Synthesis of the amino acid conjugates of epi-jasmonic acid

Article abstract of DOI:10.1007/s00726-011-0925-z

The TES ether of the C6-hydroxy derivative of naturally occurring epi-jasmonic acid (epi-JA) was designed as epimerization-free equivalent of epi-JA. The TES ether was synthesized from (1R,4S)-4-hydroxycyclopent-2-enyl acetate in 13 steps. The acid part o

Full text of DOI:10.1007/s00726-011-0925-z

Amino Acids (2012) 42:1955–1966
DOI 10.1007/s00726-011-0925-z
ORIGINAL ARTICLE
Synthesis of the amino acid conjugates of epi-jasmonic acid
•
N. Ogawa Y. Kobayashi
Received: 28 February 2011 / Accepted: 25 April 2011 / Published online: 12 May 2011
Ó Springer-Verlag 2011
Abstract The TES ether of the C6-hydroxy derivative of
naturally occurring epi-jasmonic acid (epi-JA) was designed
as epimerization-free equivalent of epi-JA. The TES ether
was synthesized from (1R,4S)-4-hydroxycyclopent-2-enyl
acetate in 13 steps. The acid part of the ether was activated
with ClCO2Bui and subjected to condensation with L-amino
acid at room temperature for 48 h. The TES group in the
condensation product was removed in HCO2H (0°C, 30 min)
and the resulting hydroxyl group was oxidized with Jones
reagent (acetone, 0°C, 30 min) to furnish the amino acid
conjugate of epi-JA. The amino acids examined are L-iso-
leucine, L-leucine, L-alanine, L-valine, and D-allo-isoleucine,
which afforded the conjugates in 48–68% yields with
89–96% diastereomeric purity over the trans isomers. Sim-
ilarly, the possible three stereoisomers of epi-JA were con-
densed with L-isoleucine successfully, producing the
corresponding stereoisomers in good yields.
Schmidt et al. 1990; Staswick and Tiryaki 2004) are the
major components of the jasmonate signaling mediators
that regulate stress responses and development in plants
(Creelman and Mullet 1997; Tamogami et al. 2008; Walter
et al. 2007; Xie et al. 1998). In 2007, the mechanism of the
signaling was disclosed at the molecular level, in which
the amino acid conjugates promote the SCFCOI1 complex
binding to JAZ repressor proteins, resulting in degradation
of JAZ proteins (Chini et al. 2007; Thines et al. 2007).
Furthermore, L-isoleucine was found to be the most active
component among the amino acids examined (Thines et al.
2007). The conjugates used for the study were synthesized
from racemic jasmonic acid (JA) that consists of natural
epi-JA (1), its enantiomer, and the two trans isomers (3 and
4) in roughly the thermodynamic ratio of \5:\5:[45:[45
(Kramell et al. 1988, 1997b). Thus, the potency of the
isoleucine conjugate 2a possessing the epi-JA component
remained unclear. Later, the conjugates 2a and the trans
isomers (7 and 8) were separated from the diastereomeric
mixture derived from racemic JA and L-isoleucine by
HPLC, and the conjugates 2a and 8 (unnatural isomer)
were found to be the active isomers for the promotion,
while the trans isomer 7 was less active (Fonseca et al.
2009).
Keywords epi-Jasmonic acid Á Amino acid conjugate Á
Isoleucine Á Asymmetric synthesis Á Stereoselective
Introduction
The amino acid conjugates of epi-JA (Fig. 1) found in
plants (Kramell et al. 1997a; Miersch et al. 1992, 1999;
Before the natural isomer 2a was elucidated to be the
most active isomer, we established a stereoselective syn-
thesis of epi-JA (1) (Ogawa and Kobayashi 2008). We then
examined condensation of 1 and L-isoleucine according to
the procedure developed for racemic JA and L-isoleucine
(Kramell et al. 1988). However, substantial epimerization
at C7 took place, producing a mixture of the desired
product 2a and the trans isomer 7 in a 3:7 ratio (Scheme 1,
method 1) (Soloshonok 2002). Since the trans isomer is
thermodynamically more stable (Seto et al. 1996, 1999),
the epimerization at C7 of the cyclopentane ring of less
Electronic supplementary material The online version of this
article (doi:10.1007/s00726-011-0925-z) contains supplementary
material, which is available to authorized users.
N. Ogawa Á Y. Kobayashi (&)
Department of Biomolecular Engineering, Tokyo Institute
of Technology, B52, Nagatsuta-cho 4259, Midori-ku,
Yokohama 226-8501, Japan
e-mail: ykobayas@bio.titech.ac.jp
123

1956
N. Ogawa, Y. Kobayashi
R
restored at the last step. In practice, the method afforded 2a
stereoselectively as communicated recently (Ogawa and
Kobayashi 2008). With 2a synthesized, we studied 2a-
promoted interaction between COI1 and JAZ proteins that
are produced by alternative splicing (Chung et al. 2010)
and succeeded in obtaining crystal structures of the com-
plex involving 2a, COI1, and JAZ and their pharmaco-
logical data (Sheard et al. 2010). In contrast to the
isoleucine conjugate, biological profiles of the natural
conjugates with other amino acids are not yet disclosed,
though the studies using the trans isomers of the conjugates
derived from racemic JA and the L-amino acids have been
reported previously. Due to the significance of the stereo-
defined amino acid conjugates of epi-JA and JA as such
and as standards for biological investigation, we describe
herein synthesis 2a–d and 5–8, demonstrating generality of
the method.
3R
7S
S
3R
7S
R for 2
CONH
CO2H
CO2H
a
b
c
d
CH(Me)Et (S)
CH2CHMe2
CH3
O
O
CHMe2
epi-JA
amino acid conjugate
2
(1)
(natural)
(natural)
S
R
CO2H
CO2H
S
R
O
O
(3R,7R)-JA
(3)
(trans isomer)
(3S,7S)-JA
(4)
(trans isomer)
R
S
CONH
CO2H
CONH
CO2H
R
O
O
isomer
6
isomer
5
Results and discussion
(cis isomer)
with allo-isoleucine
On the basis of our previous synthesis of 12-oxo-PDA and
OPC-8:0 (Ainai et al. 2003), we envisaged that condensa-
tion of an epimerization-free acid 9 with L-isoleucine fol-
lowed by desilylation would afford alcohol 10, which upon
Jones oxidation would furnish 2a stereoselectively.
S
CONH
CO2H
CONH
CO2H
R
O
O
The condensation was first examined with a diastereo-
meric mixture (dsm) of the acid dsm-9, which was synthe-
sized from racemic methyl jasmonate through hydrolysis
(aqueous NaOH), reduction (NaBH4), and silylation [TESCl
(Et3SiCl), imidazole] in 82% yield. Acid dsm-9 was acti-
vated by a reagent at room temperature for 3 h in THF and
mixed with an aqueous solution of L-isoleucine (5 equiv.)
and Et3N (5 equiv.). After 48 h at room temperature, the
TES group was removed in HCO2H (0°C, 30 min) to pro-
duce dsm-10, which was purified by chromatography on
silica gel (CHCl3/EtOAc to CHCl3/EtOAc/HCO2H). Among
the reagents examined (Table 1), ClCO2Bui gave a good
yield (entry 8). In relation to the condensation, isoleucine-
allyl was condensed to racemic JA (3 ? 4) in 31% yield, and
the allyl group in the product was removed with Bu3SnH and
Pd(PPh3)4 cat to afford a mixture of the isoleucine conjugate
of racemic JA and Ph3P-oxide. However, the mixture was
inseparable by chromatography on silica gel.
isomer
7
(trans isomer)
isomer
8
(trans isomer)
Fig. 1 epi-JA amino acid conjugates of epi-JA, and related isomers.
JA jasmonic acid
method 1: the direct condensation
1) ClCO2Bui
CONH
CO2H
epi-JA (1)
2) L-Ile
O
2a : 7 = 30 : 70
method 2: a stereoselective way
1) condensation
with L-Ile
CO2H
CONH
CO2H
2) –TES
OTES
X
With the above results in hand, we undertook synthesis
of the optically active conjugate 2a as shown in Scheme 2
starting from acetate 11 ([99% ee by HPLC), which was
converted to bis–TES ether 12 by the eight-step procedure
(Nonaka et al. 2010). Swern oxidation of 12 gave aldehyde
13, which upon Wittig reaction afforded 14 in 83% yield
over the two steps. The olefin part of 14 was then changed
to the hydroxyl group of 15 in 77% yield. The yield of 15
from 12 was higher than that reported (Nonaka et al. 2010).
9
10, X =
2a, X = O
α
-OH,
β
-H
oxidn
(CrO3, H+)
Scheme 1 Synthesis of 2a by two methods 1 and 2
stable 2a is not surprising. To detour the problem of the
epimerization, we envisioned a method delineated in
Scheme 1, method 2, in which the carbonyl group was
123

