Synthesis of the (17R)- and (17S)-isomers of volicitin, an elicitor of plant volatiles contained in the oral secretion of the beet armyworm

Article abstract of DOI:10.1271/bbb.66.1591

Both the (17R)- and (17S)-isomers of volicitin, which is contained in the oral secretion of the beet armyworm and induces corn seedlings to emit a blend of volatile compounds to attract the natural enemy of the herbivore, were synthesized via the semi-hyd

Full text of DOI:10.1271/bbb.66.1591

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Synthesis of the (17R)- and (17S)-Isomers of Volicitin,
an Elicitor of Plant Volatiles Contained in the Oral
Secretion of the Beet Armyworm
ab
b
a
a
Seiji ITOH , Shigefumi KUWAHARA , Morifumi HASEGAWA & Osamu KODAMA
a
Laboratory of Agricultural Chemicals, Faculty of Agriculture, Ibaraki University Ami-
machi, Inashiki-gun, Ibaraki 300-0393, Japan
b
Laboratory of Applied Bioorganic Chemistry, Division of Life Science, Graduate School
of Agricultural Science, Tohoku University 1-1 Tsutsumidori-Amamiyamachi, Aoba-ku,
Sendai 981-8555, Japan
Published online: 22 May 2014.
To cite this article: Seiji ITOH, Shigefumi KUWAHARA, Morifumi HASEGAWA & Osamu KODAMA (2002) Synthesis of the
(17R)- and (17S)-Isomers of Volicitin, an Elicitor of Plant Volatiles Contained in the Oral Secretion of the Beet Armyworm,
Bioscience, Biotechnology, and Biochemistry, 66:7, 1591-1596, DOI: 10.1271/bbb.66.1591
To link to this article: http://dx.doi.org/10.1271/bbb.66.1591
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Biosci. Biotechnol. Biochem., 66 (7), 1591–1596, 2002
Note
Synthesis of the (17R)- and (17S)-Isomers of Volicitin, an Elicitor of Plant
Volatiles Contained in the Oral Secretion of the Beet Armyworm
Seiji ITOH,1,2 Shigefumi KUWAHARA,2, Morifumi HASEGAWA,1 and Osamu KODAMA
†
1
1Laboratory of Agricultural Chemicals, Faculty of Agriculture, Ibaraki University, Ami-machi,
Inashiki-gun, Ibaraki 300-0393, Japan
2
Laboratory of Applied Bioorganic Chemistry, Division of Life Science, Graduate School of Agricultural
Science, Tohoku University, 1-1 Tsutsumidori-Amamiyamachi, Aoba-ku, Sendai 981-8555, Japan
Received January 23, 2002; Accepted February 18, 2002
Both the (17
R
)- and (17
S
)-isomers of volicitin, which
by transforming (
R
)- and (
S
)-7c into the corre-
)-1-
is contained in the oral secretion of the beet armyworm
and induces corn seedlings to emit a blend of volatile
compounds to attract the natural enemy of the herbi-
vore, were synthesized via the semi-hydrogenation of an
intermediary diyne and (Z )-selective oleˆnation as the
key steps. They were both obtained as crystalline com-
pounds.
sponding cabamates with a treatment by (
R
phenyethyl isocyanate. The GLC-retention times of
the resulting diastereomeric carbamates were then
compared with that of a carbamate sample derived in
the same manner from the methanolysis product of
5
)
natural volicitin. The other group reported later a
formal synthesis of (17RS)-1a by preparing ( )-7d, a
±
synthetic precursor of (17RS)-1a described by Al-
born et al., in which semi-hydrogenation of a triene
intermediate was employed as the key step to obtain
Key words: volicitin; elicitor; Spodoptera exigua; 17-
hydroxylinolenic acid
6
)
(
±
)-7d. Although the absolute conˆguration of
Volicitin (1a) was isolated by Alborn et al. in 1997
from the oral secretion of beet armyworm caterpil-
lars (Spodoptera exigua H uä ber) as an elicitor which
induces corn seedlings (Zea may L.) to release a mix-
ture of volatile terpenoids and indole when the plant
1
,2)
is damaged by the insect herbivore (Figure). The
mixture plays the role of attracting the parasitic wasp
(
Cotesia marginiventris), a natural enemy of the
caterpillar, resulting in the indirect protection of the
plant from attack by the herbivore. Alborn et al. also
accomplished the synthesis of a mixture of (17R)-
and (17
lenic acid (7d) with either a protected or unprotected
-glutamine, which resulted in the conˆrmation of
the proposed structure, excluding the stereochemistry
S)-1a via coupling racemic 17-hydroxylino-
L
1
,2)
of its 17-hydroxyl group. Since then, two research
groups have reported synthetic works on volicitin.
