.18 (q, J = 7.3 Hz, 2H, –CH2–), 5.99 (d, J = 12.8 Hz, 1H,
@CH–CO2–), 6.88 (d, J = 12.8 Hz, 1H, Ar–CH@), 7.22 (t, J = 7.8 Hz,
1H, Ar–H), 7.44–7.49 (m, 2H, Ar–H), 7.72 (s, 1H, Ar–H).
Hydrolysis of cis-140 was performed using the procedure de-
scribed above to afford cis-28 (70%) as colorless needles: mp 80–
81 °C (toluene); 1H-NMR (CDCl3, 400 MHz) d: 6.02 (d, J = 12.8 Hz,
1H, @CH–CO2–), 7.00 (d, J = 12.8 Hz, 1H, Ar–CH@), 7.23 (t,
J = 7.6 Hz, 1H, Ar–H), 7.48–7.52 (m, 2H, Ar–H), 7.72 (s, 1H, Ar–H);
13C-NMR (CDCl3, 100 MHz) d: 120.1 (d, @CH–CO2–), 122.0 (s, Ar),
128.3 (d, Ar), 129.5 (d, Ar), 132.0 (d, Ar), 132.5 (d, Ar), 136.3 (s,
Ar), 144.2 (d, Ar–CH@), 171.3 (s, C@O); IR (KBr) 1697 cmꢀ1; ESI-
MS m/z 225 (M+ꢀH); Anal. calcd for C9H7BrO2: C, 47.61; H, 3.11.
found: C, 47.66; H, 3.04.
4.2.23. (Z)-3-(3-Chlorophenyl)acrylic acid (cis-25)
Z-selective olefination of 3-chlorobenzaldehyde (81) was per-
formed using the procedure described above to provide (Z)-ethyl
3-(3-chlorophenyl)acrylate (cis-137) (97%, Z:E = 98:2, determined
by 1H-NMR spectrum) (silica gel CC, EtOAc/hexane, 4:96) as a
colorless oil: 1H-NMR (CDCl3, 270 MHz) d: 1.25 (t, J = 7.3 Hz, 3H,
–CH3), 4.18 (q, J = 7.3 Hz, 2H, –CH2–), 5.99 (d, J = 12.6 Hz, 1H,
@CH–CO2–), 6.89 (d, J = 12.6 Hz, 1H, Ar–CH@), 7.26–7.30 (m, 2H,
Ar–H), 7.42 (d, J = 7.0 Hz, 1H, Ar–H), 7.57 (s, 1H, Ar–H).
Hydrolysis of cis-137 was performed using the procedure de-
scribed above to afford cis-25 (94%) as colorless needles: mp 70–
71 °C (toluene); 1H-NMR (CDCl3, 400 MHz) d: 6.02 (d, J = 12.4 Hz,
1H, @CH–CO2–), 7.01 (d, J = 12.4 Hz, 1H, Ar–CH@), 7.34–7.29 (m,
2H, Ar–H), 7.46 (d, J = 7.2 Hz, 1H, Ar–H), 7.58 (s, 1H, Ar–H); 13C-
NMR (CDCl3, 100 MHz) d: 120.0 (d, @CH–CO2–), 127.9 (d, Ar),
129.2 (d, Ar), 129.3 (d, Ar), 129.6 (d, Ar), 133.9 (s, Ar), 136.0 (s,
Ar), 144.3 (d, Ar–CH@), 171.3 (s, C@O); IR (KBr) 1699 cmꢀ1; ESI-
MS m/z 181 (M+ꢀH); Anal. calcd for C9H7ClO2: C, 59.20; H, 3.86.
found: C, 59.13; H, 3.86.
4.2.27. (Z)-3-(4-Bromophenyl)acrylic acid (cis-29)
Z-selective olefination of 4-bromobenzaldehyde (85) was per-
formed using the procedure described above to provide (Z)-ethyl
3-(4-bromophenyl)acrylate (cis-141) (90%, Z:E = 97:3, determined
by 1H-NMR spectrum) (silica gel CC, EtOAc/hexane, 10:90) as a
colorless oil: 1H-NMR (CDCl3, 270 MHz) d: 1.26 (t, J = 7.3 Hz, 3H,
–CH3), 4.18 (q, J = 7.3 Hz, 2H, –CH2–), 5.97 (d, J = 12.8 Hz, 1H,
@CH–CO2–), 6.86 (d, J = 12.8 Hz, 1H, Ar–CH@), 7.47 (s, 4H, Ar–H);
4.2.24. (Z)-3-(4-Chlorophenyl)acrylic acid (cis-26)
Z-selective olefination of 4-chlorobenzaldehyde (82) was per-
formed using the procedure described above to provide (Z)-ethyl
3-(4-chlorophenyl)acrylate (cis-138) (98%, Z:E = 97:3, determined

K. Nishikawa et al. / Phytochemistry 96 (2013) 132–147
141
spectral data were in agreement with those in the literature (Pettit
et al., 2009).
Hydrolysis of cis-144 was performed using the procedure de-
scribed above to afford cis-32 (92%) as colorless needles: mp
126–129 °C (toluene); 1H-NMR (CDCl3, 400 MHz) d: 5.97 (d,
J = 12.8 Hz, 1H, @CH–CO2–), 6.96 (d, J = 12.8 Hz, 1H, Ar–CH@),
7.32, 7.68 (d, J = 8.4 Hz, each 2H, Ar–H); 13C-NMR (CDCl3,
100 MHz) d: 95.8 (s, Ar), 119.4 (d,@CH–CO2–), 131.6 (d, Ar),
133.7 (s, Ar), 137.2 (d, Ar), 144.9 (d, Ar–CH@), 171.3 (s, C@O); IR
Hydrolysis of cis-141 was performed using the procedure de-
scribed above to afford cis-29 (90%) as colorless needles: mp
124–127 °C (Toluene); 1H-NMR (CDCl3, 400 MHz) d: 5.98 (d,
J = 12.8 Hz, 1H, @CH–CO2–), 6.99 (d, J = 12.8 Hz, 1H, Ar–CH@),
7.47 (brs, 4H, Ar–H); 13C-NMR (CDCl3, 100 MHz) d: 119.3
(d,@CH–CO2–), 123.8 (s, Ar), 131.3 (d, Ar), 131.6 (d, Ar), 133.2 (s,
Ar), 144.8 (d, Ar–CH@), 171.1 (s, C@O); IR (KBr) 1701 cmꢀ1; ESI-
MS m/z 225 (M+ꢀH); Anal. calcd for C9H7BrO2: C, 47.61; H, 3.11.
found: C, 47.70; H, 3.13.
(KBr) 1699 cmꢀ1
;
ESI-MS m/z 273 (M+ꢀH); Anal. calcd for
C9H7IO2: C, 39.44; H, 2.57. found: C, 39.61; H, 2.57.
4.2.31. (Z)-3-(2-Nitrophenyl)acrylic acid (cis-33)
Z-selective olefination of 2-nitrobenzaldehyde (89) was per-
formed using the procedure described above to provide (Z)-ethyl
3-(2-nitrophenyl)acrylate (cis-145) (82%, Z:E = 98:2, determined
by 1H-NMR spectrum) (silica gel CC, EtOAc/hexane, 5:95) as a
colorless oil: 1H-NMR (CDCl3, 270 MHz) d: 1.11 (t, J = 7.3 Hz, 3H,
–CH3), 4.03 (q, J = 7.3 Hz, 2H, –CH2–), 6.10 (d, J = 11.8 Hz, 1H,
@CH–CO2–), 7.40 (m, 1H, Ar–H), 7.41 (d, J = 11.8 Hz, 1H, Ar–
CH@), 7.50 (t, J = 7.6 Hz, 1H, Ar–H), 7.61 (d, J = 7.6 Hz, 1H, Ar–H),
8.16 (d, J = 8.4 Hz, 1H, Ar–H).
Hydrolysis of cis-145 was performed using the procedure de-
scribed above to afford cis-33 (91%) as yellow needles: mp 147–
148 °C (toluene); 1H-NMR (CDCl3, 400 MHz) d: 6.07 (d,
J = 12.4 Hz, 1H, @CH–CO2–), 7.36 (d, J = 7.6 Hz, 1H, Ar–H), 7.48–
7.52 (m, 2H, Ar–CH@ and Ar–H), 7.59 (m, 1H, Ar–H), 8.16 (d,
J = 8.4 Hz, 1H, Ar–H); 13C-NMR (CDCl3, 100 MHz) d: 120.1 (d,
@CH–CO2–), 124.4 (d, Ar), 129.3 (d, Ar), 131.0 (d, Ar), 131.9 (s,
Ar), 133.3 (d, Ar), 144.0 (d, Ar–CH@), 146.6 (s, Ar), 170.8 (s,
C@O); IR (KBr) 1701 cmꢀ1; ESI-MS m/z 192 (M+ꢀH); Anal. calcd
for C9H7NO4: C, 55.96; H, 3.65; N, 7.25. found: C, 56.05; H, 3.67;
N, 7.25.