Synthesis of the amino acid conjugates of epi-jasmonic acid
1957
Table 1 Condensation of a model acid dsm-9a with L-isoleucine
H); isomer 7, d 2.67 (dd, J = 14.5 Hz, 4.5 Hz, 1 H)].
Furthermore, NH and a-H of the amino acid part in the H
1
1) reagent
2) L-Ile·Et3N (5 equiv)
rt, 48 h, THF-H2O
3
NMR spectra of 2a and 5 (synthesis, see below) clearly
indicated no epimerization at the a position of leucine: 2a,
d 4.63 (dd, J = 8.5 Hz, 4.5 Hz, 1 H), 6.30 (d, J = 8.5 Hz,
1 H); isomer 5, d 4.78 (dd, J = 9 Hz, 4 Hz, 1 H), 6.42 (d,
J = 9 Hz, 1 H). The conjugate 2a with this purity will be
accepted for biological study. With the 1H NMR spectra of
2a and its C7 epimer 7 in hand, we examined chemical
CO2H
CONH
CO2H
6
7
3) HCO2H, 0 °C, 30 min
OTES
OH
dsm-9
trans at C3,7
cis and trans at C6,7
dsm-10
Entry
Reagentb (equiv.)
Yieldb (%)
1
stability of 2a in CD3OD by H NMR spectroscopy. In
1
2
3
4
5
6
7
8
9
a
WSC (1.3), HOSu (1.3)
DMT-MM (1.3)
43
51
47
47
51
17
0
contrast to the partial epimerization (4%) induced by the
acid during Jones oxidation, the conjugate 2a was found to
be quite stable at room temperature for 3 weeks, whereas
addition of K2CO3 promoted rapid epimerization to afford
a 6:94 mixture of 2a and 7 after 24 h. The rate of the
epimerization appears faster than that of tuberonic acid and
much faster than 12-oxo-PDA, though we do not have any
reason to explain the difference.
BOPCl (1.3), Et3N (1.3)
HATU (1.3), Et3N (1.3)
HBTU (1.3), Et3N (1.3)
TCBC (1.5), Et3N (1.5)
DCBC (1.5), Et3N (1.5)
ClCO2Bui (1.3), Et3N (1.3)
60
42
ClCO2CH(Me)Cl (1.3), Et3N (1.3)
The above three-step sequence was applied to L-leucine,
L-alanine, and L-valine as delineated in Scheme 3. In all
cases, the condensation with the amino acids (room tem-
perature, 48 h) and the removal of the TES group (HCO2H,
0°C, 30 min) proceeded uneventfully to afford alcohols
16–18, which were oxidized to the conjugates 2b–d in
good yields. To determine epimeric purity over the trans
isomer (the C7 epimer), the epimer of 2c (see the supple-
mental material) was synthesized as well to find the spe-
A diastereomeric mixture (dsm) prepared from racemic methyl
jasmonate
b
WSC 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochlo-
ride; DMT-MM 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpho-
linium chloride; BOPCl Bis(2-oxo-3-oxazolidinyl)phosphinic chloride;
HATU 1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo(4,5-b) py-
ridinium 3-oxide hexafluorophosphate; HBTU 1-[Bis(dimethyl-
amino)methylene]-1H-benzotriazolium 3-oxide hexafluorophosphate;
TCBC 2,4,6-Trichlorobenzoyl chloride
c
1
Isolated yields by chromatography on silica gel
cific signals in the H NMR spectrum. With the diagnostic
signals for the epimer of 2c and 7 (epimer of 2a), those of
2b and 2d were assigned by analogy and the epimeric
purities for 2b–d were calculated to be 91–93%.
Oxidation of alcohol 15 to acid 9 was accomplished using
TPAP/NMO and NaClO2 in 85% yield (TPAP, tetrapro-
pylammonium perruthenate; NMO, N-methylmorpholine-
N-oxide). Condensation of 9 with L-isoleucine followed by
desilylation under the conditions established above-pro-
duced alcohol 10 in 68% yield. Finally, Jones oxidation
(CrO3, H2SO4) at 0°C for 30 min gave the isoleucine
conjugate 2a in quantitatively. The isomeric purity of 2a
over the trans isomer 7 (synthesis, see Scheme 5) was 96%
by 500 MHz 1H NMR spectroscopy [2a, d 2.84–2.94 (m, 1
Similarly, the allo-isoleucine conjugate 5 was synthe-
sized from acid 9 by condensation with D-allo-isoleucine
followed by Jones oxidation (Scheme 3). In addition,
product 5 was used to determine the epimeric purity of 2a
1
by H NMR spectroscopy (see above).
Next, we investigated synthesis of the isoleucine con-
jugates of the epi-JA isomers delineated in Fig. 1 (i.e.,
isomers 6–8).
[Ph3PC3H7]+Br–
OAc
Swern oxidn
HO
CHO
OTES
NaN(TMS)2
OTES
14
83% from 12
OTES
13
OTES
OH
11 (>99%)
12
1) ClCO2Bui, Et3N
then L-Ile, Et3N
1) NMO
TPAP (cat.)
CrO3, H+
1) Cy2BH
9
10
2a
2) H2O2
NaOH
2) NaClO2
Me2C=CHMe
2) HCO2H
97%
OTES
15
68%
85%
77%
Scheme 2 Synthesis of the conjugate 2a through acid 9
123

1958
N. Ogawa, Y. Kobayashi
a 96:4 diastereomeric ratio of 6 and the C7 isomer 8 by 1H
NMR spectroscopy (synthesis of 8, see below).
R
1) ClCO2Bui, Et3N
then L-Ile, Et3N
CONH
CO2H
9
Synthesis of the stereoisomers 7 and 8 possessing the JA
moiety required the 3,7-trans acids 31 and ent-31, respec-
tively. Although monoacetate 11 would be transformed to
these acids by a method similar to that presented as above for
the synthesis of 9 and ent-9 (Schemes 2, 4), we rather deci-
ded to utilize esters 30 and ent-30 since these intermediates
are available through the kinetic resolution of the racemic
alcohol derived from methyl jasmonate by PPL-assisted
acetylation in 5 and 6 steps (to 31 and ent-31) (Kiyota et al.
2001; Asamitsu et al. 2006), which are shorter than that
starting from monoacetate 11 (11 steps). In practice, ester 30
with 98% ee was prepared from racemic methyl jasmonate in
26% yield and transformed to acid 31 through hydrolysis
followed by silylation. The acid was subjected to the three-
step transformation developed above to furnish the trans
stereoisomer 7 in 53% yield from 31. Diastereomeric purity
of 7 over 2a was[99% by 500 MHz 1H NMR spectroscopy,
indicating slower (if any) deprotonation of the hydrogen at
C7 of 7 than that of 2a (96% purity over 7) during the oxi-
dation. The C3 acetamide chain on the cyclopentanone ring
probably prevents the access of the base to the hydrogen at
C7. In a similar manner, ent-31 obtained in 19% yield from
racemic methyl jasmonate was transformed to the stereo-
isomer 8 without detectable epimerization by 1H NMR
spectroscopy (Scheme 5).
7
2) HCO2H
HO
16, R = CH2CHMe2, 65%
17, R = Me, 62%
18, R = CHMe2, 62%
CrO3, H+
2b, 78%, 92:8a
2c, 83%, 91:9
2d, 98%, 93:7
1) ClCO2Bui, Et3N
then D-allo-Ile, Et3N
R
CONH
CO2H
9
2) HCO2H
X
α
19, X = -OH,
5, X = O
β -H
CrO3, H+
48% from 9, 89:11
a
Scheme 3 Synthesis of the amino acid conjugates. Ratio of 2: C7-
epimer
Synthesis of 6, the isoleucine conjugate with the enan-
tiomer of epi-JA, started with the same monoacetate 11 used
above ([99% ee by chiral HPLC), to which the CH2CO2Me
group was attached to give 20 with retention of the config-
uration of the acetoxy-carbon in 82% yield through palla-
dium-catalyzed allylic substitution with methyl malonate
followed by decarboxylation (Acharya and Kobayashi
2006). Transformation of 20 to ent-9 was accomplished
using the strategy developed for the synthesis of epi-JA (1)
(Nonaka et al. 2010). Condensation of ent-9 with L-isoleu-
cine followed by desilylation afforded alcohol 29 in 50%
yield. Finally, Jones oxidation furnished 6 in 92% yield with
Conclusion
In summary, we developed a method for synthesis of the
isoleucine conjugate 2a for the first time, and the method
1) CH2(CO2Me)2, t-BuOK,
Pd(PPh3) cat.
OR
MeC(OMe)2NMe2
LiBH4
75%
OAc
CO2Me
CO2Me
HO
HO
xylene, 150 °C
92%
2) KI, DMF/H2O,
82%
CONMe2
CONMe2
20
11
(>99% ee)
21
22, R = H
23, R = PMB
PMBCl,
NaH, DMF
100%
OPMB
1) (COCl)2, DMSO
then Et3N
OR
OPMB
OR
1) TPAP
I2, aq THF
71%
X
LiAlH4
2) [Ph3P(CH2)2Me]+ Br–
NaN(TMS)2
2) NaClO2
O
OTES
OR
MeCH=CMe2
O
26, R = H
27, R = TES
95%
80%
24, X = I
25, X = H
TESCl
28, R = PMB
ent-15, R = H
Bu3SnH
AIBN
DDQ
100%
84% from 24
1) ClCO2Bui, Et3N
then L-Ile, Et3N
CO2H
CrO3, H+
CONH
CO2H
6
OTES
ent-9
92%
2) HCO2H
50%
HO
29
Scheme 4 Synthesis of the isoleucine conjugate 6 with the enantiomer of epi-JA part. PMB = 4-MeOC6H4CH2
123