One group made use of a highly e‹cient one-pot
double-Wittig approach for the preparation of both
3
,4)
(
R
)- and (
to give ( )- or (
17 )- or (17
coupling with
S)-7a. Each of the esters was hydrolyzed
R
S
)-7b, which was then converted into
(
R
S)-volicitin (1a), respectively, by
L
-glutamine and subsequent removal
Figure. Reagents: a) I
Bu) NI, Na CO , DMF; c) H
Br O, Ph P, CH Cl ; e) Ph
THF-HMPA; g) LiOH, H O-THF
2
, Ph
3
P, imidazole, THF; b) CuI, (
, Lindlar catalyst, hexane; d)
2
P, CH CN; f) KN(TMS) ,
n-
of the TBS-protecting group. The absolute conˆgura-
tion of the C-17 stereogenic center of volicitin as
depicted in the Figure was determined quite recently
4
2
3
2
C
6
H
2
4
3
2
2
3
3
2
†
To whom correspondence should be addressed. Tel: +81-22-717-8783; Fax: +81-22-717-8783; E-mail: skuwahar
tohoku.ac.jp
＠
biochem.
Abbreviations: MTPA, a-methoxy-a-tri‰uorophenylacetyl; TBS, tert-butyldimethylsilyl

1
592
S. ITOH et al.
volicitin has already been established to be 17
describe here our synthesis of both (17 )- and (17
volicitin, together with the experimental details.
S
, we
spectrometer, unless otherwise stated. Optical rota-
R
S
)-
tion values were measured with a Jasco DIP-370
polarimeter. Tetrahydrofuran was puriˆed by
distilling from sodium benzophenone ketyl, and
6
)
Known acetylenic ester 2 was coupled with iodide
b, which had been obtained by treating the corre-
sponding alcohol (3a) with iodine, imidazole, and
triphenylphosphine in tetrahydrofuran, to give 4 in
3
dichloromethane was puriˆed by drying with P
2
O
5
7)
and then by distillation from CaH . Merck silica gel
2
60 (70–230 mesh) was used for silica gel column chro-
matography.
an 85
z
yield. Catalytic semi-hydrogenation of the
diyne in the presence of the Lindlar catalyst gave 5a,
the (tetrahydropyran-2-yl)oxy group of which was
Methyl 9-decynoate (
2
). This acetylenic ester was
8
)
6)
then substituted with bromine by Tanaka's method
prepared by modifying the literature procedure.
to directly give bromide 5b. Repeated chromato-
Potassium hydride (35z in mineral oil, 0.970 g,
graphic puriˆcation of this crude bromide enabled us
8.46 mmol) was washed three times with pentane
under a nitrogen atmosphere. It was then mixed with
trimethylene diamine (8 ml) in a reaction vessel
cooled with a water bath, and the mixture was stirred
at room temperature for 1 h. To the solution was
added dropwise 3-decyn-1-ol (0.500 ml, 2.84 mmol)
while cooling with the water bath. After being stirred
for 2 h, the reaction mixture was quenched by adding
ethanol (0.98 ml). The mixture was poured into sat.
to obtain geometrically pure (9Z,12Z )-5b, as judged
1
3
by C-NMR. The bromide (5b) was converted into
the corresponding phosphonium salt (5c), which was
9
)
then subjected to (
with both enantiomers of aldehyde 6.
ing triene products were repeatedly chromatographed
over silica gel to give C-NMR spectroscopically
pure ( )- and ( )-7a. In order to determine their
Z )-selective Wittig oleˆnation
10,11)
The result-
1
3
R
S
enantiomeric excess, the TBS ethers were separately
treated with tetrabutylammonium ‰uoride and then
NH
lution was successively washed with water and brine,
dried (MgSO ), and concentrated in vacuo. The
residue was chromatographed over silica gel (16 g,
hexane-ethyl acetate, 6:1) to give 0.393 g (79 ) of
4
Cl aq. and extracted with ether. The ethereal so-
with (
S
)-MTPACl to give the corresponding di-
4
1
astereomeric MTPA-esters. A H-NMR analysis rev-
ealed both of them to be optically pure. The enantio-
z
meric esters, (
with lithium hydroxide in THF to respectively aŠord
)-7b and ( )-7b, which were condensed with
glutamine via the corresponding mixed anhydrides
R
)-7a and (
S
)-7a, were hydrolyzed
9-decyn-1-ol. To a stirred solution of this alcohol
(3.46 g, 22.4 mmol) in acetone (70 ml) was added
(
R
S
L
-
dropwise the Jones reagent (2.67
M
,
12.3 ml,
32.8 mmol) at 0 C. After 2 h, the reaction mixture
9
(
7e). Finally, the TBS protecting group of the result-
was quenched with 2-propanol (2 ml), diluted with
water (70 ml) and concentrated in vacuo. The residue
was diluted with water and extracted with ether. The
ethereal solution was successively washed with water
and brine, and then concentrated again in vacuo. The
residue was dissolved in ether and extracted with
ing amides (1b) was removed to aŠord (17
R
3
)-volicitin
2
1
3)
s
[
s
mp 86.5–88.0
9
; [
a
]
D
„3.9
9
Cl
(
c
2
＝
0.90, CH
OH), lit.
