Phytochemistry, Vol. 30, No. 10,pp.

3327-3333, 1991
Printedin Great Britain.

0031-9422/91
$3.00+0.00
0 1991Papmon Pressplc

POLYACETYLENES FROM THE ROOTS OF PANAX GINSENG

KAZUHIRO HIRAKURA, MAKOTO MORITA, KAORU NAKAJIMA, YUKINOBU IKEYA

and HIROSHI MITSUHASHI

Research Institute for Biology and Chemistry, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki, Japan
(Received in reuised form 22 January
Key Word Index-Panax
oyne D; ginsenoyne E.

1991)

ginseng; Araliaceae; polyacetylene; ginsenoyne A; ginsenoyne B, ginsznoyne C; ginsen-

Abstract-Five

new polyacetylenes named ginsenoynes A, B, C, D and E were isolated from the hexane extract of the
root of Panax ginseng. These structures were determined by spectral and chemical methods.

INTRODUCTION

Panax ginseng C. A. Meyer is one of the most important

oriental medicinal plants, its many uses including psychiatric and neurologic and diabetes mellitus treatment Cl],
in Japan, Korea and China. Many saponins having
pharmacological properties [3], such as ginsenosides
Rg,, Rbi [2], have been reported from polar fractions.
Recently, the less polar components such as panaxynol
[4-6], panaxydol (6) [A, panaxydol chlorohydrine (7)
[a]. and panaxytriol (8) [9], have been reported to be
cytotoxic against L1210 [l&13]. We report five new
polyacetylenes from this plant, whose structures were
elucidated by spectral and chemical methods.

RESULTS AND DISCUSSION

The hexane extract was successively chromatographed

on a silica gel column to afford ginsenoynes A (l), B (Z), C
(3), D (4), E (5), along with four known polyacetylenes,
panaxynol, panaxydol (6), panaxydol chlorohydrine (7)
and panaxytriol (8).
Ginsenoyne E (5) [ 14,151 was obtained as a pale yellow
oil, which showed [@In -82.9. The UV spectrum of 5
exhibited Iz,, at 208, 261, 276 and 292 nm, and was
similar to that of panaxynone (falcarinone) (9) [16]. The

IR spectrum of 5 showed the presence of conjugated triple

bonds (2236cm-I),
a conjugated
carbonyl group
(1644 cm-), and conjugated double bonds (1612 cm-).
The molecular formula of 5 was determined to be
C,,H,,Oz
by HR-EIMS. The r3C NMR spectrum indicated the presence of 17 carbons: one carbonyl and one
methyl carbon, two oxygen-bearing methine and two
olefmic carbons, four conjugated acetylenic carbons, and
seven methylene carbons (Table 1). The HNMR spectrum of 5 showed signals as follows: 66.58 (lH, dd, J = 1.5
and 17 Hz), 6.41 (lH, dd, J = 9.7 and 17 Hz) and 6.23 (lH,
dd, J= 1.5 and 9.7 Hz) [vinyl protons], 3.19 (lH, ddd, .I
=6.6, 5.6 and 4.0Hz), and 2.98 (lH, br dt, 5=6 and
4.0 Hz) [epoxy protons of &-configuration], 2.77 (lH, dd,
J= 17.8 and 5.6 Hz), 2.51 (lH, dd, J= 17.8 and 6.6 Hz)
[methylene protons between a triple bond and an epoxide], 1.42-1.58 and 1.10-1.40 [12 methylene protons],
and 0.88 (3H, br t, J = 7 Hz) [terminal methyl protons]
(Table 2). On oxidation with activated MnO, [16], 6
afforded the corresponding carbonyl compound 5. On
the basis of the above results, ginsenoyne E is 9,1O-epoxy1-heptadecene-4,6-diyn-3-one
(5).
Ginsenoyne A (1) was obtained as an oil, which showed
[a]n -121.9. The UV spectrum of 1 showed typical
absorption bands for a diyne [17] chromophore (&,,,., at
201,230,243 and 250 nm). The IR spectrum of 1 showed

