Key structural features of cis-cinnamic acid as an allelochemical

Article abstract of DOI:10.1016/j.phytochem.2012.08.001

1-O-cis-cinnamoyl-β-d-glucopyranose is one of the most potent allelochemicals isolated from Spiraea thunbergii Sieb. It is suggested that it derives its strong inhibitory activity from cis-cinnamic acid, which is crucial for phytotoxicity. It was synthesized to confirm its structure and bioactivity, and also a series of cis-cinnamic acid analogues were prepared to elucidate the key features of cis-cinnamic acid for lettuce root growth inhibition. The cis-cyclopropyl analogue showed potent inhibitory activity while the saturated and alkyne analogues proved to be inactive, demonstrating the importance of the cis-double bond. Moreover, the aromatic ring could not be replaced with a saturated ring. However, the 1,3-dienylcyclohexene analogue showed strong activity. These results suggest that the geometry of the C-C double bond between the carboxyl group and the aromatic ring is essential for potent inhibitory activity. In addition, using several light sources, the photostability of the cinnamic acid derivatives and the role of the C-C double bond were also investigated.

Full text of DOI:10.1016/j.phytochem.2012.08.001

Phytochemistry 84 (2012) 56–67
Contents lists available at SciVerse ScienceDirect
Phytochemistry
journal homepage: www.elsevier.com/locate/phytochem
Key structural features of cis-cinnamic acid as an allelochemical
Masato Abe a, Keisuke Nishikawa a, Hiroshi Fukuda b, Kazunari Nakanishi b, Yuta Tazawa b,
Tomoya Taniguchi b, So-young Park c, 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 11 April 2012
Received in revised form 4 June 2012
Available online 5 September 2012
1-O-cis-cinnamoyl-b-D-glucopyranose is one of the most potent allelochemicals isolated from Spiraea
thunbergii Sieb. It is suggested that it derives its strong inhibitory activity from cis-cinnamic acid, which
is crucial for phytotoxicity. It was synthesized to confirm its structure and bioactivity, and also a series of
cis-cinnamic acid analogues were prepared to elucidate the key features of cis-cinnamic acid for lettuce
root growth inhibition. The cis-cyclopropyl analogue showed potent inhibitory activity while the satu-
rated and alkyne analogues proved to be inactive, demonstrating the importance of the cis-double bond.
Moreover, the aromatic ring could not be replaced with a saturated ring. However, the 1,3-dienylcyclo-
hexene analogue showed strong activity. These results suggest that the geometry of the C–C double bond
between the carboxyl group and the aromatic ring is essential for potent inhibitory activity. In addition,
using several light sources, the photostability of the cinnamic acid derivatives and the role of the C–C
double bond were also investigated.
Keywords:
cis-Cinnamic acid
Allelochemicals
Plant growth inhibitors
Thunberg spirea
Spiraea thunbergii
Rosaceae
Lactuca sativba L.
Lettuce
Ó 2012 Elsevier Ltd. All rights reserved.
Asteraceae
1. Introduction
2005). Consequently, cis-2 is widely considered to be an auxin
agonist (Haagen and Went, 1935). Although mechanistic investiga-
1-O-cis-Cinnamoyl-b-
D
-glucopyranose (1) (Fig. 1) was isolated
tions based on molecular biology are in progress (Chen et al., 2005;
Guo et al., 2011), the molecular mechanisms of these activities
have not yet been described. The first chemical synthesis of the
glycosyl ester 1 has already been achieved which confirmed the
proposed structure and determined the optical rotation (Matsuo
et al., 2011). Described herein is the synthesis of the analogues
(3–26) to confirm the essential structural features of cis-2 as an
allelochemical. These cis-2 analogues are expected to be new
weed-killer or weed-control agents without environmental risks
(Rice, 1995; Vyvyan, 2002; Macias et al., 2007). To measure the
bioactivity of the cis-cinnamic acid analogues, the inhibitory
activity against lettuce root growth was tested as described by
Hiradate et al. (2005).
from Spiraea thunbergii (Hiradate et al., 2004) and Spiraea prunifo-
lia (Morita et al., 2005b) and identified as a potent allelochemical.
It was found by a bioassay of the growth-inhibitory activity on root
elongation of germinated seedlings of lettuce (Lactuca sativa L.) in
56 species of woody plants grown in Japan (Morita et al., 2001,
2005a). The assay indicated that cis-cinnamic acid (cis-2), the agly-
cone of the glycosyl ester 1, is an essential structure for the bioac-
tivity because cis-2 inhibited lettuce root growth as effectively as 1,
while trans-cinnamic acid (trans-2) inhibited growth 100 times less
than the cis-isomer (Hiradate et al., 2005). trans-2 is generally con-
sidered to be physiologically inactive and antagonistic in function
with regard to the effects of auxin in plants (Koepfli et al., 1938;
van Overbeek et al., 1951). cis-2, on the other hand, is known as
the compound that inhibits the root growth of Avena sativa,
Triticum aestivum, and Arabidopsis thaliana, and it also induces epi-
nastic curvature in Solanum lycopersicum seedlings (Koepfli et al.,
1938; van Overbeek et al., 1951; Yang et al., 1999; Wong et al.,
2. Results and discussion
2.1. Design of cis-cinnamic acid analogues
In order to identify the essential features responsible for the
inhibitory activity of cis-cinnamic acid (cis-2), the structure of
cis-2 was divided into three units – carboxylic acid, cis-olefin and
⇑
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 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.phytochem.2012.08.001

M. Abe et al. / Phytochemistry 84 (2012) 56–67
57
mine the importance of the aromatic ring. As for the E,Z-dienyl
analogues 24–26, the spatial distances between the ring moiety
and the carboxylic acid are longer than that in cis-2.
2.2. Syntheses of the cis-cinnamic acid analogues
Fig. 1. Structures of 1-O-cis-cinnamoyl-b-
cinnamic acids (cis- and trans-2).
D-glucopyranose (1) and cis- and trans-
The syntheses of cis-cinnamic acid (cis-2) and its cis-analogues
4, 20, 21, 22, 23, 24, 25, and 26, were performed mainly by the
Z-selective olefination of the corresponding aldehydes with the
Ando–Emmons reagent (Ando, 1997; Ando et al., 2000), followed
by hydrolysis, as shown in Scheme 1. The glycosyl ester 1 was pre-
pared as previously reported (Matsuo et al., 2011). The methoxy-
methyl ester cis-5 and cyanoethyl ester cis-6 were prepared via
the esterification of cis-2 with MOMCl or 2-cyanoethanol, respec-
tively. The amide cis-7 was synthesized by amidation of the corre-
sponding acid chloride 28, prepared by treatment of cis-2 with
oxalyl chloride. Reduction of cis-4 with DIBAL-H provided the
alcohol cis-8, and the nitrile cis-9 was synthesized according to
the literature (Kojima et al., 2004). The phosphoric acid cis-10
was prepared via cross coupling of cis-iodostyrene (29) and diethyl
aromatic ring moieties. The analogues, the parts of which were
individually modified, were designed as shown in Fig. 2. The ana-
logues 3–11 are the carboxylic acid analogues, namely salt, ester,
amide, alcohol, nitrile, phosphoric acid and tetrazole. The ana-
logues trans-2 and 12–15 are partially modified olefin analogues,
which are the trans-isomer, ethyl, alkynyl, cyclopropyl, and oxiranyl
analogues, respectively. Compounds 16–19 are a- and b-substituted
cis- and trans-alkenyl analogues. Compounds 20–23 were designed
as cis-cinnamic acid analogues with the cyclohexyl, cyclohexenyl
or butenyl moieties replacing the phenyl ring, in order to deter-
Fig. 2. Structures of the cis-cinnamic acid analogues.

58
M. Abe et al. / Phytochemistry 84 (2012) 56–67
Scheme 4. Synthesis of the cis-cinnamic acid analogues 14 and 15: (a) Et2Zn, TFA,
CH2I2, CH2Cl2, 0 °C, 62%, (b) Deng and Jacobsen, 1992, 41%, (c) KOH, EtOH-H2O, rt,
66%.
Scheme 5. Synthesis of the cinnamic acid analogues cis-16 and trans-16: (a) ethyl
2-(diethoxyphosphoryl)acetate, NaH, THF, reflux, cis-35: 14%, trans-35: 68%, (b) 10%
NaOH aq., EtOH, rt.
Scheme 1. Syntheses of the cis-cinnamic acid analogues 4–8: (a) ethyl 2-[bis(2-
isopropylphenoxy)phosphoryl]acetate, Triton B, THF, ꢀ78 °C, 94%, Z:E = 98:2, (b)
10% NaOH aq., EtOH, rt, 97%, (c) MOMCl, diisopropylethylamine, 0 °C, 99%, (d) 2-
cyanoethanol, EDCI, DMAP, CH2Cl2, 0 °C, 91%, Z:E = 63:37, (e) (COCl)2, DMF (1 drop),
CH2Cl2, 0 °C, (f) 28% NH4OH aq., CH2Cl2, 0 °C, 59% (2 steps), (g) DIBAL-H, CH2Cl2,
ꢀ78 °C, 83%.
Scheme 2. Synthesis of the cis-cinnamic acid analogue 10: (a) HP(O)(OEt)2,
Pd(PPh3)4, Et3N, THF, 60 °C, 76%, (b) TMSBr, CH2Cl2, rt, 27%.
Scheme 6. Synthesis of the cinnamic acid analogues cis-18 and trans-18 using the
ynolate: (a) tBuLi, THF, ꢀ78 °C to rt, (b) acetophenone (34), THF, rt, then MeI, HMPA,
rt, cis-38: 20%, trans-38: 80%, (c) 10% NaOH aq., EtOH, rt.
phosphonate (Kobayashi and William, 2002, 2004) (Scheme 2)
(Hirao et al., 1982). The cis-styryl tetrazole 11 was synthesized
by the Suzuki–Miyaura coupling (Yi and Yoo, 1995) of iodotetraz-
ole and cis-styryl pinacolboronate 32 (Molander and Ellis, 2008),
followed by deprotection of cis-33 with hydrochloric acid
(Scheme 3). The compounds trans-2, 12, 13, and 19 are all commer-
cially available. The cis-cyclopropyl analogue cis-14 (Kefford, 1959)
was synthesized via a modified Simmons–Smith reaction (Furuka-
wa et al., 1966; Lorenz et al., 2004) of cis-2 (Scheme 4). The epoxide
cis-15 was prepared from cis-4 through asymmetric epoxidation
(Deng and Jacobsen, 1992) and subsequent hydrolysis. The
trisubstituted olefins cis- and trans-16, cis- and trans-17, and the
trans-analogues 20, 21, and 22 were synthesized via the Horner–
Wadsworth–Emmons (Wadsworth and Emmons, 1961) or Wittig
reaction, and the resulting trans- and cis-isomers were separated
by silica gel column chromatography (Scheme 5). The pure com-
pounds, without any geometrical isomers, were finally obtained
after recrystallization. The tetrasubstituted olefins cis- and trans-
18 were prepared via the torquoselective olefination using the yno-
late 37 (Shindo et al., 2004) (Scheme 6).