4.2.28. (Z)-3-(2-Iodophenyl)acrylic acid (cis-30)
The Z-selective olefination of 2-iodobenzaldehyde (86) was per-
formed using the procedure described above to provide (Z)-ethyl 3-
(2-iodophenyl)acrylate (cis-142) (85%, Z:E = 99:1, determined by
1H-NMR spectrum) (silica gel CC, EtOAc/hexane, 6:94) as
a
colorless oil: 1H-NMR (CDCl3, 270 MHz) d: 1.16 (t, J = 7.0 Hz, 3H,
–CH3), 4.10 (q, J = 7.0 Hz, 2H, –CH2–), 6.02 (d, J = 12.4 Hz, 1H,
@CH–CO2–), 6.97 (d, J = 12.4 Hz, 1H, Ar–CH@), 7.06 (m, 1H, Ar–
H), 7.32 (t, J = 7.6 Hz, 1H, Ar–H), 7.42 (d, J = 7.6 Hz, 1H, Ar–H),
7.85 (d, J = 7.6 Hz, 1H, Ar–H).
Hydrolysis of cis-142 was performed using the procedure de-
scribed above to afford cis-30 (95%) as colorless needles: mp
122–124 °C (toluene); 1H-NMR (CDCl3, 400 MHz) d: 6.02 (d,
J = 12.2 Hz, 1H, @CH–CO2–), 7.02 (m, 1H, Ar–H), 7.07 (d,
J = 12.2 Hz, 1H, Ar–CH@), 7.32 (t, J = 7.6 Hz, 1H, Ar–H), 7.43 (d,
J = 7.6 Hz, 1H, Ar–H), 7.86 (d, J = 7.6 Hz, 1H, Ar–H); 13C-NMR
(CDCl3, 100 MHz) d: 98.0 (s, Ar), 120.2 (d, @CH–CO2–), 127.6 (d,
Ar), 130.0 (d, Ar), 130.2 (d, Ar), 138.5 (d, Ar), 139.0 (s, Ar), 149.0
(d, Ar–CH@), 170.8 (s, C@O); IR (KBr) 1701 cmꢀ1; ESI-MS m/z 273
(M+ꢀH); Anal. calcd for C9H7IO2: C, 39.44; H, 2.57. found: C,
39.81; H, 2.57.
4.2.32. (Z)-3-(3-Nitrophenyl)acrylic acid (cis-34)
Z-selective olefination of 3-nitrobenzaldehyde (90) was per-
formed using the procedure described above to provide (Z)-ethyl
3-(3-nitrophenyl)acrylate (cis-146) (66%, Z:E = 98:2, determined
by 1H-NMR spectrum) (silica gel CC, EtOAc/hexane, 10:90) as a
colorless oil: 1H-NMR (CDCl3, 270 MHz) d: 1.25 (t, J = 7.3 Hz, 3H,
–CH3), 4.19 (q, J = 7.3 Hz, 2H, –CH2–), 6.11 (d, J = 12.4 Hz, 1H,
@CH–CO2–), 7.00 (d, J = 12.4 Hz, 1H, Ar–CH@), 7.53 (t, J = 8.1 Hz,
1H, Ar–H), 7.88, 8.19 (d, J = 8.1 Hz, each 1H, Ar–H), 8.44 (s, 1H,
Ar–H).
Hydrolysis of cis-146 was performed using the procedure de-
scribed above to afford cis-34 (93%) as yellow needles: mp 157–
158 °C (Toluene); 1H-NMR (CDCl3, 400 MHz) d: 6.14 (d,
J = 12.6 Hz, 1H,@CH–CO2–), 7.13 (d, J = 12.6 Hz, 1H, Ar–CH@),
7.55 (t, J = 8.0 Hz, 1H, Ar–H), 7.88 (d, J = 8.0 Hz, 1H, Ar–H), 8.21
(dd, J = 1.6, 8.0 Hz, 1H, Ar–H), 8.43 (s, 1H, Ar–H); 13C-NMR (CDCl3,
100 MHz) d: 123.3 (d, @CH–CO2–), 123.5 (d, Ar), 123.9 (d, Ar), 129.6
(d, Ar), 136.1 (d, Ar), 136.5 (s, Ar), 138.7 (d, Ar–CH@), 147.5 (s, Ar),
167.1 (s, C@O); IR (KBr) 1701 cmꢀ1; ESI-MS m/z 192 (M+ꢀH); Anal.
calcd for C9H7NO4: C, 55.96; H, 3.65; N, 7.25. found: C, 55.96; H,
3.65; N, 7.23.
4.2.29. (Z)-3-(3-Iodophenyl)acrylic acid (cis-31)
Z-selective olefination of 3-iodobenzaldehyde (87) was per-
formed using the procedure described above to provide (Z)-ethyl
3-(3-iodophenyl)acrylate (cis-143) (94%, Z:E = 98:2, determined
by 1H-NMR spectrum) (silica gel CC, EtOAc/hexane, 5:95) as a
colorless oil: 1H-NMR (CDCl3, 270 MHz) d: 1.26 (t, J = 7.2 Hz, 3H,
–CH3), 4.19 (q, J = 7.2 Hz, 2H, –CH2–), 5.98 (d, J = 12.6 Hz, 1H,
@CH–CO2–), 6.85 (d, J = 12.6 Hz, 1H, Ar–CH@), 7.10 (t, J = 7.8 Hz,
1H, Ar–H), 7.53, 7.66 (d, J = 7.8 Hz, each 1H, Ar–H), 7.90 (s, 1H,
Ar–H).
Hydrolysis of cis-143 was performed using the procedure de-
scribed above to afford cis-31 (88%) as colorless needles: mp
102–104 °C (toluene); 1H-NMR (CDCl3, 400 MHz) d: 5.99 (d,
J = 12.8 Hz, 1H, @CH–CO2–), 6.96 (d, J = 12.8 Hz, 1H, Ar–CH@),
7.09 (dd, J = 7.6, 8.4 Hz, 1H, Ar–H), 7.55 (d, J = 7.6 Hz, 1H, Ar–H),
7.66 (d, J = 8.4 Hz, 1H, Ar–H), 7.89 (s, 1H, Ar–H); 13C-NMR (CDCl3,
100 MHz) d: 93.7 (s, Ar), 120.0 (d, @CH–CO2–), 128.9 (d, Ar),
129.7 (d, Ar), 136.4 (s, Ar), 138.0 (d, Ar), 138.4 (d, Ar), 144.1 (d,
Ar–CH@), 171.0 (s, C@O); IR (KBr) 1699 cmꢀ1; ESI-MS m/z 273
(M+ꢀH); Anal. calcd for C9H7IO2: C, 39.44; H, 2.57. found: C,
39.44; H, 2.57.
4.2.33. (Z)-3-(4-Nitrophenyl)acrylic acid (cis-35)
Z-selective olefination of 4-nitrobenzaldehyde (91) was per-
formed using the procedure described above to provide (Z)-ethyl
3-(4-nitrophenyl)acrylate (cis-147) (70%, Z only, determined by
1H-NMR spectrum) (silica gel CC, EtOAc/hexane, 10:90) as a color-
less oil: 1H-NMR (CDCl3, 270 MHz) d: 1.25 (t, J = 7.3 Hz, 3H, –CH3),
4.18 (q, J = 7.3 Hz, 2H, –CH2–), 6.13 (d, J = 12.4 Hz, 1H, @CH–CO2–),
7.01 (d, J = 12.4 Hz, 1H, Ar–CH@), 7.67, 8.21 (d, J = 8.6 Hz, each 2H,
Ar–H).
4.2.30. (Z)-3-(4-Iodophenyl)acrylic acid (cis-32)
Z-selective olefination of 4-iodobenzaldehyde (88) was per-
formed using the procedure described above to provide (Z)-ethyl
3-(4-iodophenyl)acrylate (cis-144) (98%, Z:E = 98:2, determined
by 1H-NMR spectrum) (silica gel CC, EtOAc/hexane, 5:95) as a
colorless oil: 1H-NMR (CDCl3, 270 MHz) d: 1.24 (t, J = 7.3 Hz, 3H,
–CH3), 4.17 (q, J = 7.3 Hz, 2H, –CH2–), 5.95 (d, J = 12.6 Hz, 1H,
@CH–CO2–), 6.95 (d, J = 12.6 Hz, 1H, Ar–CH@), 7.33–7.35, 7.57–
7.59 (m, each 2H, Ar–H).
Hydrolysis of cis-147 was performed using the procedure de-
scribed above to afford cis-35 (76%) as yellow needles: mp 146–
147 °C (toluene); 1H-NMR (CDCl3, 400 MHz) d: 6.15 (d,

142
K. Nishikawa et al. / Phytochemistry 96 (2013) 132–147
J = 12.8 Hz, 1H, @CH–CO2–), 7.15 (d, J = 12.8 Hz, 1H, Ar–CH@), 7.66,
8.21 (d, J = 8.8 Hz, each 2H, Ar–H); 13C-NMR (CDCl3, 100 MHz)
d:122.0 (d,@CH–CO2–), 123.3 (d, Ar), 130.3 (d, Ar), 140.9 (s, Ar),
143.4 (d, Ar–CH@), 147.8 (s, Ar), 177.8 (s, C@O); IR (KBr)
1705 cmꢀ1; ESI-MS m/z 192 (M+ꢀH); Anal. calcd for C9H7NO4: C,
55.96; H, 3.65; N, 7.25. found: C, 56.02; H, 3.68; N, 7.23.
171.1 (s, C@O); IR (KBr) 1701 cmꢀ1; ESI-MS m/z 215 (M+ꢀH); Anal.
calcd for C10H7F3O2: C, 55.56; H, 3.26. found: C, 55.65; H, 3.33.