2
2
a
]
D
„4.0
9
9
(
c
＝
0.82, CH
2
)
t
and (17
S
3
)-volicitin
2
1
3)
mp 54–61
C; [a
]
D
+6.6
9
2
(
c
＝
0.80, CH
OH), lit.
2
2
[
a
]
D
+3
9
(c
＝
0.82, CH
2
Cl )tas crystals in both
cases. Probably due to their crystalline nature, our
synthetic samples did not dissolve very well in
dichloromethane which had been used for measuring
the speciˆc rotation values of volicitins synthesized
by Pohnert et al. Therefore, methanol was used for
this measurement instead of dichloromethane in our
case. Unfortunately, the melting point of our syn-
KOH aq. (2
aq. (12 ), the water layer was extracted with ether.
The ethereal solution was successively washed with
water and brine, dried (MgSO ), and concentrated in
vacuo to give 3.15 g (83 ) of crude 9-decynoic acid.
A mixture of this carboxylic acid (3.45 g, 20.5 mmol)
and conc. H SO (0.1 ml) in anhydrous methanol
(10 ml) was stirred for 1 h at room temperature. The
reaction mixture was then quenched with NaHCO
M
, 18 ml). After acidiˆcation with HCl
M
4
z
2
4
thetic (17S)-1a does not seem to be accurate, because
of the presence of a small amount of impurities
which could not be removed, even by reverse-phase
3
powder (0.82 g) and concentrated in vacuo. The
residue was diluted water and extracted with ether.
The ethereal solution was successively washed with
1
chromatography and recrystallization. The H- and
1
3
C-NMR spectra of (17
R
)-volicitin were indistin-
)-volicitin, and were
guishable from those of (17
S
water and brine, dried (MgSO
vacuo. The residue was distilled under reduced
pressure to give 3.28 g (87.6 ) of 2, bp 86–87 C (2
Torr). The IR and H-NMR spectral data were identi-
4
), and concentrated in
identical with authentic spectra kindly supplied by
Dr. Pohnert.
z
9
1
6
)
Experimental
cal with those reported in the literature.
IR spectra were measured as ˆlms by a Jasco FT
1-Iodo-5-[(tetrahydropyran-2-yl)oxy]-2-pentyne
W
1
13
IR-5000 spectrometer. H-NMR (500 MHz) and C-
NMR (125 MHz) spectra were recorded with TMS as
(
3b). To a solution of 3a (1.07 g, 5.80 mmol) in THF
(21 ml) was successively added imidazole (905 mg,
13.3 mmol), triphenylphosphine (1.82 g, 6.90 mmol)
an internal standard in CDCl by a JEOL JNM-A500
3

Synthesis of (17
R
)- and (17
S
)-Volicitin
1593
and iodine (1.69 g, 6.60 mmol). After being stirred
for 30 min, the mixture was poured into water and
extracted with hexane. The organic layer was succes-
matographed over silica gel to give 133 mg (88
z
) of
„
1
5a. IR nmax cm : 3014 (m), 2932 (vs), 2860 (s), 1742
(vs), 1201 (s), 1172 (s), 1139 (s), 1122 (s), 1079 (s),
1
sively washed with water, 5
z
H
2
O
2
, water, 5
z
1035 (s), 984 (m), 870 (m), 725 (m). H-NMR
1.27–1.37 (6H, m, 4-H , 5-H , 6-H ), 1.47–1.55 (4H,
m, 7-H , 4 -H ), 1.55–1.65 (4H, m, 3-H , 5 -H ),
1.68–1.74 (1H, m, 3 -H), 1.79–1.87 (1H, m, 3 -H),
2.04 (2H, br q, 7.0 Hz, 8-H ), 2.30 (2H, t,
7.5 Hz, 2-H ), 2.38 (2H, br q, 7.0 Hz, 14-H ),
2.80 (2H, br t, 7.0 Hz, 11-H ), 3.42 (1H, dt,
9.5, 7.0 Hz, 15-H), 3.47–3.53 (1H, m, 6 -H), 3.66
(3H, s, OCH ), 3.74 (1H, dt, 9.5, 7.0 Hz, 15-H),
3.88 (1H, ddd, 11.2, 8.1, 3.4 Hz, 6 -H), 4.60 (1H,
dd, 4.2, 3.0 Hz, 2 -H), 5.33 (1H, br dt, 10.5,
7.0 Hz, 9-H), 5.38 (1H, br dt, 10.5, 7.0 Hz,
10-H), 5.39–5.46 (2H, m, 12-H, 13-H). C-NMR
d:
Na aq., water and brine, dried (MgSO
2
S
2
O
3
4
), and
2
2
2
concentrated in vacuo. The residue was triturated
with hexane-ether (1:1) and chromatographed over
silica gel (30 g, hexane-ethyl acetate, 3:1, containing
2
?