2.3. Bioassay and discussions
The growth inhibitory activity of the cis-cinnamic acid ana-
logues 1–26 against root-growth of lettuce (Lactuca sativa cv.)
was measured as described by Hiradate et al. (2005). The EC50 val-
ues, which indicate the effective concentration required to induce a
half-maximum effect, are shown in Tables 1 and 2. The inhibitory
activity of the synthetic glycosyl ester 1 was below 10ꢀ5 M in EC50
value, which was identical with the reported value and that of the
Scheme 3. Synthesis of the cis-cinnamic acid analogue 11: (a) dicyclohexylborane, Et2O, rt, then AcOH, 0 °C, 69%, (b) 5-iodo-1-(methoxymethyl)-1H-tetrazole, Pd(PPh3)4,
Na2CO3, toluene-H2O, reflux, 44%, Z:E = 90:10, (c) 6 M HCl, MeOH, rt, 62%.

M. Abe et al. / Phytochemistry 84 (2012) 56–67
59
Table 1
Inhibitory activity of cis-cinnamic acid analogues 1–26. EC50 values are the effective
concentration required to induce
a half-maximum effect against root-growth of
lettuce (Lactuca sativa cv.).
Compounds
EC50
(lM)
Compounds
EC50 (lM)
1
6.8
2.5
4.7
5.8
cis-14
cis-15
cis-16
cis-17
cis-18
19
cis-20
cis-21
cis-22
cis-23
cis-24
cis-25
cis-26
3.9
343
1.7
5.9
15
123
>500
3.6
cis-2
cis-3
cis-4
cis-5
cis-6
cis-7
cis-8
cis-9
cis-10
cis-11
12
Fig. 3. Essential structural features for the phytotoxicity of the cis-cinnamic acid 2.
6.3
>500
146
>500
177
>500
>500
111
>500
requirement for inhibition and therefore could be substituted by
the 1-cyclohexenyl group, where only the sp2-hybridized carbon
at the C-1 position on the ring is necessary. The compound cis-
23, which did not have a ring moiety, was inactive, indicating that
the ring moiety is crucial for potent activity.
72
117
>500
>500
>500
13
2.3.4. Effects of the length between the carboxylic acid and the
aromatic ring
Table 2
Inhibitory activity of the trans-cinnamic acid analogues. EC50 values are the effective
Since the carbon-chain elongated compounds cis-24, cis-25, and
cis-26 did not show any inhibitory activity, it could be inferred that
the distance between the aromatic ring and the carboxylic acid
moiety plays a crucial role. The essential structural features of
cis-2 as an allelochemical are summarized in Fig. 3.
concentration required to induce
lettuce (Lactuca sativa cv.).
a half-maximum effect against root-growth of
Compounds
EC50
(lM)
Compounds
EC50 (lM)
cis-2
2.5
trans-18
trans-20
trans-21
trans-22
>500
>500
>500
>500
trans-2
trans-16
trans-17
>500
>500
>500
2.4. Photoisomerization of the cinnamic acid analogues
If the biological tests of cinnamic acid are not carried out care-
fully under dark conditions, the correct bioactivity cannot be ob-
tained due to the photochemical isomerization of the cinnamic
acid (Clampitt et al., 1962; Lippert and Lüder, 1962; Rontani
et al., 1988; Turner et al., 1993; Wong et al., 2005; Salum et al.,
2011). In order to ensure the essential bioactive moieties, the
photostability of the cinnamic acid derivatives was examined with
several light sources. Irradiation of trans-cinnamic acid (trans-2)
and the glycoside trans-1 was carried out in D2O using 5-mm glass
tubes under a xenon light (300 W) at 25 °C; the Z:E ratios were
determined by 1H NMR spectra. As shown in Fig. 4, the trans-2
was isomerized to give the photostationary state in less than a
few hours. The Z:E ratio of the photostationary state of 2 was
70:30, which is nearly consistent with that reported in the litera-
ture (Hocking, 1969). The glycoside of trans-cinnamic acid (trans-
1) was also isomerized, but slower than the aglycone trans-2.
Photochemical isomerization of cis-cinnamic acid (cis-2) was also
carried out under the same conditions to achieve a similar
synthetic 2. The potassium cis-cinnamate (3), which is more solu-
ble in water, also showed strong activity. The trans-cinnamic acid 2
did not exhibit any activity, as already indicated (Hiradate et al.,
2005).
2.3.1. Effects of modification of the carboxylic acid
Since the cis-cinnamic acid ethyl ester 4 and the methoxy-
methyl ester 5, which is labile to acid, showed similar levels of
activity to that observed with cis-2, it is likely that the ester is
metabolized to the carboxylic acid and the acid is acting as the
essential moiety, a phenomenon observed in the glycoside 1. The
cyanoethyl ester cis-6 can be easily removed under basic condi-
tions; however, it had no inhibitory activity. The substitution of a
variety of groups, such as amide (cis-7), alcohol (cis-8), nitrile
(cis-9), phosphoric acid (cis-10) and tetrazole (cis-11), gave inactive
compounds. These results indicated the importance of the carbox-
ylic acid functionality.
2.3.2. Effects of modification of the C–C double bond
Compounds 12 and 13 turned out to be inactive. However, the
cyclopropyl analogue cis-14 showed activity as potent as that of
2. These results suggest that the fixed cis-geometry, and not the
electronic effect of the p-electrons of the C–C double bond, is crit-
ical for the inhibitory activity. Since the cis-double bond can be
substituted by the cis-cyclopropane (e.g. cis-14), the conjugated
1,3-dienyl unit is not essential for good activity. However, the
epoxide cis-15 was not a potent inhibitor, perhaps due to the insta-
bility of the structure. The methylated tri- and tetra-substituted
cis-cinnamic acid analogues 16, 17, and 18 retained their potent
inhibition. The biphenyl carboxylic acid 19, having a cis-geometry,
showed low activity, probably due to steric hindrance. The de-
creased inhibitory activity of the trans-forms of 16, 17, and 18 sug-
gested again the importance of the cis-form for activity.
2.3.3. Effects of modification of the aromatic ring
The compounds cis-20, trans-20, trans-21, cis-22 and trans-22
did not show high potency, although compound cis-21 inhibited
root-growth. These results suggest that the aromatic ring is not a
Fig. 4. Photochemical isomerization of trans-cinnamic acid (trans-2) (h), its
glycoside (trans-1) (s), and cis-cinnamic acid (cis-2) (d).

60
M. Abe et al. / Phytochemistry 84 (2012) 56–67
the irradiation time was lengthened until the EC50 value of the
isomerized trans-2 finally reached nearly 100 M, in three hours.
l
These results suggest that the inactive trans-2 and its glycoside
trans-1, which are not themselves poisonous to the plant, are re-
leased from the plant and converted into the active cis-1 and -2
forms by sunlight irradiation. The resulting compounds would
act as allelochemicals and inhibit the growth of plants.
3. Conclusion
The cis-configuration of cinnamic acid is clearly essential for let-
tuce root-growth inhibition. The aromatic ring is thought to play
the role of a planar hydrophobic moiety rather than an electronic
function. In addition, it was found that the carboxylate is also
essential, presumably owing to the hydrogen bonding to the target
protein; however, it can be replaced by some esters, which are eas-
ily hydrolyzed in tissues. The spatial arrangement of the aromatic
ring and the carboxylate is likewise important for the bioactivity.
Cinnamic acids can be easily isomerized to a photostationary mix-
ture of cis- and trans-forms by sunlight. This implies that the inac-
tive trans-cinnamic acid could be used as a plant growth regulator
after photoconversion. Although the mechanistic details are still
unclear, these results, which partially clarified the SAR of cis-2,
would contribute to the design of bioprobes, clarification of the
bioactive mechanism, and the development of new herbicides. Fur-
ther SAR study of cis-2 along with chemical biology studies are in
progress.
Fig. 5. Photochemical isomerization of trans-cinnamic acid (trans-2) (ꢀ), and its
derivatives (16 (j), 17 (N) and 18 (s)) by a xenon light.
photostationary state (Z:E = 70:30) within an hour (Fig. 4). The b-
and
a-monomethylated trans-cinnamic acids 16 and 17 were
isomerized faster than trans-2, and the dimethylated cinnamic acid
trans-18 was somewhat converted by light, with the Z:E ratio of the
photostationary state being 10:90 (Fig. 5).
The cis-2 and trans-2 compounds dissolved in water were not
isomerized at all under fluorescent lighting in the laboratory, indi-
cating that the EC50 values for non-isomeric cis-cinnamic acid had
been accurately measured.
4. Experimental section
4.1. Materials
In contrast, the sunlight-irradiated isomerization of trans-2 dis-
solved in D2O proceeded in glass tubes. The isomerization experi-
ments were carried out during the daytime, outdoors under
cloudy conditions at ca. 10 °C. The photostationary state was
achieved within a matter of hours, depending on the climate con-
ditions, and the E/Z ratio was almost 1:1. These results indicate
that trans-2 might work as a plant growth inhibitor like cis-2 if
an aqueous solution of this essentially inactive compound is
sprayed on soils in daylight. To confirm this hypothesis, a prelimin-
ary lettuce growth inhibition test using trans-2 was carried out as
follows: The aqueous solutions of trans-2 at various concentrations
were placed in glass petri dishes and were irradiated by sunlight.
Then, pre-germinated lettuce seedlings were transplanted on the
trans-2-treated soils and incubated in the dark in the usual
manner. As shown in Fig. 6, the inhibitory activity increased as
Optical rotations were obtained using a Horiba SEPA-300. The
melting points were measured on a Yazawa micromelting point
BY-1. The 1H and 13C NMR spectra were recorded using a JEOL
JNM AL-400 (400 and 100 MHz), and a JNM ECA-600 spectrometer
(600 and 150 MHz). Chemical shifts were reported in ppm down-
field from the peak of Me4Si (TMS) used as the internal standard.
Splitting patterns are designed as ‘‘s, d, t, q, and m,’’ indicating ‘‘sin-
glet, doublet, triplet, quartet, and multiplet,’’ respectively. The IR
spectra were recorded on a Shimadzu FT/IR-8300 spectrometer
using either a KBr disk or a NaCl cell. Mass spectra were obtained
on a JEOL JMS-700 or a JEOL JMS-T100CS. High-resolution mass
spectra were obtained on a JEOL JMS-700 or a JEOL JMS-T100CS.
Column chromatography (CC) was performed on silica gel (Kanto
Chemical Co.) whereas thin-layer chromatography (TLC) was
Fig. 6. Inhibitory activity of trans-cinnamic acid (trans-2) exposed to sunlight. (A) The effect of concentration under the conditions of various exposed time to sunlight: 0 h
(4), 0.5 h (ꢀ), 1 h (h) and 3 h (d). (B) The effect of exposed time to sunlight at various concentrations of trans-2 [100 M (d), 300 M (s) and 1000 M (j)].
l
l
l

M. Abe et al. / Phytochemistry 84 (2012) 56–67
61
employed pre-coated plates (0.25 mm, silica gel Merck 60 F254).