4.2.37. (Z)-3-(2,4-Dimethylphenyl)acrylic acid (cis-39)
Z-selective olefination of 2,4-dimethylbenzaldehyde (95) was
performed using the procedure described above to provide (Z)-
ethyl 3-(2,4-dimethylphenyl)acrylate (cis-151) (94%, Z only, deter-
mined by 1H-NMR spectrum) (silica gel CC, EtOAc/hexane, 10:90)
as a colorless oil: 1H-NMR (CDCl3, 270 MHz) d: 1.18 (t, J = 7.0 Hz,
3H, –CH3), 2.25, 2.31 (s, each 3H, Ar–CH3), 4.10 (q, J = 7.0 Hz, 2H,
–CH2–), 5.97 (d, J = 12.2 Hz, 1H, @CH–CO2–), 6.95–6.99 (m, 2H,
Ar–H), 7.08 (d, J = 12.2 Hz, 1H, Ar–CH@), 7.26 (d, J = 7.8 Hz, 1H,
Ar–H).
Hydrolysis of cis-151 was performed using the procedure de-
scribed above to afford cis-39 (96%) as colorless needles: mp 91–
94 °C (toluene); 1H-NMR (CDCl3, 400 MHz) d: 2.25, 2,31 (s, each
3H, –CH3), 5.96 (d, J = 12.4 Hz, 1H,@CH–CO2–), 6.95 (d, J = 7.8 Hz,
1H, Ar–H), 6.99 (s, 1H, Ar–H), 7.18 (d, J = 12.4 Hz, 1H, Ar–CH@),
7.27 (d, J = 7.8 Hz, 1H, Ar–H); 13C-NMR (CDCl3, 100 MHz) d: 19.8
(q, –CH3), 21.2 (q, –CH3), 119.3 (d,@CH–CO2–), 126.1 (d, Ar),
129.1 (d, Ar), 130.6 (d, Ar), 131.3 (s, Ar), 136.0 (s, Ar), 138.9 (s,
Ar), 145.4 (d, Ar–CH@), 171.2 (s, C@O); IR (KBr) 1697 cmꢀ1; ESI-
MS m/z 175 (M+ꢀH); Anal. calcd for C11H12O2: C, 74.98; H, 6.86.
found: C, 75.03; H, 6.68.
4.2.34. (Z)-3-[2-(Trifluoromethyl)phenyl]acrylic acid (cis-36)
Z-selective olefination of 2-(trifluoromethyl)benzaldehyde (92)
was performed using the procedure described above to provide
(Z)-ethyl 3-(2-(trifluoromethyl)phenyl)acrylate (cis-148) (83%, Z
only, determined by 1H-NMR spectrum) (silica gel CC, EtOAc/hex-
ane, 10:90) as a colorless oil: 1H-NMR (CDCl3, 270 MHz) d: 1.09
(t, J = 7.0 Hz, 3H, –CH3), 4.04 (q, J = 7.0 Hz, 2H, –CH2–), 6.11 (d,
J = 12.2 Hz, 1H, @CH–CO2–), 7.30–7.50 (m, 4H, Ar–CH@ and Ar–
H), 7.66 (d, J = 7.6 Hz, 1H, Ar–H).
Hydrolysis of cis-148 was performed using the procedure de-
scribed above to afford cis-36 (89%) as colorless needles: mp
113–114 °C (Toluene); 1H-NMR (CDCl3, 400 MHz) d: 6.11 (d,
J = 12.4 Hz, 1H,@CH–CO2–), 7.37–7.44 (m, 3H, Ar–CH@ and Ar–
H), 7.49 (t, J = 7.2 Hz, 1H, Ar–H), 7.67 (d, J = 8.0 Hz, 1H, Ar–H);
13C-NMR (CDCl3, 100 MHz) d: 121.9 (d, @CH–CO2–), 122.6 (a, Ar),
125.5 (d, as a quartet, Ar), 127.2 (s, as a quartet, –CF3), 128.3 (d,
Ar), 130.3 (d, Ar), 131.2 (d, Ar), 134.0 (s, as a quartet, Ar), 143.2
(d, Ar–CH@), 171.0 (s, C@O); IR (KBr) 1705 cmꢀ1; ESIꢀMS m/z
215 (M+ꢀH); Anal. calcd for C10H7F3O2: C, 55.56; H, 3.26. found:
C, 55.68; H, 3.30.
4.2.38. (Z)-3-(4-Methoxy-2-methylphenyl)acrylic acid (cis-40)
Z-selective olefination of 4-methoxy-2-methylbenzaldehyde
(96) was performed using the procedure described above to pro-
vide (Z)-ethyl 3-(4-methoxy-2-methylphenyl)acrylate (cis-152)
(86%, Z:E = 98:2, determined by 1H-NMR spectrum) (silica gel CC,
EtOAc/hexane, 3:97) as a colorless oil: 1H-NMR (CDCl3, 400 MHz)
d: 1.20 (t, J = 7.6 Hz, 3H, –CH3), 2.28 (s, 3H, Ar–CH3), 3.80 (s, 3H,
–OCH3), 4.12 (q, J = 7.6 Hz, 2H, –CH2–), 5.93 (d, J = 12.2 Hz, 1H,
@CH–CO2–), 6.70–6.72 (m, 2H, Ar–H), 7.05 (d, J = 12.2 Hz, 1H, Ar–
CH@), 7.42 (d, J = 8.4 Hz, 1H, Ar–H).
4.2.35. (Z)-3-[3-(Trifluoromethyl)phenyl]acrylic acid (cis-37)
Z-selective olefination of 3-(trifluoromethyl)benzaldehyde (93)
was performed using the procedure described above to provide
(Z)-ethyl 3-(3-(trifluoromethyl)phenyl)acrylate (cis-149) (86%,
Z:E = 98:2, determined by 1H-NMR spectrum) (silica gel CC,
EtOAc/hexane, 5:95) as a colorless oil: 1H-NMR (CDCl3, 400 MHz)
d: 1.23 (t, J = 7.2 Hz, 3H, –CH3), 4.17 (q, J = 7.2 Hz, 2H, –CH2–),
6.05 (d, J = 12.8 Hz, 1H, @CH–CO2–), 6.96 (d, J = 12.8 Hz, 1H, Ar–
CH@), 7.47 (dd, J = 7.6, 8.0 Hz, 1H, Ar–H), 7.58 (d, J = 7.6 Hz, 1H,
Ar–H), 7.74 (d, J = 8.0 Hz, 1H, Ar–H), 7.80 (s, 1H, Ar–H).
Hydrolysis of cis-149 was performed using the procedure de-
scribed above to afford cis-37 (90%) as colorless needles: mp 56–
57 °C (Toluene); 1H-NMR (CDCl3, 400 MHz) d: 6.07 (d, J = 12.6 Hz,
1H, @CH–CO2–), 7.10 (d, J = 12.6 Hz, 1H, Ar–CH@), 7.48 (dd,
J = 7.6, 8.0 Hz, 1H, Ar–H), 7.60 (d, J = 7.6 Hz, 1H, Ar–H), 7.77 (d,
J = 8.0 Hz, 1H, Ar–H), 7.83 (s, 1H, Ar–H); 13C-NMR (CDCl3,
100 MHz) d: 120.5 (d, @CH–CO2–), 122.5 (s, Ar), 125.8 (d, as a quar-
tet, Ar), 126.6 (d, as a quartet, Ar), 128.5 (d, Ar), 130.5 (s, as a quar-
tet, –CF3), 132.9 (d, Ar), 135.6 (s, Ar), 144.3 (d, Ar–CH@), 170.8 (s,
C@O); IR (KBr) 1701 cmꢀ1; ESI-MS m/z 215 (M+ꢀH); Anal. calcd
for C10H7F3O2: C, 55.56; H, 3.26. found: C, 55.47; H, 3.26.
Hydrolysis of cis-152 was performed using the procedure de-
scribed above to afford cis-40 (96%) as colorless needles: mp
145–146 °C (toluene); 1H-NMR (CDCl3, 400 MHz) d: 2.29 (s, 3H,
–CH3), 3.80 (s, 3H, –OCH3), 5.92 (d, J = 12.4 Hz, 1H, @CH–CO2–),
6.69–6.72 (m, 2H, Ar–H), 7.16 (d, J = 12.4 Hz, 1H, Ar–CH@), 7.44
(d, J = 8.8 Hz, 1H, Ar–H); 13C-NMR (CDCl3, 100 MHz) d: 20.2
(q, –CH3), 55.2 (q, –OCH3), 110.7 (d, Ar), 115.3 (d, Ar), 118.2
(d, @CH–CO2–), 126.5 (d, Ar), 131.1 (s, Ar), 138.3 (s, Ar), 144.9
(s, Ar), 160.1 (d, Ar–CH@), 171.7 (s, C@O); IR (KBr) 1695 cmꢀ1
;
ESI-MS m/z 191 (M+ꢀH); Anal. calcd for C11H12O3: C, 68.74;
H, 6.29. found: C, 68.78; H, 6.31.
4.2.39. (Z)-3-(3,5-Dimethoxyphenyl)acrylic acid (cis-41)
Z-selective olefination of 3,5-dimethoxybenzaldehyde (97) was
performed using the procedure described above to provide (Z)-
4.2.36. (Z)-3-[4-(Trifluoromethyl)phenyl]acrylic acid (cis-38)
The Z-selective olefination of 4-(trifluoromethyl)benzaldehyde
(94) was performed using the procedure described above to pro-
vide (Z)-ethyl 3-(4-(trifluoromethyl)phenyl)acrylate (cis-150)
(90%, Z:E = 95:5, determined by 1H-NMR spectrum) (silica gel CC,
ethyl 3-(3,5-dimethoxyphenyl)acrylate (cis-153) (94%, Z only,
determined by 1H-NMR spectrum) (silica gel CC, EtOAc/hexane,
10:90) as a colorless oil: 1H-NMR (CDCl3, 400 MHz) d: 1.25 (t,
J = 6.8 Hz, 3H, –CH3), 3.78 (s, 6H, –OCH3), 4.17 (q, J = 6.8 Hz, 2H,
–CH2–), 5.94 (d, J = 12.8 Hz, 1H, @CH–CO2–), 6.45 (s, 1H, Ar–H),
6.78 (s, 2H, Ar–H), 6.84 (d, J = 12.8 Hz, 1H, Ar–CH@).