Synthesis of the amino acid conjugates of epi-jasmonic acid
1959
1) NaOH aq.
CO2H
CO2Me
2-((1R,2S,3R)-2-((Z)-Pent-2-en-1-yl)-3-
((triethylsilyl)oxy)cyclopentyl)ethanol (15)
2) TESCl, imidazole
100%
OTES
ODNB
30, 98% ee
To a solution of (COCl)2 (0.379 mL, 4.55 mmol) in CH2Cl2
(13 mL) was added DMSO (0.646 mL, 9.10 mmol) at
-78°C. The mixture was stirred at -78°C for 40 min and a
solution of TES ether 12 (350 mg, 0.910 mmol) in CH2Cl2
(2 mL) was added dropwise. After 1 h at -78°C, Et3N
(1.27 mL, 9.10 mmol) was added. The resulting mixture
was warmed to room temperature with vigorous stirring and
diluted with saturated NaHCO3. The product was extracted
with CH2Cl2 twice. The combined extracts were washed
with brine, dried over MgSO4, and concentrated to afford
aldehyde 13, which was used for the next reaction without
further purification.
31
1) L-Ile, Et3N
ClCO2Bui
CrO3, H+
89%
CONH
CO2H
7
2) HCO2H
OH
60%
32
1) L-Ile, Et3N
ClCO2Bui
CO2Me
CO2H
To an ice-cold suspension of [Ph3P(CH2)2CH3]?Br-
(1.05 g, 2.73 mmol) in THF (7 mL) was added NaHMDS
(3.0 mL, 1.0 M solution in THF, 3.0 mmol), and the
resulting yellow mixture was stirred at 0°C for 1 h and cool
to -78°C. DMF (0.76 mL) and a solution of the above
aldehyde in THF (2 mL) were added. The resulting mixture
was stirred at -78°C for 2 h, warmed to room temperature
slowly, stirred overnight, and diluted with saturated
NH4Cl. The product was extracted with EtOAc twice, and
the combined extracts were washed with brine, dried over
MgSO4, and concentrated to give the residue, which was
purified by chromatography on silica gel (hexane/EtOAc)
to give olefin 14 (222 mg, 83% from 12).
2) HCO2H
100%
OTES
ODNB
41%
ent-30, 99% ee
ent-31
S
CONH
CO2H
α
33, X = -OH,
8, X = O
β-H
X
CrO3, H+
89%
Scheme 5 Synthesis of the isoleucine conjugates of JA and the
enantiomer of JA. DNB = 3,5-(NO2)2C6H3C(=O)–
To an ice-cold solution of olefin 14 (111.4 mg,
0.378 mmol) in THF (5 mL) was added Cy2BH (Cy =
c-C6H11) (2.3 mL, 0.5 M solution in THF, 1.15 mmol) pre-
pared freshly. The solution was stirred at 0°C for 20 min, and
3 N NaOH (5 mL) and 35% H2O2 (5 mL) were added to the
solution. The resulting mixture was warmed to room tem-
perature slowly and stirred for 2 h. The product was extracted
with Et2O twice. The combined extracts were washed with
brine, dried over MgSO4, and concentrated to afford the
residue, which was purified by chromatography on silica gel
(hexane/EtOAc) to give alcohol 15 (90.9 mg, 77%):
Rf = 0.41 (hexane/EtOAc 5:1). The 1H NMR spectrum of 15
was identical with that reported (Nonaka et al. 2010).
was successfully applied to synthesis of its stereoisomers
5–8 and the conjugates 2b–d with other amino acids. These
compounds are definitely useful not only for the biological
study at molecular level but also as standards for estimation
of these compounds from natural sources.
Experimental section
General
The IR, specific rotations, and melting points (uncorrected)
were measured on a JASCO A-100 spectrophotometer, a
JASCO Digital Polarimeter DIP-370, and a Yanako MP-
2-((1R,2S,3R)-3-((Triethylsilyl)oxy)-2-((Z)-pent-2-en-
1-yl)cyclopentyl)acetic acid (9)
1
S3, respectively. The 300 MHz H and 75 MHz 13C NMR
spectra were measured on a Varian Mercury 300, while
1
500 MHz H NMR spectra were done on a Varian VXR-
To a suspension of MS4A (145 mg) in CH2Cl2 (1.0 mL),
NMO (50.8 mg, 0.434 mmol), TPAP (10.2 mg, 0.0290
mmol), and a solution of alcohol 15 (90.3 mg, 0.289 mmol)
in CH2Cl2 (2.0 mL) were added. The mixture was stirred at
room temperature for 30 min, and passed through a short col-
umn of silica gel (hexane to hexane/EtOAc) to give the corre-
sponding aldehyde, which was used for the next reaction
500 s. The chemical shifts of the carbons accompany
minus (for C and CH2) and plus (for CH and CH3) signs of
APT experiments (Attached Proton Test). Chromato-
graphic purification was carried out using spherical silica
gel 60 N purchased from Kanto, Japan. TLC plate was
purchased from Merck (Silica gel 60 F254).
123

1960
N. Ogawa, Y. Kobayashi
without further purification: Rf = 0.77 (hexane/EtOAc 5:1);
1H NMR (300 MHz, CDCl3) d 0.58 (q, J = 7.5 Hz, 6 H), 0.96
(t, J = 7.5 Hz, 9 H), 0.97 (t, J = 7.5 Hz, 3 H), 1.37–2.24
(m, 10 H), 2.39–2.65 (m, 2 H), 4.12–4.20 (m, 1 H), 5.28–5.44
(m, 2 H), 9.74 (t, J = 1.5 Hz, 1 H).
14.3 (?), 15.4 (?), 20.8 (-), 23.2 (-), 25.3 (-), 29.0 (-),
33.0 (-), 36.8 (?), 37.8 (?), 38.4 (-), 48.2 (?), 56.5 (?),
75.6 (?), 127.6 (?), 132.9 (?), 173.9 (-), 174.5 (-);
HRMS (FAB) calcd for C18H32NO4 [(M ? H)?] 326.2331,
found 326.2334.
To a solution of the above aldehyde in t-BuOH (1.0 mL),
2-methyl-2-butene (0.33 mL, 2.9 mmol), phosphate buffer
(1.0 mL, pH 6.8), and NaClO2 (44 mg, 80%, 0.43 mmol)
were added. The mixture was stirred at room temperature
for 2 h and diluted with H2O. The product was extracted
with EtOAc several times. The combined extracts were
washed with brine, dried over MgSO4, and concentrated.
The residue was purified by chromatography on silica gel
(hexane/EtOAc) to give acid 9 (80 mg, 85% from 15):
Rf = 0.35 (hexane/EtOAc 5:1); [a]2D5 ?5 (c 0.60, CHCl3);
epi-Jasmonoyl-L-isoleucine (2a)
To an ice-cold solution of alcohol 10 (12.2 mg, 0.0375
mmol) in acetone (1 mL), Jones reagent (2 drops, 4 M
solution) was added dropwise. The mixture was stirred at
0°C for 30 min and i-PrOH was added to quench the excess
reagent. The mixture was subjected directly to chroma-
tography on silica gel (CHCl3/EtOAc/HCO2H) to give
the isoleucine conjugate 2a (11.7 mg, 97%): Rf = 0.32
(CHCl3/EtOAc/HCO2H 14:6:1); [a]2D7 ?59 (c 0.35,
IR (neat) 3,000, 1,708, 1,413, 1,017 cm-1 1H NMR
;
(300 MHz, CDCl3) d 0.58 (q, J = 7.5 Hz, 6 H), 0.96 (t,
J = 7.5 Hz, 9 H), 0.97 (t, J = 7.5 Hz, 3 H), 1.50–1.96 (m, 5
H), 1.96–2.25 (m, 4 H), 2.35–2.57 (m, 3 H), 4.12–4.19 (m, 1
H), 5.30–5.43 (m, 2 H); 13C NMR (75 MHz, CDCl3) d 5.0
(-), 7.0 (?), 14.3 (?), 20.8 (-), 23.2 (-), 29.4 (-), 34.1
(-), 36.0 (?), 36.9 (-), 48.7 (?), 75.3 (?), 128.2 (?),
132.2 (?), 180.7 (-); HRMS (FAB) calcd for C18H35O3Si
[(M ? H)?] 327.2355, found 327.2359.
CHCl3); IR (neat) 3,346, 1,727, 1,641, 1,546 cm-1 1H
;
NMR (500 MHz, CDCl3) d 0.94 (t, J = 7.5 Hz, 3 H), 0.95
(d, J = 7.5 Hz, 3 H), 0.96 (t, J = 7.5 Hz, 3 H), 1.16–1.38
(m, 2 H), 1.44–1.54 (m, 1 H), 1.82–2.10 (m, 7 H),
2.19–2.30 (m, 2 H), 2.34–2.44 (m, 2 H), 2.84–2.94 (m, 1
H), 4.63 (dd, J = 8.5, 4.5 Hz, 1 H), 5.34 (dt, J = 10.5,
7.5 Hz, 1 H), 5.45 (dt, J = 10.5, 7.5 Hz, 1 H), 6.30 (d,
J = 8.5 Hz, 1 H), 6.1–6.8 (br s, 1 H); 1H NMR (500 MHz,
CD3OD) d 0.93 (t, J = 7.5 Hz, 3 H), 0.95 (d, J = 7.5 Hz,
3 H), 0.96 (t, J = 7.5 Hz, 3 H), 1.20–1.36 (m, 2 H),
1.47–1.56 (m, 1 H), 1.84–2.16 (m, 6 H), 2.17–2.43 (m, 5
H), 2.76–2.90 (m, 1 H), 4.37 (d, J = 6.0 Hz, 1 H),
5.32–5.48 (m, 2 H); 13C NMR (75 MHz, CDCl3) d 11.7
(?), 14.2 (?), 15.5 (?), 20.7 (-), 23.0 (-), 25.2 (-), 25.4
(–), 35.3 (-), 35.8 (-), 36.1 (?), 37.6 (?), 53.1 (?), 56.6
(?), 125.5 (?), 133.6 (?), 172.2 (-), 175.3 (-), 219.9 (-);
HRMS (FAB) calcd for C18H30NO4 [(M ? H)?] 324.2175,
found 324.2183.
(2S,3S)-2-(2-((1R,2S,3R)-3-Hydroxy-2-((Z)-pent-2-en-
1-yl)cyclopentyl)acetamido)-3-methylpentanoic acid
(10)
To a solution of acid 9 (25.0 mg, 0.0766 mmol) in THF
(1 mL), Et3N (0.014 mL, 0.099 mmol) and ClCO2Bui
(0.013 mL, 0.10 mmol) were added. The mixture was
stirred at room temperature for 3 h and filtered through a
piece of paper. The remaining precipitates were washed
with THF (3 mL). A solution of L-isoleucine (50 mg,
0.38 mmol) and Et3N (0.053 mL, 0.38 mmol) in H2O
(4 mL) was added to the combined filtrates. The mixture
was stirred at room temperature for 48 h, and diluted with
saturated NH4Cl. The resulting mixture was extracted with
CHCl3 several times. The combined extracts were dried
over MgSO4 and concentrated. The residue was diluted
with HCO2H (2 mL) at 0°C. After 30 min at 0°C, the
solution was concentrated to give a residue, which was
purified by chromatography on silica gel (CHCl3/EtOAc/
HCO2H) to give alcohol 10 (17.0 mg, 68%): Rf = 0.24
(CHCl3/EtOAc/HCO2H 14:6:1); [a]2D5 ?46 (c 0.34,
epi-Jasmonoyl-L-leucine (2b)
According to the synthesis of the conjugate 2a, acid 9
(24.2 mg, 0.0741 mmol) was condensed with L-leucine
(48.6 mg, 0.371 mmol) and the TES group was removed
with HCO2H (1 mL) to afford alcohol 16 (15.7 mg, 65%):
Rf = 0.27 (CHCl3/EtOAc/HCO2H 14:6:1); [a]2D3 ?6
1
(c 0.42, CHCl3); H NMR (500 MHz, CDCl3) d 0.92–1.00
(m, 9 H), 1.23–1.32 (m, 1 H), 1.53–1.95 (m, 7 H), 1.96–2.47
(m, 6 H), 2.47–2.58 (m, 1 H), 4.19–4.28 (m, 1 H), 4.54–4.66
(m, 1 H), 5.32–5.49 (m, 2 H), 5.6 (br s, 2 H), 6.61 (d,
J = 7.5 Hz, 1 H); 13C NMR (75 MHz, CDCl3) d 14.3 (?),
20.8 (-), 21.9 (?), 22.9 (?), 23.2 (-), 24.9 (?), 28.8 (-),
33.1 (-), 36.6 (?), 38.3 (-), 41.2 (-), 48.1 (?), 51.0 (?),
75.3 (?), 127.6 (?), 132.7 (?), 174.5 (-), 176.1 (-).
Alcohol 16 (13.5 mg, 0.0415 mmol) was oxidized with
Jones reagent (4 drops, 4 M solution) to give the leucine
conjugate 2b (10.5 mg, 78%): Rf = 0.32 (CHCl3/EtOAc/
CHCl3); IR (neat) 3,355, 3,300, 1,718, 1,457, 1,064 cm-1
;
1H NMR (300 MHz, CDCl3) d 0.94 (t, J = 7.5 Hz, 3 H),
0.95 (d, J = 7.5 Hz, 3 H), 0.97 (t, J = 7.5 Hz, 3 H),
1.11–1.71 (m, 5 H), 1.82–2.31 (m, 9 H), 2.55 (dd, J = 14,
4 Hz, 1 H), 4.23 (t, J = 4 Hz, 1 H), 4.61 (dd, J = 8.5,
5 Hz, 1 H), 4.0–4.9 (br s, 2 H), 5.33–5.50 (m, 2 H), 6.10 (d,
J = 8.5 Hz, 1 H); 13C NMR (75 MHz, CDCl3) d 11.7 (?),
123