Reaction mixtures were stirred magnetically. The stereochemistry
was determined by NOE experiments, unless otherwise noted.
ture of cis-6 and trans-6 (0.165 g, 0.822 mmol, 91%, E:Z = 37:63,
determined by 1H NMR analysis). A part of the mixture was further
separated by HPLC (Mightysil Si 60, EtOAc/hexane, 3:97) to give
only cis-6 as colorless needles: mp 70–71 °C (CH2Cl2/hexane,
5:95); 1H NMR (CDCl3, 400 MHz) d: 2.66 (t, J = 6.0 Hz, 2H, –CH2–
CN), 4.30 (t, J = 6.0 Hz, 2H, –CO2–CH2–), 5.97 (d, J = 12.6 Hz, 1H,
@CH–CO2–), 7.05 (d, J = 12.6 Hz, 1H, Ar–CH@), 7.32–7.42 (m, 3H,
Ar–H), 7.59–7.62 (m, 2H, Ar–H); 13C NMR (CDCl3, 100 MHz) d:
17.8 (t, –CH2–CN), 58.4 (t, –CO2–CH2–), 116.7 (s, –CN), 118.2 (d,
@CH–CO2–), 128.0 (d, Ar), 129.3 (d, Ar), 129.7 (d, Ar), 134.5 (s,
Ar), 145.4 (d, Ar–CH@), 165.1 (s, C@O); IR (KBr) 2249,
1713 cmꢀ1; FAB–MS m/z 185 (M+); Anal. calcd for C12H11NO2: C,
71.63; H, 5.51; N, 6.96. found: C, 71.53; H, 5.54; N, 7.03.
4.2. Synthesis
4.2.1. (Z)-Ethyl 3-Phenylacrylate (cis-4)
To
a
solution of ethyl 2-[bis(2-isopropylphenoxy)phos-
phoryl]acetate (3.26 g, 8.05 mmol) in tetrahydrofuran (THF)
(73 mL) was added dropwise Triton B (40% in MeOH, 4.04 mL,
10.2 mmol) at ꢀ78 °C under an argon atmosphere. After 15 min
of stirring, a solution of benzaldehyde (27) (0.777 g, 7.32 mmol)
in THF (24 mL) was added dropwise to the solution. After 10 h,
the mixture was quenched with saturated aqueous NH4Cl and ex-
tracted with EtOAc. The organic layer was washed with H2O, satu-
rated aqueous NaHCO3 and brine, dried over MgSO4, filtered and
concentrated in vacuo. The crude product was purified by silica
gel CC (EtOAc/hexane, 5:95) to give cis-4 (94%, 6.87 mmol,
E:Z = 5:95, determined by 1H NMR spectroscopic analysis) as a col-
orless oil: 1H NMR (CDCl3, 400 MHz) d: 1.24 (t, J = 7.2 Hz, 3H, -CH3),
4.17 (q, J = 7.2 Hz, 2H, -CH2-), 5.95 (d, J = 12.8 Hz, 1H, @CH–CO2–),
6.95 (d, J = 12.8 Hz, 1H, Ar–CH@), 7.32–7.38 (m, 3H, Ar–H), 7.57–
7.59 (m, 2H, Ar–H); The observed characterization data were
consistent with those previously reported (Ando, 1997).
4.2.5. (Z)-3-Phenylacrylamide (cis-7)
To a solution of cis-2 (0.200 g, 1.35 mmol) in CH2Cl2 (2.0 mL)
were added Dimethylformamide (DMF) (1 drop) and oxalyl chlo-
ride (0.240 mL, 2.80 mmol) at 0 °C under argon atmosphere. After
40 min of stirring, the mixture was concentrated in vacuo to afford
the crude (Z)-3-phenylacryloyl chloride as a yellow oil. The crude
product was employed directly in the following reaction. A solu-
tion of the crude (Z)-3-phenylacryloyl chloride in CH2Cl2
(0.80 ml) was poured into 28% aqueous NH3 solution (2.0 mL) at
0 °C under an argon atmosphere. After 10 min of stirring, the mix-
ture was extracted with CH2Cl2, washed with brine, dried over
MgSO4, filtered and concentrated in vacuo. The residue was puri-
fied by recrystallization (EtOAc/hexane, 10:90) to give cis-7
(0.122 g, 0.830 mmol, 59% in 2 steps) as colorless needles: mp
86–87 °C; 1H NMR (CDCl3, 400 MHz) d: 5.45 (brs, 2H, –NH2), 5.99
(d, J = 12.8 Hz, 1H, @CH–CO2–), 6.86 (d, J = 12.8 Hz, 1H, Ar–CH@),
7.31–7.40 (m, 3H, Ar–H), 7.48 (brd, J = 7.6 Hz, 2H, Ar–H); 13C
NMR (CDCl3, 100 MHz) d: 123.8 (d, @CH–CO2–), 128.6 (d, Ar),
128.8 (d, Ar), 128.9 (d, Ar), 134.8 (s, Ar), 137.6 (d, Ar–CH@); IR
(KBr) 1667, 1618 cmꢀ1; EI-MS m/z 147 (M+); Anal. calcd for
C9H9NO: C, 73.45; H, 6.16; N, 9.52. found: C, 73.37; H, 6.19; N, 9.42.
4.2.2. (Z)-3-Phenylacrylic Acid (cis-cinnamic acid) (cis-2)
To a solution of cis-4 (1.21 g, 6.87 mmol) in EtOH (14 mL) was
added 10% NaOH (28 mL) at room temperature. After 12 h, the
mixture was adjusted to pH 1.0 with 1 M HCl, and then extracted
with EtOAc. The organic layer was washed with brine, dried over
MgSO4, filtered and concentrated in vacuo. The residue was puri-
fied by recrystallization (CH2Cl2/hexane, 5:95) to afford cis-2
(0.983 g, 6.64 mmol, 97%) as colorless needles: mp 55–57 °C
(CH2Cl2/hexane, 5:95); 1H NMR (CDCl3, 400 MHz) d: 5.97 (d,
J = 12.8 Hz, 1H, @CH–CO2–), 7.07 (d, J = 12.8 Hz, 1H, Ar–CH@), 7.35–
7.37 (m, 3H, Ar–H), 7.59–7.62 (m, 2H, Ar–H); The observed character-
ization data were consistent with those reported (Reed et al., 1993).
4.2.6. (Z)-3-Phenylprop-2-en-1-ol (cis-8)
After a solution of cis-4 (0.470 g, 2.67 mmol) in CH2Cl2 (8.9 mL)
was cooled to ꢀ78 °C under an argon atmosphere, DIBAL-H (1.0 M
in hexane, 6.41 mL, 6.41 mmol) was added dropwise to the solu-
tion. The mixture was stirred for 2 h, quenched with MeOH and a
trace amount of H2O at 0 °C, filtered through Celite pad, and the fil-
trate was washed with CH2Cl2 and concentrated in vacuo. Purifica-
tion using silica gel CC (EtOAc/hexane, 20:80) yielded cis-8
(0.298 g, 2.22 mmol, 83%) as a colorless oil: 1H NMR (CDCl3,
400 MHz) d: 1.43 (brs, 1H, –OH), 4.45 (dd, J = 1.4, 6.4 Hz, 2H,
–CH2–OH), 5.88 (dt, J = 6.3, 12.0 Hz, 1H,@CH–CH2–), 6.58 (d,
J = 12.0 Hz, 1H, Ar–CH@), 7.20–7.38 (m, 5H, Ar–H); The observed
characterization data were consistent with those reported (Denis
et al., 1986).
4.2.3. (Z)-Methoxymethyl 3-phenylacrylate (cis-5)
To a solution of cis-2 (0.114 g, 0.770 mmol) in CH2Cl2 (11 mL)
were
added
dropwise diisopropylethylamine
(0.784 mL,
4.62 mmol) and MOMCl (methoxymethyl chloride, 0.290 mL,
3.85 mmol) at 0 °C under an argon atmosphere. After 1.5 h, the
reaction was quenched with saturated aqueous NaHCO3, extracted
with EtOAc, and the organic layer was washed with brine, dried
over MgSO4, filtered and concentrated in vacuo. The crude product
was purified by silica gel CC (EtOAc/hexane, 5:95) to afford cis-5
(0.147 g, 0.764 mmol, 99%) as a colorless oil: 1H NMR (CDCl3,
400 MHz) d: 3.38 (s, 3H, –OCH3), 5.25 (s, 2H, –CH2–), 5.96 (d,
J = 12.6 Hz, 1H,@CH–CO2–), 6.98 (d, J = 12.6 Hz, 1H, Ar–CH@),
7.28–7.38 (m, 3H, Ar–H), 7.57–7.64 (m, 2H, Ar–H); 13C NMR (CDCl3,
100 MHz) d: 57.5 (q, –OCH3), 90.2 (t, CH2), 119.0 (d, @CH–CO2–),
127.9 (d, Ar), 129.0 (d, Ar), 129.7 (d, Ar), 134.5 (s, Ar), 144.2 (d,
Ar–CH@), 165.3 (s, C@O); IR (neat) 1722 cmꢀ1; EI-MS m/z 192
(M+), 147 (M+ꢀMOM); HR EI-MS m/z 192.0783 (M+, calcd for
4.2.7. (Z)-Styrylphosphonic Acid (cis-10)
To a degassed THF solution of (Z)-(2-iodovinyl)benzene (cis-29)
(1.00 g, 4.34 mmol), Pd(PPh3)4 (0.745 g, 0.645 mmol) and
HP(O)(OEt)2 (0.527 ml, 4.12 mmol) at room temperature under
an argon atmosphere, Et3N (0.570 ml, 4.12 mmol) was added. The
resulting mixture was bubbled with N2 gas for 3 min and stirred
for 24 h at 60 °C. The reaction was quenched with saturated aque-
ous NaHCO3, extracted with EtOAc, and the organic layer was
washed with brine, dried over MgSO4, filtered and concentrated
in vacuo. The crude residue was purified by silica gel CC (MeOH/
CHCl3, 10:90) to afford (Z)-diethyl styrylphosphonate (cis-30)
C11H12O3 192.0786).
