Synthesis and bioactivity of potassium β-D-glucopyranosyl 12-hydroxy jasmonate and related compounds

Article abstract of DOI:10.1271/bbb.80338

Albizzia saman, a leguminous plant, is known to open its leaves in the daytime and sleep at night with the leaves folded. β-D-Glucopyranosyl 12-hydroxyjasmonate (1) was isolated as an endogenous chemical factor controlling this leafmovement. We developed a concise synthesis of optically pure (-)-1 in 9 steps from (+)-2 with a total yield of 58%. Similarly, such analogs of 1 as epi-LCF (13), enantiomer (14), and galactoside (19) were synthesized for a structure activity relationship (SAR) study. The results of this SAR study strongly suggest that the mechanism for the leaf-closing activity of 1 would be different from that of methyl jasmonate, and also suggest the involvement of a different kind of target protein which recognizes the trans-isomer of a jasmonate derivative.

Full text of DOI:10.1271/bbb.80338

Biosci. Biotechnol. Biochem., 72 (11), 2867–2876, 2008
Synthesis and Bioactivity of Potassium ꢀ-D-Glucopyranosyl
12-Hydroxy Jasmonate and Related Compounds
y
Yoko NAKAMURA, Ryoji MIYATAKE, Sho INOMATA, and Minoru UEDA
Department of Chemistry, Faculty of Science, Tohoku University,
6-3 Aramaki-aza Aoba, Aoba-ku, Sendai 980-8578, Japan
Received May 16, 2008; Accepted July 16, 2008; Online Publication, November 7, 2008
[doi:10.1271/bbb.80338]
Albizzia saman, a leguminous plant, is known to open
its leaves in the daytime and sleep at night with the
leaves folded. ꢀ-D-Glucopyranosyl 12-hydroxyjasmo-
nate (1) was isolated as an endogenous chemical factor
controlling this leafmovement. We developed a concise
synthesis of optically pure (À)-1 in 9 steps from (+)-2
with a total yield of 58%. Similarly, such analogs of 1 as
Fig. 1. Structure of LCF for Albizzia saman.
epi-LCF (13), enantiomer (14), and galactoside (19) were
synthesized for a structure activity relationship (SAR)
study. The results of this SAR study strongly suggest
that the mechanism for the leaf-closing activity of 1
would be different from that of methyl jasmonate, and
also suggest the involvement of a different kind of target
protein which recognizes the trans-isomer of a jasmo-
nate derivative.
Results and Discussion
Optical resolution of commercially available racemic
methyl jasmonate was carried out according to the
previously reported method13,14) to give optically pure
methyl jasmonate. Synthetic intermediates (+)-2
28
(>99:5% ee, ½ꢁꢀD +86.9) and (ꢁ)-2 (>99:5% ee,
29
Key words: potassium ꢀ-D-glucopyranosyl 12-hydroxy
jasmonate; tuberonic acid glucoside; nycti-
nasty; leaf-closing factor; Albizzia saman
½ꢁꢀD ꢁ86:8) were used in the subsequent syntheses.
The synthesis of (ꢁ)-methyl 12-hydroxyjasmonate
((ꢁ)-9), a natural-type aglycon of 1, from optically pure
alcohol (+)-2 is shown in Scheme 1. Alcohol (+)-2 was
protected with TBSCl and, following ozonolysis, gave
aldehyde (+)-4. Wittig reaction of (+)-4 under the salt-
free condition then predominantly gave (Z)-isomer (+)-
6. This Wittig reaction resulted in a low yield in THF-
DMF,15) and addition of 18-crown-6 to achieve the salt-
free condition16,17) selectively gave the (Z)-isomer in a
20% yield with 49% of recovered (+)-4 (Table 1). The
addition of an excess amount of reagents then predom-
inantly gave (Z)-isomer (+)-6 in a 95% yield (Table 1).
Resulting (+)-6 was deprotected by TBAF, oxidized by
Dess-Martin periodinane, and deprotected by TsOH to
give (ꢁ)-9. The deprotection by TsOH induced epime-
rization at the ꢁ-position (7-position) to give the cis-
congener in an up to 8% yield. Resulting trans-isomer
(ꢁ)-8 could be easily separated from its cis-congener by
column chromatography. Enantiomeric aglycon (+)-9
was also synthesized as shown in Scheme 1.
A leguminous plant opens its leaves in the daytime
and sleeps at night with the leaves folded.1) This
biological phenomenon is known as nyctinasty. Electro-
physiological studies and molecular biological studies of
the channels related to nyctinasty have been carried out
by Satter2,3) and Moran,4–7) using pulvini or motor cells
of Albizzia saman, a leguminous plant. We have
previously found that nyctinastic plants had an endog-
enous leaf-movement factor that could control nycti-
nasty.8,9) Potassium ꢀ-D-glucopyranosyl 12-hydroxy-
jasmonate (1) was isolated as the leaf-closing factor
(LCF) for genus Albizzia10) (Fig. 1). We have studied
the mechanism for nyctinastic leafmovement by using
LCF as a molecular probe.11) We have reported in
previous papers the synthesis of LCF 1.11,12) However,
the low yield prevented the structure-activity relation-
ship (SAR) to be studied by using 1. We report in this
paper an improved synthesis of 1 and related com-
pounds, including enantiomer 14, and SAR studies using
them.
An enantio pair of aglycons, (ꢁ)-9 and (+)-9, were
used for further syntheses. Konigs-Knorr glycosylation
¨
of (ꢁ)-9 with benzoyl-protected ꢁ-D-glucopyranosyl
bromide 1018) gave (ꢁ)-11 (Scheme 2). (ꢁ)-11 and
y
To whom correspondence should be addressed. Tel/Fax: +81-22-795-6553; E-mail: ueda@mail.tains.tohoku.ac.jp

2868
Y. NAKAMURA et al.
Scheme 1. Syntheses of Aglycon (ꢁ)-9 and (+)-9.
Table 1. Reaction Conditions for the (Z)-Selective Wittig Reaction
of 4
(ꢁ)-11 were then successively deprotected in high yields
to give LCF 1. No epimerization was apparent by
treating with NaOMe, but hydrolysis by KOH gave a
1:20 mixture of the cis-13 and trans-1 isomers. This
ratio of cis-13 and trans-1 is equal to the natural
abundance of 1 isolated from nature,10) so this mixture
was used as synthetic 1 in the subsequent bioassay. All
physical data for synthetic 1 were in full agreement with
those of isolated natural 1. We completed this concise
synthesis of optically pure (ꢁ)-1 in 9 steps from (+)-2
with a total yield of 58%.
Content
of
Z-olefinꢄ
5
(eq.) (eq.)
KHMDS 18-c-6 Yield
(eq.)
Entry
Solvent
of 6
1
2ꢄꢄ
THF:DMF = 12:1 3.3
THF
3
2
—
2
22%
20%
—
100%
2
(4:49%)
3ꢄꢄ
THF
5
5
4.9 95%
100%
ꢄEstimated by 1H- and 13C-NMR analyses.
ꢄꢄUnder salt-free conditions.
Similarly, 14, an enantiomer of 1, was synthesized
from (+)-9 and benzoyl-protected ꢁ-D-glucopyranosyl
bromide 1518) (Scheme 3). Additionally, galactoside 19
was also synthesized from (ꢁ)-9 and benzoyl-protected
ꢁ-D-galactopyranosyl bromide 1619) (Scheme 4). Epi-
LCF 13 was separated from 1, which was a 1:20 mixture
of cis-13 and trans-1 isomers by using HPLC
(Scheme 4). This route enabled a large-scale supply of
1 and its analogs for bioorganic studies of nyctinasty.
The resulting synthetic analogs were tested in a
bioassay using a leaf of Albizzia saman. All analogs
were converted into their potassium salt before being
used in this bioassay. The results of SAR studies are
summarized in Table 3. Comparing the bioactivity of
both enantiomers, only the solution of 1 (5 ꢃ 10ꢁ4 M)
made the leaves close, even in the daytime. Enantiomer
14 showed no leaf-closing activity, even at 1 ꢃ 10ꢁ3 M.
Clear difference was observed between a pair of
successive (ꢁ)-12 were obtained as a 20:1 stereo-
isomeric mixture regarding the ꢁ-position of the ketone
(asterisked in Scheme 2). The conditions for the
glycosylation reaction were examined as shown in
Table 2. Surprisingly, the reactivity of the primary
hydroxyl group in aglycon (ꢁ)-9 was very low, and
normal Konigs-Knorr conditions (Table 2, entry 1) gave
¨
only a 19% yield of glycosylated product (ꢁ)-11 with
58% of recovered aglycon (ꢁ)-9. We then added an
excess amount of 10 at rt to give 35% of (ꢁ)-11 with
37% of recovered (ꢁ)-9. This result was due to the
decomposition of 10 at rt. The highest yield was
achieved when the addition of AgOTf was carried out
at 10 ꢂC and then the temperature of the reaction mixture
was gradually raised to rt (Table 2, entry 3). Under these
conditions, (ꢁ)-11 was obtained in an 85% yield without
the recovery of unreacted (ꢁ)-9. All protective groups in

Synthesis of Potassium ꢀ-D-Glucopyranosyl 12-Hydroxy Jasmonate
2869
Scheme 2. Synthesis of LCF 1 (ꢄ20:1 mixture with epi-form).