Synthesis of the amino acid conjugates of epi-jasmonic acid
1961
HCO2H 14:6:1); [a]2D4 ?19 (c 0.23, CHCl3); 1H NMR
(500 MHz, CDCl3) d 0.90–1.04 (m, 9 H), 1.20–1.34 (m, 1
H), 1.50–1.76 (m, 4 H), 1.82–2.13 (m, 5 H), 2.14–2.49 (m,
4 H), 2.84–2.94 (m, 1 H), 4.50–4.72 (m, 1 H), 5.22–5.58
(m, 2 H), 6.17–6.30 (m, 1 H), 6.6 (br s, 1 H); 13C NMR
(75 MHz, CDCl3) d 14.2 (?), 20.7 (-), 21.8 (?), 22.9 (?),
25.0 (?), 25.3 (-), 29.8 (-), 35.3 (-), 35.6 (-), 36.0 (?),
41.1 (-), 46.9 (?), 53.1 (?), 125.5 (?), 133.6 (?), 172.5
(-), 173.8 (-), 220.0 (-); HRMS (FAB) calcd for
C18H29NO4Na [(M ? Na)?] 346.1994, found 346.2005.
(?), 20.8 (-), 23.2 (-), 28.8 (-), 31.1 (?), 33.0 (-), 36.7
(?), 38.3 (-), 48.2 (?), 57.2 (?), 75.4 (?), 127.6 (?),
132.8 (?), 174.5 (-), 174.7 (-).
Alcohol 18 (13.8 mg, 0.0443 mmol) was oxidized with
Jones reagent (3 drops, 4 M solution) to give the valine
conjugate 2d (13.5 mg, 98%): Rf = 0.39 (CHCl3/EtOAc/
HCO2H 14:6:1); [a]2D3 ?29 (c 0.18, CHCl3); 1H NMR
(500 MHz, CDCl3) d 0.90–1.02 (m, 9 H), 1.22–1.38 (m, 3
H), 1.56–1.67 (m, 1 H), 1.81–1.92 (m, 1 H), 1.95–2.13 (m,
3 H), 2.16–2.30 (m, 2 H), 2.31–2.44 (m, 2 H), 2.82–2.94
(m, 1 H), 4.54 (br s, 1 H), 5.22–5.58 (m, 2 H), 5.7 (br s, 1
H), 6.23–6.47 (m, 1 H); 13C NMR (75 MHz, CDCl3) d 14.2
(?), 17.8 (?), 19.1 (?), 20.7 (-), 23.0 (-), 25.4 (-), 30.9
(?), 35.3 (-), 35.8 (-), 36.1 (?), 53.1 (?), 57.1 (?), 125.5
(?), 133.6 (?), 172.4 (-), 175.4 (-), 219.9 (-); HRMS
(FAB) calcd for C17H27NO4Na [(M ? Na)?] 332.1838,
found 332.1833.
epi-Jasmonoyl-L-alanine (2c)
According to the synthesis of the conjugate 2a, acid 9
(21.6 mg, 0.0661 mmol) was condensed with L-alanine
(29.4 mg, 0.330 mmol) and the TES group was removed
with HCO2H (1 mL) to afford alcohol 17 (11.6 mg, 62%):
Rf = 0.30 (CHCl3/EtOAc/HCO2H 14:6:1); [a]2D3 ?8
1
(c 0.48, CHCl3); H NMR (500 MHz, CDCl3) d 0.91 (d,
epi-Jasmonoyl-D-allo-isoleucine (5)
J = 7 Hz, 3 H), 0.96 (t, J = 7.5 Hz, 3 H), 1.34–1.40 (m, 1
H), 1.54–1.67 (m, 1 H), 1.70–1.95 (m, 4 H), 1.96–2.58 (m,
6 H), 4.21–4.28 (m, 1 H), 4.48–4.62 (m, 1 H), 5.30–5.49
(m, 2 H), 6.0 (br s, 1 H), 6.98 (d, J = 7.5 Hz, 1 H); 13C
NMR (75 MHz, CDCl3) d 14.3 (?), 18.2 (?), 19.0 (?),
20.8 (-), 23.2 (-), 28.9 (-), 33.0 (-), 36.6 (?), 38.2 (-),
48.4 (?), 75.4 (?), 127.6 (?), 132.8 (?), 174.3 (-), 175.8
(-).
According to the synthesis of the conjugate 2a, acid 9
(26.5 mg, 0.0812 mmol) was condensed with D-allo-iso-
leucine (53.3 mg, 0.406 mmol) and the TES group was
removed with HCO2H (2 mL) to afford alcohol 19
(12.6 mg, 48%): Rf = 0.25 (CHCl3/EtOAc/HCO2H 14:6:1);
[a]D26 ?21 (c 0.162, CHCl3); IR (neat) 3346 cm-1; 1H NMR
(500 MHz, CDCl3) d 0.80–1.01 (m, 9 H), 1.06–1.20 (m, 1
H), 1.22–1.36 (m, 1 H), 1.38–1.54 (m, 1 H), 1.60–1.71 (m, 1
H), 1.72–1.84 (m, 1 H), 1.85–2.40 (m, 8 H), 2.42–2.58 (m, 2
H), 3.9 (br s, 2 H), 4.30 (s, 1 H), 4.64–4.77 (m, 1 H),
5.32–5.50 (m, 2 H), 6.91 (d, J = 8.5 Hz, 1 H).
Alcohol 17 (16.2 mg, 0.0572 mmol) was oxidized with
Jones reagent (4 drops, 4 M solution) to give the alanine
conjugate 2c (13.5 mg, 83%): Rf = 0.33 (CHCl3/EtOAc/
HCO2H 14:6:1); [a]2D3 ?18 (c 0.17, CHCl3); 1H NMR
(500 MHz, CDCl3) d 0.84–1.06 (m, 6 H), 1.24–1.36 (m, 1
H), 1.44–2.74 (m, 10 H), 2.82–2.95 (m, 1 H), 4.58–4.68 (m,
1 H), 5.24–5.58 (m, 2 H), 6.20–6.42 (m, 1 H), 6.4–7.2 (br s,
1 H); 13C NMR (75 MHz, CDCl3) d 14.2 (?), 18.0 (?),
19.0 (?), 20.7 (-), 22.9 (-), 25.3 (-), 35.2 (-), 35.6 (-),
35.9 (?), 53.2 (?), 125.5 (?), 133.6 (?), 172.2 (-), 173.0
(-), 220.1 (-); HRMS (FAB) calcd for C15H24NO4
[(M ? H)?] 282.1705, found 282.1708.
Alcohol 19 (7.9 mg, 0.024 mmol) was oxidized with
Jones reagent (2 drops, 4 M solution) to afford the D-allo-
isoleucine conjugate 5 (7.9 mg, 100%): Rf = 0.32 (CHCl3/
EtOAc/HCO2H 14:6:1); 1H NMR (500 MHz, CDCl3) d
0.90 (d, J = 7 Hz, 3 H), 0.96 (t, J = 7 Hz, 3 H), 0.97 (t,
J = 7 Hz, 3 H), 1.15–1.36 (m, 3 H), 1.38–1.49 (m, 1 H),
1.81–1.90 (m, 1 H), 1.96–2.10 (m, 5 H), 2.26–2.33 (m, 2
H), 2.34–2.45 (m, 3 H), 2.85–2.95 (m, 1 H), 4.78 (dd,
J = 9, 4 Hz, 1 H), 5.31–5.38 (m, 1 H), 5.40–5.48 (m, 1 H),
6.42 (d, J = 9 Hz, 1 H).
epi-Jasmonoyl-L-valine (2d)
According to the synthesis of the conjugate 2a, acid 9
(21.3 mg, 0.0652 mmol) was condensed with L-valine
(38.2 mg, 0.326 mmol) and the TES group was removed
with HCO2H (1 mL) to afford alcohol 18 (12.4 mg, 62%):
Rf = 0.36 (CHCl3/EtOAc/HCO2H 14:6:1); [a]2D2 ?24
Methyl 2-((1S,2R)-2-(2-(dimethylamino)-2-
oxoethyl)cyclopent-3-en-1-yl)acetate (21)
To a solution of alcohol 20 (901 mg, 5.77 mmol) in xylene
(12 mL), MeC(OMe)2NMe2 (4.69 mL, 90% purity,
28.9 mmol) was added. The solution was stirred at 150°C
(oil bath temperature) for 24 h, cooled to room tempera-
ture, and concentrated. The residue was passed through a
column of silica gel (hexane/EtOAc) to give amide 21
(1.19 g, 92%): Rf = 0.23 (hexane/EtOAc 1:1); [a]2D6 ?89
1
(c 0.54, CHCl3); H NMR (500 MHz, CDCl3) d 0.96–1.00
(m, 9 H), 1.23–1.35 (m, 2 H), 1.57–1.67 (m, 1 H),
1.71–1.95 (m, 3 H), 1.96–2.32 (m, 5 H), 2.36–2.48 (m, 1
H), 2.50–2.58 (m, 1 H), 4.22–4.32 (m, 1 H), 4.52–4.62 (m,
1 H), 5.24–5.61 (m, 2 H), 5.4 (br s, 2 H), 6.62–6.78 (m, 1
H); 13C NMR (75 MHz, CDCl3) d 14.3 (?), 17.8 (?), 19.0
(c 1.09, CHCl3); IR (neat) 1,735, 1,636, 1,146 cm-1; H
1
123