Haa

11 12 13 14 15

HC~=SHEHt.ESSr~-C_~~-~H-~H,~HICHICHI~~

Hlb

IL

R
R
1

2
2a

OH
OH
OAc

R*

R=

L
R
/

?H=C\

-o-

CH-CH,
CH=CH,
CH=CHI
CH=CH2

Cl
Ck
OH
OAc

OH
OAc
OH
OAc

12

1-R4

OH

3a
3b

OAc

6
7

OH
OH

OH

CL

CH2Me

OH

OH

OH

CH*Me

OH

--O-C(Me),--O-

CH=CH2
CH,Me

-o-

3321

HIlP
HI 7b

3328

-o-

10

OH

RZ
OH

the presence of a hydroxy group (br 3436 cm-), triple

bonds (2256 cm- ), and double bonds (1640 cm- ). The
molecular formula of 1 was determined to be C,,H,,O1
by HR-CIMS.
The HNMR spectrum of 1 was similar to that of 6,
except for the C-15-C-17 protons, and showed that the

Table 1. 13C

C-15-C-17 moiety of 1 is an ally1 group [5.81(1H, ddt, J

=17.1, 10.2 and 6.7 Hz), 4.94 (lH, ddt, J= 10.2, 2.1 and
1.5 Hz), 5.01 (lH, ddt, J= 17.1,2.1 and 1.5 Hz)] (Tables 2
and 3). This was also supported by the i3CNMR spectrum of 1 (Table 1). These spectral data suggested that 1
corresponded to a C-16, 17 unsaturated panaxydol.
Oxidation of 1 with activated MnO, gave a yellow oil
(la).
The IR spectrum of la showed the presence of
conjugated triple bonds (2 156 cm - ), a conjugated
carbonyl group (1644cm-), and conjugated double
bonds (1612 cm-). The UV spectrum of la showed A,,,,,
at 209,249 (in@, 261,275 and 291 nm, indicating that the
chromophore of la is similar to that of 5. These results
suggested that 1 has a 1-hepten-4,6-diyn-3-01 moiety.

NMR spectral data for compounds 14 (6 in CDCI,)

1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17

116.9
136.3
63.3
75.4
70.6
66.5
76.5
19.4
54.4
57.0
27.4
26.3
28.9
28.7
33.6
138.9
114.4

117.2
136.0
63.5
15.0
70.8
66.7
*

117.2
136.1
63.5
74.8
70.9
66.5
78.1
25.0
72.2
73.1
33.5
25.4
28.8
29.0
33.7
139.0
114.4

9.3
30.7
64.0
77.5
69.5
66.5
76.0
19.4
54.4
57.0
27.5
26.5
29.4
29.2
31.8
22.6
14.1

134.2
137.7
177.5
84.5
71.0
65.6
76.4
19.8
53.8
56.9
27.5
26.4
29.4
29.1
31.7
22.6
14.1

116.9
136.2
63.4
75.2
70.7
66.4
76.6
19.5
54.4
57.1
27.5
26.5
29.4
29.2
31.7
22.6
14.1

117.2
136.0
63.5
75.0
70.9
66.7
76.8
25.8
72.1
66.8
34.8
26.7
29.1
29.0
31.8
22.6
14.1

117.2
136.1
63.5
74.8
70.9
66.5
78.2
25.6
72.2
73.1
33.6
25.0
29.6
29.2
31.8
22.7
14.1

25.8
72.1
66.7
34.8
26.5
28.7
28.5
33.6
138.9
114.5

Signal assignments were based on 13C-lH COSY and DEPT experiments.

Assignments may be interchanged in each column.
*This signal was overlapping with the solvent signals.