Scheme 3. Synthesis of Enantiomer 14 (ꢄ20:1 mixture with epi-form).
onic acid glucoside 13,22,23) epi-tuberonic acid,24) and
epi-jasmonate21) is cis. The cis-forms have been reported
to have stronger bioactivity than the trans-congeners in
such assays as tuber forming, root growth, and plant
response to wounding.25) However, all of these cis-
isomers were biologically inactive in the leaf-closing
bioassay when using A. saman. It should be emphasized
that completely opposite bioactivity was observed
between 21 and 1 against the leaves of A. saman. It is
of importance that the bioactivity of 21 was completely
reversed by the addition of a hydrophilic terminal
glucoside. These results strongly suggest that the
mechanism for the leaf-closing activity of 1 would be
different from that of methyl jasmonate, and also
suggest the involvement of a different kind of target
protein which recognizes the trans-isomer of jasmonate
derivative 1.
Table 2. Conditions for Glycosylation Using 9 and 10
Entry
10 (eq.)
AgOTf (eq.)
Temp.
Yield of 11
1
2
3
1.5
3
1.5
3.1
2
0 ꢂC-rt
rt
10 ꢂC-rt
19% (9:58%)
35% (9:37%)
85%
2
enantiomers. Epi-LCF 13 had no leaf-closing activity,
although ꢀ-D-galactopyranoside 19 showed leaf-closing
activity as strong as that of 1. Together with the result
that optically pure aglycons (ꢁ)-20 and (+)-20
(Scheme 5) had no leaf-closing activity (Table 3), it
was revealed that an aglycon moiety of LCF 1 would be
important for the leaf-closing activity, whereas a sugar
moiety could be modified with the retention of bio-
activity. Additionally, potassium jasmonate (21)12) was
also revealed to have no leaf-closing activity at
5 ꢃ 10ꢁ4 M. However, leaves treated with 21 were open
even at night and turned yellowish, which can be
attributed to the senescence activity of methyl jasmo-
nate.20) On the other hand, optically pure enantiomer
2221) had no leaf-closing activity. These SAR results will
be important for the design of molecular probes based
on the structure of 1.
Experimental
NMR spectra were recorded on a Jeol JNM-AL300
instrument [1H (300 MHz) and 13C (75 MHz)], using
TMS in CDCl3, CD2HOD in CD3OH (1H, 3.33 ppm; 13C,
49.8 ppm), or t-BuOH (1H, 1.23 ppm; 13C, 32.1 ppm) in
D2O as internal standard at various temperatures. The
ESI-MS and HR ESI-MS data were recorded with Bruker
Esquire 4000 and Bruker APEX-III instruments, respec-
tively. The IR spectra were recorded with a JASCO FT/
Our SAR study also revealed the important result of
the bioactivity of 1. It is well known that the genuine
bioactive form of such jasmonate derivatives as tuber-

2870
Y. NAKAMURA et al.
Scheme 4. Syntheses of Galactoside 19 and epi-LCF 13.
Scheme 5. Syntheses of (ꢁ)- and (+)-Tuberonic Acids (20).
IR-410 instrument, and specific rotation was measured
by JASCO DIP-360 polarimeter. HPLC purification was
carried out with a Shimadzu LC-6A pump equipped with
an SPD-6A detector and using a Cosmosil 5C18-AR
column (ꢂ20 ꢃ 250 mm; Nakalai Tesque Co.). Silica gel
column chromatography was performed on silica gel 60
K070 (Katayama Chemical Co.) or silica gel 60N (Kanto
Chemical Co.). TLC was performed on silica gel F254
(0.25 mm or 0.5 mm, Merck) or RP-18F254S (0.25 mm,
Merck).
HRMS (ESI, positive) m=z ½M þ Naꢀþ: calcd. for
C19H36O3SiNa, 363.2326; found, 363.2324.
(+)-Methyl (1R,2R,3S)-3-tert-butyldimethylsilyloxy-
2-(formylmethyl)cyclopentaneacetate ((+)-4). To a solu-
tion of (+)-3 (1.58 g, 4.64 mmol) in anhydrous CH2Cl2
(40 ml) and anhydrous MeOH (40 ml) was bubbled
ozone at ꢁ78 ꢂC until (+)-3 had disappeared by a TLC
analysis. The excess amount of ozone was removed by
argon gas, and then Me2S (2 ml) was added dropwise
at rt. The mixture was stirred for 19 h and concentrated
in vacuo. The residue was purified by silica gel column
chromatography (n-hexane/EtOAc = 20/1–5/1) to
afford (+)-4 (1.32 g, 4.20 mmol, 90%) as a colorless
(+)-Methyl (1R,2R,3S,20Z)-3-tert-butyldimethylsily-
loxy-2-(pent-20-enyl) cyclopentaneacetate ((+)-3). To a
solution of (+)-2 (456 mg, 2.02 mmol) in DMF (10 ml)
were added TMSCl (759 mg, 5.04 mmol) and imidazole
(1.10 g, 16.12 mmol) at 0 ꢂC under an argon atmosphere.
The solution was stirred at 40 ꢂC for 20 h, then diluted
with H2O at 0 ꢂC and extracted with Et2O. The extract
was successively washed with 1 M HCl aq., satd.
NaHCO3 aq. and brine, dried over Na2SO4, and then
concentrated in vacuo. The residue was purified by silica
gel column chromatography (n-hexane/EtOAc = 10/1)
to afford (+)-3 (675 mg, 1.98 mmol, 98%) as a colorless
1
oil. H-NMR (300 MHz, CDCl3) ꢃ: 9.80 (s, 1H), 4.28–
4.24 (m, 1H), 3.65 (s, 3H), 2.74 (dd, J ¼ 18:0, 9.3 Hz,
1H), 2.44–2.35 (m, 2H), 2.23–1.80 (m, 5H), 1.62–1.54
(m, 1H), 1.29–1.18 (m, 1H), 0.85 (s, 9H), 0.01 (s, 3H),
ꢁ0:03 (s, 3H); 13C-NMR (75 MHz, CDCl3) ꢃ: 202.4,
173.4, 74.2, 51.5, 45.1, 43.0, 39.0, 38.6, 34.1, 29.0, 25.8,
17.9, ꢁ4:5, ꢁ5:1; IR (film) cmꢁ1: 2930, 2858, 2714,
28
1740, 1437, 1256, 1063, 837; ½ꢁꢀD +68.2 (c 8.8,
MeOH); HRMS (ESI, positive) m=z ½M þ Naꢀþ: calcd.
1
oil. H-NMR (300 MHz, CDCl3) ꢃ: 5.42–5.31 (m, 2H),
for C16H30O4SiNa, 337.1806; found, 337.1807.
4.16 (bs, 1H), 3.66 (s, 3H), 2.54 (dd, J ¼ 19:5, 9.3 Hz,
1H), 2.19–1.97 (m, 7H), 1.77–1.54 (m, 2H), 1.37–1.20
(m, 2H), 0.95 (t, J ¼ 7:5 Hz, 3H), 0.87 (s, 9H), 0.026 (s,
6H); 13C-NMR (75 MHz, CDCl3) ꢃ: 173.8, 132.1, 128.2,
74.7, 51.8, 51.4, 39.7, 38.6, 33.8, 28.9, 25.8, 25.6, 20.6,
18.0, 14.2, ꢁ4:3, ꢁ5:0; IR (film) cmꢁ1: 2932, 2858,
Methyl (1R,2R,3S,20Z)-3-tert-butyldimethylsilyloxy-2-
[50-(tetrahydropyran-200-yl)oxy-pent-20-enyl]-cyclopen-
taneacetate ((+)-6). To a mixture of 3-tetrahydropyr-
anyloxypropyltriphenylphosphonium bromide (5)26)
(3.01 g, 6.20 mmol) and 18-crown-6 (1.63 g, 6.21 mmol)
in anhydrous THF (40 ml) was slowly added KHMDS
27
1744, 1254, 1057, 912; ½ꢁꢀD +73.6 (c 1.75, MeOH);

Synthesis of Potassium ꢀ-D-Glucopyranosyl 12-Hydroxy Jasmonate
2871
cmꢁ1 2943, 2858, 1740, 1437, 1362, 1254, 1121, 1034,
Table 3. Results of SAR Studies on 1
24
837; ½ꢁꢀD +45.9 (c 1.04, MeOH); HRMS (ESI,
Half-
Concen- Closed
closed
positive) m=z ½M þ Naꢀþ calcd for C24H44O5SiNa
Open Total
leaves leaves
tration
leaves
463.2850, found 463.2848.
leaves
Methyl (1R,2R,3S,20Z)-3-hydroxy-2-[50-tetrahydro-
pyran-200-yl]oxy-pent-20-enyl]cyclopentaneacetate, ((+)-
7). To a suspension of (+)-6 (157 mg, 0.356 mmol) and
5 ꢃ 10ꢁ4
M
M
45
12
4
7
61
10
˚
MS5 A (190 mg) in anhydrous THF (3.6 ml) was added
1 ꢃ 10ꢁ3
1 ꢃ 10ꢁ3
5 ꢃ 10ꢁ4
5 ꢃ 10ꢁ4
5 ꢃ 10ꢁ4
5 ꢃ 10ꢁ4
5 ꢃ 10ꢁ4
0
0
7
0
0
0
0
3
3
2
2
2
1
1
TBAF (3.6 ml, 3.6 mmol as a 1.0 M solution in THF)
under an argon atmosphere. The mixture was stirred for
23.5 h, filtered through a pad of Celite, diluted with H2O
and extracted with EtOAc. The extract was washed with
brine, dried over Na2SO4 and concentrated in vacuo.