1962
N. Ogawa, Y. Kobayashi
NMR (300 MHz, CDCl3) d 2.05 (ddq, J = 16, 8, 2 Hz, 1
H), 2.16 (dd, J = 15, 9 Hz, 1 H), 2.30 (dd, J = 15, 9 Hz, 1
H), 2.35 (dd, J = 15, 6 Hz, 1 H), 2.47 (dd, J = 15, 7 Hz, 1
H), 2.44–2.56 (m, 1 H), 2.70–2.88 (m, 1 H), 2.95 (s, 3 H),
2.99 (m, 3 H), 3.15–3.27 (m, 1 H), 3.68 (s, 3 H), 5.70–5.80
(m, 2 H); 13C NMR (75 MHz, CDCl3) d 33.2 (-), 35.2 (-),
35.4 (?), 37.28 (?), 37.31 (-), 43.1 (?), 51.5 (?), 129.8
(?), 134.8 (?), 171.9 (-), 173.6 (-); HRMS (FAB) calcd
for C12H19NO3Na [(M ? Na)?] 248.1263, found
248.1263.
(s, 2 H), 5.69–5.769 (m, 1 H), 5.78–5.85 (m, 1 H), 6.88
(dm, J = 9 Hz, 2 H), 7.22–7.30 (m, 2 H); 13C NMR
(75 MHz, CDCl3) d 30.7 (-), 33.4 (-), 37.2 (-), 37.4 (?),
38.3 (?), 43.6 (?), 55.3 (?), 69.7 (-), 72.8 (-), 113.8 (?),
129.4 (?), 130.2 (?), 130.6 (-), 135.6 (?), 159.5 (-),
172.5 (-); HRMS (FAB) calcd for C19H28NO3 [(M ? H)?]
318.2069, found 318.2064.
(3aR,4R,6R,6aR)-6-Iodo-4-(2-((4-
methoxybenzyl)oxy)ethyl)hexahydro-2H-
cyclopenta[b]furan-2-one (24)
2-((1R,5S)-5-(2-Hydroxyethyl)cyclopent-2-en-1-yl)-
N,N-dimethylacetamide (22)
To an ice-cold solution of amide 23 (331 mg, 1.04 mmol)
in THF (10 mL) and H2O (10 mL), I2 (528 mg,
2.08 mmol) was added. The mixture was stirred at room
temperature for 3 h and diluted with aqueous Na2S2O3. The
resulting mixture was extracted with EtOAc twice. The
combined extracts were washed with brine, dried over
MgSO4, and concentrated to give the residue, which was
purified by chromatography on silica gel (hexane/EtOAc)
to give iodolactone 24 (307 mg, 71%): Rf = 0.72 (hexane/
EtOAc 3:1); [a]2D7 –11 (c 0.99, CHCl3); IR (neat) 1,784,
To an ice-cold solution of amide 21 (993 mg, 4.41 mmol) in
Et2O (8.8 mL), EtOH (0.38 mL, 6.62 mmol) and LiBH4
(3.3 mL, 2.0 M solution in THF, 6.6 mmol) were added. The
mixture was stirred at room temperature overnight and
diluted with H2O and EtOAc. The organic phase was sepa-
rated, and the aqueous phase was extracted with EtOAc
twice. The combined extracts were dried over MgSO4 and
concentrated. The residue was purified by chromatography
on silica gel (hexane/EtOAc to EtOAc) to give alcohol 22
(652 mg, 75%): Rf = 0.15 (EtOAc); [a]2D3 ?116 (c 0.772,
CHCl3); IR (neat) 3,405, 1,629, 1,400, 1,055 cm-1; 1H NMR
(300 MHz, CDCl3) d 1.48–1.80 (m, 3 H), 2.03 (ddq, J = 19,
11, 2.5 Hz, 1 H), 2.16 (dd, J = 15, 9 Hz, 1 H), 2.32–2.50 (m,
3 H), 2.96 (s, 3 H), 2.99 (s, 3 H), 3.08–3.24 (m, 1 H),
3.60–3.78 (m, 2 H), 5.71–5.77 (m, 1 H), 5.78–5.83 (m, 1 H);
13C NMR (75 MHz, CDCl3) d 33.3 (-), 33.5 (-), 35.6 (?),
37.2 (-), 37.5 (?), 37.8 (?), 43.5 (?), 62.2 (-), 130.2 (?),
135.4 (?), 172.9 (-); HRMS (FAB) calcd for C11H20NO2
[(M ? H)?] 198.1494, found 198.1491.
1
1,611, 1,512, 1,171 cm-1; H NMR (300 MHz, CDCl3) d
1.60–1.84 (m, 3 H), 2.08 (dd, J = 15, 6 Hz, 1 H), 2.49 (dd,
J = 19, 5 Hz, 1 H), 2.57 (dd, J = 19, 10 Hz, 1 H),
2.76–2.93 (m, 1 H), 3.04–3.17 (m, 1 H), 3.38–3.53 (m, 2
H), 3.80 (s, 3 H), 4.38–4.48 (m, 3 H), 5.25 (d, J = 6.5 Hz,
1 H), 6.89 (dm, J = 9 Hz, 2 H), 7.26 (dm, J = 9 Hz, 2 H);
13C NMR (75 MHz, CDCl3) d 28.0 (?), 29.0 (-), 30.1 (-),
37.8(?), 39.3(?), 40.3(-), 55.3(?), 68.4(-), 72.8(-), 92.8
(?), 113.9 (?), 129.3 (?), 130.3 (-), 159.3 (-), 176.5 (-);
HRMS (FAB) calcd for C17H21O4NaI [(M ? Na)?]
439.0382, found 439.0385.
2-((1R,5S)-5-(2-((4-Methoxybenzyl)oxy)ethyl)
cyclopent-2-en-1-yl)-N,N-dimethylacetamide (23)
(1S,2R,3S)-2-(2-Hydroxyethyl)-3-(2-((4-
methoxybenzyl)oxy)ethyl)cyclopentanol (26)
To an ice-cold mixture of NaH (143 mg, 60% dispersion in
mineral oil, 3.58 mmol) in DMF (25 mL) was added
alcohol 22 (641 mg, 3.25 mmol) in DMF (8 mL). After
10 min at 0°C, PMBCl (p-MeOC6H4CH2Cl) (0.488 mL,
3.58 mmol) was added. The mixture was stirred at room
temperature for 24 h, and diluted with H2O. The product
was extracted with EtOAc several times. The combined
extracts were washed with brine, dried over MgSO4, and
concentrated. The residue was purified by chromatography
on silica gel (hexane/EtOAc) to give the PMB ether 23
(1.03 g, 100%): Rf = 0.68 (EtOAc); [a]2D3 ?101 (c 1.11,
To a solution of iodolactone 24 (752 mg, 1.81 mmol) in
benzene (18 mL), Bu3SnH (0.974 mL, 3.62 mmol) and
AIBN (3.0 mg, 0.018 mmol) were added. After being stirred
at 110°C (oil bath temperature) overnight, the solution was
cooled to room temperature and diluted with 1 N NaOH. The
resulting mixture was extracted with EtOAc twice. The
combined extracts were dried over MgSO4 and concentrated.
The residue was passed through a short column of silica gel
(hexane/EtOAc) to afford lactone 25, which was used for the
next reaction without further purification: Rf = 0.52 (hex-
1
ane/EtOAc 3:1); H NMR (300 MHz, CDCl3) d 1.17–1.41
CHCl3); IR (neat) 1,735, 1,647, 1,248, 1,036 cm-1
;
1H
(m, 1 H), 1.62–1.80 (m, 4 H), 1.97–2.15 (m, 2 H), 2.41 (dd,
J = 19, 6 Hz, 1 H), 2.49 (dd, J = 19, 10 Hz, 1 H), 2.88–3.01
(m, 1 H), 3.39–3.52 (m, 2 H), 3.81 (s, 3 H), 4.42 (s, 2 H), 5.02
(t, J = 7 Hz, 1 H), 6.88 (dm, J = 8.5 Hz, 2 H), 7.22 (dm,
J = 8.5 Hz, 2 H).
NMR (300 MHz, CDCl3) d 1.50–1.66 (m, 1 H), 1.72–1.86
(m, 1 H), 1.93–2.07 (m, 1 H), 2.11 (dd, J = 15, 10 Hz, 1
H), 2.31–2.45 (m, 3 H), 2.96 (s, 3 H), 2.99 (s, 3 H),
3.05–3.20 (m, 1 H), 3.41–3.54 (m, 2 H), 3.80 (s, 3 H), 4.44
123