2
2
?
2
?
?
J
＝
2
1
z
triethylamine) to give 1.46 g (85
z
) of 3b. IR
n
max
J
＝
2
J
＝
2
„
1
cm : 2940 (s), 1175 (m), 1135 (s), 1120 (s), 1070 (s),
030 (s), 965 (m), 870 (m), 815 (m). H-NMR
J
＝
2
J
＝
1
1
1
1
2
d
2
:
?
.48–1.56 (2H, m, 4
.69–1.75 (1H, m, 3
.50 (2H, tt, 7.0, 2.5 Hz, 4-H
-H), 3.54 (1H, dt, 9.5, 7.0 Hz, 5-H), 3.69
2H, t, 2.5 Hz, 1-H ), 3.80 (1H, dt, 9.5,
.0 Hz, 5-H), 3.89 (1H, ddd, 11.2, 8.1, 3.4 Hz,
-H), 4.65 (1H, br t, 3.6 Hz, 2 -H). Anal
. Calcd. for C10 I: C,
?
?
-H
-H), 1.80–1.88 (1H, m, 3
), 3.49–3.54 (1H,
2
), 1.56–1.64 (2H, m, 5
?
?
-H
),
3
J
＝
-H),
J
＝
?
J
＝
2
J
＝
?
J
＝
m, 6
?
J
＝
J
＝
1
3
(
J
＝
2
J
＝
d:
7
J
＝
19.59, 24.93, 25.49, 25.74, 27.21, 27.99, 29.09,
29.11, 29.15, 29.55, 30.73, 34.10, 51.43, 62.30,
66.99, 98.76, 125.86, 127.74, 130.09, 130.29, 174.30.
6
?
J
＝
?
.
Found: C, 41.13; H, 5.14
1.16; H, 5.14
z
H
15
O
2
4
z
.
Anal. Found: C, 71.55; H, 10.04
: C, 71.55; H, 10.29
z
. Calcd. for
C
21
H
36
O
4
z
.
Methyl 15-[(tetrahydropyran-2-yl)oxy]-9,12-pen-
tadecadiynoate ). Cuprous iodide (0.291 g,
.53 mmol), tetrabutylammonium iodide (0.414 g,
.12 mmol) and sodium carbonate (0.205 g,
.93 mmol) were placed in a reaction vessel under a
nitrogen atmosphere. To the mixture were successive-
ly added a solution of 3b (0.300 g, 1.02 mmol) in
DMF (2 ml), a solution of 2 (0.204 g, 1.12 mmol) in
DMF (2 ml), and DMF (0.5 ml). After being stirred
for 17 h at room temperature, the mixture was
poured into water and extracted with ether. The
ethereal solution was successively washed with water
(
4
Methyl (9Z,12Z)-15-bromo-1,12-pentadecadieno-
1
1
1
ate (5b). To a stirred solution of triphenylphosphine
(214 mg, 0.816 mmol) in dichloromethane (2 ml)
was added 2,4,4,6-tetrabromo-2,5-cyclohexadienone
(0.314 g, 0.766 mmol) at 09C. After 2 h, a solution of
5a (100 mg, 0.284 mmol) in dichloromethane (1 ml)
was added, and the resulting mixture was stirred for
5 h at room temperature. The mixture was poured
into water and extracted with ether. The ethereal
solution was successively washed with water and
brine, dried (MgSO
4
), and concentrated in vacuo.