The residue was purified by silica gel column chroma-
tography (n-hexane/EtOAc = 9/1–1/1) to afford (+)-7
(diastereomeric mixture, 116 mg, 0.383 mmol, quant.) as
a colorless oil. 1H-NMR (500 MHz, CDCl3) ꢃ: 5.50–5.34
(m, 2H), 4.59–4.56 (m, 1H), 4.16–4.10 (m, 1H), 3.88–
3.76 (m, 2H), 3.65 (s, 3H), 3.51–3.48 (m, 1H), 3.45 (dt,
J ¼ 14:0, 4.5 Hz, 0.5H), 3.36 (dt, J ¼ 14:0, 4.5 Hz,
0.5H), 2.69–2.44 (m, 3H), 2.37–2.32 (m, 1H), 2.22–2.00
(m, 5H), 1.88–1.49 (m, 8H), 1.42–1.38 (m, 1H), 1.30–
1.24 (m, 1H); 13C-NMR (75 MHz, CDCl3) ꢃ: 173.6,
130.3, 130.1, 127.50, 127.46, 99.2, 98.9, 73.5, 73.4,
67.2, 66.9, 62.3, 62.2, 51.4, 51.20, 51.18, 39.009,
39.002, 38.5, 38.4, 32.83, 32.77, 30.31, 30.26, 29.6,
29.5, 27.97, 27.95, 25.8, 25.7, 25.30, 25.27, 19.41,
19.39; IR (film) cmꢁ1: 3491, 2935, 2870, 1736, 1439,
M
M
M
M
M
M
7
10
10
10
11
5
1
8
9
4ꢄ
4
5
29
1342, 1121, 984, 905; ½ꢁꢀD +61.2 (c 0.78, MeOH);
HRMS (ESI, positive) m=z ½M þ Naꢀþ: calcd. for
ꢄThe leaves treated with 21 were open even at night and turned yellow.
C18H30O5Na, 349.1985; found, 349.1984.
Methyl (1R,2R,20Z)-3-oxo-2-[50-tetrahydropyran-200-
yl]oxy-pent-20-enyl]cyclopentaneacetate ((ꢁ)-8). To a
solution of (+)-7 (193 mg, 0.591 mmol) and pyr. (285 ml,
3.55 mmol) in anhydrous CH2Cl2 (10 ml) was added
DMP (1.003 g, 2.37 mmol) at 0 ꢂC under an argon
atmosphere. The solution was stirred at rt for 10 h. The
mixture was filtered through Hyflo Super-Celꢀ, diluted
with 15% Na2S2O3 aq. and extracted with EtOAc. The
extract was washed three times with brine, dried over
Na2SO4 and concentrated in vacuo. The residue was
purified by silica gel column chromatography (n-
hexane/EtOAc = 3/1) to afford (ꢁ)-8 (diastereomeric
mixture, 180 mg, 0.555 mmol, 94%) as a colorless oil.
1H-NMR (300 MHz, CDCl3) ꢃ: 5.48 (dt, J ¼ 10:8,
7.2 Hz, 1H), 5.37 (dt, J ¼ 10:8, 7.2 Hz, 1H), 4.56 (dd,
J ¼ 4:2, 2.4 Hz, 1H), 3.81 (ddd, J ¼ 11:4, 7.2, 3.6 Hz,
1H), 3.75–3.69 (m, 4H), 3.47 (dt, J ¼ 11:4, 4.8 Hz, 1H),
3.42–3.33 (m, 1H), 2.68 (dd, J ¼ 19:2, 8.4 Hz, 1H),
2.38–2.17 (m, 8H), 2.08 (ddd, J ¼ 18:6, 11.1, 8.4 Hz,
1H), 1.92–1.85 (m, 1H), 1.83–1.75 (m, 1H), 1.69 (dt,
J ¼ 12:3, 2.7 Hz, 1H), 1.57–1.40, (m, 5H); 13C-NMR
(75 MHz, CDCl3) ꢃ: 218.7, 172.4, 128.2, 127.6, 98.7,
66.8, 62.2, 53.8, 51.5, 38.7, 37.9, 37.6, 30.6, 28.0, 27.1,
25.6, 25.4, 19.5; IR (film) cmꢁ1: 2949, 2870, 1740,
(12.2 ml, 6.10 mmol as a 0.5 M solution in toluene) at
0 ꢂC under an argon atmosphere. The mixture was
stirred for 10 min at rt to form a phosphonium ylide. To
a solution of (+)-4 (390 mg, 1.24 mmol) in anhydrous
THF (12 ml) was slowly added the supernatant solution
of this ylide at ꢁ78 ꢂC over 1.2 h through a dropping
funnel. The mixture was allowed to warm to rt and
stirred for 11 h. To the mixture was added satd. NH4Cl
aq., before it was extracted twice with EtOAc, washed
with brine, dried over Na2SO4, and concentrated in
vacuo. The residue was purified by silica gel column
chromatography (n-hexane/EtOAc = 20/1–10/1) to
afford (+)-6 (diastereomeric mixture, 503 mg, 1.14
mmol, 92%) as a colorless oil. 1H-NMR (300 MHz,
CDCl3) ꢃ: 5.51 (dt, J ¼ 10:5, 7.2 Hz, 1H), 5.40 (dt,
J ¼ 10:5, 7.2 Hz, 1H), 4.59–4.58 (m, 1H), 4.18–4.15 (m,
1H), 3.89–3.83 (m, 1H), 3.73 (dt, J ¼ 9:3, 7.2 Hz, 1H),
3.66 (s, 3H), 3.53–3.47 (m, 1H), 3.40 (dt, J ¼ 9:3,
7.2 Hz, 1H), 2.53 (dd, J ¼ 21:0, 10.5 Hz, 1H), 2.39–2.32
(m, 1H), 2.17–1.99 (m, 5H), 1.86–1.51 (m, 8H), 1.39–
1.19 (m, 2H), 0.87 (s, 9H), 0.03 (s, 6H); 13C-NMR
(75 MHz, CDCl3) ꢃ: 173.8, 130.7, 126.2, 98.7, 74.6,
67.0, 62.2, 51.7, 51.4, 39.7, 38.6, 33.8, 30.7, 28.9, 28.1,
25.8 (t-Bu), 25.8, 25.5, 19.6, 18.0, ꢁ4:3, ꢁ5:0; IR (film)
23
1439, 1200, 1032; ½ꢁꢀD ꢁ44:9 (c 2.0, MeOH); HRMS

2872
Y. NAKAMURA et al.
(ESI, positive) m=z ½M þ Naꢀþ: calcd. for C18H28O5Na,
347.1829; found, m=z 347.1829.
4.24 (m, 1H), 3.65 (s, 3H), 2.74 (dd, J ¼ 18:0, 9.0 Hz,
1H), 2.44–2.34 (m, 2H), 2.22–1.80 (m, 5H), 1.63–1.54
(m, 1H), 1.30–1.20 (m, 1H), 0.85 (s, 9H), 0.02 (s, 3H),
ꢁ0:03 (s, 3H); 13C-NMR (75 MHz, CDCl3) ꢃ: 202.3,
173.4, 74.2, 51.5, 45.1, 43.0, 39.0, 38.6, 34.1, 29.0,
Methyl (1R,2R,20Z)-2-(50-hydroxy-pent-20-enyl)-3-oxo-
cyclopentaneacetate ((ꢁ)-9, methyl 12-hydroxyjasmo-
nate). To a solution of (ꢁ)-8 (43 mg, 0.133 mmol) in
28
25.8, 17.9, ꢁ4:5, ꢁ5:1; ½ꢁꢀD ꢁ68:3 (c 7.0, MeOH);
MeOH (10 ml) was added p-TsOH H2O (5 mg, 0.032
HRMS (ESI, positive) m=z ½M þ Naꢀþ: calcd. for
.
mmol) at 0 ꢂC under an argon atmosphere. After stirring
for 1 h at rt, the mixture was diluted with satd. NaHCO3
aq., extracted with EtOAc, washed with brine, dried over
Na2SO4 and concentrated in vacuo. The residue was
purified by silica gel column chromatography (n-
hexane/EtOAc = 2/1) to afford (ꢁ)-9 (30 mg, 0.123
mmol, 93%) as a colorless oil. 1H-NMR (300 MHz,
CDCl3) ꢃ: 5.50 (dt, J ¼ 10:8, 6.3 Hz, 1H), 5.46 (dt,
J ¼ 10:8, 6.3 Hz, 1H), 3.70 (s, 3H), 3.66 (t, J ¼ 6:3 Hz,
2H), 2.70 (dd, J ¼ 18:9, 8.1 Hz, 1H), 2.48–1.90 (m,
10H), 1.59–1.41 (m, 1H); 13C-NMR (75 MHz, CDCl3,
22 ꢂC) ꢃ: 219.1, 172.7, 128.5, 128.3, 62.0, 53.9, 51.7,
38.8, 37.8, 37.7, 30.9, 27.2, 25.3; IR (film) cmꢁ1: 3447,
C16H30O4SiNa, 337.1806; found, 337.1805.