EtOAc/hexane, 10:90) as
a
colorless oil: 1H-NMR (CDCl3,
270 MHz) d: 1.24 (t, J = 7.0 Hz, 3H, –CH3), 4.17 (q, J = 7.0 Hz, 2H, –
CH2–), 6.06 (d, J = 12.7 Hz, 1H, @CH–CO2–), 6.98 (d, J = 12.7 Hz,
1H, Ar–CH@), 7.60, 7.64 (d, J = 8.9 Hz, each 2H, Ar–H).
Hydrolysis of cis-150 was performed using the procedure de-
scribed above to afford cis-38 (87%) as colorless needles: mp 90–
93 °C (toluene); 1H-NMR (CDCl3, 400 MHz) d: 6.09 (d, J = 12.6 Hz,
1H, @CH–CO2–), 7.11 (d, J = 12.6 Hz, 1H, Ar–CH@), 7.61, 7.66 (d,
J = 8.8 Hz, each 2H, Ar–H); 13C-NMR (CDCl3, 100 MHz) d: 120.8
(d, @CH–CO2–), 122.5 (s, Ar), 125.0 (d, as a quartet, Ar), 129.9 (d,
Ar), 130.9 (s, as a quartet, –CF3), 137.9 (s, Ar), 144.3 (d, Ar–CH@),
Hydrolysis of cis-153 was performed using the procedure de-
scribed above to afford cis-41 (97%) as colorless needles: mp 99–
100 °C (toluene); 1H-NMR (CDCl3, 400 MHz) d: 3.77 (s, 6H,
–OCH3), 5.95 (d, J = 12.6 Hz, 1H, @CH–CO2–), 6.47 (s, 1H, Ar–H),
6.79 (s, 2H, Ar–H), 6.97 (d, J = 12.6 Hz, 1H, Ar–CH@); 13C-NMR
(CDCl3, 100 MHz) d: 55.3 (q, –OCH3), 102.0 (d, Ar), 107.8 (d, Ar),
119.0 (d,@CH–CO2–), 136.0 (s, Ar), 145.5 (d, Ar–CH@), 160.3 (s,
Ar), 171.4 (s, C@O); IR (KBr) 1705 cmꢀ1; ESI-MS m/z 207 (M+ꢀH);
Anal. calcd for C11H12O4: C, 63.45; H, 5.81. found: C, 63.22; H, 5.79.

K. Nishikawa et al. / Phytochemistry 96 (2013) 132–147
143
4.2.40. (Z)-3-(2,3,4-Trimethoxyphenyl)acrylic acid (cis-42)
Z-selective olefination of 2,3,4-trimethoxybenzaldehyde (98)
was performed using the procedure described above to provide
(KBr) 1688 cmꢀ1; ESI-MS m/z 399 (M+ꢀH); Anal. calcd for C9H6Cl6-
O2: C, 27.03; H, 1.51. found: C, 27.28.; H, 1.49.
(Z)-ethyl 3-(2,3,4-trimethoxyphenyl)acrylate (cis-154) (92%,
Z
only, determined by 1H-NMR spectrum) (silica gel CC, EtOAc/hex-
ane, 5:95) as a colorless oil: 1H-NMR (CDCl3, 270 MHz) d: 1.25 (t,
J = 7.0 Hz, 3H, –CH3), 3.87 (s, 6H, –OCH3), 3.88 (s, 3H, –OCH3),
4.16 (q, J = 7.0 Hz, 2H, –CH2–), 5.91 (d, J = 12.6 Hz, 1H, @CH–CO2–
), 6.66 (d, J = 8.8 Hz, 1H, Ar–H), 7.09 (d, J = 12.6 Hz, 1H, Ar–CH@),
7.51 (d, J = 8.8 Hz, 1H, Ar–H).
Hydrolysis of cis-154 was performed using the procedure de-
scribed above to afford cis-42 (93%) as colorless needles: mp 96–
98 °C (Toluene); 1H-NMR (CDCl3, 400 MHz) d: 3.86 (s, 3H,
–OCH3), 3.88 (s, 6H, –OCH3), 5.92 (d, J = 12.8 Hz, 1H, @CH–CO2–),
6.65 (d, J = 8.8 Hz, 1H, Ar–H), 7.15 (d, J = 12.8 Hz, 1H, Ar–CH@),
7.51 (d, J = 8.8 Hz, 1H, Ar–H); 13C-NMR (CDCl3, 100 MHz) d: 56.0
(q, –OCH3), 60.9 (q, –OCH3), 61.4 (q, –OCH3), 106.7 (d, Ar), 117.6
(d,@CH–CO2–), 121.3 (s, Ar), 126.0 (d, Ar), 140.7 (d, Ar–CH@),
141.6 (s, Ar), 152.6 (s, Ar), 155.0 (s, Ar), 171.4 (s, C@O); IR (KBr)
1695 cmꢀ1; ESI-MS m/z 237 (M+ꢀH); Anal. calcd for C12H14O5: C,
60.50; H, 5.92. found: C, 60.53; H, 5.92.
4.2.43. (Z)-3-[3,5-Bis(trifluoromethyl)phenyl]acrylic acid (cis-45)
Z-selective olefination of 3,5-bis(trifluoromethyl)benzaldehyde
(101) was performed using the procedure described above to pro-
vide (Z)-ethyl 3-(3,5-bis(trifluoromethyl)phenyl)acrylate (cis-157)
(85%, Z:E = 93:7, determined by 1H-NMR spectrum) (silica gel CC,
EtOAc/hexane, 5:95) as a colorless oil: 1H-NMR (CDCl3, 400 MHz)
d: 1.23 (t, J = 7.2 Hz, 3H, –CH3), 4.18 (q, J = 7.2 Hz, 2H, –CH2–),
6.15 (d, J = 12.8 Hz, 1H, @CH–CO2–), 6.99 (d, J = 12.8 Hz, 1H, Ar–
CH@), 7.83 (s, 1H, Ar–H), 7.99 (s, 2H, Ar–H).
Hydrolysis of cis-157 was performed using the procedure de-
scribed above to afford cis-45 (93%) as colorless needles: mp
102–103 °C (CH2Cl2/hexane, 20:80); 1H-NMR (CDCl3, 400 MHz) d:
6.18 (d, J = 12.4 Hz, 1H, @CH–CO2–), 7.14 (d, J = 12.4 Hz, 1H, Ar–
CH@), 7.85 (s, 1H, Ar–H), 8.00 (s, 2H, Ar–H); 13C-NMR (CDCl3,
100 MHz) d: 122.3 (d, @CH–CO2–), 122.6 (d, as a quartet, Ar),
123.1 (s, as a quartet, –CF3), 129.7 (d, Ar), 131.4 (s, as a quartet,
Ar), 136.2 (s, Ar), 142.8 (d, Ar–CH@), 170.4 (s, C@O); IR (KBr)
1709 cmꢀ1; ESI-MS m/z 283 (M+ꢀH); Anal. calcd for C11H6F6O2:
C, 46.50; H, 2.13. found: C, 45.59; H, 2.04.
4.2.41. (Z)-3-(2,4-Dichlorophenyl)acrylic acid (cis-43)
Z-selective olefination of 2,4-dichlorobenzaldehyde (99) was
performed using the procedure described above to provide (Z)-
ethyl 3-(2,4-dichlorophenyl)acrylate (cis-155) (85%, Z:E = 98:2,
determined by 1H-NMR spectrum) (silica gel CC, EtOAc/hexane,
3:97) as a colorless oil: 1H-NMR (CDCl3, 270 MHz) d: 1.21 (t,
J = 7.0 Hz, 3H, –CH3), 4.13 (q, J = 7.0 Hz, 2H, –CH2–), 6.09 (d,
J = 12.2 Hz, 1H, @CH–CO2–), 7.05 (d, J = 12.2 Hz, 1H, Ar–CH@),
7.22 (dd, J = 2.2, 8.4 Hz, 1H, Ar–H), 7.41 (d, J = 2.2 Hz, 1H, Ar–H),
7.48 (d, J = 8.4 Hz, 1H, Ar–H).
The hydrolysis of cis-155 was performed using the procedure
described above to afford cis-43 (91%) as colorless needles: mp
137–138 °C (Toluene); 1H-NMR (CDCl3, 400 MHz) d: 6.09 (d,
J = 12.0 Hz, 1H, @CH–CO2–), 7.17 (d, J = 12.0 Hz, 1H, Ar–CH@),
7.21 (dd, J = 1.8, 8.3 Hz, 1H, Ar–H), 7.41 (d, J = 1.8 Hz, 1H, Ar–H),
7.46 (d, J = 8.3 Hz, 1H, Ar–H); 13C-NMR (CDCl3, 100 MHz) d: 121.3
(d, @CH–CO2–), 126.6 (d, Ar), 129.0 (d, Ar), 131.8 (d, Ar), 131.9 (s,
Ar), 134.0 (s, Ar), 135.4 (s, Ar), 141.9 (d, Ar–CH@), 169.9 (s,
C@O); IR (KBr) 1710 cmꢀ1; ESI-MS m/z 215 (M+ꢀH); Anal. calcd
for C9H6Cl6O2: C, 49.80; H, 2.79. found: C, 49.93; H, 2.80.