Polyacetylenes from Panaxginseng

On the other hand, the partial structure of 1 (C-IO-C17) was determinated as follows. Treatment of 1 with
dilute H,SO, gave the glycol(3), which was oxidized with
NaIO,. The reaction products were reduced by NaBH,
to give two alcohols. One of them was identified as 7octen-l-01 (14) compared with the authentic sample by
GC-MS analysis [18]. The authentic sample was synthesized from 1,8-nonadiene (11) (Scheme 1). The connection of C-8-C-17 was determined by the H-H COSY
spectrum. The irradiation of H-3 (64.90 lH, br d, J
= 5.4 Hz) decoupled the long range coupling between
H-3 and H-8 (7J= 1.0 Hz) [19]. From the above results,
ginsenoyne A is 9,10-epoxy-1,16-heptadecadiene-4,6diyn-3-01 (1).
Ginsenoyne B (2) was obtained as an oil, which showed
[cl]n -33.0. The UV spectrum of 2 showed typical
absorption bands for a diyne chromophore (&,,,, at 201,
230,243 and 257 nm). The IR spectrum of 2 showed the
presence of a hydroxy group (br 3450 cm-), triple bonds
(2256cm-), and double bonds (1640cm-). The CI
mass spectrum of 2 showed a quasimolecular ion at m/z
297 and 295, and its spectral peaks gave a characteristic
pattern for the presence of a chlorine atom in the
molecule. The molecular formula of 2 was determined to
be C,,H,,O,Cl
by HR-CIMS. On acetylation of 2 with
Ac,O, it gave a diacetate (2a m/z 381, 379 [M + HI+).
Except for the C-15-C-17 moiety, the H NMR spectrum
of 2 was similar to that of 7 which is a chlorohydrine
derivative (Tables 2 and 3). The H and 13C NMR spectra
showed that 2 is the C-16, 17 dehydro derivative of 7

- -7
OH

(Table 1). Finally, the structure of 2 was determined by

chemical correlation with 1, as follows.
Treatment of 1 with HCl gave 2 [8]. From the above
results, ginsenoyne B is lO-chloro-1,16_heptadecadiene4,6-diyne-3,9-diol (2).
Ginsenoyne C (3) was obtained as an amorphous
powder, which showed [r]n - 16.5. The UV spectrum of
3 showed typical absorption bands for a diyne chromophore (L,, at 201,231,243 and 257 nm). The IR spectrum
of 3 showed the presence of hydroxy groups (br
3350 cm- ), triple bonds (2260 cn- ), and double bonds
(1644 cm- ). The molecular formula was determined to
be C,,Hz403 by HR-CIMS. On acetylation of 3 with
acetic anhydride, it gave a triacetate (3a m/z 403 [M
+ H] ), and treatment of 3 with 2,2_dimethoxypropane
gave the acetonide (3b m/z 317 [M +H]+). The H and
r3C NMR spectra of 3 were assigned by comparison with
those of 8 (Tables l-3). The structure of 3 was easily
derived from the connectivities of carbon and hydrogen
atoms established by H-l H and 3C-1 H COSY spectra.
Finally, the structure of 3 was confirmed by chemical
correlation with compound 1, as treatment of 1 with
dilute H,SO, gave 3. From the above results, ginsenoyne
C is 1,16-heptadecadiene-4,6-diyne-3,9,10-trio1
(3).
Ginsenoyne D (4) was obtained as an oil, which showed
[cl]n -90.7. The UV spectrum of 4 showed typical
absorption bands for a diyne chromophore (L,,, at 200,
230,241 and 255 nm). The IR spectrum of 4 showed the
presence of a hydroxy group (br 3350 cn- ) and triple
bonds (2256 cm- ).

-TP---

w-z
--

3329

11

osoe

dil.H2S04

=y+

HO
HO

12

NalO.,

NalO,

OHC-

NaBH4
HO

14
CC-MS

Scheme 1. Synthesis of compound 14.