Methyl (1S,2S,3R,20Z)-3-tert-butyldimethylsilyloxy-2-
[50-(tetrahydropyran-200-yl)oxy-pent-20-enyl]-cyclopen-
taneacetate ((ꢁ)-6). To a mixture of 3-tetrahydropyr-
anyloxypropyltriphenylphosphonium bromide (5) (5.15
g, 10.6 mmol) and 18-crown-6 (2.80 g, 10.7 mmol) in
anhydrous THF (65 ml) was slowly added KHMDS
(20.9 ml, 10.5 mmol as a 0.5 M solution in toluene) at
0 ꢂC under an argon atmosphere. The mixture was
stirred for 10 min at rt to form a phosphonium ylide. To
a solution of (ꢁ)-4 (671 mg, 2.13 mmol) in anhydrous
THF (20 ml) was slowly added the supernatant solution
of this ylide at ꢁ78 ꢂC over 1.25 h through a dropping
funnel. The mixture was allowed to warm to rt and
stirred for 10 h. To the mixture was added satd. NH4Cl
aq., and the mixture was extracted twice with EtOAc,
washed with brine, dried over Na2SO4, and concentrated
in vacuo. The residue was purified by silica gel column
chromatography (n-hexane/EtOAc = 15/1–10/1) to
afford (ꢁ)-6 (diastereomeric mixture, 895 mg, 2.03
mmol, 95%) as a colorless oil. 1H-NMR (300 MHz,
CDCl3) ꢃ: 5.51 (dt, J ¼ 10:5, 7.2 Hz, 1H), 5.40 (dt,
J ¼ 10:5, 7.2 Hz, 1H), 4.59 (m, 1H), 4.16 (m, 1H), 3.89–
3.83 (m, 1H), 3.73 (dt, J ¼ 9:3, 7.2 Hz, 1H), 3.65 (s,
3H), 3.53–3.47 (m, 1H), 3.40 (dt, J ¼ 9:3, 7.2 Hz, 1H),
2.53 (dd, J ¼ 20:7, 10.2 Hz, 1H), 2.38–2.31 (m, 1H),
2.17–1.98 (m, 5H), 1.86–1.51 (m, 8H), 1.39–1.19 (m,
2H), 0.87 (s, 9H), 0.03 (s, 6H); 13C-NMR (75 MHz,
CDCl3) ꢃ: 173.8, 130.7, 126.2, 98.7, 74.6, 67.0, 62.2,
51.7, 51.3, 39.7, 38.6, 33.8, 30.7, 28.9, 28.0, 25.8 (t-Bu),
25.8, 25.5, 19.5, 18.0, ꢁ4:3, ꢁ5:0; IR (film) cmꢁ1: 2943,
24
2953, 1736, 1437, 1165, 1049, 772; ½ꢁꢀD ꢁ67:9 (c 0.5,
MeOH); HRMS (ESI, positive) m=z ½M þ Naꢀþ: calcd.
for C13H18O4Na, 263.1254; found, 263.1255.
(ꢁ)-Methyl (1S,2S,3R,20Z)-3-tert-butyldimethylsily-
loxy-2-(pent-20-enyl) cyclopentaneacetate ((ꢁ)-3). To a
solution of (ꢁ)-2 (397 mg, 1.75 mmol) in DMF (10 ml)
were added TMSCl (661 mg, 5.04 mmol) and imidazole
(955 mg, 14.02 mmol) at 0 ꢂC under an argon atmo-
sphere. The solution was stirred at 40 ꢂC for 20 h, diluted
with H2O at 0 ꢂC and extracted with Et2O. The extract
was successively washed with 1 M HCl, satd. NaHCO3
aq. and brine, then dried over Na2SO4 and concentrated
in vacuo. The residue was purified by silica gel column
chromatography (n-hexane/EtOAc = 10/1) to afford
(ꢁ)-3 (597 mg, 1.75 mmol, quant.) as a colorless oil. 1H-
NMR (300 MHz, CDCl3) ꢃ: 5.42–5.31 (m, 2H), 4.16 (bs,
1H), 3.66 (s, 3H), 2.53 (dd, J ¼ 19:5, 9.3 Hz, 1H), 2.19–
1.99 (m, 7H), 1.77–1.53 (m, 2H), 1.39–1.19 (m, 2H),
0.95 (t, J ¼ 7:5 Hz, 3H), 0.87 (s, 9H), 0.029 (s, 6H);
13C-NMR (75 MHz, CDCl3) ꢃ: 173.8, 132.1, 128.2, 74.7,
51.8, 51.4, 39.7, 38.6, 33.8, 28.9, 25.8, 25.6, 20.6,
24
2857, 1740, 1437, 1362, 1254, 1121, 1034, 837; ½ꢁꢀD
ꢁ54:6 (c 1.64, MeOH); HRMS (ESI, positive) m=z
½M þ Naꢀþ: calcd. for C24H44O5SiNa, 463.2850; found,
463.2847.
26
18.0, 14.2, ꢁ4:3, ꢁ5:0; ½ꢁꢀD ꢁ69:1 (c 1.57, MeOH);
HRMS (ESI, positive) m=z ½M þ Naꢀþ: calcd. for
C19H36O3SiNa, 363.2326; found, 363.2324.
Methyl (1S,2S,3R,20Z)-3-hydroxy-2-[50-tetrahydropy-
ran-200-yl]oxy-pent-20-enyl]cyclopentaneacetate ((ꢁ)-7).
To a suspension of (ꢁ)-6 (250 mg, 0.567 mmol) and
(ꢁ)-Methyl (1S,2S,3R)-3-tert-butyldimethylsilyloxy-2-
(formylmethyl)cyclopentaneacetate ((ꢁ)-4). To a solu-
tion of (ꢁ)-3 (628 g, 1.84 mmol) in anhydrous CH2Cl2
(15 ml) and anhydrous MeOH (15 ml) was bubbled
ozone at ꢁ78 ꢂC until (ꢁ)-3 had disappeared by a TLC
analysis. The excess amount of ozone was removed by
argon gas, and Me2S (0.24 ml) was then added dropwise
at rt. The mixture was stirred for 18 h and concentrated
in vacuo. The residue was purified by silica gel column
chromatography (n-hexane/EtOAc = 15/1–5/1) to
afford (ꢁ)-4 (579 mg, 1.84 mmol, quant.) as a colorless
˚
MS4 A (550 mg) in anhydrous THF (5 ml) was added
TBAF (1.4 ml, 1.4 mmol as a 1.0 M solution in THF)
under an argon atmosphere. The mixture was stirred for
3.5 h, filtered through a pad of Celite, diluted with satd.
NH4Cl aq. and extracted with EtOAc. The extract was
washed with brine, dried over Na2SO4 and concentrated
in vacuo. The residue was purified by silica gel column
chromatography (n-hexane/EtOAc = 4/1) to afford
(ꢁ)-7 (diastereomeric mixture, 178 mg, 0.545 mmol,
1
96%) as a colorless oil. H-NMR (500 MHz, CDCl3) ꢃ:
1
oil. H-NMR (300 MHz, CDCl3) ꢃ: 9.80 (s, 1H), 4.28–
5.50–5.34 (m, 2H), 4.59–4.56 (m, 1H), 4.16–4.10 (m,

Synthesis of Potassium ꢀ-D-Glucopyranosyl 12-Hydroxy Jasmonate
2873
1H), 3.88–3.76 (m, 2H), 3.65 (s, 3H), 3.51–3.48 (m, 1H),
3.45 (dt, J ¼ 14:0, 4.5 Hz, 0.5H), 3.36 (dt, J ¼ 14:0,
4.5 Hz, 0.5H), 2.69–2.44 (m, 3H), 2.37–2.32 (m, 1H),
2.22–2.00 (m, 5H), 1.88–1.49 (m, 8H), 1.42–1.38 (m,
1H), 1.30–1.24 (m, 1H); 13C-NMR (75 MHz, CDCl3) ꢃ:
173.6, 130.2, 130.1, 127.44, 127.41, 99.2, 98.9, 73.4,
73.4, 67.2, 66.8, 62.3, 62.2, 51.4, 51.2, 39.0, 38.43,
38.36, 32.83, 32.76, 30.28, 30.25, 29.53, 29.46, 28.0,
25.8, 25.7, 25.28, 25.25, 19.4; IR (film) cmꢁ1: 3514,
Methyl (1R,2R,20Z)-3-oxo-2-[50-(20,30,40,60-tetra-O-ben-
zoyl-ꢀ-D-glucopyranosyl)oxy-pent-20-enyl]-cyclopentane-
acetate ((ꢁ)-11). To a solution of (ꢁ)-9 (45 mg, 187
mmol), 10 (247 mg, 375 mmol) and dried molecular
˚
sieves 4 A in anhydrous CH2Cl2 (2.6 ml) was slowly
added AgOTf (96 mg, 375 mmol) in toluene (2.5 ml) at
10 ꢂC under an argon atmosphere in the dark. The
reaction mixture was stirred for 3.5 h at rt. The reaction
mixture was then diluted with CHCl3 and filtered
through a pad of Celite. The filtrate was successively
washed with brine and satd. NaHCO3 aq. The organic
layer was dried over Na2SO4, and concentrated in
vacuo. The residue was purified by silica gel column
chromatography (n-hexane/EtOAc = 10/1–2/1) and
preparative TLC (silica gel F254, n-hexane/EtOAc =
1/1) to afford (ꢁ)-11 (130 mg, 159 mmol, 85%) as a
27
2943, 2870, 1717, 1437, 1121, 1032, 905; ½ꢁꢀD ꢁ62:4
(c 1.54, MeOH); HRMS (ESI, positive) m=z ½M þ Naꢀþ:
calcd. for C18H30O5Na, 349.1985; found, 349.1984.