(
3 times) and brine (4 times), dried (K
2
CO ), and
3
The residue was chromatographed over silica gel
concentrated in vacuo. The residue was chro-
z
(hexane-ether, 2:1) to give 93.0 mg (99 ) of 5b. IR
„1
matographed over silica gel (40 g, hexane-ethyl
acetate, 10:1, containing 1
n
max cm : 3016 (m), 2930 (s), 2858 (s), 1742 (vs),
1
z
triethylamine) to give
1199 (s), 1174 (s), 725 (m). H-NMR
d
: 1.27–1.38
),
7.0 Hz,
), 2.65 (2H, br q,
), 2.79 (2H, br t, 7.2 Hz,
), 3.38 (2H, t, 7.2 Hz, 15-H ), 3.67 (3H, s,
), 5.32 (1H, ddt, 11.0, 7.0, 1.5 Hz, 10-H or
12-H), 5.36–5.43 (2H, m, 9-H, 13-H), 5.52 (1H, dtt,
11.0, 7.5, 1.5 Hz, 10-H or 12-H). Anal. Found:
C, 58.07; H, 8.00 . Calcd. for C16 Br: C,
58.01; H, 8.21
„1
0
2
1
.291 g (82
z
) of 4. IR
n
max cm : 2940 (s), 2855 (m),
(6H, m, 4-H
1.57–1.66 (2H, m, 3-H
8-H ), 2.30 (2H, t, 7.5 Hz, 2-H
7.2 Hz, 14-H
11-H
OCH
2
, 5-H
2
, 6-H
2
), 1.51–1.57 (2H, m, 7-H
2
1
210 (w), 1735 (vs), 1200 (s), 1035 (s). H-NMR
d
:
2
), 2.05 (2H, br q, J
＝
.29–1.40 (6H, m, 4-H
2
, 5-H
2
, 6-H
2
), 1.45–1.55 (4H,
, 5 -H ),
-H),
2
J
＝
2
m, 7-H
2
, 4
?
-H
2
), 1.55–1.65 (4H, m, 3-H
2
?
2
J
＝
2
J
＝
1
2
7
3
.68–1.74 (1H, m, 3
?
-H), 1.80–1.87 (1H, m, 3
?
2
J
＝
J
＝
2
.14 (2H, tt,
.5 Hz, 2-H
.11 (2H, qui,
J
＝
7.1, 2.4 Hz, 8-H
2
), 2.30 (2H, t,
J
＝
3
2
), 2.47 (2H, tt,
J
＝
7.0, 2.4 Hz, 14-H
), 3.48–3.53 (1H, m,
9.5, 7.0 Hz, 15-H), 3.67 (3H,
), 3.80 (1H, dt, 9.5, 7.0 Hz, 15-H), 3.88
11.2, 8.1, 3.4 Hz, 6 -H), 4.64 (1H, br t,
-H). Anal. Found: C, 72.31; H, 9.13
: C, 72.37; H, 9.26
2
),
J
＝
2.4 Hz, 11-H
2
J
＝
6
?-H), 3.54 (1H, dt,
J
＝
z
H
27
O
2
s, OCH
3
J
＝
z.
(
J
1H, ddd,
J
＝
?
?
＝
3.6 Hz, 2
z.
[(3Z,6Z)-14-Methoxycarbonyl-3,6-tetradecadienyl]
Calcd. for C21
H
32
O
4
z
.
triphenylphosphonium bromide (5c). A mixture of
5
b (1.03 g, 3.11 mmol) and triphenylphosphine
Methyl (9Z,12Z)-15-[(tetrahydropyran-2-yl)oxy]-
,12-pentadecadienoate (5a). A mixture of 4 (150 mg,
.431 mmol) and the Lindlar catalyst (22.4 mg) in
hexane (3 ml) was stirred for 10 min in an at-
mosphere of hydrogen. The mixture was ˆltered
through a Celite pad, and the ˆltrate was concentrat-
ed in vacuo. The residue was repeatedly chro-
(0.817 g, 3.11 mmol) in acetonitrile (11 ml) was
stirred at re‰ux for 120 h under a nitrogen at-
mosphere and then concentrated in vacuo. The
residue was dissolved in acetonitrile (2 ml), before
dry ether (10 ml) was added to the solution while stir-
ring to give a two-phase mixture. The supernatant so-
lution containing unreacted triphenylphosphine was
9
0

1
594
S. ITOH et al.
removed. This treatment was repeated 3 times, and
CHCl
3
). Anal. Found: C, 71.20; H, 10.80
z. Calcd.