4.2.4. (Z)-2-Cyanoethyl 3-phenylacrylate (cis-6)
To a solution of cis-2 (0.134 g, 0.905 mmol) in CH2Cl2 (11 mL)
were added DMAP (4-(N,N–dimethylamino)pyridine, 22.1 mg,
18.1 lmol), 2-cyanoethanol (68.0 lL, 0.996 mmol) and EDCI
(0.208 g, 1.09 mmol) at 0 °C under argon atmosphere. After
5 min, the reaction was quenched with H2O, extracted with CH2Cl2,
washed with saturated aqueous NaHCO3 and brine, dried over
MgSO4, filtered and concentrated in vacuo. The crude product
was purified by silica gel CC (EtOAc/hexane, 10:90) to afford a mix-
(0.792 g, 3.30 mmol, 76%) as
a
brown oil; 1H NMR (CDCl3,
400 MHz) d: 1.19 (t, J = 7.2 Hz, 6H, –CH3), 3.99 (q, J = 7.2 Hz, 4H,
–CH2–), 5.81 (dd, J = 14.5, 15.8 Hz, 1H, @CH–PO3Et2), 7.29 (dd,
J = 14.5, 52.0 Hz, 1H, Ar–CH@), 7.31–7.42 (m, 3H, Ar–H), 7.66–

62
M. Abe et al. / Phytochemistry 84 (2012) 56–67
7.71 (m, 2H, Ar–H); 13C NMR (CDCl3, 100 MHz) d: 16.1 (q, as a
14.4 mmol) was slowly added to the solution. The reaction was
stirred for 30 min at ꢀ78 °C, warmed to 0 °C and stirred for an
additional 30 min. The reaction was quenched with saturated
aqueous NH4Cl, extracted with EtOAc, and the organic layer was
washed with saturated aqueous Na2S2O3 and brine, dried over
MgSO4, filtered and concentrated in vacuo. The residue was puri-
fied by bulb to bulb distillation (0.8 mmHg, 150 °C) to give
5-iodo-1-(methoxymethyl)-1H-tetrazole (1.10 g, 4.58 mmol, 38%)
as a yellow oil: 1H NMR (CDCl3, 400 MHz) d: 3.49 (s, 3H, –OCH3),
5.86 (s, 2H, –CH2–); 13C NMR (CDCl3, 100 MHz) d: 58.5 (q,
3
2
doublet, JP–C = 6.2 Hz, –CH3), 61.7 (t, as a doublet, JP–C = 4.6 Hz,
1
–CH2–). 116.6 (d, as
a doublet, JP–C = 185.5 Hz,=CH–PO3Et2),
128.1 (d, Ar), 129.3 (d, Ar), 129.5 (d, Ar), 135.2 (s, as a doublet,
3JP–C = 9.2 Hz, Ar), 148.3 (d, Ar–CH@); IR (neat) 1250, 1609, 2984,
3443 cmꢀ1; EI-MS m/z 240 (M+); FAB-MS m/z 240 (M+); HR EI-
MS m/z 240.0917 (M+, calcd for C12H17O3P 240.0915); Spectro-
scopic data were consistent with those reported in the literature
(Kobayashi and William, 2002).
To a solution of cis-30 (0.250 g, 1.04 mmol) in CH2Cl2 (2.5 mL)
was added TMSBr (0.302 mL, 2.29 mmol) at room temperature un-
der an argon atmosphere. The mixture was stirred for 1.5 h. After
the solvent was removed in vacuo, the residue was dissolved in
H2O and the mixture was washed with Et2O/hexane (10:90). After
the mixture was concentrated in vacuo, the crude product was
purified by recrystallization (CH3CN) to give cis-10 (51.1 mg,
0.278 mmol, 27%) as light brown plates: mp 131–133 °C; 1H NMR
(CD3OD, 400 MHz) d: 5.82 (t, J = 14.5 Hz, 1H, @CH–PO3H2), 7.02
(dd, J = 14.5, 48.4 Hz, 1H, Ar–CH@), 7.19–7.47 (m, 3H, Ar–H),
7.68–7.85 (m, 2H, Ar–H); 13C NMR (CD3OD, 100 MHz) d: 120.5 (d,
–OCH3), 82.6 (t, –CH2–), 112.5 (s, tetrazole); IR (neat) 2941 cmꢀ1
;
EI-MS m/z 240 (M+); HR EI-MS m/z 239.9507 (M+, calcd for C3H5N4
OI 239.9508).
To a solution of Pd(PPh3)4 (0.285 g, 0.247 mmol) and Na2CO3
(0.355 g, 3.35 mmol) in toluene (80 mL) and H2O (8.0 mL) was
added
a
solution of 5-iodo-1-(methoxymethyl)-1H-tetrazole
(0.418 g, 1.74 mmol) and cis-32 (0.400 g, 1.74 mmol) in toluene
(40 mL) at room temperature under an argon atmosphere. The
mixture was heated until reflux began this being continued for
3 h, then the whole cooled to room temperature, quenched with
saturated aqueous NH4Cl and extracted with EtOAc. The combined
organic phase was washed with brine, dried over MgSO4, filtered
and concentrated in vacuo. The crude product was purified by silica
gel CC (EtOAc/hexane, 15:85) and following bulb to bulb distilla-
tion (0.4 mm Hg, 150 °C) to provide (Z)-1-(methoxymethyl)-5-sty-
ryl-1H-tetrazole (cis-33) (0.162 g, 0.750 mmol, 44%, E:Z = 10:90,
determined by 1H NMR spectrum) as a yellow oil: 1H NMR (CDCl3,
400 MHz) d: 3.46 (s, 3H, –OCH3), 5.80 (s, 2H, –CH2–), 6.67 (d,
J = 12.8 Hz, 1H, Ar–CH = CH–), 7.09 (d, J = 12.8 Hz, 1H, Ar–CH@),
7.30–7.43 (m, 3H, Ar–H), 7.61 (d, J = 7.6 Hz, 2H, Ar–H); 13C NMR
(CDCl3, 100 MHz) d: 58.2 (q, –OCH3), 82.1 (t, –CH2–), 114.3 (d,
Ar–CH = CH–), 128.0 (d, Ar), 128.5 (d, Ar), 129.4 (d, Ar), 135.5 (s,
1
as a doublet, JP–C = 182.9 Hz, @CH2–PO3H2), 129.1 (d, Ar), 130.0
3
(d, Ar), 130.8 (d, Ar), 137.0 (s, as a doublet, JP–C = 8.2 Hz, Ar),
147.3 (d, Ar–CH@); IR (KBr) 2855, 2299 cmꢀ1; FAB-MS m/z 185
(M++H); HR FAB-MS m/z 185.0.370 (M++H, calcd for C3H10O3P
185.0368); Anal. calcd for C3H9O3P: C, 52.18, H, 4.93, found: C,
52.23, H, 4.88.
4.2.8. (Z)-5-Styryl-1H-tetrazole (cis-11)
To a solution of cyclohexene (0.787 mL, 7.77 mmol) in Et2O
(5.0 mL) was added dropwise BH3-SMe2 (0.352 mL, 3.70 mmol) at
0 °C under an argon atmosphere. After 1 h, the resulting solid
was allowed to settle without stirring. The supernatant organic
solution was removed by syringe, and the residual solid was dried
under reduced pressure to afford dicyclohexylborane as a colorless
solid, which was used without purification in the next reaction. To
the dicyclohexylborane was added a solution of 4,4,5,5-tetra-
methyl-2-(phenylethynyl)-1,3,2-dioxaborolane (cis-31) (0.800 g,
3.51 mmol) in Et2O (10 mL) at room temperature under an argon
atmosphere. After the mixture was stirred for 1.5 h, AcOH
(0.261 mL, 4.56 mmol) was added dropwise to the solution at
0 °C. After 10 min, ethanolamine (0.424 mL, 7.02 mmol) was added
to the mixture. After 15 min, the resulting mixture was diluted
with hexane, filtered through a plugged column, washed with
EtOAc/hexane (10:90) and concentrated in vacuo. The crude prod-
uct was purified by bulb to bulb distillation (1.5 mmHg, 150 °C) to
afford (Z)-4,4,5,5-tetramethyl-2-styryl-1,3,2-dioxaborolane (cis-
32) (0.557 g, 2.42 mmol, 69%) as a colorless oil: 1H NMR (CDCl3,
400 MHz) d: 1.29 (s, 12H, –CH3), 5.59 (d, J = 15.6 Hz, 1H, @CH–
BO2–), 7.21 (d, J = 15.6 Hz, 1H, Ar–CH@), 7.25–7.32 (m, 3H, Ar–H),
7.49–7.57 (m, 2H, Ar–H); FAB-MS m/z 230 (M+); The spectroscopic
data were consistent with those reported in the literature
(Molander and Ellis, 2008).
To a solution of 1H-tetrazole (2.10 g, 30.0 mmol) in THF (30 mL)
was added Et3N (5.40 mL, 39.0 mmol) at 0 °C under an argon atmo-
sphere. After 30 min, MOMCl (2.87 mL, 39.0 mmol) was added to
the resulting mixture. The reaction was warmed to room temper-
ature and stirred for 5 h. The reaction was quenched with H2O, ex-
tracted with EtOAc, and the organic layer was washed with brine,
dried over MgSO4, filtered and concentrated in vacuo to afford a
mixture of 1-(methoxymethyl)-1H-tetrazole and 2-(methoxy-
methyl)-2H-tetrazole (2.70 g, 21.1 mmol, 70%) as a colorless oil.
The mixture was used in the next step without purification. After
Ar), 137.7 (d, Ar–CH@), 163.3 (s, tetrazole); IR (neat) 1643 cmꢀ1
;
EI-MS m/z 216 (M+); HR ESI-MS m/z 217.1087 (M++H, calcd for
C11H13N4O 217.1089).
To a solution of cis-33 (0.140 g, 0.648 mmol) in MeOH (15 mL)
was added 6 M HCl (11 mL) at room temperature. The mixture
was stirred for 12 h, diluted with H2O, neutralized with 10% NaOH
and extracted with CHCl3. The combined organic layers were
washed with brine, dried over MgSO4, filtered and concentrated
in vacuo. Purification over silica gel CC (Et2O/hexane, 10:90) gave
cis-11 (69.0 mg, 0.401 mmol, 62%) as colorless needles: mp 114–
115 °C; 1H NMR (CD3OD, 400 MHz) d: 6.58 (d, J = 12.4 Hz, 1H, Ar–
CH = CH–), 7.18 (d, J = 12.4 Hz, 1H, Ar–CH@), 7.31–7.35 (m, 5H,
Ar–H); 13C NMR (CD3OD, 100 MHz) d: 111.4 (d, Ar–CH = CH–),
129.6 (d, Ar), 130.0 (d, Ar), 130.1 (d, Ar), 136.1 (s, Ar), 141.3 (d,
Ar–CH@), 153.9 (s, tetrazole); IR (KBr) 1653 cmꢀ1; FAB-MS m/z
173 (M++H); Anal. calcd for C9H8N4: C, 62.78; H, 4.68; N, 32.54.
found: C, 62.83; H, 4.66; N, 32.50.