Methyl (1S,2S,20Z)-3-oxo-2-[50-tetrahydropyran-200-yl]-
oxy-pent-20-enyl]cyclopentaneacetate ((+)-8). To a so-
lution of (ꢁ)-7 (104 mg, 0.319 mmol) and pyridine
(154 ml, 1.91 mmol) in anhydrous CH2Cl2 (9 ml) was
added DMP (541 mg, 1.27 mmol) at 0 ꢂC under an argon
atmosphere. The solution was stirred at rt for 12 h. The
mixture was filtered through Hyflo Super-Celꢀ, diluted
with 15% Na2S2O3 aq. and extracted with EtOAc. The
extract was washed three times with brine, dried over
Na2SO4 and concentrated in vacuo. The residue was
purified by silica gel column chromatography (n-
hexane/EtOAc = 3/1) to afford (+)-8 (diastereomeric
mixture, 98 mg, 0.302 mmol, 95%) as a colorless oil. 1H-
NMR (300 MHz, CDCl3) ꢃ: 5.48 (dt, J ¼ 10:5 7.5 Hz,
1H), 5.37 (dt, J ¼ 10:5 7.5 Hz, 1H), 4.56 (bs, 1H), 3.88–
3.79 (m, 1H), 3.75–3.66 (m, 4H), 3.51–3.34 (m, 2H),
2.68 (dd, J ¼ 18:9, 8.1 Hz, 1H), 2.37–2.02 (m, 9H),
1.90–1.67 (m, 3H), 1.55–1.36, (m, 5H); 13C-NMR
(75 MHz, CDCl3) ꢃ: 218.8, 172.4, 128.2, 127.5, 98.7,
98.7, 66.7, 62.2, 53.8, 51.5, 38.6, 38.0, 37.9, 37.6, 30.6,
27.9, 27.1, 25.6, 25.4, 19.5; IR (film) cmꢁ1: 2949, 2870,
1
white crystal. H-NMR (500 MHz, CDCl3) ꢃ: 8.01 (d,
J ¼ 8:5 Hz, 2H), 7.95 (d, J ¼ 8:5 Hz, 2H), 7.90 (d,
J ¼ 8:5 Hz, 2H), 7.83 (d, J ¼ 8:5 Hz, 2H), 7.56–7.37
(m, 4H), 7.40 (t, J ¼ 8 Hz, 2H), 7.40 (t, J ¼ 8 Hz, 2H),
7.34 (t, J ¼ 8 Hz, 2H), 7.28 (t, J ¼ 8 Hz, 2H), 5.90 (t,
J ¼ 9:5 Hz, 1H), 5.68 (t, J ¼ 9:5 Hz, 1H), 5.52 (dd,
J ¼ 9:5, 8.0 Hz, 1H), 5.33 (dt, J ¼ 10:5, 7.0 Hz, 1H),
5.21 (dt, J ¼ 10:5, 8.0 Hz, 1H), 4.88 (d, J ¼ 8:0 Hz,
1H), 4.64 (dd, J ¼ 12:0, 3.0 Hz, 1H), 4.50 (dd, J ¼ 12:0,
5.0 Hz, 1H), 4.17 (ddd, J ¼ 9:5, 5.0, 3.0 Hz, 1H), 3.92
(dt, J ¼ 9:5, 6.5 Hz, 1H), 3.67 (s, 3H), 3.56 (dt, J ¼ 9:5,
6.5 Hz, 1H), 2.61 (dd, J ¼ 15:0, 3.5 Hz, 1H), 2.37–2.15
(m, 8H), 2.07–2.00 (m, 1H), 1.82–1.78 (m, 1H), 1.50–
1.41 (m, 1H); 13C-NMR (125 MHz, CDCl3) ꢃ: 218.6,
172.4, 166.1, 165.8, 165.2, 165.0, 133.4, 133.2, 133.14,
133.08, 129.79, 129.75, 129.72, 129.70, 129.6, 129.4,
128.83, 128.80, 128.36, 128.33, 128.31, 128.25, 127.9,
127.3, 101.2, 72.9, 72.2, 71.8, 69.8, 69.5, 63.2, 53.8,
1740, 1437, 1200, 1032; ½ꢁꢀD +54.2 (c 2.68, MeOH);
51.6, 38.7, 37.9, 37.6, 27.7, 27.1, 25.4; IR (film) cmꢁ1
:
22
HRMS (ESI, positive) m=z ½M þ Naꢀþ: calcd. for
3445, 3020, 1733, 1267, 1177, 1107, 1094, 1069, 710;
29
C18H28O5Na, 347.1829; found, 347.1830.
½ꢁꢀD ꢁ3:6 (c 1.13, CHCl3); HRMS (ESI, positive) m=z
½M þ Naꢀþ: calcd. for C47H46O13Na, 841.2831; found,
Methyl (1R,2R,20Z)-2-(50-hydroxy-pent-20-enyl)-3-oxo-
cyclopentaneacetate ((+)-9, methyl 12-hydroxyjasmo-
nate). To a solution of (+)-8 (11 mg, 33.3 mmol) in
841.2825.
Methyl (1R,2R,20Z)-2-{50-(ꢀ-D-glucopyranosyloxy)-
pent-20-enyl}-3-oxo-cyclopentaneacetate ((ꢁ)-12). To a
solution of (ꢁ)-11 (102 mg, 0.125 mmol) in MeOH
(9 ml) was added NaOMe (27 mg, 0.505 mmol) at 0 ꢂC
under an argon atmosphere. The solution was stirred at rt
for 4 h, and then the reaction mixture was neutralized
with 1 M HCl aq. and concentrated in vacuo. The residue
was purified by silica gel column chromatography
(CHCl3/MeOH = 6/1) to afford (ꢁ)-12 (48 mg, 0.119
mmol, 96%) as a colorless viscous oil.
.
MeOH (1.0 ml) was added p-TsOH H2O (5 mg, 0.032
mmol) at 0 ꢂC under an argon atmosphere. After stirring
for 1 h at rt, the mixture was diluted with satd. NaHCO3
aq., extracted with EtOAc, washed with brine, dried over
Na2SO4 and concentrated in vacuo. The residue was
purified by silica gel column chromatography (n-
hexane/EtOAc = 2/1) to afford (+)-9 (7 mg, 29.1
mmol, 87%) as a colorless oil. 1H-NMR (300 MHz,
CDCl3) ꢃ: 5.49 (dt, J ¼ 10:8, 6.3 Hz, 1H), 5.42 (dt, J ¼
10:8, 6.3 Hz, 1H), 3.68 (s, 3H), 3.64 (t, J ¼ 6:3 Hz, 2H),
2.70 (dd, J ¼ 8:1, 18.9 Hz, 1H), 2.48–1.90 (m, 10H),
1.54–1.41 (m, 1H); 13C-NMR (75 MHz, CDCl3) ꢃ:
219.1, 172.7, 128.5, 128.3, 62.0, 53.9, 51.7, 38.8, 37.8,
37.7, 30.9, 27.2, 25.3; IR (film) cmꢁ1: 3445, 2953, 1732,
(1R,2R,20Z)-2-{50-(ꢀ-D-Glucopyranosyloxy)-pent-20-
enyl}-3-oxo-cyclopentaneacetic acid (ꢀ-D-glucopyrano-
syl 12-hydroxyjasmonate, 1). To a solution of (ꢁ)-12
(14.6 mg, 36.3 mmol) in MeOH (2 ml) and H2O (1 ml)
was added 1 M KOH aq. (54 ml, 54.4 mmol). The solution
was refluxed for 3 h at 90 ꢂC, and then the reaction
mixture was neutralized with 1 M HCl aq. and concen-
22
1437, 1165, 754; ½ꢁꢀD +72.8 (c 1.79, MeOH); HRMS
(ESI, positive) m=z ½M þ Naꢀþ: calcd. for C13H18O4Na,
263.1254; found, 263.1255.

2874
Y. NAKAMURA et al.
trated in vacuo. The residue was purified by ODS TLC
(RP-18, H2O/MeOH = 3/2) to afford 1 containing 5%
of its 7-epi-isomer (13) (14.1 mg, 36.3 mmol, quant.) as a
colorless viscous oil. ½ꢁꢀD ꢁ53:5 (c 0.5, MeOH).
(ESI, positive) m=z ½M þ Naꢀþ: calcd. for C47H46O13Na,
841.2831; found, 841.2825.