1
the residue was concentrated in vauo to give 1.75 g
for C25
H
46
O
3
Si: C, 71.03; H, 10.97 . The IR, H-
z
„
1
13
(
95
z
) of 5c as a sticky oil. IR
n
max cm : 3056 (m),
and C-NMR spectra were identical with those of
3
012 (m), 2930 (s), 2858 (s), 1734 (s), 1589 (m), 1485
(R)-7a.
1
(
m), 1195 (s), 1114 (s), 748 (s), 721 (s), 694 (s). H-
NMR : 1.17–1.34 (6H, m, 4-H , 5-H , 6-H ),
), 1.87 (2H, br q,
7.5 Hz, 2-H
d
2
2
2
Determination of the enantiomeric excesses of (R)-
7a and (S)-7a Two milligrams (6.4 mol) of ( )-7c,
easily obtainable by treating ( )-7a with a 1 solu-
tion of tetrabutylammonium ‰uoride in THF, was
dissolved in pyridine (25 l), and ( )-MTPACl
(5.0 l, 27 mol) was added. The mixture was stirred
1
7
(
.48–1.64 (4H, m, 3-H
2
, 7-H
2
J
＝
.
m
R
M
.0 Hz, 8-H ), 2.30 (2H, t,
2
J
＝
2
), 2.48
R
2H, br q,
J
＝
7.0 Hz, 14-H
2
), 2.53 (2H, br t,
J
＝
7.5,
1
7
1
1-H
.5 Hz, 15-H
0-H), 5.31 (1H, br dt,
10.5, 8.0 Hz, 12-H), 5.60 (1H, br dt,
10.5, 7.0 Hz, 13-H), 7.70 (6H, td, 7.5, 3.4 Hz,
-H ), 7.78 (3H, tm, 7.5 Hz, -H ), 7.89 (6H, br
12.5, 7.5 Hz, -H ). This phosphonium salt
2
), 3.66 (3H, s, OCH
3
), 4.01 (2H dt,
J
＝
12.5,
m
S
2
), 5.15 (1H, br dt,
J
＝
10.5, 7.0 Hz,
m
m
J
＝
10.5, 8.0 Hz, 9-H), 5.37
for 12 h at room temperature, and then diluted with
ether. The ethereal solution was successively washed
(
1H, br dt, J
＝
＝
J
J
3
＝
with sat. CuSO
and concentrated in vacuo to give the (R
4
aq., water and brine, dried (MgSO
)-MTPA-
)-7c was treat-
)-MTPA-ester of
4
),
m
6
J
＝
o
p
dd,
J
＝
6
ester of (
ed with (
R
S
)-7c. In the same manner, (
)-MTPACl to give the (
S
was employed for the next step without further
puriˆcation.
R
1
(
S
)-7c. These MTPA-esters were analyzed by H-
NMR (500 MHz, CDCl ) without any puriˆcation. A
doublet signal due to the terminal methyl of the
MTPA-ester derived from )-7c appeared at
1.33 ppm ( 6.5 Hz), while in the NMR spectrum of
the MTPA-ester derived from ( )-7c, the doublet
was observed at 1.40 ppm ( 6.5 Hz). In each spec-
3
Methyl (9Z,12Z,15Z,17R)-17-[(tert-butyldimethyl-
silyl)oxy]-9,12,15-octadecatrienoate [(R)-7a]. To a
stirred solution of 5c (389 mg, 0.656 mmol) in THF-
HMPA (4:1, 4 ml) was added a solution of potassium
(
R
J
＝
S
hexamethyldisilazide (0.5
.660 mmol) at 0 C. After 1 h, the mixture was
cooled to „78 C, and a solution of ( )-6 (160 mg,
.851 mmol) in THF (1.6 ml) was added. The mix-
ture was stirred at „78 C for 10 min and then grad-
ually warmed to 0
poured into sat. NH
M
in toluene, 1.32 ml,
J
＝
0
9
trum, no doublet signal due to the terminal methyl
group of the diastereomer of the MTPA-ester was
observed. Therefore, both (
evaluated to be optically pure.
9
R
0
R)-7a and (S)-7a were
9
9
4
C over 2 h. The mixture was
Cl aq. and extracted with ether.