4.2.44. (Z)-3-(Naphthalen-1-yl)acrylic acid (cis-46)
Z-selective olefination of 1-naphthaldehyde (102) was per-
formed using the procedure described above to provide (Z)-ethyl
3-(naphthalen-1-yl)acrylate (cis-158) (93%, Z:E = 99:1, determined
by 1H-NMR spectrum) (silica gel CC, EtOAc/hexane, 10:90) as a
colorless oil: 1H-NMR (CDCl3, 400 MHz) d: 1.01 (t, J = 7.2 Hz, 3H,
–CH3), 4.00 (q, J = 7.2 Hz, 2H, –CH2–), 6.24 (d, J = 12.2 Hz, 1H,
@CH–CO2–), 7.43–7.52 (m, 4H, Ar–H), 7.56 (d, J = 12.2 Hz, 1H, Ar–
CH@), 7.82–7.91 (m, 3H, Ar–H). The spectroscopic data were in
agreement with those in the literature (Oyamada and Kitamura,
2007).
Hydrolysis of cis-158 was performed using the procedure de-
scribed above to afford cis-46 (91%) as colorless needles: mp
163–164 °C (Toluene); 1H-NMR (CDCl3, 400 MHz) d: 6.20 (d,
J = 12.6 Hz, 1H, @CH–CO2–), 7.42 (t, J = 7.6 Hz, 1H, Ar–H), 7.47–
7.52 (m, 3H, Ar–H), 7.65 (d, J = 12.6 Hz, 1H, Ar–CH@), 7.81–7.86
(m, 3H, Ar–H); The physical and spectral data were consistent with
those reported in the literature (Oyamada and Kitamura, 2007).
4.2.42. (Z)-3-(3,5-Diiodophenyl)acrylic acid (cis-44) (Li et al., 1998;
Zhou and Zhao, 2009)
The methyl esterification of 4-amino-3,5-diiodobenzoic acid
(173), deamination with isopentyl nitrite, DIBAL-H reduction, and
PCC oxidation, using procedures according to the literature (Li
et al., 1998), produced 3,5-diiodobenzaldehyde (100) (23% in 4
steps) as colorless needles: 1H-NMR (CDCl3, 270 MHz) d: 8.15 (s,
2H, Ar–H), 8.30 (s, 1H, Ar–H), 9.83 (s, 1H, –CHO).
Z-selective olefination of 100 was performed using the proce-
dure described above to provide (Z)-ethyl 3-(3,5-diiodophe-
nyl)acrylate (cis-156) (88%, Z:E = 96:4, determined by 1H-NMR
spectrum) (silica gel CC, EtOAc/hexane, 3:97) as a colorless oil:
1H-NMR (CDCl3, 270 MHz) d: 1.26 (t, J = 6.8 Hz, 3H, –CH3), 4.18
(q, J = 6.8 Hz, 2H, –CH2–), 6.00 (d, J = 12.8 Hz, 1H, @CH–CO2–),
6.75 (d, J = 12.8 Hz, 1H, Ar–CH@), 7.82 (s, 2H, Ar–H), 8.00 (s, 1H,
Ar–H).
Hydrolysis of cis-156 was performed using the procedure de-
scribed above to afford cis-44 (95%) as colorless needles: mp
170–172 °C (CH2Cl2/hexane, 20:80); 1H-NMR (CDCl3, 400 MHz) d:
6.02 (d, J = 12.6 Hz, 1H, @CH–CO2–), 6.88 (d, J = 12.6 Hz, 1H, Ar–
CH@), 7.84 (s, 2H, Ar–H), 8.01 (s, 1H, Ar–H); 13C-NMR (CDCl3,
100 MHz) d: 94.1 (s, Ar), 121.1 (d, @CH–CO2–), 137.5 (d, Ar),
128.0 (s, Ar), 142.3 (d, Ar), 145.3 (d, Ar–CH@), 169.8 (s, C@O); IR
4.2.45. (Z)-3-(Phenanthren-9-yl)acrylic acid (cis-47)
Z-selective olefination of phenanthrene-9-carbaldehyde (103)
was performed using the procedure described above to provide
(Z)-ethyl 3-(phenanthren-9-yl)acrylate (cis-159) (85%,
Z only,
determined by 1H-NMR spectrum) (silica gel CC, EtOAc/hexane,
5:95) as a colorless oil: 1H-NMR (CDCl3, 270 MHz) d: 0.95 (t,
J = 7.3 Hz, 3H, –CH3), 4.00 (q, J = 7.3 Hz, 2H, –CH2–), 6.30 (d,
J = 11.9 Hz, 1H, @CH–CO2–), 7.54–7.68 (m, 5H, Ar–H and Ar–
CH@), 7.76 (s, 1H, Ar–H), 7.86, 7.96 (d, J = 7.6 Hz, each 1H, Ar–H),
8.67, 8.73 (d, J = 7.9 Hz, each 1H, Ar–H).
Hydrolysis of cis-159 was performed using the procedure de-
scribed above to afford cis-47 (77%) as colorless needles: mp
218–219 °C (toluene); 1H-NMR (DMSO-d6, 270 MHz) d: 6.30 (d,
J = 11.9 Hz, 1H, @CH–CO2–), 7.58–7.76 (m, 6H, Ar–CH = and Ar–
H), 7.96 (d, J = 7.6 Hz, 2H, Ar–H), 8.85 (m, 2H, Ar–H); 13C-NMR
(DMSO-d6, 100 MHz) d: 122.8 (d,@CH–CO2–), 123.3 (d, Ar), 124.3
(d, Ar), 125.2 (d, Ar), 126.6 (d, Ar), 126.8 (d, Ar), 126.9 (d, Ar),
127.0 (d, Ar), 127.1 (d, Ar), 128.7 (d, Ar), 129.6 (s, Ar), 129.7 (s,
Ar), 129.7 (s, Ar), 130.8 (s, Ar), 132.0 (s, Ar), 140.6 (d, Ar–CH@),
166.9 (s, C@O); IR (KBr) 1684 cmꢀ1; ESI-MS m/z 247 (M+ꢀH); Anal.
calcd for C17H12O2: C, 82.24; H, 4.87. found: C, 82.07; H, 4.93.

144
K. Nishikawa et al. / Phytochemistry 96 (2013) 132–147
4.2.46. (Z)-3-(Anthracen-9-yl)acrylic acid (cis-48)
4.2.49. (Z)-3-(2,3-Dihydrobenzofuran-5-yl)acrylic acid (cis-51)
Z-selective olefination of 2,3-dihydrobenzofuran-5-carbalde-
hyde (107) was performed using the procedure described above
to provide (Z)-ethyl 3-(2,3-dihydrobenzofuran-5-yl)acrylate (cis-
163) (78%, Z:E = 93:7, determined by 1H-NMR spectrum) (silica
gel CC, EtOAc/hexane, 3:97) as a colorless oil: 1H-NMR (CDCl3,
400 MHz) d: 1.26 (t, J = 7.4 Hz, 3H, –CH3), 3.22 (t, J = 8.8 Hz, 2H,
dihydrofuran-H), 4.19 (q, J = 7.4 Hz, 2H, –CH2–), 4.60 (t, J = 8.8 Hz,
2H, dihydrofuran-H), 5.78 (d, J = 12.8 Hz, 1H, @CH–CO2–), 6.75 (d,
J = 8.4 Hz, 1H, Ar–H), 6.82 (d, J = 12.8 Hz, 1H, Ar–CH@), 7.42 (d,
J = 8.4 Hz, 1H, Ar–H), 7.79 (s, 1H, Ar–H).
Hydrolysis of cis-163 was performed using the procedure de-
scribed above to afford cis-51 (98%) as colorless needles: mp
123–125 °C (CH2Cl2/hexane, 20:80); 1H-NMR (CDCl3, 400 MHz) d:
3.22 (t, J = 8.8 Hz, 2H, dihydrofuran-H), 4.61 (t, J = 8.8 Hz, 2H, dihy-
drofuran-H), 5.81 (d, J = 12.8 Hz, 1H, @CH–CO2–), 6.77 (d,
J = 8.4 Hz, 1H, Ar–H), 6.94 (d, J = 12.8 Hz, 1H, Ar–CH@), 7.74 (d,
J = 8.4 Hz, 1H, Ar–H), 7.75 (s, 1H, Ar–H); 13C-NMR (CDCl3,
100 MHz) d: 29.3 (t, dihydrofuran), 71.8 (t, dihydrofuran), 108.9
(d, Ar), 115.2 (d, @CH–CO2–), 127.0 (s, Ar), 127.1 (s, Ar), 127.5 (d,
Ar), 132.3 (d, Ar), 146.3 (d, Ar–CH@), 161.6 (s, Ar), 171.7 (s,
C@O); IR (KBr) 1692 cmꢀ1; ESI-MS m/z 189 (M+ꢀH); Anal. calcd
for C11H10O3: C, 69.46; H, 5.30. found: C, 69.65; H, 5.26.