Synthesis of the amino acid conjugates of epi-jasmonic acid
1963
To an ice-cold solution of the above lactone in Et2O
(18 mL), LiAlH4 (206 mg, 5.43 mmol) was added at 0°C.
After 1 h of stirring at room temperature, the reaction was
quenched by the addition of 10% NaOH (1.6 mL) and H2O
(2.0 mL). The resulting mixture was filtered through a pad
of Celite, and the filtrate was concentrated to afford the
residue, which was passed through a short column of silica
gel (hexane/EtOAc to EtOAc) to give diol 26 (445 mg,
1.9 mmol) to afford olefin 28 (230 mg, 95% from 27):
Rf = 0.73 (hexane/EtOAc 3:1); [a]2D5 –27 (c 0.43, CHCl3);
1
IR (neat) 1,513, 1,248, 1,006 cm-1; H NMR (300 MHz,
CDCl3) d 0.57 (q, J = 7.5 Hz, 6 H), 0.95 (t, J = 7.5 Hz,
12 H), 1.08–1.44 (m, 3 H), 1.48–1.62 (m, 2 H), 1.64–2.24
(m, 7 H), 3.36–3.52 (m, 2 H), 3.80 (s, 3 H), 4.17 (dt, J = 3,
5 Hz, 1 H), 4.40 (d, J = 11.5 Hz, 1 H), 4.45 (d,
J = 11.5 Hz, 1 H), 5.29–5.47 (m, 2 H), 6.87 (dm,
J = 9 Hz, 2 H), 7.26 (dm, J = 9 Hz, 2 H); 13C NMR
(75 MHz, CDCl3) d 5.1 (-), 7.0 (?), 14.4 (?), 20.7 (-),
25.7 (-), 29.0 (-), 34.1 (-), 35.6 (-), 38.9 (?), 52.3 (?),
55.3 (?), 69.7 (-), 72.6 (-), 74.7 (?), 113.8 (?), 128.8
(?), 129.3 (?), 130.9 (-), 131.8 (?), 159.1 (-); HRMS
(FAB) calcd for C26H44O3SiNa [(M ? Na)?] 455.2957,
found 455.2963.
1
84% from 24): Rf = 0.38 (EtOAc); H NMR (300 MHz,
CDCl3) d 1.40–2.14 (m, 10 H), 2.20–2.80 (m, 2 H),
3.35–3.54 (m, 2 H), 3.64 (ddd, J = 10, 9, 4 Hz, 1 H), 3.81
(s, 3 H), 3.75–3.89 (m, 1 H), 4.22–4.30 (m, 1 H), 4.40 (d,
J = 11.5 Hz, 1 H), 4.44 (d, J = 11.5 Hz, 1 H), 6.84–6.92
(m, 2 H), 7.22–7.30 (m, 2 H).
((1S,2R,3S)-3-(2-((4-Methoxybenzyl)oxy)ethyl)-2-(2-
((triethylsilyl)oxy)ethyl)-1-
2-((1S,2R,3S)-3-((Triethylsilyl)oxy)-2-((Z)-pent-2-en-
1-yl)cyclopentyl)ethanol (ent-15)
((triethylsilyl)oxy))cyclopentane (27)
A solution of diol 26 (445 mg, 1.51 mmol), TESCl
(0.76 mL, 4.53 mmol), and imidazole (411 mg, 6.44
mmol) in DMF (15 mL) was stirred at room temperature
for 18 h, and diluted with saturated NaHCO3. The resulting
mixture was extracted with EtOAc twice. The combined
extracts were washed with brine, dried over MgSO4, and
concentrated to give the residue, which was purified by
chromatography on silica gel (hexane/EtOAc) to give TES
ether 27 (812 mg, 100%): Rf = 0.77 (hexane/EtOAc 3:1);
[a]2D7 –0.4 (c 0.89, CHCl3); IR (neat) 1,513, 1,247,
To an ice-cold solution of the PMB ether 28 (201 mg,
0.465 mmol) in CH2Cl2 (4.8 mL), H2O (0.25 mL) and
DDQ (158 mg, 0.696 mmol) were added. The mixture was
stirred at 0°C for 3 h and diluted with saturated NaHCO3.
The resulting mixture was extracted with EtOAc twice. The
combined extracts were washed with brine, dried over
MgSO4, and concentrated. The residue was purified by
chromatography on silica gel (hexane/EtOAc to EtOAc) to
give alcohol ent-15 (144 mg, 100%): Rf = 0.46 (hexane/
EtOAc 3:1); [a]2D4 –5 (c 0.43, CHCl3); IR (neat) 3,344,
1,056, 1,005 cm-1; 1H NMR (300 MHz, CDCl3) d 0.58 (q,
J = 8 Hz, 6 H), 0.95 (t, J = 8 Hz, 9 H), 0.96 (t, J = 7.5 Hz,
3 H), 1.11–1.46 (m, 4 H), 1.55–2.40 (m, 8 H), 3.56–3.78 (m, 2
H), 4.18 (dt, J = 5, 8 Hz, 1 H), 5.31–5.47 (m, 2 H); 13C NMR
(75 MHz, CDCl3) d 5.1, 7.0, 14.4, 20.7, 25.8, 29.0,
34.1, 38.4, 38.9, 52.1, 62.4, 74.7, 128.8, 132.0; HRMS
(FAB) calcd for C18H37O2Si [(M ? H)?] 313.2563, found
313.2561.
1,096 cm-1 1H NMR (300 MHz, CDCl3) d 0.58 (q,
;
J = 8 Hz, 6 H), 0.59 (q, J = 8 Hz, 6 H), 0.95 (t, J = 8 Hz,
9 H), 0.97 (t, J = 8 Hz, 9 H), 1.36–1.86 (m, 9 H),
1.90–2.06 (m, 1 H), 3.34–3.51 (m, 2 H), 3.52–3.64 (m, 1
H), 3.65–3.75 (m, 1 H), 3.80 (s, 3 H), 4.12 (q, J = 4 Hz, 1
H), 4.39 (d, J = 12 Hz, 1 H), 4.44 (d, J = 12 Hz, 1 H),
6.87 (dm, J = 8.5 Hz, 2 H), 7.26 (dm, J = 8.5 Hz, 2 H);
13C NMR (75 MHz, CDCl3) d 4.5 (-), 5.0 (-), 6.9 (?), 7.0
(?), 28.2 (-), 28.6 (-), 31.7 (-), 33.5 (-), 36.3 (?), 44.1
(?), 55.3 (?), 62.6 (-), 69.6 (-), 72.5 (-), 75.4 (-), 76.7
(?), 113.8 (?), 129.2 (?), 131.0 (-), 159.1 (-); HRMS
(FAB) calcd for C29H55O4Si2 [(M ? H)?] 523.3639, found
523.3634.
2-((1S,2R,3S)-3-((Triethylsilyl)oxy)-2-((Z)-pent-2-en-
1-yl)cyclopentyl)acetic acid (ent-9)
According to the oxidation of alcohol 15 to acid 9, alcohol
ent-15 (110 mg, 0.353 mmol) was oxidized with NMO
(62 mg, 0.53 mmol) and TPAP (12.4 mg, 0.0353 mmol) to
give the corresponding aldehyde, which was used for the
next reaction without further purification: 1H NMR
(300 MHz, CDCl3) d 0.58 (q, J = 8 Hz, 6 H), 0.95 (t,
J = 8 Hz, 9 H), 0.96 (t, J = 7.5 Hz, 3 H), 1.12–1.42 (m, 2
H), 1.56–1.84 (m, 2 H), 1.96–2.36 (m, 5 H), 2.63 (dq, J = 2,
12 Hz, 1 H), 4.19 (dt, J = 2.5, 6 Hz, 1 H), 5.32–5.44
(m, 2 H).
((1S,2R,3S)-3-(2-((4-Methoxybenzyl)oxy)ethyl)-2-((Z)-
pent-2-en-1-yl)-1-((triethylsilyl)oxy))cyclopentane (28)
According to the conversion of silyl ether 12 to the Wittig
product 14, TES ether 27 (300 mg, 0.559 mmol) was con-
verted to the aldehyde with (COCl)2 (0.24 mL, 2.8 mmol),
DMSO (0.40 mL, 5.6 mmol), and Et3N (0.78 mL, 5.59
mmol). The crude aldehyde was subjected to Wittig reaction
with anion derived from [Ph3P(CH2)2CH3]? Br- (647 mg,
1.68 mmol) and NaHMDS (1.9 mL, 1.0 M solution in THF,
The above aldehyde was further oxidized with NaClO2
(60 mg, 80% purity, 0.53 mmol) to afford acid ent-9
123