(9Z,12Z,15Z,17R)-17-[(tert-Butyldimethylsilyl)
The ethereal solution was successively washed with
oxy]-9,12,15-octadecatienoic acid [(R)-7b]. To a
water and brine, dried (MgSO
4
), and concentrated in
stirred mixture of (R)-7a (159 mg, 0.377 mmol) in
vacuo. The residue was repeatedly chromatoraphed
THF-water (9:7, 3.2 ml) was added lithium
hydroxide monohydrate (66.0 mg, 1.57 mmol). After
12 h, the reaction mixture was neutralized with a so-
lution of oxalic acid dihydrate (199 mg, 1.57 mmol)
in water (6 ml), and extracted with ether. The
ethereal solution was successively washed with water
over silica gel (30 g, benzene-hexane, 2:1) to give
2
4
1
69 mg (61
z
n
) of „(
R
)-7a, [
a
]
D
9
„20.7 (c 1.01,
＝
1
CHCl ). IR
3
max cm : 3018 (m), 2930 (vs), 2860 (s),
1
1
744 (s), 1087 (s), 835 (s), 777 (s). H-NMR
d
: 0.05
), 0.88 (9H, s,
6.2 Hz, 18-H ), 1.27–1.38
, 7-H ), 1.62 (2H, qui,
), 2.05 (2H, br q, 7.0 Hz, 8-H ), 2.30
7.5 Hz, 2-H ), 2.80 (2H, br t, 7.0 Hz,
), 2.81 (2H, br t, 7.0 Hz, 14-H ), 3.67 (3H,
), 4.63 (1H, dqd, 8.2, 6.2, 1.3 Hz, 17-H),
.25 (1H, dtd, 11.0, 7.5, 1.3 Hz, 15-H), 5.30–5.46
5H, m, 9-H, 10-H, 12-H, 13-H, 16-H). C-NMR
4.70, „4.48, 18.25, 24.83, 25.00, 25.68, 25.93,
(
t
(
3H, s, SiCH
-Bu), 1.19 (3H, d,
8H, m, 4-H , 5-H , 6-H
.5 Hz, 3-H
2H, t,
3
), 0.06 (3H, s, SiCH
3
J
＝
3
and brine, dried (MgSO
cuo. The residue was chromatographed over silica gel
z
(10 g, hexane-ethyl acetate, 1:1) to give 151 mg (98 )
4
), and concentrated in va-
2
2
2
2
J
＝
7
2
J
＝
2
2
4
(
1
J
＝
2
J
＝
of (
R
)-7b, [
a
]
D
„21.0
9(c
＝
1.01, CHCl
3
) IR
n
max
„
1
1-H
2
J
＝
2
cm : 3018 (m), ¿3000 (br), 2930 (vs), 2860 (s), 2660
s, OCH
5
3
J
＝
(w), 1713 (vs), 1464 (m), 1367 (w), 1253 (m), 1129
1
J
＝
(m), 1087 (s), 1006 (m), 872 (m), 835 (s), 777 (m). H-
1
3
(
d
:
NMR
0.88 (9H, s,
1.28–1.39 (8H, m, 4-H
qui, 7.5 Hz, 3-H ), 2.05 (2H, br q,
), 2.34 (2H, t, 7.5 Hz, 2-H ), 2.80 (2H, br t,
7.0 Hz, 11-H ), 2.81 (2H, br t, 7.0 Hz,
4-H ), 4.63 (1H, br qui, 7.0 Hz, 17-H), 5.25
11.0, 7.5 Hz, 15-H), 5.30–5.46 (5H,
d
: 0.05 (3H, s, SiCH
-Bu), 1.19 (3H, d,
, 5-H , 6-H
3
), 0.06 (3H, s, SiCH
6.2 Hz, 18-H
, 7-H
3
),
),
„
t
J
＝
2
3
2
6
1
5.97, 27.29, 29.18, 29.22, 29.62, 34.17, 51.53,
5.19, 126.13, 127.76, 127.88, 128.90, 130.65,
2
2
2
), 1.64 (2H,
7.0 Hz,
J
＝
2
J
＝
35.91, 174.56. Anal. Found: C, 71.23; H, 10.81
Si: C, 71.03; H, 10.97
z.
8-H
2
J
＝
2
Calcd. for C25
H
46
O
3
z
.
J
＝
2
J
＝
1
2
J
＝
Methyl (9Z,12Z,15Z,17S)-17-(tert-butyldimethyl-
silyloxy)-9,12,15-octadecatrienoate [(S)-7a]. In the
same manner as that described for the preparation of
(1H, br dt,
J
＝
m, 9-H, 10-H, 12-H, 13-H, 16-H). Anal. Found: C,
70.58; H, 10.60 . Calcd. for C24 Si: C, 70.53;
H, 10.85
z
H
44
O
3
(
R
)-7a, 5c (396 mg, 0.668 mmol) was allowed to
react with aldehyde ( )-6 (147 mg, 0.781 mmol) to
give 144 mg (51 ) of (
z
.