Methyl (1S,2S,20Z)-2-{50-(ꢀ-
L-glucopyranosyloxy)-pent-
20
20-enyl}-3-oxo-cyclopentaneacetate ((+)-12). To a solu-
tion of (+)-11 (71 mg, 86.7 mmol) in MeOH (6.3 ml) was
added NaOMe (43 mg, 0.794 mmol) at 0 ꢂC under an
argon atmosphere. The solution was stirred at rt for 5 h,
and then the reaction mixture was neutralized with 1 M
HCl aq. and concentrated in vacuo. The residue was
purified by silica gel column chromatography (CHCl3/
MeOH = 6/1) to afford (+)-12 (34.5 mg, 85.7 mmol,
99%) as a colorless viscous oil. 1H-NMR (500 MHz,
CD3OD) ꢃ: 5.51 (dt, J ¼ 10:5, 7.0 Hz, 1H), 5.39 (dt,
J ¼ 10:5, 7.5 Hz, 1H), 4.27 (d, J ¼ 7:5 Hz, 1H), 3.90–
3.83 (m, 2H), 3.68 (s, 3H), 3.68–3.63 (m, 1H), 3.55 (dt,
J ¼ 9:5, 7.0 Hz, 1H), 3.34 (t, J ¼ 9:0 Hz, 1H), 3.28–3.23
(m, 2H), 3.16 (dd, J ¼ 9:0, 8.0 Hz, 1H), 2.72 (dd,
J ¼ 14:5, 3.5 Hz, 1H), 2.44–2.28 (m, 7H), 2.23–2.15
(m, 1H), 2.09 (ddd, J ¼ 19:5, 11.0, 8.5 Hz, 1H), 1.99
(dtd, J ¼ 11:0, 5.5, 1.0 Hz, 1H), 1.56–1.46 (m, 1H);
13C-NMR (125 MHz, CD3OD) ꢃ: 221.6, 174.5, 129.0,
128.9, 104.3, 78.1, 77.9, 75.1, 71.6, 70.2, 62.7, 55.0,
(1R,2S,20Z)-2-{50-(ꢀ-D-Glucopyranosyloxy)-pent-20-
enyl}-3-oxo-cyclopentaneacetic acid (ꢀ-D-glucopyrano-
syl 12-hydroxyjasmonate, 13). A 20:1 mixture of 1 and
13 (3.6 mg) was separated by HPLC, using a Cosmosil
5C18AR column (ꢂ20 ꢃ 250 mm, Nacalai Tesque Co.)
with 7% MeCNaq. containing 0.1% CH3COONH4, and
then desalting in the Cosmosil 5C18AR column with
MeOH–H2O (2:98, 50:50) to give ꢀ-D-glucopyranosyl
12-hydroxy-7-epi-jasmonic acid (purity > 90%, ca. 0.4
mg). In the course of concentration in vacuo, separated
13 was gradually epimerized to give a mixture of 13 and
1 (ca. 9:1). The purity of 13 was estimated from its
1H-NMR spectrum.
Methyl (1S,2S,20Z)-3-oxo-2-[50-(200,300,400,600-tetra-O-
benzoyl-ꢀ-L-glucopyranosyl-oxy)-pent-20-enyl]-cyclopen-
taneacetate ((+)-11). To a solution of (+)-9 (36.6 mg,
152 mmol), 15 (201 mg, 305 mmol) and dried molecular
sieves 4 A in anhydrous CH2Cl2 (2.0 ml) was slowly
52.1, 39.5, 39.2, 38.6, 29.0, 28.1, 26.4; IR (film) cmꢁ1
:
˚
added AgOTf (78 mg, 305 mmol) in toluene (2.0 ml) at
10 ꢂC under an argon atmosphere in the dark. The
reaction mixture was stirred for 22 h at rt. The reaction
mixture was then diluted with CHCl3 and filtered through
a pad of Celite. The filtrate was successively washed with
brine and satd. NaHCO3 aq. The organic layer was dried
over Na2SO4 and concentrated in vacuo. The residue was
purified by silica gel column chromatography (n-hexane/
EtOAc = 10/1–2/1) and preparative TLC (silica gel
3418, 2952, 2925, 2888, 1734, 1438, 1164, 1079, 1038,
27
897; ½ꢁꢀD +60.0 (c 1.00, MeOH); HRMS (ESI,
positive) m=z ½M þ Naꢀþ: calcd. for C19H30O9Na,
425.1782; found, 425.1780.
(1S,2S,20Z)-2-{50-(ꢀ- -Glucopyranosyloxy)-pent-20-enyl}-
L
3-oxo-cyclopentane-acetic acid (14). To a solution of
(+)-12 (10.0 mg, 24.8 mmol) in MeOH (1 ml) and H2O
(0.5 ml) was added 1 M KOH aq. (37.0 ml, 37.0 mmol) at
0 ꢂC. The solution was refluxed for 3 h at 90 ꢂC. The
reaction mixture was then neutralized with 1 M HCl aq.
and concentrated in vacuo. The residue was purified by
ODS TLC (RP-18, H2O/MeOH = 3/2) to afford 14
(9.6 mg, 24.8 mmol, quant.) as a colorless viscous oil.
1H-NMR (500 MHz, CD3OD) ꢃ: 5.51 (dt, J ¼ 11:0,
7.0 Hz, 1H), 5.39 (dt, J ¼ 11:0, 7.5 Hz, 1H), 4.27 (d,
J ¼ 8:0 Hz, 1H), 3.90–3.83 (m, 2H), 3.68–3.63 (m, 1H),
3.55 (dt, J ¼ 10:0, 7.0 Hz, 1H), 3.34 (t, J ¼ 8:0 Hz, 1H),
3.28–3.23 (m, 2H), 3.16 (dd, J ¼ 9:0, 8.0 Hz, 1H), 2.67
(d, J ¼ 11 Hz, 1H), 2.45–2.19 (m, 8H), 2.09 (ddd, J ¼
19:0, 11.0, 8.5 Hz, 1H), 1.99 (dtd, J ¼ 11:0, 5.5, 1.0 Hz,
1H), 1.57–1.47 (m, 1H); 13C-NMR (125 MHz, CD3OD)
ꢃ: 221.9, 176.3, 129.0, 128.9, 104.3, 78.1, 77.9, 75.1,
71.7, 70.2, 62.8, 55.1, 40.0, 39.2, 38.7, 29.0, 28.2, 26.4;
IR (film) cmꢁ1: 3403, 2923, 1727, 1408, 1200, 1166,
F
254, n-hexane/EtOAc = 2/1) to afford (+)-11 (89.1
1
mg, 109 mmol, 72%) as a white crystal. H-NMR (500
MHz, CDCl3) ꢃ: 8.02 (d, J ¼ 7:5 Hz, 2H), 7.95
(d, J ¼ 7:5 Hz, 2H), 7.90 (d, J ¼ 7:5 Hz, 2H), 7.82
(d, J ¼ 7:5 Hz, 2H), 7.54 (t, J ¼ 7:5 Hz, 1H), 7.51
(t, J ¼ 7:5 Hz, 1H), 7.49 (t, J ¼ 7:5 Hz, 1H), 7.42
(t, J ¼ 7:5 Hz, 1H), 7.40 (t, J ¼ 7:5 Hz, 2H), 7.38
(t, J ¼ 7:5 Hz, 2H), 7.34 (t, J ¼ 7:5 Hz, 2H), 7.28
(t, J ¼ 7:5 Hz, 2H), 5.90 (t, J ¼ 9:5 Hz, 1H), 5.68
(t, J ¼ 9:5 Hz, 1H), 5.52 (dd, J ¼ 9:5, 8.5 Hz, 1H),
5.32 (dt, J ¼ 10:5, 7.0 Hz, 1H), 5.21 (dt, J ¼ 10:5,
8.0 Hz, 1H), 4.87 (d, J ¼ 8:5 Hz, 1H), 4.64 (dd, J ¼ 12:0,
3.0 Hz, 1H), 4.50 (dd, J ¼ 12:0, 5.0 Hz, 1H), 4.17 (ddd,
J ¼ 9:5, 5.0, 3.0 Hz, 1H), 3.92 (dt, J ¼ 9:5, 6.5 Hz, 1H),
3.67 (s, 3H), 3.56 (dt, J ¼ 9:5, 6.5 Hz, 1H), 2.61 (dd,
J ¼ 14:5, 3.0 Hz, 1H), 2.37–2.15 (m, 8H), 2.03 (ddd,
J ¼ 19:0, 11.0, 8.5 Hz, 1H), 1.80 (dt, J ¼ 9:0, 5.5 Hz,
1H), 1.45 (t, J ¼ 11:0, 9.0 Hz, 1H); 13C-NMR (125 MHz,
CDCl3) ꢃ: 218.7, 172.5, 166.1, 165.8, 165.2, 165.0,
133.4, 133.2 (2 ꢃ C), 133.1, 129.7 (4 ꢃ C), 129.6, 129.4,
128.8 (2 ꢃ C), 128.34 (3 ꢃ C), 128.27, 127.9, 127.3,
101.2, 72.9, 72.2, 71.8, 69.8, 69.5, 63.2, 53.8, 51.6, 38.7,
37.9, 37.6, 27.7, 27.1, 25.4; IR (film) cmꢁ1: 2953, 1732,
1602, 1451, 1370, 1315, 1267, 1177, 1107, 1094, 1069,
20
1079, 1038; ½ꢁꢀD +54.2 (c 0.5, MeOH); HRMS (ESI,
positive) m=z ½M þ Naꢀþ: calcd. for C18H28O9Na,
411.1626; found, 411.1625.