3330

K. HIRAKURAet al.
Table 2. IH NMR spectral data for compounds l-5 (6 in CDCI,)

la
lb
2
3
8a
8b
9
10
11
12
13
14
15

5.23 ddd
(10.3, 1.5, 1.0)
5.45 ddd
(17.0, 1.5, 1.0)
5.93 ddd
(17.0, 10.3, 5.4)
4.90 hr d
(5.4)
2.38 ddd
(17.7, 7.2, 1.0)
2.71 ddd
(17.7, 5.5, 1.0)
3.15 ddd
(7.2, 5.5, 4.1)
2.98 br td
(6, 4.1)

17a
17b
OH-3
OH-9
OH-10

4.13 In
1.80-1.84 m
1.28-1.50 m
1.52-1.60 m

2.06 br qt
(6, 1.5)

16

5.26 dt
(10.2, 1.0)
5.47 ddd
(17.0, 1.5, 1.0)
5.94 ddd
(17.0, 10.2, 5.4)
4.92 br d
(5)
2.67 ddd
(17.5, 6.6, 1.0)
2.64 ddd
(17.5, 6.4, 1.0)
3.86 br

5.81 ddt
(17.1, 10.2, 6.7)
4.94 ddt
(10.2, 2.1, 1.5)
5.01 ddt
(17.1, 2.1, 1.5)
3.11 br

6.23 dd
(9.7, 1.5)
6.58 dd

5.25 ddd
(10.4, 1.4, 1.0)
5.47 ddd
(17.1, 1.4, 1.0)
5.94 ddd
(17.1, 10.4, 5.4)
4.92 br d
(5.4)
2.54 ddd
(17.4, 6.6, 1.0)
2.60 ddd
(17.4, 5.7, 1.0)
3.64 ddd
(6.6, 5.7, 4.3)
3.59 ddd
(6.7, 5.1, 4.3)
1.45-1.55 m

2.06 br qt
(6.5, 1.4)
5.81 ddt
(17.0, 10.3, 6.7)
4.95 ddt
(10.3, 2.2, 1.4)
5.00 ddt
(17.0, 2.2, 1.4)
2.21 br
1.64 br

1.30-1.45 m
2.06 br qt
(7, 1.4)
5.81 ddt
(17.1, 10.3, 6.7)
4.94 ddt
(10.3, 2.1, 1.5)
5.00 ddt
(17.1, 2.1, 1.5)
1.71 br
2.20 br
2.35 br

(17, 1.5)
6.41 dd
(17, 9.7)

1.69-1.80 m
4.35 br t
(6)

2.38 ddd
(17.7, 7.2, 1.0)
2.70 ddd
(17.7, 5.4, 1.0)
3.15 ddd
(7.2, 5.4, 4.1)
2.97 br td
(6, 4.1)
1.43-1.54 m

2.51 dd
(17.8, 6.6)
2.77 dd
(17.8, 5.6)
3.19 ddd
(6.6, 5.6, 4.0)
2.98 br td
(6, 4.0)
1.42-1.58 m

1.25-1.40 m

1.10-1.40 m

0.89 br t
(7)

0.88 br t
(7)

2.17 br

I_
-

Coupling constants (J) in Hz are given in parentheses.

Signal assignments were based on H-H COSY and spin decoupling experiments.

The molecular formula was determined

to be
C1,Hz602 by HR-CIMS. The HNMR spectrum of 4
gave the following signals: 6 3.15 (lH, ddd, J = 7.2,5.4 and
4.1 Hz) and 2.97 (lH, br td, J = 6 and 4.1 Hz) [epoxy
protons of cis-configuration], 2.17 (lH, br) [a hydroxy
proton], 4.35 (lH, br E, J=6 Hz), 1.69-1.80 (2H, m), and
1.01 (3H, t, J=7.4 Hz) [oxypropyl protons], 1.43-1.54
and 1.25-1.40 [12 methylene protons], 0.89 (3H, br t,
J=7 Hz) [terminal methyl protons] (Table 2). The
13C NMR spectrum of 4 indicated 17 carbons: one oxymethine carbon, two oxygen-bearing methine, two methyl
carbons, four conjugated acetylenic carbons and eight
methylene carbons (Table 1). These NMR spectral data
suggested that 4 corresponds to the dihydro derivative of
6. Treatment of 4 with dilute H,SO, [20] gave an
amorphous powder which was confirmed as the known
dihydropanaxacol (10) by comparison with the known
spectral data. From the above results, ginsenoyne D is
9,10-epoxy-4,6-heptadecadiyn-3-01
(4).
EXPERIMENTAL
The H and 13CNMR spectra were taken with 400,200 and
500 MHz instruments and measured in CDCI,. For the NMR
data, chemical shifts are expressed in S ppm from tetramethylsil-