4.2.9. (1RS,2SR)-2-Phenylcyclopropanecarboxylic acid (cis-14)
To a solution of Et2Zn (1.0 M in hexane, 4.08 mL, 4.08 mmol) in
CH2Cl2 (3.0 mL) was added a solution of TFA (0.314 mL, 4.08 mmol)
in CH2Cl2 (1.5 mL) at 0 °C under an argon atmosphere. After
20 min, a solution of CH2I2 (0.329 mL, 4.08 mmol) in CH2Cl2
(1.5 mL) was added to the mixture. After 20 min of stirring, a solu-
tion of cis-2 (0.200 g, 1.36 mmol) in CH2Cl2 (4.0 mL) was added to
the mixture. The reaction was stirred at room temperature for 5 h,
quenched with saturated aqueous NH4Cl, extracted with Et2O, and
the organic layer was dried over MgSO4, filtered and concentrated
in vacuo. The residue was purified by silica gel CC (EtOAc/hexane,
30:70) and, following recrystallization (toluene), yielded cis-14
(0.137 g, 0.845 mmol, 62%) as colorless needles; mp 103–105 °C;
1H NMR (CDCl3, 400 MHz) d: 1.39 (m, 1H, c-Pr), 1.69 (m, 1H,
c-Pr), 2.07 (m, 1H, –CH–CO2–), 2.66 (dd, J = 8.8, 16.8 Hz, 1H, Ar–
CH–), 7.13–7.38 (m, 5H, Ar–H); 13C NMR (CDCl3, 100 MHz) 12.0
a
solution of a mixture of the protected tetrazole (1.50 g,
11.7 mmol) in THF (75 mL) was cooled to ꢀ78 °C, n-BuLi (2.48 M
in hexane, 5.81 mL, 14.4 mmol) was added dropwise to the solu-
tion under an argon atmosphere. After 30 min, I2 (3.66 g,

M. Abe et al. / Phytochemistry 84 (2012) 56–67
63
(t, c-Pr), 21.3 (d, c-Pr), 26.5 (d, c-Pr), 126.8 (d, Ar), 128.0 (d, Ar),
Hydrolysis of trans-35 was performed using the procedure de-
scribed above to afford trans-16 (78%) as colorless needles: mp
98–99 °C (CH2Cl2/hexane, 5:95); 1H NMR (CDCl3, 400 MHz) d:
2.61 (d, J = 1.4 Hz, 3H, –CH3), 6.18 (d, J = 1.4 Hz, 1H, @CH–CO2–),
7.35–7.42 (m, 3H, Ar–H), 7.47–7.52 (m, 2H, Ar–H); 13C NMR (CDCl3,
100 MHz) d: 18.3 (q, –CH3), 116.5 (d, @CH–CO2–), 126.4 (d, Ar),
128.5 (d, Ar), 129.3 (d, Ar), 142.0 (s, Ar), 158.5 (s, Ar–C(CH3)@),
172.4 (s, C@O); IR (KBr) 1678 cmꢀ1; FAB-MS m/z 162 (M+); Anal.
calcd for C10H10O2: C, 74.06; H, 6.21. Found: C, 74.15; H, 6.23;
The spectroscopic data were in agreement with those in the
literature (Takimoto et al., 2001).
129.3 (d, Ar), 135.9 (s, Ar), d 176.3 (s, C@O);; IR (KBr) 1703 cmꢀ1
;
ESI-MS m/z 161 (M+ꢀH); Anal. calcd for C9H8O2: C, 74.06; H, 6.21.
Found: C, 73.82; H, 6.29; The spectroscopic data were in agreement
with those in the literature (Concellón et al., 2007).
4.2.10. Potassium (2R,3R)-3-Phenyloxirane-2-carboxylate (cis-15)
The epoxidation of cis-4 was performed according to the litera-
ture (Deng and Jacobsen, 1992) to give (2R,3R)-ethyl 3-phenyloxi-
rane-2-carboxylate (41%) and its separable trans-form (11%) as a
25
yellow oil: cis-form: [a] D+18.1 (c 2.20, CHCl3); The product was
not enantiomerically pure, but enantiomerically enriched; 1H
NMR (CDCl3, 400 MHz) d: 1.02 (t, J = 7.2 Hz, 3H, –CH3), 3.82 (d,
J = 4.8 Hz, 1H, –CH–CO2–), 4.00 (m, 2H, –CH2–), 4.27 (d, J = 4.8 Hz,
1H, Ar–CH–), 7.30–7.35 (m, 3H, Ar–H), 7.40–7.43 (m, 2H, Ar–H);
The spectroscopic data were in agreement with those in the liter-
ature (Deng and Jacobsen, 1992).
4.2.12. (Z)-2-Methyl-3-phenylacrylic acid (cis-17) and (E)-2-Methyl-
3-phenylacrylic acid (trans-17)
The E-selective olefination of 27 using ethyl 2-(triphenylphos-
phoranylidene)propanoate was performed using the procedure de-
scribed above to provide (E)-ethyl 2-methyl-3-phenylacrylate
(quant., E only) (silica gel column chromatography, EtOAc/hexane,
3:97) as a colorless oil: 1H NMR (CDCl3, 400 MHz) d: 1.35 (t,
J = 7.6 Hz, 3H, –CH2–CH3), 2.12 (brs, 3H, @C(CH3)–CO2–), 4.28 (q,
J = 7.6 Hz, 2H, –CH2–), 7.22–7.51 (m, 5H, Ar–H), 7.69 (d,
J = 1.2 Hz, 1H, Ar–CH@); The spectral data were in agreement with
those in the literature (Maji et al., 2010).
A solution of (E)-ethyl 2-methyl-3-phenylacrylate (0.300 g,
1.58 mmol) in CH2Cl2 (0.32 mL) was irradiated with a xenon light
(300 W) at room temperature for 4 h. After the removal of the
solvent, purification over silica gel CC (EtOAc/hexane, 3:97) gave
(Z)-ethyl 2-methyl-3-phenylacrylate (minor, 46.8 mg, 0.246 mmol,
16%) and the recovered E-form (major, 0.249 g, 1.31 mmol, 83%) as
a colorless oil: Z-form: 1H NMR (CDCl3, 400 MHz) d: 1.11 (t,
J = 7.4 Hz, 3H, –CH2–CH3), 2.10 (brs, 3H, @C(CH3)–CO2–), 4.11 (q,
J = 7.4 Hz, 2H, –CH2–), 6.71 (brs, 1H, Ar–CH@), 7.18–7.41 (m, 5H,
Ar–H); The spectroscopic data were in agreement with those in
the literature (Maji et al., 2010).
To a solution of (2R,3R)-ethyl 3-phenyloxirane-2-carboxylate
(120 mg, 0.625 mmol) in EtOH (5.0 mL) was added 0.52 M KOH
(1.2 mL) at room temperature. The mixture was stirred for 4 h.
After the solvent was removed in vacuo, the crude product was
purified by recrystallization (iPrOH) to give cis-15 (84.0 mg,
0.416 mmol, 67%) as a colorless solid; 1H NMR (CD3OD, 400 MHz)
d: 3.67 (d, J = 4.8 Hz, 1H, –CH–CO2–), 4.10 (d, J = 4.8 Hz, 1H, Ar–
CH–), 7.20–7.30 (m, 3H, Ar–H), 7.45–7.47 (m, 2H, Ar–H); 13C
NMR (CD3OD, 100 MHz) d: 58.3 (d, epoxide), 60.0 (d, epoxide),
128.0 (d, Ar), 128.7 (d, Ar), 128.8 (d, Ar), 136.9 (s, Ar), 173.8 (s,
C@O); IR (KBr) 1603 cmꢀ1; FAB-MS m/z 163 (M+ꢀK); The physical
and spectroscopic data were consistent with those reported in
the literature (Becker et al., 2005).
4.2.11. (Z)-3-Phenylbut-2-enoic acid (cis-16) and (E)-3-phenylbut-2-
enoic acid (trans-16)
To a solution of NaH (60% in oil, 0.430 g, 10.8 mmol) in THF
(33 mL) was added a solution of ethyl 2-(diethoxyphosphoryl)ace-
tate (2.00 mL, 10.0 mmol) in THF (5.0 mL) at 0 °C for 30 min under
an Ar atmosphere. After a solution of acetophenone (34) (0.650 mL,
8.30 mmol) in THF (5.0 mL) was added to the solution, the result-
ing mixture was refluxed for 6 h. The reaction was quenched with
saturated aqueous NH4Cl and extracted with EtOAc. The organic
layers were washed with H2O and brine, dried over MgSO4, filtered
and concentrated in vacuo. The residue was purified by silica gel CC
(EtOAc/hexane, 3:97) to afford (Z)-ethyl 3-phenylbut-2-enoate
(cis-35) (minor, 0.220 g, 1.16 mmol, 14%) and (E)-ethyl 3-phenyl-
but-2-enoate (trans-35) (major, 1.07 g, 5.62 mmol, 68%) as color-
less oils: cis-35: 1H NMR (CDCl3, 400 MHz) d: 1.08 (t, J = 7.2 Hz,
3H, –CH2–CH3), 2.18 (d, J = 1.2 Hz, 3H, Ar–C(CH3)@), 4.00 (q,
J = 7.2 Hz, 2H, –CH2–), 5.91 (d, J = 1.2 Hz, 1H, @CH–CO2–), 7.14–
7.26 (m, 2H, Ar–H), 7.26–7.41 (m, 3H, Ar–H); The observed charac-
terization data were consistent with those reported (Miura et al.,
2009); trans-35: 1H NMR (CDCl3, 400 MHz) d: 1.32 (t, J = 7.2 Hz,
3H, –CH2–CH3), 2.58 (s, 3H, Ar–C(CH3)@), 4.22 (q, J = 7.2 Hz, 2H,
–CH2–), 6.14 (s, 1H, @CH–CO2–), 7.31–7.44 (m, 3H, Ar–H), 7.44–
7.58 (m, 2H, Ar–H); The physical and spectroscopic data were
consistent with those reported in the literature (Miura et al., 2009).
Hydrolysis of cis-35 was performed using the procedure de-
scribed above to give cis-16 (76%) as colorless needles: mp 125–
126 °C (CH2Cl2/hexane, 5:95); 1H NMR (CDCl3, 400 MHz) d 2.20
(brs, 3H, –CH3), 5.91 (brs, 1H, @CH–CO2–), 7.18–7.27 (m, 2H, Ar–
H), 7.27–7.39 (m, 3H, Ar–H); 13C NMR (CDCl3, 100 MHz) d 27.5
(q, –CH3), 116.9 (d, @CH–CO2–), 126.8 (d, Ar), 127.9 (d, Ar), 128.0
(d, Ar), 140.2 (s, Ar), 158.2 (s, Ar–C(CH3)@), 171.0 (s, C@O); IR
Hydrolysis of (Z)-ethyl 2-methyl-3-phenylacrylate was per-
formed using the procedure described above to afford cis-17
(70%) as colorless needles: mp 82–83 °C (CH2Cl2/hexane, 5:95);
1H NMR (CDCl3, 400 MHz) d: 2.12 (d, J = 1.4 Hz, 3H, –CH3), 6.86
(q, J = 1.4 Hz, 1H, Ar–CH@), 7.20–7.36 (m, 5H, Ar–H); 13C NMR
(CDCl3, 100 MHz) d: 21.5 (q, –CH3), 128.0 (d, Ar), 128.1 (s,
@C(CH3)–CO2–), 128.3 (d, Ar), 128.4 (d, Ar), 135.9 (s, Ar), 137.7
(d, Ar–CH@), 172.5 (s, C@O); IR (KBr) 1684 cmꢀ1; EI-MS m/z 162
(M+); HR EI-MS m/z 162.0679 (M+, calcd for C10H10O2 162.0681);
Anal. calcd for C10H10O2: C, 74.06; H, 6.21. Found: C, 73.76; H,
6.27; The spectroscopic data were in agreement with those in
the literature (Rudler and Durand-Réville, 2001).
Hydrolysis of (E)-ethyl 2-methyl-3-phenylacrylate was per-
formed using the procedure described above to afford trans-17
(quant.) as colorless needles: mp 80–82 °C (CH2Cl2/hexane, 5:95);
1H NMR (CDCl3, 400 MHz) d: 2.16 (d, J = 1.2 Hz, 3H, –CH3), 7.24–
7.48 (m, 5H, Ar–H), 7.84 (q, J = 1.2 Hz, 1H, Ar–CH@); 13C NMR
(CDCl3, 100 MHz) d: 13.7 (q, –CH3), 127.5 (s, @C(CH3)–CO2–),
128.5 (d, Ar), 128.7 (d, Ar), 129.8 (d, Ar), 135.6 (s, Ar), 141.1 (d,
Ar–CH@), 174.0 (s, C@O); IR (KBr) 1670 cmꢀ1; EI-MS m/z 162
(M+); HR EI-MS m/z 162.0675 (M+, calcd for C10H10O2 162.0681);
Anal. calcd for C10H10O2: C, 74.06; H, 6.21. Found: C, 74.08; H,
6.27; The spectroscopic data were in agreement with those in
the literature (Rudler and Durand-Réville, 2001).