1964
N. Ogawa, Y. Kobayashi
(92.5 mg, 80%): Rf = 0.37 (hexane/EtOAc 3:1); [a]2D4 ?3
(c 0.35, CHCl3); IR (neat) 3,100, 1,709, 1,413, 1,057,
2-((1R,2R,3S)-3-((Triethylsilyl)oxy)-2-((Z)-pent-2-en-
1-yl)cyclopentyl)acetic acid (31)
1
1,005, 742 cm-1; H NMR (300 MHz, CDCl3) d 0.57 (q,
A mixture of ester 30 (50.0 mg, 0.119 mmol, 98% ee) and
3 N NaOH (1 mL) in MeOH (1 mL) and THF (1 mL) was
stirred at room temperature for 30 min and acidified with
1 N HCl. The mixture was extracted with EtOAc twice.
The combined extracts were washed with brine, dried over
MgSO4, and concentrated to give the alcohol acid, which
was used for the next reaction without further purification.
To an ice-cold solution of the above alcohol and
imidazole (32.4 mg, 0.476 mmol) in DMF (6 mL), TESCl
(0.060 mL, 0.36 mmol) was added. The solution was
stirred at room temperature for 24 h and diluted with
saturated NH4Cl. The resulting mixture was extracted
with EtOAc twice. The combined extracts were washed
with brine, dried over MgSO4, and concentrated. The
residue was purified by chromatography on silica gel
(hexane/EtOAc) to afford TES ether 31 (38.8 mg, 100%):
Rf = 0.37 (hexane/EtOAc 3:1); [a]2D5 ?69 (c 0.55,
J = 8 Hz, 6 H), 0.95 (t, J = 8 Hz, 9 H), 0.96 (t,
J = 7.5 Hz, 3 H), 1.20–1.42 (m, 2 H), 1.54–1.82 (m, 2 H),
1.96–2.26 (m, 7 H), 2.59 (dd, J = 13, 2 Hz, 1 H), 4.19 (dt,
J = 3, 4.5 Hz, 1 H), 5.34–5.44 (m, 2 H); 13C NMR
(75 MHz, CDCl3) d 5.1 (-), 7.0 (?), 14.3 (?), 20.7 (-),
25.8 (-), 29.1 (-), 34.0 (-), 38.5 (?), 39.8 (-), 51.7 (?),
74.7 (?), 128.2 (?), 132.3 (?), 180.0 (-); HRMS (FAB)
calcd for C18H34O3SiNa [(M ? Na)?] 349.2175, found
349.2178.
(2S,3S)-2-(2-((1S,2RS,3S)-3-Hydroxy-2-((Z)-pent-2-en-
1-yl)cyclopentyl)acetamido)-3-methylpentanoic acid
(29)
According to the synthesis of the conjugate 10, acid ent-9
(50.0 mg, 0.153 mmol) was condensed with L-isoleucine
(100 mg, 0.765 mmol) and the TES group was removed
with HCO2H (2 mL) to afford alcohol 29 (25.0 mg, 50%):
Rf = 0.33 (CHCl3/EtOAc/HCO2H 14:6:1); [a]2D5 ?31
CHCl3); IR (neat) 3,000, 1,709, 1,057, 1,005 cm-1 1H
;
NMR (300 MHz, CDCl3) d 0.58 (q, J = 8 Hz, 6 H), 0.95
(t, J = 8 Hz, 9 H), 0.96 (t, J = 7.5 Hz, 3 H), 1.20–1.42
(m, 2 H), 1.54–1.66 (m, 1 H), 1.68–1.82 (m, 1 H),
1.96–2.28 (m, 7 H), 2.52–2.66 (m, 1 H), 4.19 (dt, J = 2.5,
6 Hz, 1 H), 5.32–5.44 (m, 2 H); 13C NMR (75 MHz,
CDCl3) d 5.1 (-), 7.0 (?), 14.3 (?), 20.7 (-), 25.8 (-),
29.1 (-), 34.0 (-), 38.5 (?), 39.8 (-), 51.7 (?), 74.7
(?), 128.2 (?), 132.3 (?), 179.6 (-); HRMS (FAB)
calcd for C18H34O3SiNa [(M ? Na)?] 349.2175, found
349.2172.
(c 0.21, CHCl3); IR (neat) 3,346, 1,718, 1,647, 1,214 cm-1
;
1H NMR (300 MHz, CDCl3) d 0.93 (t, J = 8 Hz, 3 H),
0.95 (t, J = 7 Hz, 3 H), 0.97 (d, J = 7 Hz, 3 H), 1.11–1.72
(m, 4 H), 1.82–2.32 (m, 10 H), 2.56 (dd, J = 14, 3 Hz, 1
H), 4.22 (t, J = 4 Hz, 1 H), 4.60 (dd, J = 8, 4.5 Hz, 1 H),
5.33–5.50 (m, 2 H), 5.8 (br s, 2 H), 6.32 (dd, J = 8, 4 Hz, 1
H); 13C NMR (75 MHz, CDCl3) d 11.7 (?), 14.3 (?),
15.5 (?), 20.7 (-), 25.2 (-), 25.4 (-), 29.2 (-), 33.1 (-),
37.7 (?), 39.3 (?), 41.7 (-), 51.4 (?), 56.6 (?), 74.5
(?), 127.4 (?), 132.9 (?), 173.3 (-), 174.8 (-); HRMS
(FAB) calcd for C18H32NO4 [(M ? H)?] 326.2331, found
326.2326.
2-((1R,2R,3S)-3-Hydroxy-2-((Z)-pent-2-en-1-
yl)cyclopentyl)-N-((2R,3S)-3-methylpentan-2-
yl)acetamide (32)
(ent-epi-Jasmonoyl)-L-isoleucine (6)
According to the synthesis of the conjugate 10, acid 31
(25.2 mg, 0.0772 mmol) was condensed with L-isoleucine
(50.6 mg, 0.386 mmol) and the TES group was removed
with HCO2H (2 mL) to afford alcohol 32 (15.1 mg, 60%):
Rf = 0.36 (CHCl3/EtOAc/HCO2H 14:6:1); [a]2D4 ?66
According to the synthesis of the conjugate 2a, alcohol 29
(9.8 mg, 0.030 mmol) was oxidized with Jones reagent (2
drops, 4 M solution) to afford the title conjugate 6 (9.0 mg,
92%): Rf = 0.42 (CHCl3/EtOAc/HCO2H 14:6:1); [a]D23
?6 (c 0.18, CHCl3); IR (neat) 3,410, 3,334, 1,646,
(c 0.41, CHCl3); IR (neat) 3,313, 1,696, 1,458, 1,249 cm-1
;
1H NMR (300 MHz, CDCl3) d 0.93 (t, J = 7.5 Hz, 3 H),
0.97 (t, J = 7.5 Hz, 3 H), 0.98 (d, J = 7.5 Hz, 3 H),
1.10–1.74 (m, 6 H), 1.82–2.30 (m, 8 H), 2.55 (dd, J = 14,
4 Hz, 1 H), 4.1 (br s, 2 H), 4.23 (t, J = 4 Hz, 1 H), 4.60
(dd, J = 8, 5 Hz, 1 H), 5.34–5.52 (m, 2 H), 6.23 (d,
J = 8 Hz, 1 H); 13C NMR (75 MHz, CDCl3) d 11.7 (?),
14.4 (?), 15.6 (?), 20.7 (-), 25.2 (-), 25.5 (-), 29.3 (-),
33.1 (-), 37.6 (?), 39.2 (?), 41.8 (-), 51.4 (?), 56.6 (?),
74.5 (?), 127.4 (?), 133.0 (?), 173.2 (-), 174.9 (-);
HRMS (FAB) calcd for C18H32NO4 [(M ? H)?] 326.2331,
found 326.2324.
1,463 cm-1 1H NMR (500 MHz, CDCl3) d 0.94 (t,
;
J = 7 Hz, 3 H), 0.95 (t, J = 7 Hz, 3 H), 0.96 (d, J = 7 Hz,
3 H), 1.16–1.32 (m, 2 H), 1.44–1.56 (m, 1 H), 1.82–2.10
(m, 6 H), 2.18–2.44 (m, 5 H), 2.85–2.94 (m, 1 H), 4.64 (dd,
J = 8.5, 5 Hz, 1 H), 5.30–5.50 (m, 2 H), 6.21 (d,
J = 8.5 Hz, 1 H), 7.2 (br s, 1 H); 13C NMR (75 MHz,
CDCl3) d 11.7 (?), 14.2 (?), 15.6 (?), 20.8 (-), 23.0 (-),
25.2 (–), 25.5 (–), 29.8 (–), 35.3 (–), 35.8 (–), 36.1 (?), 37.6
(?), 53.1 (?), 125.6 (?), 133.6 (?), 172.1 (–), 175.4 (–),
219.8 (–); HRMS (FAB) calcd for C18H30NO4 [(M ? H)?]
324.2175, found 324.2173.
123