ane as int. standard and coupling constants (J) are given in Hz.
Silica gel (Merck 70-230 mesh) was used for CC and silica gel 60
F 2s4r0.25 mm, was used for TLC. Prep. HPLC employed a CIG
221#~
x 100 mm or 50#1x 500 mm column system (Kusano Scientific Co., Tokyo) and the stationary phase used was silica gel
(50 q). Prep. reversed phase HPLC used 204 x 300 mm packed
column YMC S-343 (Yamamura Chemical Laboratories, Co.,
Ltd, Kyoto).
Isolation of compounds. The dried and crushed drug 14 kg was
extracted x 5 by refluxing with hexane (200 1).The hexane soln
was coned under red. pres. to give a hexane extract of 140 g. The
hexane extract was chromatographed on a silica gel (4 kg)
column, eluted by use of hexane, hexane-EtOAc, EtOAc,
MeOH. The eluates were divided into 7 portions: F-l (5.5 g,
hexane), F-2 (71 g, hexane_EtOAc,
9: l), F-3 (log,
hexane-EtOAc, 4: l), F-4 (25 g, hexane-EtOAc, 7:3), F-5 (5 g,
hexane_EtOAc, 1: l), F-6 (5 g, EtOAc), F-7 (5 & MeOH).
F-4 was separated on prep. HPLC with hexane-EtOAc (7:3)
to give 4 frs (F-4-l to F-4-4). F-4-3 was rechromatographed on
prep. HPLC with hexane-Me&O (5: 1) to give ginsenoynes A (1)
(180 mg), D (4) (100 mg), E (5) (100 mg) and panaxydol(6) (5 g).
F-5 was rechromatographed
on prep. HPLC
with
hexane_EtOAc (7: 3), CHCI-MeOH
(100: 1) successively and
then on prep. reversed phase HPLC, eluted with MeOH-H,O
(4: 1) to give ginsenoyne B (2) (22 mg) and panaxydol chloro-

3331

Polyacetylenes from Panax ginseng

Table 3. H NMR spectral data for compounds 6-S (6 in CDCI,)
H

la

5.24 ddd
(10.1, 1.5, 1.0)
5.46 ddd
(17.1, 1.5, 1.0)
5.94 ddd
(17.1, 10.1, 5.4)
4.92 br (5)
2.39 ddd
(17.7, 7.1, 1.0)
2.70 ddd
(17.7, 5.4, 1.0)
3.15 ddd
(7.1, 5.5, 4.1)
2.97 br td

5.26 ddd
(10.5, 1.5, 1.0)
5.47 ddd
(17.1, 1.5, 1.0)
5.94 ddd
(17.f, 10.5, 5.4)
4.92 br t (5)
2.67 ddd
(17.3, 6.5, 1.0)
2.64 ddd
(17.3, 6.4, 1.0)
3.86 dtd
(8.3, 6.5, 3.0)
4.13 m

5.26 ddd
(10.1, 1.4, 1.0)
5.47 ddd
(17.1, 1.4, 1.0)
5.94 ddd
(17.1, 10.1, 5.4)
4.92 br d (5)
2.56 ddd
(17.3, 6.6, 1.0)
2.61 ddd
(17.3, 5.7, 1.0)
3.65 br td
(6.2, 4.1)
3.59 br td

lb
2
3
8a
8b
9
10

V44.1)

11
12
13
14
15
16
17a
17b
OH-3

(6,4)

1.78-1.85 m
1.43, 1.54 (each m)

1.50 m
1.54 m

1.23-1.36 m

1.20-1.48 m

0.89 b t (7)

0.89 br t (7)

1 0.89 br t (7)

2.71 br

1.45-1.55 m

1.25-1.40 m

OH-9

205 d (6.5)
220 d (8.3)

OH-10

2.14 br
2.22 br
2.50 br

Coupling constants (J) in Hz are given in parentheses.