Methyl(1R,2R,20Z)-3-oxo-2-[50-(20,30,40,60-tetra-O-ben-
zoyl-ꢀ-D-galactopyranosyl)-oxy-pent-20-enyl]-cyclopen-
taneacetate (17). To a solution of (ꢁ)-9 (26.7 mg,
˚
0.111 mmol), 16 (128.3 mg, 0.239 mmol) and MS4 A
29
1027, 756, 710; ½ꢁꢀD +3.7 (c 1.00, CHCl3); HRMS
(270 mg) in anhydrous CH2Cl2 (1.0 ml) was slowly

Synthesis of Potassium ꢀ-D-Glucopyranosyl 12-Hydroxy Jasmonate
2875
added AgOTf (63.8 mg, 0.248 mmol) in anhydrous
toluene (1.0 ml) at 10 ꢂC, and the mixture was then
stirred at room temperature for 18 h under an argon
atmosphere in the dark. The reaction mixture was
diluted with EtOAc and filtered through a pad of Celite.
The filtrate was washed with water and brine. The
organic layer was dried over Na2SO4, and concentrated
in vacuo. The residue was purified by silica gel column
chromatography (n-hexane/EtOAc = 2:1) and prepara-
tive TLC (silica gel F254, toluene/EtOAc = 3:1) to
afford 17 (67.0 mg, 96.1 mmol. 87%) as colorless
viscous oil. 1H-NMR (500 MHz, CDCl3) ꢃ: 8.10 (dt,
J ¼ 7:0, 1.5 Hz, 2H), 8.02 (dt, J ¼ 6:5, 1.5 Hz, 2H), 7.96
(dt, J ¼ 7:5, 1.5 Hz, 2H), 7.79 (dt, J ¼ 7:0, 1.5 Hz, 2H),
7.62 (tt, J ¼ 7:0, 1.5 Hz, 1H), 7.56 (tt, J ¼ 7:5, 1.5 Hz,
1H), 7.51 (tt, J ¼ 7:5, 1.5 Hz, 1H), 7.48 (t, J ¼ 7:5 Hz,
3H), 7.41–7.45 (m, 3H), 7.38 (t, J ¼ 7:5 Hz, 2H), 7.24
(t, J ¼ 7:5 Hz, 2H), 6.00 (dd, J ¼ 3:5, 1.0 Hz, 1H), 5.79
(dd, J ¼ 10:0, 3.0 Hz, 1H), 5.61 (dd, J ¼ 10:5, 3.5 Hz,
1H), 5.35 (dt, J ¼ 11:0, 7.5 Hz, 1H), 5.21 (dt, J ¼ 11:0,
7.5 Hz, 1H), 4.86 (d, J ¼ 8:0 Hz, 1H), 4.69 (dd,
J ¼ 11:0, 7.0 Hz, 1H), 4.42 (dd, J ¼ 11:0, 7.0 Hz, 1H),
4.34 (t, J ¼ 6:5 Hz, 1H), 3.99 (dt, J ¼ 9:5, 6.5 Hz, 1H),
3.68 (s, 3H), 3.59 (dt, J ¼ 9:5, 7.0 Hz, 1H), 2.60 (dd,
J ¼ 15:0, 3.0 Hz, 1H), 2.16–2.40 (m, 8H), 2.04 (ddd,
J ¼ 19:0, 11.5, 8.5 Hz, 1H), 1.80 (ddt, J ¼ 10:0, 5.5,
1.0 Hz, 1H), 1.62 (d, J ¼ 4:5 Hz, 1H), 1.46 (tt, J ¼ 11:0,
3.0 Hz, 1H); 13C-NMR (125 MHz, CDCl3) ꢃ: 218.6,
172.5, 166.0, 165.56 (2 ꢃ C), 165.2, 133.5, 133.26,
133.23, 133.16, 130.0, 129.75 (2 ꢃ C), 129.71, 129.5,
129.4, 129.0, 128.8, 128.6, 128.5, 128.33, 128.25, 127.9,
127.3, 101.6, 71.7, 71.3, 69.7, 68.1, 62.0, 53.8, 51.6,
38.7, 37.9, 37.6, 27.7, 27.2, 25.3; IR (film) cmꢁ1: 3064,
3015, 2953, 2929, 1731, 1602, 1584, 1492, 1451, 1438,
1407, 1374, 1336, 1315, 1268, 1176, 1110, 1070, 1028,
5.5, 1.0 Hz, 1H), 1.47–1.56 (m, 1H); 13C-NMR (125
MHz, CD3OD) ꢃ: 221.6, 174.5, 129.0, 128.9, 105.0,
76.6, 75.0, 72.5, 70.3, 70.2, 62.5, 55.0, 52.1, 39.5, 39.2,
38.6, 29.1, 28.1, 26.4; IR (film) cmꢁ1: 3420, 2952, 2918,
1734, 1438, 1407, 1374, 1336, 1267, 1231, 1199, 1164,
23
1117, 1073, 984, 915, 893, 700, 668; ½ꢁꢀD ꢁ41:5 (c
0.50, MeOH); HRMS (ESI, positive) m=z ½M þ Naꢀþ:
calcd. for C19H30O9Na, 425.1782; found, 425.1779.
(1R,2R,20Z)-2-{50-(ꢀ-D-Galactopyranosyloxy)-pent-20-
enyl}-3-oxo-cyclopentaneacetic acid (19). Glycoside 18
(15.0 mg, 37.3 mmol) in MeOH/H2O = 3:1 (400 ml) was
refluxed with 1 M KOH (56 ml) aq. for 2 h at 90 ꢂC. After
being cooled to room temperature, the mixture was
diluted with MeOH and neutralized with Amberlite
IR120B. After filtration, the mixture was concentrated in
vacuo. The residue was purified by HPLC in a
COSMOSIL 5C18-AR column (ꢂ20:0 ꢃ 25:0 mm, 15%
MeCN aq.) to afford 19 (11.9 mg, 30.6 mmol, 82%) as a
1
colorless viscous oil. H-NMR (500 MHz, CD3OD) ꢃ:
5.51 (dt, 1H, J ¼ 11:0, 7.0 Hz), 5.40 (dt, 1H, J ¼ 11:0,
7.5 Hz), 4.23 (d, 1H, J ¼ 7:5 Hz), 3.87 (dt, 1H, J ¼ 9:5,
7.0 Hz), 3.82 (dd, 1H, J ¼ 3:0, 1.0 Hz), 3.75 (dd, 1H,
J ¼ 12:0, 7.0 Hz), 3.71 (dd, 1H, J ¼ 11:0, 5.0 Hz), 3.57
(dt, 1H, J ¼ 9:0, 7.0 Hz), 3.48–3.52 (m, 2H), 3.45 (dd,
1H, J ¼ 9:5, 3.0 Hz), 2.27–2.43 (m, 8H), 2.20–2.26 (m,
1H), 2.09 (ddd, 1H, J ¼ 18:5, 11.5, 9.0 Hz), 1.99 (ddt,
1H, J ¼ 10:5, 5.5, 1.0 Hz), 1.53 (m, 1H); 13C-NMR
(125 MHz, CD3OD) ꢃ: 222.0, 176.6, 129.0, 110.3, 105.0,
76.6, 75.0, 72.6, 70.3, 70.2, 62.5, 55.2, 40.3, 39.3, 38.7,
29.1, 28.2, 26.4; IR (film) cmꢁ1: 3409, 3013, 2930,
2896, 1728, 1550, 1407, 1374, 1335, 1232, 1200, 1146,
1117, 1075, 984, 918, 893, 781, 760, 703, 667, 619;
24
½ꢁꢀD ꢁ39:2 (c 0.50, MeOH); HRMS (ESI, positive)
m=z ½M þ Naꢀþ calcd. for C18H28O9Na 411.1626;
found, m=z 411.1624.
937, 910, 856, 803, 756, 711, 687, 617 cmꢁ1; ½ꢁꢀD
24
+50.8 (c 0.50, CHCl3); HRMS (ESI, positive) m=z
½M þ Naꢀþ: calcd. for C47H46O13Na, 841.2831; found,
841.2826.