4.2.13. (Z)-2-Methyl-3-phenylbut-2-enoic Acid (cis-18) and (E)-2-
Methyl-3-phenylbut-2-enoic Acid (trans-18)
The olefination of 34 using the ynolate was performed accord-
ing to the literature (Shindo et al., 2004) to give the (Z)-methyl
2-methyl-3-phenylbut-2-enoate (cis-38) (minor, 20%) and the
(E)-methyl 2-methyl-3-phenylbut-2-enoate (trans-38) (major,
80%) (silica gel CC, EtOAc/hexane, 3:97) as colorless oils: cis-38:
(KBr): 1695 cmꢀ1
;
ESI-MS m/z 161 (M+ꢀH); Anal. calcd for
C10H10O2: C, 74.06; H, 6.21. Found: C, 74.06; H, 6.15); The spectro-
scopic data were in agreement with those in the literature (Bellas-
soued et al., 2005).

64
M. Abe et al. / Phytochemistry 84 (2012) 56–67
1H NMR (CDCl3, 400 MHz) d: 2.04 (s, 3H, @C(CH3)–CO2–), 2.10 (s,
3H, Ar–C(CH3)@), 3.39 (s, 3H, –OCH3), 7.10–7.15 (m, 2H, Ar–H),
7.24–7.43 (m, 3H, Ar–H); trans-38: 1H NMR (CDCl3, 400 MHz) d:
1.76 (d, J = 1.6 Hz, 3H, @C(CH3)–CO2–), 2.27 (d, J = 1.6 Hz, 3H,
Ar–C(CH3)@), 3.80 (s, 3H, –OCH3), 7.10–7.19 (m, 2H, Ar–H), 7.24–
7.43 (m, 3H, Ar–H); The physical and spectroscopic data were con-
sistent with those reported in the literature (Shindo et al., 2004).
Hydrolysis of cis-38 was performed using the procedure de-
scribed above to afford cis-18 (58%) as colorless needles: mp
110–111 °C (CH2Cl2/hexane, 5:95); 1H NMR (CDCl3, 400 MHz) d:
2.04 (s, 3H, @C(CH3)–CO2–), 2.11 (s, 3H, Ar–C(CH3)@), 7.12–7.16
(m, 2H, Ar–H), 7.25–7.32 (m, 3H, Ar–H); 13C NMR (CDCl3,
150 MHz) d 16.3 (q, @C(CH3)–CO2–), 22.7 (q, Ar–C(CH3)@), 124.6
(s, @C(CH3)–CO2–), 126.8 (d, Ar), 127.2 (d, Ar), 128.1 (d, Ar),
143.7 (s, Ar), 146.3 (s, Ar–C(CH3)@), 173.6 (s, C@O); IR (KBr)
1686 cmꢀ1; EI-MS m/z 176 (M+); ESI-MS m/z 175 (M+ꢀH); HR EI-
MS m/z 176.0843 (M+, calcd for C11H12O2 176.0837); Anal. calcd
for C11H12O2: C, 74.98; H, 6.86. Found: C, 74.73; H, 6.98.
The hydrolysis of (E)-ethyl 3-cyclohexylacrylate, using the pro-
cedure described above, afforded trans-20 (78%) as colorless nee-
dles: mp 46–47 °C (hexane); 1H NMR (CDCl3, 400 MHz) d: 1.09–
1.38 (m, 5H, c-Hex-H), 1.63–1.85 (m, 5H, c-Hex-H), 2.18 (m, 1H,
c-Hex-H), 5.78 (d, J = 16.0 Hz, 1H, @CH–CO2–), 7.01 (dd,
J = 6.8 Hz, 16.0 Hz, 1H, c-Hex-CH@); 13C NMR (CDCl3, 100 MHz) d
25.7 (t, c-Hex), 25.9 (t, c-Hex), 31.6 (t, c-Hex), 40.5 (d, c-Hex),
118.0 (d, @CH–CO2–), 157.1 (d, c-Hex-CH@), 171.3 (s, C@O); IR
(KBr): 1686 cmꢀ1; EI-MS m/z 154 (M+); FAB-MS m/z 154 (M+); HR
FAB-MS m/z 154.0995 (M+, calcd for C9H14O2 154.0994); Anal.
calcd for C9H14O2: C, 70.10; H, 9.15. Found: C, 70.01; H, 9.18; The
spectroscopic data were in agreement with those in the literature
(Alhamadsheh et al., 2007).
4.2.16. (Z)-3-(Cyclohex-1-en-1-yl)acrylic Acid (cis-21)
The Z-selective olefination of cyclohex-1-enecarboxaldehyde
was performed using the procedure described above to provide
(Z)-ethyl 3-(cyclohex-1-en-1-yl)acrylate (53%, Z only) (silica gel
CC, EtOAc/hexane, 5:95) as a colorless oil: 1H NMR (CDCl3,
400 MHz) d: 1.29 (t, J = 7.2 Hz, 3H, -CH3), 1.54–1.73 (m, 4H, c-Hex-
ene-H), 2.15–2.22 (m, 2H, c-Hexene-H), 2.22–2.35 (m, 2H, c-Hex-
ene-H), 4.17 (q, J = 7.2 Hz, 2H, –CH2–), 5.59 (d, J = 12.8 Hz, 1H,
@CH–CO2–), 6.01 (brs, 1H, c-Hexene-H), 6.32 (d, J = 12.8 Hz, 1H,
c-Hexene-CH@); FAB-MS m/z 180 (M+).
The hydrolysis of (Z)-ethyl 3-(cyclohex-1-en-1-yl)acrylate was
performed using the procedure described above to afford cis-21
(85%) as colorless needles: mp 62–64 °C (CH2Cl2/hexane, 5:95);
1H NMR (CDCl3, 400 MHz) d: 1.59–1.64 (m, 4H, c-Hexene-H),
2.16–2.26 (m, 2H, c-Hexene-H), 2.26–2.32 (m, 2H, c-Hexene-H), 5.63
(d, J = 12.4 Hz, 1H, @CH–CO2–), 6,08 (brs, 1H, c-Hexene-H), 6.45
(d, J = 12.4 Hz, 1H, c-Hexene-CH@); 13C NMR (CDCl3, 100 MHz) d:
21.6 (t, c-Hexene), 22.5 (t, c-Hexene), 26.4 (t, c-Hexene), 27.0
(t, c-Hexene), 114.9 (d, @CH–CO2–), 135.4 (s, c-Hexene), 137.2 (d,
c-Hexene-CH@), 147.4 (d, c-Hexene), 172.2 (s, C@O); IR (KBr)
1684 cmꢀ1; EI-MS m/z 152 (M+); FAB-MS m/z 152 (M+); HR EI-MS
m/z 152.0832 (M+, calcd for C9H12O2 152.0837); Anal. calcd for
Hydrolysis of trans-38 was performed using the procedure de-
scribed above to afford trans-18 (62%) as colorless needles; mp
101–103 °C (CH2Cl2/hexane, 5:95); 1H NMR (CDCl3, 400 MHz) d:
1.80 (d, J = 1.2 Hz, 3H, @C(CH3)–CO2–), 2.38 (d, J = 1.2 Hz, 3H, Ar–
C(CH3)@), 7.13–7.17 (m, 2H, Ar–H), 7.24–7.41 (m, 3H, Ar–H); 13C
NMR (CDCl3, 100 MHz) d 17.3 (q, @C(CH3)–CO2–), 23.7 (q, Ar–
C(CH3)@), 123.7 (s, @C(CH3)–CO2–), 127.0 (d, Ar), 127.2 (d, Ar),
128.4 (d, Ar), 143.8 (s, Ar), 150.2 (s, Ar–C(CH3)@), 174.8 (s, C@O);
IR (KBr) 1684 cmꢀ1
;
EI-MS m/z 176 (M+); ESI-MS m/z 175
(M+ꢀH); HR EI-MS m/z 176.0834 (M+, calcd for C11H12O2
176.0837); Anal. calcd for C11H12O2: C, 74.98; H, 6.86. Found: C,
74.89; H, 6.86.
4.2.14. (Z)-3-Cyclohexylacrylic acid (cis-20)
The Z-selective olefination of cyclohexanecarboxaldehyde was
performed using the procedure described above to provide the
(Z)-ethyl 3-cyclohexylacrylate (62%, Z only) (silica gel CC, EtOAc/
hexane, 3:97) as a colorless oil: 1H NMR (CDCl3, 400 MHz) d
1.01–1.42 (m, 5H, c-Hex-H), 1.29 (t, J = 7.2 Hz, 3H, –CH3), 1.63–
1.80 (m, 5H, c-Hex-H), 3.29 (m, 1H, c-Hex-H), 4.16 (q, J = 7.2 Hz,
2H, –CH2–), 5.65 (d, J = 11.6 Hz, 1H, @CH–CO2–), 6.02 (dd, J = 9.2,
11.6 Hz, 1H, c-Hex-CH@); The spectroscopic data were in agree-
ment with those in the literature (Miura et al., 2009).
Hydrolysis of (Z)-ethyl 3-cyclohexylacrylate was performed
using the procedure described above to afford cis-20 (88%) as col-
orless needles: mp 41–42 °C (hexane); 1H NMR (CDCl3, 400 MHz)
d: 1.04–1.46 (m, 5H, c-Hex-H), 1.63–1.82 (m, 5H, c-Hex-H), 3.30
(m, 1H, c-Hex-H), 5.68 (d, J = 11.2 Hz, 1H, @CH–CO2–), 6.16 (dd,
J = 9.9, 11.2 Hz, 1H, c-Hex-CH@); 13C NMR (CDCl3, 100 MHz) d:
25.4 (t, c-Hex), 25.9 (t, c-Hex), 32.2 (t, c-Hex), 37.4 (d, c-Hex),
116.5 (d,@CH–CO2–), 158.1 (d, c-Hex-CH@), 171.2 (s, C@O); IR
(KBr) 1701 cmꢀ1; EI-MS m/z 154 (M+); FAB-MS m/z 154 (M+); HR
EI-MS m/z 154.0992 (M+, calcd for C9H14O2 154.0994); Anal. calcd
for C9H14O2: C, 70.10; H, 9.15. Found: C, 70.14; H, 9.23; The spec-
troscopic data were in agreement with those in the literature
(Vuagonoux-d’ and Alexakis, 2007).
C10H11O2: C, 71.03; H, 7.95. Found: C, 71.05; H, 8.00.