Synthesis of the amino acid conjugates of epi-jasmonic acid
Jasmonoyl-L-isoleucine (7)
1965
Rf = 0.36 (CHCl3/EtOAc/HCO2H 14:6:1); [a]2D5 –17
(c 0.68, CHCl3); IR (Nujol) 3,312, 1,697, 1,602, 1,249 cm-1
;
1H NMR (300 MHz, CDCl3) d 0.89–1.00 (m, 9 H),
1.10–1.72 (m, 5 H), 1.82–2.30 (m, 9 H), 2.56 (dd, J = 13,
4 Hz, 1 H), 4.18–4.27 (m, 1 H), 4.60 (dd, J = 10, 5 Hz, 1 H),
5.30–5.60 (m, 2 H), 5.7 (br s, 2 H), 6.34 (d, J = 8 Hz, 1 H);
13C NMR (75 MHz, CDCl3) d 11.7 (?), 14.4 (?), 15.6 (?),
20.7 (-), 25.2 (-), 25.5 (-), 29.3 (-), 33.1 (-), 37.6 (?),
39.2 (?), 41.8 (-), 51.4 (?), 56.6 (?), 74.5 (?), 127.4 (?),
133.0 (?), 173.2 (-), 175.0 (-); HRMS (FAB) calcd for
C18H32NO4 [(M ? H)?] 326.2331, found 326.2332.
According to the synthesis of the conjugate 2a, alcohol 32
(10 mg, 0.031 mmol) was oxidized with Jones reagent (2
drops, 4 M solution) to afford the title conjugate 7 (8.8 mg,
89%): Rf = 0.43 (CHCl3/EtOAc/HCO2H 14:6:1); mp
153–154°C; [a]2D1 –38 (c 0.26, MeOH); [a]2D7 ?3 (c 0.22,
CHCl3); IR (neat) 3,313, 1,740, 1,701, 1,245 cm-1 1H
;
NMR (500 MHz, CDCl3) d 0.94–1.00 (m, 9 H), 1.16–1.28
(m, 2 H), 1.44–1.58 (m, 2 H), 1.88–2.28 (m, 7 H),
2.30–2.43 (m, 3 H), 2.67 (dd, J = 14.5, 4.5 Hz, 1 H), 4.62
(dd, J = 8, 4.5 Hz, 1 H), 5.29 (dt, J = 7.5, 11 Hz, 1 H),
5.46 (dt, J = 11, 7.5 Hz, 1 H), 5.6 (br s, 1 H), 6.12 (d,
(ent-Jasmonoyl)-L-isoleucine (8)
1
J = 8 Hz, 1 H); H NMR (500 MHz, CD3OD) d 0.94 (t,
J = 7.5 Hz, 3 H), 0.96 (d, J = 7.5 Hz, 3 H), 0.96 (t,
J = 7.5 Hz, 3 H), 1.21–1.35 (m, 2 H), 1.48–1.60 (m, 2 H),
1.84–1.96 (m, 2 H), 2.00–2.12 (m, 2 H), 2.13–2.21 (m, 1
H), 2.26–2.41 (m, 5 H), 2.57–2.66 (m, 1 H), 4.36 (d,
J = 5.5 Hz, 1 H), 5.28 (dt, J = 6, 11 Hz, 1 H), 5.43 (dt,
J = 11, 6 Hz, 1 H); 13C NMR (75 MHz, CDCl3) d 11.7
(?), 14.2 (?), 15.6 (?), 20.7 (-), 25.2 (-), 25.8 (-), 27.2
(-), 37.6 (?), 37.8 (-), 38.8 (?), 41.1 (-), 54.1 (?), 56.5
(?), 125.3 (?), 134.1 (?), 171.8 (-), 175.5 (-), 219.6 (-);
HRMS (FAB) calcd for C18H30NO4 [(M ? H)?] 324.2175,
found 324.2172.
According to the synthesis of the conjugate 2a, alcohol 33
(11.6 mg, 0.0356 mmol) was oxidized with Jones reagent
(2 drops, 4 M solution) to give the title conjugate 8
(10.3 mg, 89%): Rf = 0.43 (CHCl3/EtOAc/HCO2H
14:6:1); [a]2D5 ?57 (c 0.43, CHCl3); IR (Nujol) 3,316,
1
1,740, 1,696, 1,245 cm-1; H NMR (500 MHz, CDCl3) d
0.92–1.00 (m, 9 H), 1.16–1.28 (m, 2 H), 1.44–1.58 (m, 2
H), 1.87–2.28 (m, 7 H), 2.32–2.44 (m, 3 H), 2.68 (dd,
J = 14, 4 Hz, 1 H), 4.65 (dd, J = 8.5, 5 Hz, 1 H),
5.23–5.32 (m, 1 H), 5.42–5.50 (m, 1 H), 6.10 (d,
J = 8.5 Hz, 1 H), 6.8 (br s, 1 H); 13C NMR (75 MHz,
CDCl3) d 11.7 (?), 14.2 (?), 15.6 (?), 20.7 (-), 25.2 (-),
25.6 (-), 27.1 (-), 37.7 (?), 37.8 (-), 38.6 (?), 41.3 (-),
54.2 (?), 56.5 (?), 125.1 (?), 134.2 (?), 171.8 (-), 175.5
(-), 219.7 (-); HRMS (FAB) calcd for C18H30NO4
[(M ? H)?] 324.2175, found 324.2182.
Cf. lit. mp 155.5–156.5°C; [a]D –39.7 (c 1.6, MeOH)
(Fonseca et al. 2009).
2-((1S,2S,3R)-3-((Triethylsilyl)oxy)-2-((Z)-pent-2-en-
1-yl)cyclopentyl)acetic acid (ent-31)
Acknowledgments Racemic methyl jasmonate was kindly provided
by Zeon Co. Ltd., Japan. This work was supported by a Grant-in-Aid
for Scientific Research from the Ministry of Education, Science,
Sports, and Culture, Japan.
According to the synthesis of acid 31, ester ent-30 (50.3 mg,
0.120 mmol) was hydrolyzed with 3 N NaOH (1 mL) and
the resulting alcohol was silylated with TESCl (0.060 mL,
0.36 mmol) to afford the TES ether ent-31 (39.0 mg, 100%):
Rf = 0.37 (hexane/EtOAc 3:1); 1H NMR (300 MHz,
CDCl3) d 0.52 (q, J = 8 Hz, 6 H), 0.93 (t, J = 8 Hz, 12 H),
1.20–1.40 (m, 2 H), 1.54–1.66 (m, 1 H), 1.68–1.81 (m, 1 H),
1.96–2.27 (m, 7 H), 2.54–2.66 (m, 1 H), 4.16–4.22 (m, 1 H),
5.12–5.44 (m, 2 H); 13C NMR (75 MHz, CDCl3) d 6.5 (-),
6.9 (?), 14.3 (?), 20.7 (-), 25.8 (-), 29.1 (-), 34.0 (-), 38.5
(?), 39.7 (-), 51.7 (?), 74.7 (?), 128.2 (?), 132.3 (?),
179.2 (-); HRMS (FAB) calcd for C18H35O3Si [(M ? H)?]
327.2355, found 327.2359.
References
Acharya HP, Kobayashi Y (2006) Highly efficient total synthesis of
D12-PGJ2, 15-deoxy-D12,14-PGJ2, and their analogues. Tetrahe-
dron 62:3329–3343
Ainai T, Matsuumi M, Kobayashi Y (2003) Efficient total synthesis of
12-oxo-PDA and OPC-8:0. J Org Chem 68:7825–7832
Asamitsu Y, Nakamura Y, Ueda M, Kuwahara S, Kiyota H (2006)
Synthesis and odor description of both enantiomers of methyl
4,5-didehydrojasmonate, a component of jasmin absolute. Chem
Biodivers 3:654–659
2-((1S,2S,3R)-3-Hydroxy-2-((Z)-pent-2-en-1-
yl)cyclopentyl)-N-((2R,3S)-3-methylpentan-2-
yl)acetamide (33)
´
Chini A, Fonseca S, Fernandez G, Adie B, Chico JM, Lorenzo O,
´
´
Garcıa-Casado G, Lopez-Vidriero I, Lozano FM, Ponce MR,
Micol JL, Solano R (2007) The JAZ family of repressors is the
missing link in jasmonate signalling. Nature 448:666–671
Chung HS, Cooke TF, DePew CL, Patel LC, Ogawa N, Kobayashi Y,
Howe GA (2010) Alternative splicing expands the repertoire
of dominant JAZ repressors of jasmonate signaling. Plant J
63:613–622
According to the synthesis of the conjugate 10, acid ent-31
(39.3 mg, 0.120 mmol) was condensed with L-isoleucine
(78.7 mg, 0.600 mmol) and the TES group was removed
with HCO2H (2 mL) to afford alcohol 33 (16.1 mg, 41%):
123

1966
N. Ogawa, Y. Kobayashi
Creelman RA, Mullet JE (1997) Biosynthesis and action of jasmo-
nates in plants. Annu Rev Plant Physiol Plant Mol Biol 48:
355–381
Fonseca S, Chini A, Hamberg M, Adie B, Porzel A, Kramell R,
Miersch O, Wasternack C, Solano R (2009) (?)-7-iso-Jasmo-
noyl-L-isoleucine is the endogenous bioactive jasmonate. Nature
Chem Biol 5:344–350
Kiyota H, Higashi E, Koike T, Oritani T (2001) Lipase-catalyzed
preparation of both enantiomers of methyl jasmonate. Tetrahe-
dron Asymmetry 12:1035–1038
Kramell R, Schmidt J, Schneider G, Sembdner G, Schreiber K (1988)
Synthesis of N-(jasmonoyl)amino acid conjugates. Tetrahedron
44:5791–5807
Kramell R, Miersch O, Hause B, Ortel B, Parthier B, Wasternack C
(1997a) Amino acid conjugates of jasmonic acid induce
jasmonate-responsive gene expression in barley (Hordeum
vulgare L.) leaves. FEBS Lett 414:197–202
Kramell R, Schneider G, Miersch O (1997b) Chiral separation of
amide conjugates of jasmonic acid by liquid chromatography.
Chromatographia 45:104–108
Miersch O, Bru¨ckner B, Schmidt J, Sembdner G (1992) Cyclopentane
fatty acids from Gibberella Fujikuroi. Phytochemistry 31:3835–
3837
Miersch O, Bohlmann H, Wasternack C (1999) Jasmonates and
related compounds from Fusarium oxysporum. Phytochemistry
50:517–523
Nonaka H, Ogawa N, Maeda N, Wang YG, Kobayashi Y (2010)
Stereoselective synthesis of epi-jasmonic acid, tuberonic acid,
and 12-oxo-PDA. Org Biomol Chem 8:5212–5223
Ogawa N, Kobayashi Y (2008) Strategy for synthesis of the
isoleucine conjugate of epi-jasmonic acid. Tetrahedron Lett 49:
7124–7127
Schmidt J, Kramell R, Bru¨ckner C, Schneider G, Sembdner G,
Schreiber K, Stach J, Jensen E (1990) Gas chromatographic/
mass spectrometric and tandem mass spectrometric investiga-
tions of synthetic amino acid conjugates of jasmonic acid and
endogenously occurring related compounds from Vicia faba L.
Biomed Environ Mass Spectrom 19:327–338
Seto H, Fujioka S, Fujisawa H, Goto K, Nojiri H, Yamane H, Yoshida
S (1996) Preparation of ( )-2-(2,3–2H2)jasmonic acid and its
methyl ester, methyl ( )-2-(2,3-2H2)jasmonate. Biosci Biotech-
nol Biochem 60:1709–1711
Seto H, Nomura E, Fujioka S, Koshino H, Suenaga T, Yoshida S
(1999) Easy preparation of methyl 7-epi-jasmonate and four
stereoisomers of methyl cucurbate, and assessment of the
stereogenic effect of jasmonate on phytohormonal activities.
Biosci Biotechnol Biochem 63:361–367
Sheard LB, Tan X, Mao H, Withers J, Ben-Nissan G, Hinds TR,
Kobayashi Y, Hsu FF, Sharon M, Browse J, He SY, Rizo J, Howe
GA, Zheng N (2010) Jasmonate perception by inositol-phos-
phate-potentiated COI1–JAZ co-receptor. Nature 468:400–405
Soloshonok VA (2002) Highly diastereoselective Michael addition
reactions between nucleophilic glycine equivalents and b-
substituted-a,b-unsaturated carboxylic acid derivatives; a gen-
eral approach to the stereochemically defined and sterically
v-constrained a-amino acids. Curr Org Chem 6:341–364
Staswick PE, Tiryaki I (2004) The oxylipin signal jasmonic acid is
activated by an enzyme that conjugates it to isoleucine in
arabidopsis. Plant Cell 16:2117–2127
Tamogami S, Rakwal R, Agrawal GK (2008) Interplant communi-
cation: airborne methyl jasmonate is essentially converted into
JA and JA-Ile activating jasmonate signaling pathway and VOCs
emission. Biochem Biophys Res Commun 376:723–727
Thines B, Katsir L, Melotto M, Niu Y, Mandaokar A, Liu G, Nomura
K, He SY, Howe GA, Browse J (2007) JAZ repressor proteins
are targets of the SCFCOI1 complex during jasmonate signalling.
Nature 448:661–665
Walter A, Mazars C, Maitrejean M, Hopke J, Ranjeva R, Boland W,
¨
Mithofer A (2007) Structural requirements of jasmonates and
synthetic analogues as inducers of Ca2? signals in the nucleus and
the cytosol of plant cells. Angew Chem Int Ed 46:4783–4785
Xie DX, Feys BF, James S, Nieto-Rostro M, Turner JG (1998) COI1:
an arabidopsis gene required for jasmonate-regulated defense
and fertility. Science 280:1091–1094
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