Z-selective olefination of anthracene-9-carbaldehyde (104) was
performed using the procedure described above to provide (Z)-
ethyl 3-(anthracen-9-yl)acrylate (cis-160) (45%, Z only, determined
by 1H-NMR spectrum) (silica gel CC, EtOAc/hexane, 3:97) as a
colorless oil: 1H-NMR (CDCl3, 270 MHz) d: 0.55 (t, J = 7.3 Hz, 3H,
–CH3), 3.71 (q, J = 7.3 Hz, 2H, –CH2–), 6.61 (d, J = 12.2 Hz, 1H,
@CH–CO2–), 7.43–7.47 (m, 4H, Ar–H), 7.77 (d, J = 12.2 Hz, 1H, Ar–
CH@), 7.99–8.06 (m, 4H, Ar–H), 8.42 (s, 1H, Ar–H).
Hydrolysis of cis-160 was performed using the procedure de-
scribed above to afford cis-48 (85%) as yellow needles: mp 261–
263 °C (Toluene); 1H-NMR (DMSO-d6, 270 MHz) d: 6.61 (d,
J = 12.2 Hz, 1H, @CH–CO2–), 7.49–7.53 (m, 4H, Ar–H), 7.79 (d,
J = 12.2 Hz, 1H, Ar–CH@), 7.99–8.02, 8.07–8.11 (m, each 2H, Ar–
H), 8.55 (s, 1H, Ar–H); 13C-NMR (CDCl3, 100 MHz) d: 125.3 (d),
125.5 (d), 125.8 (d, Ar), 126.3 (d, Ar), 126.9 (d, Ar), 127.9 (s, Ar),
128.6 (d, Ar), 130.8 (s, Ar), 131.5 (s, Ar), 140.4 (d, Ar–CH@), 166.2
(s, C@O); IR (KBr) 1701 cmꢀ1; ESI-MS m/z 247 (M+ꢀH); Anal. calcd
for C17H12O2: C, 82.24; H, 4.87. found: C, 82.00; H, 4.91.
4.2.47. (Z)-3-(Dibenzo[b,d]furan-4-yl)acrylic acid (cis-49)
Z-selective olefination of dibenzo[b,d]furan-4-carbaldehyde
(105) was performed using the procedure described above to pro-
vide (Z)-ethyl 3-(dibenzo[b,d]furan-4-yl)acrylate (cis-161) (60%,
Z:E = 98:2, determined by 1H-NMR spectrum) (silica gel CC,
EtOAc/hexane, 5:95) as a colorless oil: 1H-NMR (CDCl3, 270 MHz)
d: 1.15 (t, J = 7.3 Hz, 3H, –CH3), 4.14 (q, J = 7.3 Hz, 2H, –CH2–),
6.20 (d, J = 12.7 Hz, 1H, @CH–CO2–), 7.30–7.39 (m, 2H, Ar–H),
7.39 (d, J = 12.7 Hz, 1H, Ar–CH@), 7.46 (t, J = 7.6 Hz, 1H, Ar–H),
7.57, 7.82 (d, J = 7.6 Hz, each 1H, Ar–H), 7.92–7.96 (m, 2H, Ar–H).
Hydrolysis of cis-161 was performed using the procedure de-
scribed above to afford cis-49 (82%) as colorless needles: mp
160–163 °C (toluene); 1H-NMR (CDCl3, 270 MHz) d: 6.18 (d,
J = 12.6 Hz, 1H, @CH–CO2–), 7.29–7.36 (m, 2H, Ar–H), 7.45 (t,
J = 7.6 Hz, 1H, Ar–H), 7.50 (d, J = 12.6 Hz, 1H, Ar–CH@), 7.56, 7.78
(d, J = 7.6 Hz, each 1H, Ar–H), 7.91–7.95 (m, 2H, Ar–H); 13C-NMR
(CDCl3, 100 MHz) d: 111.7 (d, @CH–CO2–), 120.1 (s, Ar), 121.2 (d,
Ar), 121.5 (d, Ar), 122.7 (d, Ar), 123.3 (d, Ar), 123.5 (s, Ar), 123.5
(s, Ar), 123.9 (d, Ar), 127.7 (s, Ar), 127.7 (d, Ar), 133.8 (s, Ar),
153.2 (d, Ar–CH@), 155.3 (s, Ar), 167.3 (s, C@O); IR (KBr)
1699 cmꢀ1; ESI-MS m/z 237 (M+ꢀH); Anal. calcd for C15H10O3: C,
75.62; H, 4.23. found: C, 75.62; H, 4.23.
4.2.50. (Z)-3-(Benzofuran-5-yl)acrylic acid (cis-52) (Saitoh et al.,
2009)
NBS (0.656 g, 3.69 mmol) and AIBN (8.10 mg, 49.2 lmol) were
added to a solution of 107 (0.364 g, 2.46 mmol) in chlorobenzene
(7.3 mL) at room temperature under an argon atmosphere. After
stirring for 1 h at 80 °C, the mixture was cooled to room tempera-
ture and diluted with EtOAc. The organic layers were washed with
saturated aqueous NaHCO3 and brine, dried (Na2SO4), filtered, and
concentrated in vacuo. The residue was purified by silica gel CC
(EtOAc/hexane, 3:97) to afford benzofuran-5-carbaldehyde (108)
(0.268 g, 1.84 mmol, 75%) as a colorless oil: 1H-NMR (CDCl3,
400 MHz) d: 6.82 (d, J = 2.0 Hz, 1H, furan-H), 7.54 (d, J = 8.8 Hz,
1H, Ar–H), 7.65 (d, J = 2.0 Hz, 1H, furan-H), 7.79 (d, J = 8.8 Hz, 1H,
Ar–H), 8.07 (s, 1H, Ar–H), 9.99 (s, 1H, –CHO); spectroscopic data
were consistent with those reported in the literature (van Otterlo
et al., 2005).
Z-selective olefination of 108 was performed using the
procedure described above to provide (Z)-ethyl 3-(benzofuran-5-
yl)acrylate (cis-164) (96%, Z:E = 97:3, determined by 1H-NMR
spectrum) (silica gel CC, EtOAc/hexane, 3:97) as a colorless oil:
1H-NMR (CDCl3, 400 MHz) d: 1.25 (t, J = 7.6 Hz, 3H, –CH3), 4.13
(q, J = 7.6 Hz, 2H, –CH2–), 5.93 (d, J = 12.6 Hz, 1H, @CH–CO2–),
6.76 (d, J = 2.0 Hz, 1H, furan-H), 7.01 (d, J = 12.6 Hz, 1H, Ar–CH@),
7.46 (d, J = 8.8 Hz, 1H, Ar–H), 7.56 (d, J = 8.8 Hz, 1H, Ar–H), 7.60
(d, J = 2.0 Hz, 1H, furan-H), 7.99 (s, 1H, Ar–H).
Hydrolysis of cis-164 was performed using the procedure de-
scribed above to afford cis-52 (96%) as colorless needles: mp 82–
83 °C (CH2Cl2/hexane, 10:90); 1H-NMR (CDCl3, 400 MHz) d: 5.97
(d, J = 12.8 Hz, 1H, @CH–CO2–), 6.79 (d, J = 2.0 Hz, 1H, furan-H),
7.16 (d, J = 12.8 Hz, 1H, Ar–CH@), 7.48, 7.59 (d, J = 8.6 Hz, each
1H, Ar–H), 7.63 (d, J = 2.0 Hz, 1H, furan-H), 7.98 (s, 1H, Ar–H);
13C-NMR (CDCl3, 100 MHz) d: 106.9 (d, furan), 111.0 (d, Ar),
117.5 (d,@CH–CO2–), 123.5 (d, Ar), 127.0 (d, furan), 127.3 (s, Ar),
129.2 (s, Ar), 145.6 (d, Ar–CH@), 146.3 (d, Ar), 155.3 (s, Ar), 171.4
(s, C@O); IR (KBr) 1715 cmꢀ1; ESI-MS m/z 187 (M+ꢀH); Anal. calcd
for C11H8O3: C, 70.21; H, 4.29. found: C, 69.57; H, 4.19.
4.2.48. (Z)-3-(Naphthalen-2-yl)acrylic acid (cis-50)
Z-selective olefination of 2-naphthaldehyde (106) was per-
formed using the procedure described above to provide (Z)-ethyl
3-(naphthalen-2-yl)acrylate (cis-162) (83%, Z:E = 99:1, determined
by 1H-NMR spectrum) (silica gel CC, EtOAc/hexane, 3:97) as a
colorless oil: 1H-NMR (CDCl3, 270 MHz) d: 1.25 (t, J = 7.3 Hz, 3H,
–CH3), 4.20 (q, J = 7.3 Hz, 2H, –CH2–), 6.02 (d, J = 12.7 Hz, 1H,
@CH–CO2–), 7.10 (d, J = 12.7 Hz, 1H, Ar–CH@), 7.46–7.50 (m, 2H,
Ar–H), 7.73 (dd, J = 1.6, 8.6 Hz, 1H, Ar–H), 7.79–7.86 (m, 3H, Ar–
H), 8.03 (s, 1H, Ar–H).