S
S
2
4
z
)-7a, [
a
]
D
+18.1
9
(
c
＝
1.01,
(9Z,12Z,15Z,17S)-17-(tert-Butyldimethylsilyl)oxy-

Synthesis of (17
R
)- and (17
S
)-Volicitin
1595
9
,12,15-octadecatienoic acid [(S)-7b]. In the same
manner as that described for the preparation of ( )-
)-7a (136 mg, 0.320 mmol) was converted into
26.79, 26.86, 28.18, 28.71, 30.23, 30.28, 30.34,
30.71, 32.82, 36.89, 53.51, 64.39, 128.69 (probably
two overlapping peaks), 129.18, 129.66, 131.23,
135.43, 175.36, 176.35, 177.80.
R
7
0
1
b, (
S
2
4
.131 mg (quantitative) of (
S
)-7b, [
) Its IR and H-NMR spectra were identi-
)-7b. Anal. Found: C, 70.56; H,
a
]
D
+18.69(c
＝
1
.07, CHCl
3
cal with those of (
1
1
R
N-[(S)-17-Hydroxylinolenoyl]-L-glutamine [(17S)-
1a, volicitin]. In the same manner as that described
0.62
0.85
z
z
. Calcd. for C24
.
H
44
O
3
Si: C, 70.53; H,
for the preparation of (17
R
)-1a, (
S
)-7b (68.0 mg,
0
.160 mmol) was converted into 99.4 mg of crude
N - [(R) - 17 - Hydroxylinolenoyl] - L - glutamine
(17R)-1a]. To a stirred solution of ( )-7b (139 mg,
l, 0.409 mmol)
l,
C. After being stirred for 2 h at the
(17
S
)-1b, a portion (97.0 mg) of which was then
in two steps) of
+6.6 0.80,
[
R
m
transformed into 31.7 mg (46
z
2
1
0
.341 mmol) and triethylamine (57.0
(17
S
)-1a, mp 54–61
9
C,
[a
]
D
9 (c
＝
1
13
in THF (2.4 ml) was added pivaloyl chloride (45.6
0
m
methanol). The IR, H- and C-NMR spectra of
.370 mmol) at 0
9
(17S)-1a were indistinguishable from those of (17R)-
same temperature, the mixture was quickly ˆltered
and the ˆlter cake was washed with THF (2.5 ml).
The combined ˆltrate and washings containing mixed
anhydride 7e were diluted with 1,4-dioxane (2.2 ml)
and used as the acylating agent in the next operation.
1a.
Acknowledgments
We are grateful to Dr. Pohnert of Max-Planck-
Institute fur Chemische Okologie for providing the
Meanwhile, to a stirred solution of
L
-glutamine
ä
Ä
(
99.4 mg, 0.680 mmol) in water (0.8 ml) was added
NMR spectra. This work was supported, in part, by
grant-aid for scientiˆc research (C) from the Ministry
of Education, Science, Sports and Culture of Japan
(No. 13660103).
triethylamine (95.0
m
l, 0.682 mmol) at room temper-
ature, and the mixture was stirred for 2 h. To the
resulting solution was added the solution of (
prepared as already described at room temperature.
After 20 min, triethylamine (48.0 l, 0.344 mmol)
was added again to the mixture, and stirring was con-
tinued for 4 h at room temperature. The mixture was
adjusted to pH 3 with dil. HCl aq., poured into water
and extracted with dichloromethane. The organic
R)-7e
m
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2
)
)
Alborn, H. T., Turlings, T. C. J., Jones, T. H.,
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R
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1
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.90, methanol). H-NMR (in CD
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7.0 Hz, 8 -H ), 2.12–2.20 (1H, m, 3-H), 2.24
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.82 (2H, t,
-H ), 4.38 (1H, dd,
R
)-1a, mp 86.5–88.0
9
C, [
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a
]
D
„3.9
9
(
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＝
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0
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＝
7
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Blanchette, M. A., Malamas, M. S., Nantz, M. H.,
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?
2
?
2
(
?
2
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＝
?
2
(
J
＝
?
-H
2
), 2.27–2.35 (2H, m, 4-H
2
),
), 2.85–2.90 (2H, m,
9.0, 5.0 Hz, 2-H), 4.62
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2
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1
J
＝
6.0 Hz, 11
?-H
2
8
)
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2
J
＝
(
1H, dq, J 7.0, 6.4 Hz, 17?
＝
13
3
C
D
3
d
＝
4
d

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1
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