Signal assignments were based on IH-H COSY and spin decoupling experiments,

hydrine (7) (19Omg). F-6 was rechromatographed on prep.

HPLC with hexane-Me&O
(3: 1), CHCl,-MeOH (25: 1) and
hexane-Me&O
(5 :2), successively to give ginsenoyne C (3)
(16 mg) and panaxytriol (8) (200 mg).
Gi~enoy~
E (5). Pale yellow oil. [aID -829 (CHCl,; c 0.8).
IR vE;ls cm- : 2236 (0,
1644 (C=O), 1612 (C-=X). UV
J-i%:nm (loge): 208 (4.12X 261 (3.67), 276 (3.84), 292 (3.&o),
FDMS m/z: 259 fM + H] +. EIMS 20 eV, m/z (rel. int.): 258 [M]
(2.8); HR-EIMS m/z 258.1623 (Calcd for C1,H2r02 CM]:
258.1620).
Formation ofcompound
Sfiom compound 6. Activated MnOz
was added to the sofn of 6 (20 mg) in CH,Cl, and the mixt. was
stirred at 0 for 40 min. The reaction mixt. was filtered and the
residue was washed with CH,Cl, and Me&O. The filtrate was
coned under red. pres. The residue was purified by prep. HPLC,
eluted with hexane-EtOAc (5: 1) to give a pale yellow oil (7.5 mg)
which was identified as 5 by the physical data.
Ghenoyne
A (1). Oil. [a&, -121.9
(CHCls c 1.0).
IR vcHc13
max cm-: 3436 (br OH), 2256 (CkC), 1640 (C==C).
UV ,%EzHnm (loge): 201 (3.821,230 (2.80), 243 (2.761,256 (2.54).
FDMS m/z: 259 [M+H]+. CIMS @o-butane) 2OeV, m/z (rel.
int.): 259 w f HJ+ (22), 241 [M + H - Hz01 + (31). HR-CIMS
m/z 259.1702. (Calcd for C1rHz302 [M+H)+:
259.1699),
H NMR see Table 2. r3C NMR see Table 1.
Oxidation ofcompound 1 by activated MnO,. Activated MnOs
(160 mg) was added to the soln of 1 (29 mg) in CH,Cl, (15 ml)
and the mixt. was stirred at 0C for 10 min. The reaction mixt.
was treated by the above method, and purified by prep. HPLC,
eluted with hexane-Me&O (18: 1) to give a pale yellow oil la
cm-i: 2928,2236
(20 mg). MD -78.6 (CHCI,; c 1.6). IR vz

(CkC), 2156 (C=C), 1644 (C=O), 1612 (CkC), 1402, 980.