(1S,2S,20Z)-2-(50-Hydroxy-pent-20-enyl)-3-oxo-cyclo-
pentaneacetic acid ((+)-20). To a solution of (+)-9
(10.8 mg, 44.9 mmol) in MeOH (1 ml) and H2O (0.5 ml)
was added 1 M KOH aq. (89.8 ml, 2 equiv.) at 0 ꢂC. The
solution was refluxed for 1 h at 90 ꢂC. The reaction
mixture was then neutralized with 1 M HCl aq. and
concentrated in vacuo. The residue was purified by
ODS TLC (RP-18, H2O/MeOH = 2/1) to afford (+)-
20 (8.1 mg, 35.8 mmol, 80%) as a colorless oil. 1H-
NMR (500 MHz, CD3OD) ꢃ: 5.48 (dt, J ¼ 11:0, 7.0 Hz,
1H), 5.42 (dt, J ¼ 11:0, 7.0 Hz, 1H), 3.54 (t, J ¼
6:5 Hz, 2H), 2.68 (dt, J ¼ 11:0, 8.0 Hz, 1H), 2.39 (t,
J ¼ 6:5 Hz, 2H), 2.36–2.18 (m, 6H), 2.09 (ddd, J ¼
19:0, 11.0, 9.0 Hz, 1H), 2.00 (dt, J ¼ 9:5, 5.0 Hz, 1H),
1.58–1.48 (m, 1H); 13C-NMR (125 MHz, CD3OD)
ꢃ: 221.8, 176.2, 129.1, 129.1, 62.6, 55.1, 39.8, 39.2,
38.6, 31.8, 28.2, 26.4; IR (film) cmꢁ1: 3424, 2954,
1731, 1681, 1408, 1203, 1139, 1049, 838, 800, 723;
(1R,2R,20Z)-2-{50-(ꢀ-D-Galactopyranosyloxy)-pent-20-
enyl}-3-oxo-cyclopentane-acetate (18). To a solution of
17 (67.0 mg, 96.1 mmol) in MeOH (1.0 ml) was added
NaOMe (25.8 mg, 0.478 mmol) at 0 ꢂC, and the mixture
was stirred for 4 h at rt under an argon atmosphere. The
reaction mixture was then diluted with MeOH and
neutralized with Amberlite IR120B. After filtration, the
filtrate was concentrated in vacuo. The residue was
purified by ODS TLC (RP-18, H2O/MeOH = 3:2) to
afford 18 (28.0 mg, 69.6 mmol, 72%) as a colorless
1
viscous oil. H-NMR (500 MHz, CD3OD) ꢃ: 5.52 (dt,
J ¼ 11:0, 7.5 Hz, 1H), 5.39 (dt, J ¼ 11:0, 7.5 Hz, 1H),
4.23 (d, J ¼ 7:5 Hz, 1H), 3.87 (dt, J ¼ 9:5, 7.0 Hz, 1H),
3.82 (dd, J ¼ 3:0, 1.0 Hz, 1H), 3.69–3.76 (m, 2H), 3.68
(s, 3H), 3.56 (dt, J ¼ 9:5, 7.0 Hz, 1H), 3.48–3.52 (m,
2H), 3.45 (dd, J ¼ 10:0, 3.0 Hz, 1H), 2.71 (dd, J ¼ 15:5,
4.0 Hz, 1H), 2.29–2.42 (m, 8H), 2.16–2.22 (m, 1H), 2.09
(ddd, J ¼ 19:0, 11.0, 9.0 Hz, 1H), 1.99 (ddt, J ¼ 10:5,
22
½ꢁꢀD +74.1 (c 0.50, MeOH); HRMS (ESI, positive)
m=z ½M þ Naꢀþ calcd. for C12H18O4Na 249.1096;
found, 249.1097.

2876
Y. NAKAMURA et al.
12) Nakamura, Y., Kiyota, H., Kumagai, T., and Ueda, M.,
Bioassay. Albizzia saman was grown in a biotron
Direct observation of the target cell for jasmonate-type
Leaf-closing factor: genus-specific binding of leaf-
movement factor to the plant motor cell. Tetrahedron
Lett., 47, 2893–2897 (2006).
(NIPPON MEDICAL & CHEMICAL INSTRUMENTS
CO.), with 12 h light: 12 h dark cycle, at 32 ꢂC in the
daytime and 22 ꢂC in the nighttime. Young leaves of
A. saman were used for the bioassay. The young leaves
were detached from the stem of A. saman with a sharp
razor blade in water at around 4:00 p.m. One leaf was
placed in H2O (ca. 300 ml) in a 20-ml glass vial and
allowed to stand overnight. The leaves which opened
again in the morning were used for the bioassay. Each
test solution was carefully poured into a test tube with a
micropipette at around 10:00 am. The leaves immersed
in the sample solution were put into a bell funnel, and
decompressed by an aspirator. The sample solution was
then pumped up through the vessel under reduced
pressure. The bioactive fraction made the leaves close,
even in the daytime.
13) Kiyota, H., Higashi, E., Koike, T., and Oritani, T.,
Lipase-catalyzed preparation of both enantiomers of
methyl jasmonate. Tetrahedron: Asymmetry, 12, 1035–
1038 (2001).
14) Asamitsu, Y., Nakamura, Y., Ueda, M., Kuwahara, S.,
and Kiyota, H., Synthesis and odor descriptions of both
enantiomers of methyl 4,5-didehydrojasmonate, a com-
ponent of jasmin absolute. Chem. Biodivers., 3, 654–659
(2006).
15) Nonaka, H., Wang, Y.-G., and Kobayashi, Y., First total
synthesis of tuberonic acid. Tetrahedron Lett., 48, 1745–
1748 (2007).
16) Inoue, M., and Kitahara, T., Synthesis of both the
enantiomers of methyl tuberonate, natural methyl ꢀ-D-
glucopyranosyloxyjasmonate and its epimer. Tetrahe-
dron, 55, 4621–4630 (1999).
References
1) Darwin, C., ‘‘The Power of Movement in Plants Third
Thousand,’’ John Murray, London (1882).
2) Satter, R. L., and Galston, A. W., Mechanisms of control
of leaf movements. Annu. Rev. Plant Physiol., 32, 83–
110 (1981).
3) Satter, R. L., ‘‘The Pulvinus: Motor Organ for Leaf
Movement,’’ eds. Satter, R. L., Gorton, H. L., and
Vogelmann, T. C., American Society of Plant Physiol-
ogy, Rockville, pp. 1–9 (1990).
17) Sarkar, T. K., Mukherjee, B., and Ghosh, S. K., An
enantiospecific synthesis of (+)-methyl epijasmonate
and (ꢁ)-methyl cucurbate from L-glutamic acid. Tetra-
hedron, 54, 3243–3254 (1998).
18) Trujillo, M., Morales, E.-Q., and Vazquez, J.-T., Tetra-
O-benzoylglucosylation: a new 1H nuclear magnetic
resonance method for determination of the absolute
configuration of secondary alcohols. J. Org. Chem., 59,
6637–6642 (1994).
4) Suh, S., Moran, N., and Lee, Y., Blue light activates
potassium-efflux channels in flexor cells from Samanea
saman motor organs via two mechanisms. Plant Phys-
iol., 123, 833–843 (2000).
5) Moshelion, M., and Moran, N., Potassium-efflux chan-
nels in extensor and flexor cells of the motor organ of
Samanea saman are not identical. effects of cytosolic
calcium. Plant Physiol., 124, 911–919 (2000).
6) Moshelion, M., Becker, D., Biela, A., Uehlein, N.,
Hedrich, R., Otto, B., Levi, H., Moran, N., and
Kaldenhoff, R., Diurnal and circadian regulation of
putative potassium channels in a leaf moving organ.
Plant Physiol., 128, 634–642 (2002).
19) Bernlind, C., and Oscarson, S., Synthesis of L-glycero-D-
manno-heptopyranose-containing oligosaccharide struc-
tures found in lipopolysaccharides from Haemophilus
influenza. Carbohydr. Res., 297, 251–260 (1997).
20) Ueda, J., and Kato, J., Isolation and identification of
a senescence-promoting substance from wormwood
(Artemisia absinthium L.). Plant Physiol., 66, 246–249
(1980).
21) Holbrook, L., Tung, P., Ward, K., Reid, D. M., Abrams,
S., Lamb, N., Quail, J. W., and Moloney, M. M.,
Importance of the chiral centers of jasmonic acid in the
responses of plants (activities and antagonism between
natural and synthetic analogs). Plant Physiol., 114, 419–
428 (1997).
7) Moshelion, M., Becker, D., Czempinski, K., Mulleer-
Roeber, B., Attali, B., Hedrich, R., and Moran, N.,
Plasma membrane aquaporins in the motor cells of
Samanea saman: diurnal and circadian regulation. Plant
Cell, 14, 727–739 (2002).
22) Koda, Y., Omer, E. A., Yoshihara, T., Shibata, H.,
Sakamura, S., and Okazawa, Y., Isolation of a specific
potato tuber-inducing substance from potato leaves.
Plant Cell Physiol., 29, 1047–1051 (1988).
8) Ueda, M., and Yamamura, S., Chemistry and biology of
plant leaf movements. Angew. Chem. Int. Ed., 39, 1400–
1414 (2000).
9) Ueda, M., and Nakamura, Y., Metabolites involved in
plant movement and ‘memor’: nyctinasty of legumes and
trap movement in the Venus flytrap. Nat. Prod. Rep., 23,
548–557 (2006).
10) Ueda, M., Okazaki, M., Ueda, K., and Yamamura, S.,
A leaf-closing substance of Albizzia julibrissin Durazz.
Tetrahedron, 56, 8101–8105 (2000).
11) Nakamura, Y., Miyatake, R., Matsubara, A., Kiyota, H.,
and Ueda, M., Enantio-differential approach to identify
the target cell for glucosyl jasmonate-type leaf-closing
factor, by using fluorescence-labeled probe compounds.
Tetrahedron, 62, 8805–8813 (2006).
23) Yoshihara, T., Omer, E. A., Koshino, H., Sakamura, S.,
Kikuta, Y., and Koda, Y., Structure of a tuber-inducing
stimulus from potato leaves (Solanum tuberosum L.).
Agric. Biol. Chem., 53, 2835–2837 (1989).
24) Fujita, T., Terato, K., and Nakayama, M., Two jasmo-
noid glucosides and a phenylvaleric acid glucoside from
Perilla frutescens. Biosci. Biotechnol. Biochem., 60,
732–735 (1996).
25) Turner, J. G., Ellis, C., and Devoto, A., The jasmonate
signal pathway. Plant Cell, 14 (Suppl.), S153–S164
(2002).
26) Schow, S. R., and McMorris, T. C., Utility of the Wittig
reaction for the construction of side chains of steroids
starting from pregnenolone. J. Org. Chem., 44, 3760–
3765 (1979).