4.2.17. (E)-3-(Cyclohex-1-en-1-yl)acrylic Acid (trans-21)
The E-selective olefination of cyclohex-1-enecarboxaldehyde
was performed according to the literature (Piva and Comesse,
2000) to give (E)-ethyl 3-(cyclohex-1-en-1-yl)acrylate (53%, E only)
(silica gel CC, EtOAc/hexane, 3:97) as a colorless oil: 1H NMR
(CDCl3, 400 MHz) d: 1.29 (t, J = 7.2 Hz, 3H, -CH3), 1.49–1.78 (m,
4H, c-Hexene-H), 2.04–2.25 (m, 4H, c-Hexene-H), 4.20 (q,
J = 7.2 Hz, 2H, –CH2–), 5.77 (d, J = 15.8 Hz, 1H, @CH–CO2–), 6.16
(s, 1H, c-Hexene-H), 7.28 (d, J = 15.8 Hz, 1H, c-Hexene-CH@); The
physical and spectroscopic data were consistent with those re-
ported in the literature (Piva and Comesse, 2000).
The hydrolysis of (E)-ethyl 3-(cyclohex-1-en-1-yl)acrylate,
using the procedure described above, afforded trans-21 (quant.)
as colorless needles: mp 116–117 °C (CH2Cl2/hexane, 5:95); 1H
NMR (CDCl3, 400 MHz) d: 1.54–1.75 (m, 4H, c-Hexene-H), 2.14–
2.25 (m, 4H, c-Hexene-H), 5.77 (d, J = 16.4 Hz, 1H, @CH–CO2–),
6.23 (m, 1H, c-Hexene-H), 7.36 (d, J = 16.4 Hz, 1H, c-Hexene-
CH@); 13C NMR(CDCl3, 100 MHz) d: 21.9 (t, c-Hexene), 22.0
(t, c-Hexene), 24.1 (t, c-Hexene), 26.5 (t, c-Hexene), 113.7 (d,
@CH–CO2–), 134.9 (s, c-Hexene), 140.3 (d, c-Hexene-CH@), 150.4
(d, c-Hexene), 173.3 (s, C@O); IR (KBr) 1684 cmꢀ1; FAB-MS m/z
152 (M+); Anal. calcd for C10H11O2: C, 71.03; H, 7.95. Found: C,
70.94; H, 7.93; The spectroscopic data were in agreement with
those in the literature. (Chackalamannil et al., 1999).
4.2.15. (E)-3-Cyclohexylacrylic acid (trans-20)
The E-selective olefination of cyclohexanecarboxaldehyde was
performed using the previously described procedure (Alhamad-
sheh et al., 2007) to provide (E)-ethyl 3-cyclohexylacrylate (78%,
E only) (silica gel CC, EtOAc/hexane, 3:97) as a colorless oil: 1H
NMR (CDCl3, 400 MHz) d: 1.05–1.26 (m, 5H, c-Hex-H), 1.29 (t,
J = 7.2 Hz, 3H, –CH3), 1.72–1.82 (m, 5H, c-Hex-H), 2.12 (m, 1H,
c-Hex-H), 4.18 (q, J = 7.2 Hz, 2H, –CH2–), 5.76 (d, J = 16.2 Hz, 1H,
@CH–CO2–), 6.91 (dd, J = 6.8, 16.2 Hz, 1H, c-Hex-CH@); The physi-
cal and spectroscopic data were consistent with those reported in
the literature (Ando, 1997).
4.2.18. (Z)-3-(Cyclohex-3-en-1-yl)acrylic Acid (cis-22)
The Z-selective olefination of cyclohex-3-enecarboxaldehyde
was performed using the procedure described above to provide

M. Abe et al. / Phytochemistry 84 (2012) 56–67
65
(Z)-ethyl 3-(cyclohex-3-en-1-yl)acrylate (59%, Z only) (silica gel CC,
EtOAc/hexane, 3:97) as a colorless oil: 1H NMR (CDCl3, 400 MHz) d:
1.29 (t, J = 7.2 Hz, 3H, –CH3), 1.46 (m, 1H, c-Hexene-H), 1.72–1.92
(m, 2H, c-Hexene-H), 2.00–2.29 (m, 3H, c-Hexene-H), 3.58 (m,
1H, c-Hexene-H), 4.17 (q, J = 7.2 Hz, 2H, –CH2–), 5.62–5.81 (m,
2H, c-Hexene-H), 5.72 (d, J = 11.6 Hz, 1H, @CH–CO2–), 6.11 (dd,
J = 10.0, 11.6 Hz, 1H, c-Hexene-CH@).
H@C(CH3)–), 14.9 (q, C(CH3)H@), 115.2 (d,@CH–CO2–), 133.7 (s,
C(CH3)H@C(CH3)–), 134.3 (d, C(CH3)H@), 148.7 (d, –CH@CH–CO2–),
171.9 (s, C@O); IR (neat) 1694 cmꢀ1; EI-MS m/z 126 (M+), 111
(M+ꢀMe); HR EI-MS m/z 126.0681 (M+, calcd for C7H10O2
126.0681).
4.2.21. (2Z,4E)-5-Phenylpenta-2,4-dienoic Acid (cis-24)
The hydrolysis of (Z)-ethyl 3-(cyclohex-3-en-1-yl)acrylate was
performed using the procedure described above to afford cis-22
(78%) as colorless needles: mp 64–65 °C (CH2Cl2/hexane, 5:95);
1H NMR (CDCl3, 400 MHz) d: 1.47 (m, 1H, c-Hexene-H), 1.72–
1.95 (m, 2H, c-Hexene-H), 1.99–2.29 (m, 3H, c-Hexene-H), 3.59
(m, 1H, c-Hexene-H), 5.62–5.83 (m, 2H, c-Hexene-H), 5.75 (d,
J = 11.6 Hz, 1H, @CH–CO2–), 6.26 (dd, J = 10.2, 11.6 Hz, 1H, c-Hex-
ene-CH@); 13C NMR (CDCl3, 100 MHz) d: 24.0 (t, c-Hexene), 28.0
(t, c-Hexene), 30.4 (t, c-Hexene), 33.2 (d, c-Hexene), 117.7 (d,
@CH–CO2–), 125.3 (d, c-Hexene), 127.0 (d, c-Hexene), 157.3
(d, c-Hexene-CH@), 171.5 (s, C@O); IR (KBr) 1686 cmꢀ1; EI-MS
m/z 152 (M+); HR EI-MS m/z 152.0835 (M+, calced for C9H12O2
152.0837); Anal. calcd for C9H12O2: C, 71.03; H, 7.95. Found: C,
70.99; H, 7.78.
The Z-selective olefination of cinnamaldehyde was performed
using the procedure described above to provide (2Z,4E)-ethyl 5-
phenylpenta-2,4-dienoate (74%, 2E:2Z = 23:77, determined by 1H
NMR spectrum) (silica gel CC, EtOAc/hexane, 3:97) as a colorless
oil: 1H NMR (CDCl3, 400 MHz) d: 1.33 (t, J = 7.4 Hz, 3H, –CH3),
4.23 (q, J = 7.4 Hz, 2H, –CH2–), 5.72 (d, J = 11.2 Hz, 1H,=CH–CO2–),
6.74 (dd, J = 11.2, 11.6 Hz, 1H, –CH@CH–CO2–), 6.81 (d,
J = 16.4 Hz, 1H, Ar–CH@CH–), 7.22–7.43 (m, 3H, Ar–H), 7.47–7.60
(m, 2H, Ar–H), 8.16 (dd, J = 11.6, 16.4 Hz, 1H, Ar–CH@CH–); FAB-
MS m/z 202 (M+); The spectroscopic data were in agreement with
those in the literature. (Miura et al., 2009).
The hydrolysis of (2Z,4E)-ethyl 5-phenylpenta-2,4-dienoate was
performed using the procedure described above to give cis-24
(94%) as colorless needles: mp 134–136 °C (CH2Cl2/hexane, 5:95);
1H NMR (CDCl3, 400 MHz) d: 5.77 (d, J = 11.2 Hz, 1H,@CH–CO2–),
6.86 (dd, J = 11.2, 11.6 Hz, 1H, –CH@CH–CO2–), 6.88 (d,
J = 16.4 Hz, 1H, Ar–CH@), 7.28–7.43 (m, 3H, Ar–H), 7.40–7.49 (m,
2H, Ar–H), 8.10 (dd, J = 11.6, 16.4 Hz, 1H, Ar–CH@CH–); 13C NMR
(CDCl3, 100 MHz) d: 116.5 (d, @CH–CO2–), 124.8 (d, Ar–CH@CH–
), 127.7 (d, Ar), 128.8 (d, Ar), 129.2 (d, Ar), 136.1 (s, Ar), 142.5 (d,
Ar–CH@), 147.1 (d, –CH@CH–CO2–), 172.1 (s, C@O); IR (KBr)
1690 cmꢀ1; ESI-MS m/z 173 (M+ꢀH); Anal. calcd for C11H10O2: C,
75.83; H, 5.79. Found: C, 75.53; H, 5.79; The spectroscopic data
were in agreement with those in the literature (Concepcion et al.,
1995).
4.2.19. (E)-3-(Cyclohex-3-en-1-yl)acrylic Acid (trans-22)
The E-selective olefination of cyclohex-3-enecarboxaldehyde
was performed using the procedure described above to provide
(E)-ethyl 3-(cyclohex-3-en-1-yl)acrylate (89%, E only) (silica gel
CC, EtOAc/hexane, 3:97) as a colorless oil: 1H NMR (CDCl3,
400 MHz) d: 1.29 (t, J = 7.2 Hz, 3H, -CH3), 1.47 (m, 1H, c-Hexene-
H), 1.83 (m, 1H, c-Hexene-H), 1.93 (m, 1H, c-Hexene-H), 2.03–
2.25 (m, 3H, c-Hexene-H), 2.44 (m, 1H, c-Hexene-H), 4.19 (q,
J = 7.2 Hz, 2H, –CH2–), 5.63–5.76 (m, 2H, c-Hexene-H), 5.82 (dd,
J = 1.4, 16.2 Hz, 1H, @CH–CO2–), 6.98 (dd, J = 7.4, 16.2 Hz, 1H,
c-Hexene-CH@)
Hydrolysis of (E)-ethyl 3-(cyclohex-3-en-1-yl)acrylate was per-
formed by using the procedure described above to give trans-22
(72%) as colorless needles: mp 43–44 °C (CH2Cl2/hexane, 5:95); H
NMR (CDCl3, 400 MHz) d: 1.49 (m, 1H, c-Hexene-H), 1.78–2.01
(m, 2H, c-Hexene-H), 2.03–2.28 (m, 3H, c-Hexene-H), 2.48 (m,
1H, c-Hexene-H), 5.62–5.78 (m, 2H, c-Hexene-H), 5.84 (dd, J = 1.0,
16.0 Hz, 1H, @CH–CO2–), 7.10 (dd, J = 7.0, 16.0 Hz, 1H, c-Hexene-
CH@); 13C NMR (CDCl3, 100 MHz) d: 24.3 (t, c-Hexene), 27.4
(t, c-Hexene), 29.9 (t, c-Hexene), 36.5 (d, c-Hexene), 118.9 (d,
@CH–CO2–), 125.1 (d, c-Hexene), 127.0 (d, c-Hexene), 156.1 (d,
c-Hexene-CH@), 172.0 (s, C@O); IR (KBr) 1690 cmꢀ1; EI-MS m/z
152 (M+); HR EI-MS m/z 152.0842 (M+, calcd for C9H12O2
152.0837); Anal. calcd for C9H12O2: C, 71.03; H, 7.95. Found: C,
71.05; H, 7.98.