UVnLyr nm (logs): 209 (4.12), 249 (infl. 3.60), 261 (3.651, 275
(3.83), 291(3.78). H NMR (500 MHz): 6 1.35-1.45 and 1.50-1.56
(each4H, m, H-11-H-14), 2.06(2H,brqt,J=1.5and
7 Hz, H-15),
2.50 (lH, dd, 5=7 and 18H2, H-8a), 2.77 (lH, dd, 5=6 and
18H~H-gbA2.99(lH,~H-lO),3.l$(lH,~,~=4,6and7~
H-9), 4.94 (lH, ddt, J= 1.5,2 and 10 Hz, H-17a), 5.00 (lH, ddt,J
=1.5,2and17Hz,H-17b),5.81(1H,ddt,J=7,10and17Hz,H16), 6.22 (lH, dd, J=O.7 and 10 Hz, H-la), 6.41 (lH, dd, J= 10
and 17H2, H-2), 6.55 (lH, dd, J=O.7 and 17 Hz, H-lb).
i3CNMR (125 MHz): 619.9 (t, C-8), 26.3, 27.5, 28.8 and 28.9
(each t, C-11-C-14), 33.6 (t, C-15), 53.9 (d, C-9), 56.9 (d, C-lo),
65.7,71.1,76.4and 84.5(each s,C4C-7), 114.5(t,C-17), 134.3(t,
C-l), 137.8 (dl C-16), 138.8 (d, C-2), 177.6 (s, C-3). EIMS 20 eV,
m/z (rel. ink): 256 [MI+ (131, 131 (32). HR-CIMS m/z 257.1528
(Calcd for C,,H,,O,
[M-t-H]+: 257.1540).
Gimrenoyrze 23 (2). Oil. [orlo -33.0 (CHC13; c 2.0).
IRv~c13m-.
3450 (br OH), 2256 (CzC), 1640 (C==CJ
UVTip nm (kg+ 201 (3.8% 230 (2.86), 243 (2.801,257 (2.55).
CIMS @o-butane) 20 eV, m/z (rel. int.): 297 (9), 295 (21) [each M
+ H] +, 279 (33), 277 (68) [each M + H - HaO]+, 223 (70), 93
(lOOk HR-CIMS m/z 295.1473 (Calcd for C1,Hz40a 35Cl [M
i-H]+: 295.1465). iHNMR see Table 2. i3CNMR see Table 1.
Ginsenoyne B diacetate (ti). The mixt, of 2 (22 mg), Ac,O
(20 &, Et,N (15 ,ul) and 4-dimethylaminopyridine
(catalytic
amount) in CH,Cl, (4 ml) was stirred at room temp. for 30 min.
The reaction mixt. was treated as usual, and purified by prep.
HPLC, eluted with hexane-Me&O
(10: 1) to give an oil (2%
23 mg). [aft, + 32.8 (CHCI,; c2.04), IR yzJ3 cm-r: 2260
(C=C), 1742 (C=O), 1640 (C=C). UVnEay nm (loge): 200 (3.94),

3332

K.

HIRAKURA

et at.

220 (2.93).232 (2.95),244 (2.92), 2.57 (2.72).CIMS (iso-butane)