Hydrolysis of cis-162 was performed using the procedure de-
scribed above to afford cis-50 (91%) as colorless needles: mp
135–137 °C (Toluene); 1H-NMR (CDCl3, 400 MHz) d: 6.05 (d,
J = 12.7 Hz, 1H, @CH–CO2–), 7.23 (d, J = 12.7 Hz, 1H, Ar–CH@),
7.51–7.47 (m, 2H, Ar–H), 7.85–7.76 (m, 4H, Ar–H), 8.05 (s, 1H,
Ar–H); 13C-NMR (CDCl3, 100 MHz) d: 118.7 (d,@CH–CO2–), 126.3
(d, Ar), 127.0 (d, Ar), 127.0 (d, Ar), 127.5 (d, Ar), 127.6 (d, Ar),
128.6 (d, Ar), 130.4 (d, Ar), 131.9 (s, Ar), 132.8 (s, Ar), 133.6 (s,
Ar), 145.9 (d, Ar–CH@), 171.7 (s, C@O); IR (KBr) 1697 cmꢀ1; ESI-
MS m/z 197 (M+ꢀH); Anal. calcd for C13H10O2: C, 78.77; H, 5.09.
found: C, 78.69; H, 5.11.
4.2.51. (Z)-3-(Benzofuran-6-yl)acrylic acid (cis-53) (Tasker et al.,
1997)
Potassium carbonate (8.82 g, 63.8 mmol) was added to a solu-
tion of 3-bromophenol (174) (10.0 g, 58.0 mmol) and bromoacetal-
dehyde diethyl acetal (11.1 g, 56.1 mmol) in DMSO (58 mL) at

K. Nishikawa et al. / Phytochemistry 96 (2013) 132–147
145
room temperature under Ar. After the mixture was stirred for 12 h
at 160 °C, H2O and EtOAc were added to the reaction. The mixture
was extracted with EtOAc, washed with brine, dried (MgSO4), fil-
tered and concentrated in vacuo. The crude product was purified
by silica gel CC (EtOAc/hexane, 5:95) to give 1-bromo-3-(2,2-dieth-
oxyethoxy)benzene (175) (14.4 g, 50.1 mmol, 86%) as a colorless
oil: 1H-NMR (CDCl3, 400 MHz) d: 1.25 (t, J = 6.8 Hz, 6H, –CH3),
3.59–3.67, 3.72–3.80 (m, each 2H, –OCH2–), 3.98 (d, J = 5.0 Hz,
2H, ArO–CH2–), 4.82 (t, J = 5.0 Hz, –CH–(OEt)2), 6.85–6.87 (m, 1H,
Ar–H), 7.07–7.15 (m, 3H, Ar–H).
Z:E = 94:6, determined by 1H-NMR spectrum) (silica gel CC,
EtOAc/hexane, 5:95) as a colorless oil: 1H-NMR (CDCl3, 400 MHz)
d: 1.24 (t, J = 6.8 Hz, 3H, –CH3), 4.19 (q, J = 6.8 Hz, 2H, –CH2–),
5.97 (d, J = 12.6 Hz, 1H,@CH–CO2–), 7.03 (d, J = 12.6 Hz, 1H, Ar–
CH@), 7.32 (d, J = 5.8 Hz, 1H, thiophene-H), 7.41 (d, J = 5.8 Hz, 1H,
thiophene-H), 7.59, 7.82 (d, J = 8.6 Hz, each 1H, Ar–H), 8.11 (s,
1H, Ar–H).
Hydrolysis of cis-166 was performed using the procedure de-
scribed above to afford cis-54 (96%) as colorless needles: mp
125–126 °C (CH2Cl2/hexane, 10:90); 1H-NMR (CDCl3, 400 MHz) d:
5.99 (d, J = 12.8 Hz, 1H,@CH–CO2–), 7.18 (d, J = 12.8 Hz, 1H, Ar–
CH@), 7.33, 7.45 (d, J = 5.4 Hz, each 1H, thiophene–H), 7.62, 7.84
(d, J = 8.4 Hz, each 1H, Ar–H), 8.09 (s, 1H, Ar–H); 13C-NMR (CDCl3,
100 MHz) d: 118.1 (d,@CH–CO2–), 122.0 (d), 124.2 (d), 125.6 (d),
126.0 (d), 127.1 (d), 130.6 (s, Ar), 139.4 (s, Ar), 140.8 (s, Ar),
146.2 (d, Ar–CH@), 171.1 (s, C@O); IR (KBr) 1684 cmꢀ1; ESI-MS
m/z 203 (M+ꢀH); Anal. calcd for C11H8O2S: C, 64.69; H, 3.95. found:
C, 64.48; H, 3.95.
Polyphosphoric acid (PPA) (0.743 g, 6.83 mmol) was added to a
solution of 175 (0.656 g, 2.28 mmol) in toluene (4.6 mL) at room
temperature under Ar. The mixture was headed until reflux began,
this being maintained for 4 h, then cooled to room temperature,
quenched with cooled H2O and extracted with EtOAc. The organic
layers were washed with brine, dried (MgSO4), filtered and concen-
trated in vacuo. The crude product was purified by silica gel CC
(EtOAc/hexane, 2:98) to give 6-bromobenzofuran (176) (major,
0.206 g, 1.05 mmol, 46%) and 4-bromobenzofuran (177) (minor,
0.183 g, 0.935 mmol, 41%) as colorless oils: 176: 1H-NMR (CDCl3,
400 MHz) d: 1H-NMR (CDCl3, 400 MHz) d: 6.75 (d, J = 1.6 Hz, 1H,
furan-H), 7.36 (dd, J = 1.2, 8.4 Hz, 1H, Ar–H), 7.46 (d, J = 8.4 Hz,
1H, Ar–H), 7.60 (d, J = 1.6 Hz, 1H, furan-H), 7.69 (s, 1H, Ar–H);
177: 1H-NMR (CDCl3, 400 MHz) d: 6.82 (d, J = 2.4 Hz, 1H, furan-
H), 7.17 (dd, J = 7.6, 8.4 Hz, Ar–H), 7.40 (d, J = 7.6 Hz, 1H, Ar–H),
7.45 (d, J = 8.4 Hz, 1H, Ar–H), 7.66 (d, J = 2.4 Hz, 1H, furan-H).tBuLi
(0.652 mL, 1.59 M in pentane, 1.00 mmol) was added to a solution
of 176 (99.0 mg, 0.502 mmol) in Et2O (2.5 mL) at ꢀ78 °C under Ar.
After 5 min of stirring, DMF (0.117 mL, 1.51 mmol) was added to
the reaction. The mixture was warmed to 0 °C and then stirred
for 30 min. The mixture was diluted with Et2O, washed with
H2O, 1 M HCl and brine, dried over Na2SO4, filtered and concen-
trated in vacuo. The crude product was purified by silica gel CC
(EtOAc/hexane, 5:95) to give benzofuran-6-carbaldehyde (109)
(51.0 mg, 0.271 mmol, 54%) as a colorless oil: 1H-NMR (CDCl3,
400 MHz) d: 6.87 (d, J = 2.2 Hz, 1H, furan-H), 7.73 (d, J = 7.6 Hz,
1H, Ar–H), 7.80 (dd, J = 1.6, 7.6 Hz, 1H, Ar–H), 7.83 (d, J = 2.2 Hz,
1H, furan-H), 8.02 (s, 1H, Ar–H), 10.08 (s, 1H, –CHO); spectroscopic
data were consistent with those reported in the literature (Cole-
man et al., 2004).
4.2.53. (Z)-3-(Pyridin-2-yl)acrylic acid (cis-55)
Z-selective olefination of picolinaldehyde (111) was performed
using the procedure described above to provide (Z)-ethyl 3-(pyri-
din-2-yl)acrylate (cis-167) (78%, Z:E = 92:8, determined by 1H-
NMR spectrum) (silica gel CC, EtOAc/hexane, 10:90) as a colorless
oil: 1H-NMR (CDCl3, 400 MHz) d: 1.26 (t, J = 7.2 Hz, 3H, –CH3),
4.21 (q, J = 7.2 Hz, 2H, –CH2–), 6.14 (d, J = 12.8 Hz, 1H, @CH–CO2–
), 6.95 (d, J = 12.8 Hz, 1H, Ar–CH@), 7.22 (m, 1H, Py–H), 7.64–7.70
(m, 2H, Py–H), 8.59 (d, J = 4.8 Hz, 1H, Py–H); spectroscopic data
were consistent with those reported in the literature (Tsukada
et al., 1998; Beveridge and Arndtsen, 2010).
Hydrolysis of cis-167 was performed using the procedure de-
scribed above to afford cis-55 (89%) as colorless needles: mp
107–108 °C (Toluene); 1H-NMR (CDCl3, 400 MHz) d: 6.32 (d,
J = 13.6 Hz, 1H, @CH–CO2–), 6.86 (d, J = 13.6 Hz, 1H, Py–CH@),
7.53–7.48 (m, 2H, Py–H), 8.61 (dt, J = 1.6, 7.6 Hz, 1H, Py-H), 8.61
(d, J = 4.8 Hz, 1H, Py–H); 13C-NMR (CDCl3, 100 MHz) d: 124.7
(d,@CH–CO2–), 127.4 (d, Py), 130.1 (d, Py), 135.1 (d, Py), 139.9 (d,
Py), 146.0 (d, Py–CH@), 151.3 (s, Py), 166.7 (s, C@O); IR (KBr)
1695 cmꢀ1; ESI-MS m/z 148 (M+ꢀH); Anal. calcd for C8H7NO2: C,
64.42; H, 4.73; N, 9.39. found: C, 64.42; H, 4.65; N, 9.44.