4.2.22. (2Z,4E)-5-(Cyclohex-1-en-1-yl)penta-2,4-dienoic Acid (cis-25)
DIBAL-H (1.03 M in hexane, 21.9 mL, 22.6 mmol) was added to a
solution of (E)-ethyl 3-(cyclohex-1-en-1-yl)acrylate (1.94 g,
10.8 mol) in THF (43 mL) at ꢀ78 °C under an argon atmosphere.
The mixture was stirred for 2 h, quenched with saturated aqueous
NH4Cl and extracted with CH2Cl2. The combined organic layers
were washed with H2O and brine, dried over MgSO4, filtered and
concentrated in vacuo. The crude (E)-3-(cyclohex-1-en-1-yl)prop-
2-en-1-ol was immediately employed in the next reaction. To a
solution of crude (E)-3-(cyclohex-1-en-1-yl)prop-2-en-1-ol in
CH2Cl2 (30 mL) were added Na2CO3 (3.70 g, 35.1 mmol) and
MnO2 (3.00 g, 34.5 mmol) at room temperature under an argon
atmosphere. The mixture was stirred for 6 h, filtered through a
Celite pad, washed with CH2Cl2 and concentrated in vacuo. Purifi-
cation using silica gel CC (EtOAc/hexane, 10:90) provided (E)-3-
(cyclohex-1-en-1-yl)acrylaldehyde (1.35 g, 9.91 mmol, 92% in 2
steps) as a colorless oil: 1H NMR (CDCl3, 400 MHz) d: 1.57–1.90
(m, 4H, c-Hexene-H), 2.13–2.23 (m, 2H, c-Hexene-H), 2.23–2.42
(m, 2H, c-Hexene-H), 6.08 (dd, J = 8.2, 15.8 Hz, 1H, @CH–CHO),
6.31 (brs, 1H, c-Hexene-H), 7.09 (d, J = 16.0 Hz, 1H, c-Hexene-
CH@), 9.56 (d, J = 8.2 Hz, 1H, CHO); The spectroscopic data were in
agreement with those in the literature (Trost and Livingston, 2008).
The Z-selective olefination of (E)-3-(cyclohex-1-en-1-yl)acrylal-
dehyde was performed using the procedure described above to
provide (2Z,4E)-ethyl 5-(cyclohex-1-en-1-yl)penta-2,4-dienoate
(60%, 2E:2Z = 25:75, determined by 1H NMR spectrum) (silica gel
CC, EtOAc/hexane, 3:97) as a colorless oil: 1H NMR (CDCl3,
400 MHz) d: 1.30 (t, J = 7.4 Hz, 3H, –CH3), 1.53–1.78 (m, 4H, c-Hex-
ene-H), 2.13–2.35 (m, 4H, c-Hexene-H), 4.19 (q, J = 7.4 Hz, 2H,
–CH2–), 5,60 (d, J = 11.2 Hz, 1H, @CH–CO2–), 5.98 (brs, 1H, c-Hex-
ene-H), 6.47 (d, J = 15.4 Hz, 1H, c-Hexene-CH@), 6.63 (dd, J = 11.2,
11.6 Hz, 1H, –CH@CH–CO2–), 7.45 (dd, J = 11.6, 15.4 Hz, 1H, c-Hex-
ene-CH@CH–).
4.2.20. (2Z,4E)-4-Methylhexa-2,4-dienoic Acid (cis-23)
The Z-selective olefination of (E)-2-methylbut-2-enal (tiglic
aldehyde) was performed using the procedure described above to
provide (2Z,4E)-ethyl 4-methylhexa-2,4-dienoate (31%, 2E:2Z =
14:86, determined by analysis of the 1H NMR spectrum) (silica gel
column chromatography, EtOAc/hexane, 3:97) as a colorless oil:
1H NMR (CDCl3, 400 MHz) d: 1.30 (t, J = 7.2 Hz, 3H, –CH2–CH3),
1.74 (d, J = 6.8 Hz, 3H, C(CH3)H@), 1.87 (s, 3H, C(CH3)H@C(CH3)–),
4.23 (q, J = 7.2 Hz, 2H, –CH2–), 5.60 (d, J = 12.8 Hz, 1H, @CH–CO2–),
5.81 (q, J = 6.8 Hz, 1H, C(CH3)H@), 6.38 (d, J = 12.8 Hz, 1H, –CH@
CH–CO2–).
Hydrolysis of (2Z,4E)-ethyl 4-methylhexa-2,4-dienoate was
performed using the procedure described above to yield cis-23
(85%) (silica gel CC, EtOAc/hexane, 10:90) as a colorless oil: 1H
NMR (CDCl3, 400 MHz) d: 1.76 (d, J = 6.8 Hz, 3H, C(CH3)H@), 1.88
(s, 3H, C(CH3)H@C(CH3)–), 5.63 (d, J = 12.6 Hz, 1H, @CH–CO2–),
5,88 (q, J = 6.8 Hz, 1H, C(CH3)H@), 6.53 (d, J = 12.6 Hz, 1H, –
CH@CH–CO2–); 13C NMR (CDCl3, 100 MHz) d: 14.3 (q, C(CH3)-

66
M. Abe et al. / Phytochemistry 84 (2012) 56–67
The hydrolysis of (2Z,4E)-ethyl 5-(cyclohex-1-en-1-yl)penta-
required to induce a half-maximum effect, was calculated from a
dose response curve of the phytotoxicity for each compound by
applying a statistical model, probit model (Bliss, 1934), using the
computer program, SPSS 13.0J.
2,4-dienoate was performed by using the procedure described
above to afford cis-25 (89%) as colorless needles: mp 125–126 °C
(hexane); 1H NMR (CDCl3, 400 MHz) d: 1.52–1.81 (m, 4H, c-Hex-
ene-H), 2.14–2.33 (m, 4H, c-Hexene-H), 5,63 (d, J = 11.2 Hz, 1H,
@CH–CO2–), 6.02 (brs, 1H, c-Hexene-H), 6.51 (d, J = 15.8 Hz, 1H,
c-Hexene-CH@), 6.73 (dd, J = 11.2, 11.6 Hz, 1H, –CH@CH–CO2–),
7.39 (dd, J = 11.6, 15.8 Hz, 1H, c-Hexene-CH@CH–); 13C NMR
(CDCl3, 100 MHz) d: 22.19 (t, c-Hexene), 22.21 (t, c-Hexene),
24.5 (t, c-Hexene), 26.4 (t, c-Hexene), 114.8 (d, @CH–CO2–),
121.7 (d, c-Hexene-CH@CH2–), 135.9 (d, c-Hexene-CH@), 136.4
(s, c-Hexene), 146.6 (d, –CH@CH–CO2–), 148.1 (d, c-Hexene),
172.4 (s, C@O); IR (KBr): 1684 cmꢀ1; EI-MS m/z 178 (M+); FAB-
MS m/z 178 (M+); HR EI-MS m/z 178.0992 (M+, calcd for
4.4. Photoisomerization of cinnamic acid and its analogues by a xenon
light
A solution of cinnamic acid in D2O (5 mM) was irradiated in a
glass tube placed at 3 cm from a xenon light (300 W) at 25 °C.
The Z:E ratios of the cinnamic acids were determined by 1H NMR
spectra every 10 min until the achievement of the photostationary
states.
C
11H14O2 178.0994); Anal. calcd for C11H14O2: C, 74.13; H, 7.92.
Acknowledgements
Found: C, 73.99; H, 7.91.
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
Program (Sekisui Chemical).’’
4.2.23. (2Z,4E)-5-Cyclohexylpenta-2,4-dienoic Acid (cis-26)
The DIBAL-H reduction of (E)-ethyl 3-cyclohexylacrylate and
subsequent MnO2 oxidation were performed using the procedure
described above to give (E)-3-cyclohexylacrylaldehyde (79% yield
in 2 steps) (silica gel CC, EtOAc/hexane, 10:90) as a colorless oil:
1H NMR (CDCl3, 400 MHz) d: 1.07–1.43 (m, 5H, c-Hex-H), 1.62–
1.87 (m, 5H, c-Hex-H), 2.28 (m, 1H, c-Hex-H), 6.07 (dd, J = 7.6,
16.4 Hz, 1H, @CH–CHO), 6.78 (dd, J = 6.8, 16.4 Hz, 1H, c-Hex-
CH@), 9.50 (d, J = 7.6 Hz, 1H, –CHO); The spectroscopic data were
in agreement with those in the literature (Stiller et al., 2011).
The Z-selective olefination of (E)-3-cyclohexylacrylaldehyde
was performed using the procedure described above to provide
(2Z,4E)-ethyl 5-cyclohexylpenta-2,4-dienoate (64%, 2Z only) (silica
gel CC, EtOAc/hexane, 3:97) as a colorless oil: 1H NMR (CDCl3,
400 MHz) d: 1.07–1.38 (m, 5H, c-Hex-H), 1.30 (t, J = 7.2 Hz, 3H,
-CH3), 1.59–1.86 (m, 5H, c-Hex-H), 2.13 (m, 1H, c-Hex-H), 4.18
(q, J = 7.2 Hz, 2H, –CH2–), 5,57 (d, J = 11.2 Hz, 1H, @CH–CO2–),
6.01 (dd, J = 6.8, 15.6 Hz, 1H, c-Hex-CH@), 6.54 (dd, J = 11.2,
11.6 Hz, 1H, –CH@CH–CO2–), 7.34 (dd, J = 11.6, 15.6 Hz, 1H,
c-Hex-CH@CH–); FAB-MS m/z 208 (M+).
Hydrolysis of the (2Z,4E)-ethyl 5-cyclohexylpenta-2,4-dienoate
was performed using the procedure described above to give cis-
26 (78%) as colorless needles: mp 57–58 °C (hexane); 1H NMR
(CDCl3, 400 MHz) d: 1.08–1.39 (m, 5H, c-Hex-H), 1.59–1.85 (m,
5H, c-Hex-H), 2.16 (m, 1H, c-Hex-H), 5,59 (d, J = 11.2 Hz, 1H,
@CH–CO2–), 6.06 (dd, J = 7.6, 15.6 Hz, 1H, c-Hex-CH@), 6.65 (dd,
J = 11.2, 11.8 Hz, 1H, –CH@CH–CO2–), 7.32 (dd, J = 11.8, 15.6 Hz,
1H, c-Hex-CH@CH–); 13C NMR (CDCl3, 100 MHz) d: 25.8 (t,
c-Hex), 26.0 (t, c-Hex), 32.3 (t, c-Hex), 41.3 (d, c-Hex), 114.5 (d,
@CH–CO2–), 124.6 (d, c-Hex-CH@CH–), 148.1 (d, c-Hex-CH@),
152.5 (d, –CH@CH–CO2–), 171.2 (s, C@O) IR (KBr): 1686 cmꢀ1; EI-
MS m/z 180 (M+); FAB-MS m/z 180 (M+); HR EI-MS m/z 180.1153
(M+, calcd for C11H16O2 180.1150); Anal. calcd for C11H16O2: C,
73.03; H, 8.95. Found: C, 73.23; H, 8.79.
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