Z-selective olefination of 109 was performed using the proce-
dure described above to provide (Z)-ethyl 3-(benzofuran-6-
yl)acrylate (cis-165) (82%, Z:E = 94:6, determined by 1H-NMR
spectrum) (silica gel CC, EtOAc/hexane, 3:97) as a colorless oil:
1H-NMR (CDCl3, 400 MHz) d: 1.27 (t, J = 7.2 Hz, 3H, –CH3), 4.21
(q, J = 7.2 Hz, 2H, –CH2–), 5.95 (d, J = 12.8 Hz, 1H, @CH–CO2–),
6.76 (d, J = 2.0 Hz, 1H, furan-H), 7.02 (d, J = 12.8 Hz, 1H, Ar–CH@),
7.45 (d, J = 8.0 Hz, 1H, Ar–H), 7.55 (d, J = 8.0 Hz, 1H, Ar–H), 7.66
(d, J = 2.0 Hz, 1H, furan-H), 7.96 (s, 1H, Ar–H).
4.2.54. (Z)-3-(6-Methoxypyridin-2-yl)acrylic acid (cis-56)
Z-selective olefination of 6-methoxypicolinaldehyde (112) was
performed using the procedure described above to provide (Z)-
ethyl
3-(6-methoxypyridin-2-yl)acrylate
(cis-168)
(83%,
Z:E = 99:1, determined by 1H-NMR spectrum) (silica gel CC,
EtOAc/hexane, 3:97) as a colorless oil: 1H-NMR (CDCl3, 400 MHz)
d: 1.27 (t, J = 7.2 Hz, 3H, –CH3), 3.89 (s, 3H, –OCH3), 4.24 (q,
J = 7.2 Hz, 2H, –CH2–), 6.35 (d, J = 12.8 Hz, 1H, @CH-CO2–), 6.66
(d, J = 8.4 Hz, 1H, Py–H), 6.72 (d, J = 12.8 Hz, 1H, Ar–CH@), 7.05
(d, J = 7.2 Hz, 1H, Py–H), 7.54 (t, J = 7.2, 8.4 Hz, 1H, Py–H).
Hydrolysis of cis-168 was performed using the procedure de-
scribed above to afford cis-56 (91%) as colorless needles: mp
107–108 °C (toluene); 1H-NMR (CDCl3, 400 MHz) d: 4.06 (s, 3H,
–OCH3) 6.20 (d, J = 13.4 Hz, 1H, @CH–CO2–), 6.76 (d, J = 13.4 Hz,
1H, Py–CH@), 6.91 (d, J = 8.8 Hz, 1H, Py–H), 7.04 (d, J = 7.6 Hz,
1H, Py–H), 7.78 (dd, J = 7.6, 8.8 Hz, 1H, Py–H); 13C-NMR (CD3OD,
100 MHz) d: 55.9 (q, –OCH3), 114.1 (d, Py), 122.1 (d, @CH–CO2–),
126.6 (d, Py), 138.1 (d, Py), 143.5 (d, Py–CH@), 149.8 (s, Py),
164.2 (s, Py), 170.0 (s, C@O); IR (KBr) 1701 cmꢀ1; ESI-MS m/z 178
(M+ꢀH); Anal. calcd for C9H9NO3: C, 60.33; H, 5.06; N, 7.82. found:
C, 58.50; H, 5.06; N, 7.82.
Hydrolysis of cis-165 was performed using the procedure de-
scribed above to afford cis-53 (99%) as colorless needles: mp
98–100 °C (Et2O/hexane, 10:90); 1H-NMR (CDCl3, 400 MHz) d:
5.98 (d, J = 12.8 Hz, 1H, @CH–CO2–), 6.77 (d, J = 2.0 Hz, 1H, fur-
an-H), 7.15 (d, J = 12.8 Hz, 1H, Ar-CH=), 7.47 (d, J = 8.4 Hz, 1H,
Ar–H), 7.56 (d, J = 8.4 Hz, 1H, Ar–H), 7.67 (d, J = 2.0 Hz, 1H, fur-
an–H), 7.98 (s, 1H, Ar–H); 13C-NMR (CDCl3, 100 MHz) d: 106.7
(d, furan), 113.2 (d, Ar), 117.7 (d,@CH–CO2–), 120.5 (d, Ar),
125.6 (d, Ar), 128.8 (s, Ar), 130.7 (s, Ar), 146.0 (d), 146.7 (d),
170.5 (s, C@O); IR (KBr) 1688 cmꢀ1
;
ESI-MS m/z 211
([M + Na]+); Anal. calcd for C11H3O3: C, 70.21; H, 4.29. found:
C, 69.98; H, 4.23.
4.2.52. (Z)-3-(Benzo[b]thiophen-5-yl)acrylic acid (cis-54)
Z-selective olefination of benzo[b]thiophene-5-carbaldehyde
(110) was performed using the procedure described above to pro-
vide (Z)-ethyl 3-(benzo[b]thiophen-5-yl)acrylate (cis-166) (89%,
4.2.55. (Z)-3-(6-Methylpyridin-2-yl)acrylic acid (cis-57)
Z-selective olefination of 6-methylpicolinaldehyde (113) was
performed using the procedure described above to provide (Z)-

146
K. Nishikawa et al. / Phytochemistry 96 (2013) 132–147
ethyl 3-(6-methylpyridin-2-yl)acrylate (cis-169) (83%,
Z only,
References
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J = 7.2 Hz, 3H, –CH3), 2.53 (s, 3H, Py–CH3), 4.22 (q, J = 7.2 Hz, 2H,
–CH2–), 6.11 (d, J = 12.8 Hz, 1H, @CH–CO2–), 6.90 (d, J = 12.8 Hz,
1H, Ar–CH@), 7.07, 7.40 (d, J = 7.6 Hz, each 1H, Py–H), 7.56 (t,
J = 7.6 Hz, 1H, Py–H).
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Hydrolysis of cis-169 was performed using the procedure de-
scribed above to afford cis-57 (85%) as colorless needles: mp
131–132 °C (EtOAc); 1H-NMR (CD3OD, 270 MHz) d: 2.66 (s, 3H,
–CH3), 6.31 (d, J = 13.0 Hz, 1H, @CH–CO2–), 6.77 (d, J = 13.0 Hz,
1H, Py–CH@), 7.32–7.28 (m, 2H, Py–H), 7.85 (t, J = 7.8 Hz, 1H, Py–
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CO2–), 127.1 (d, Py), 130.8 (d, Py), 136.6 (d, Py), 142.7 (d, Py–
CH@), 150.9 (s, Py), 156.9 (s, Py), 170.5 (s, C@O); IR (KBr)
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Z-selective olefination of nicotinaldehyde (114) was performed
using the procedure described above to provide (Z)-ethyl 3-(pyri-
din-3-yl)acrylate (cis-170) (93%, Z:E = 96:4, determined by 1H-
NMR spectrum) (silica gel CC, EtOAc/hexane, 15:85) as a colorless
oil: 1H-NMR (CDCl3, 270 MHz) d: 1.25 (t, J = 7.3 Hz, 3H, –CH3), 4.18
(q, J = 7.3 Hz, 2H, –CH2–), 6.08 (d, J = 12.6 Hz, 1H, @CH–CO2–), 6.93
(d, J = 12.6 Hz, 1H, Ar–CH@), 7.31 (m, 1H, Py–H), 8.08 (d, J = 7.8 Hz,
1H, Py–H), 8.54 (d, J = 4.6 Hz, 1H, Py–H), 8.65 (s, 1H, Py–H).
Hydrolysis of cis-170 was performed using the procedure de-
scribed above to afford cis-58 (53%) as colorless needles: mp
154–156 °C (toluene); 1H-NMR (CD3OD, 400 MHz) d: 6.14 (d,
J = 12.8 Hz, 1H, @CH–CO2–), 7.01 (d, J = 12.8 Hz, 1H, Py–CH@),
7.43 (dd, J = 4.8, 8.2 Hz, 1H, Py–H), 8.11 (dd, J = 1.6, 8.2 Hz, 1H,
Py–H), 8.45 (dd, J = 1.6, 4.8 Hz 1H, Py–H), 8.68 (d, J = 1.6 Hz, 1H,
Py–H); 13C-NMR (CDCl3, 100 MHz) d: 124.4 (d, @CH–CO2–), 124.7
(d, Py), 133.3 (s, Py), 139.0 (d, Py), 139.3 (d, Py), 149.3 (d, Py–
CH@), 150.6 (d, Py), 169.0 (s, C@O); IR (KBr) 1706 cmꢀ1; ESI-MS
m/z 148 (M+ꢀH); Anal. calcd for C8H7NO2: C, 64.42; H, 4.73; N,
9.39. found: C, 64.32; H, 4.81; N, 9.32.
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4.3. Measurement of phytotoxic activities against lettuce root growth
Phytotoxic activity was measured according to the method de-
scribed by Hiradate et al. (2004). Filter paper was placed in a glass
petri dish. The test compound was dissolved in H2O at various con-
centrations and a portion of each test solution was added on to the
filter paper in the petri dish for each treatment. Fifteen pre-germi-
nated (25 °C in the dark) seedlings of lettuce (Lactuca sativa cv.
Great Lakes 366) were used as a replicate for each treatment. Seed-
lings were incubated for 48 h at 25 °C in the dark, and the inhibi-
tory activity of each test solution on root elongation was
determined by measuring the length of each root and comparing
it with that of the untreated control (using only distilled water).
An EC50 value, which indicates the effective concentration required
to induce a half-maximum effect, was calculated from a dose re-
sponse curve of the phytotoxicity for each compound by applying
a statistical model, probit model (Bliss, 1934), using the computer
program, SPSS 13.0 J.
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Acknowledgements
This work is supported by the Program for Promotion of Basic
and Applied Research for Innovations in the Bio-oriented Industry
(BRAIN) and ‘‘Innovations Inspired by Nature Research Support
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