hexane-Me,CO
(5: 1) to give an oil 3b (13 mg). [aIn
20 eV, m/z(rel. intf: 381 (S), 379(20) [each M+H]+, 321(27), 319 -21.2 (CHCI,; c 1.26).IR vzzu cm- : 34OOJbrOH), 2936.2256
(34) [each M + H - HOAc] +, 279 (ll), 277 (25), 261 (40), 259 (85) (C=C), 1640 (C=C), 1374, 984, 914. UVizEn nm (logs): 200
[each M+H-2HOAc]+,
223 (85). iHNMR (5OOMHz): (4.04), 229 (3.05),242 (2.92), 257 (2.74). CIMS (rso-butane) 20 eV,
61.27-1.47 and 1.52-1.61 (6H, m, H-12-H-14), 1.66-1.75 (2H, m, m/.z(rel. int.): 317 [M-i-H] (24), 301(24), 241 LM +H-Me&O
H-11), 2.10 and 2.12 (each 3H, s, AC), 2.06 (2H, br q, J=6Hz,
-H,OJ+ (32), 223 [M+H-MelCO-2H,O]+
(17), 197 (100).
H-15), 2.70 (lH, ddd, J=O.9, 6.0 and 17.3 Hz, H-8b), 2.78 (IH,
H NMR (500 MHz): S 1.32-1.45 and 1.47-1.65 (8H, m, H-l t--Hddd,J=O.9,7.1 and 17.3H~H-8a),4.13~lH,~H-lO),4.94~lH,
14), l.~(6H,s,~em-methyl),
1.97(1H, hrd, J=6 Hz. OH-3),2.06
ddt,J=1.2,2.1andlO.l
Hz,H-17a),5.00(1H,ddt,J=l.5,2.1and
(2H,brqt,J=lSand7
Hz,H-15),2.61 (2H,dd,J=O.gandSHz,
17.1 Hz, H-17b), 5.11 (lH,ddd, J=3.3,6.Oand 7.1 Hz, H-9}, 5.34 H-8), 3.72 (iH, td, J=5 and 7 Hz, H-9), 3.80 (1H. td, J=4 and
7 H~H-l~),4.92(lH,br,H-3),4.94(iH,ddr,
J= lS,2and 10 Hz,
(lH, d-like, J-lOHz,
H-la), 5.53 (lH, d-like, J=17 Hz, H-lb),
5.8O(lH,ddt,J=6.6,
10.1 and 17.1 Hz, H-16),5.84-590(1H. m, H-17a),5.OO(lH,ddt,J=i.5,2and
17Hz,H-17b),5,25(1H,ddd,
H-2), 5.90 (lH, br d, J=6 Hz, H-3). i3CNMR (125 MHz): 620.8 J=1,1.5and1OHz,H-la),5.46(lH,ddd,J=1,1.5andl7Hz,Hand 20.9 (each q. AC), 22.7 (t. C-8), 26.3, 28.5 and 28.6 (each t, lb), 5.81 (iH, ddt, J=6.6, 10 and 17 Hz, H-16). 5.94 (lH, ddd. J
C-12-C-14), 33.6(t, C-15), 34.4(&C-11), 62.3 (d,C-lo), 64.5 (d,C=5, 10 and 17 Hz, H-2). i3CNMR (125 MHz): 623.6 (t, C-8),
3), 66.7, 71.3, 71.7 and 76.2jeach s, C-4-C-7), 72.5 (d, C-9), 114.5 25.8, 28.8 and 29.1 (each t, C-12-C-14), 27.1 and 27.4 (each q,
(t, C-17), 119.6 (t, C-i). 132.1 (d, C-2). 138.8 (d. C-16), 169.4 and
gem-methyl), 32.9 (t, C-l 1 or C-15). 33.7 (t, C-15 or C-i l), 63.5 (d,
170.0 (each st AC).
C-3), 66.5,71.0,74.7 and 77.3 (each s, C-4-C-7), 78.1 (d. C-9), 80.5
~or~~~on of compound 2 from coleus
1. The mixt. of 1 (d, C-lo), 108.8(s, Me&O,), 114.3 (r, C-l?), 117.1 (t, C-l), 136.1
(d, C-2), 139.1 (d, C-16).
(30 mg) and 2% HCI-Me&O (2: 1) (4 ml) was stirred at room
temp. for 2.25 hr. The reaction mixt. was freed of Me&O under a
Formatzon ef compound 3 from compound 1. The mixt. of 1
stream of N, and extracted with EtOAc (10 ml x 2). The EtOAc
(52 mg) and l%H,SO*-THF
(1:2) 5 ml was stirred at room
layer was dried over MgSO, and coned under red. pres. The temp. for 22 hr, and at 40 for I hr. The reaction mixt. was added
to satd NaCl soln (10 ml) and extracted with EtOAc (20 ml x 2).
residue was purified by prep. HPLC, eluted with
hexane-Me&O (3: 1) to give an oil (22 mg) which was identified
The EtOAc layer was dried over MgSO,, and coned under red.
pres. The residue was purified by prep. HPLC, eluted with
as 2 by the physical data.
Ginsenoyne C (3). Amorphous powder. [alo - 16.5 (CHCI,;
hexane-Me&O (3 : 1) to give an amorphous powder which was
c 1.5). IR v:f: cm-i: 3350 (br OH), 2260 (C&), 1644 (C=C).
identified as 3 by the physical data.
Ginsenoyne D (4). Oil. [c?]n -90.7
(CHCI,; ~3.0).
UV iE$rr nm (log E): 201 (4.51), 231 (2.88), 243 (2.84), 257 (2.61).
CIMS (iso-butane) 20 eV, m/z (rei. int.): 277 [M + H] (62k 259 IR vgf? cm- : 3350 (br OH), 2256 (C&). UV /1:2 nm (logs):
[M+H-HaO]+
(lOO), 241 [M+H-2H,O]+,
145 (65), 131 200 (3.68), 230 (2.76), 241 (2.75). 255 (2.62). CIMS (&o-butane)
(65); HR-CIMS m/z 277.1799 (Calcd for C,,H,,O,
[M+H]:
2t?eV, m/z (rel. int.): 263 [M+H]+ (191, 245 [MtH-H,O]+
(lOO),227 [M +H-2H,O]+
(2); HR-CIMSm/z 263.2015. (Calcd
277.1803). HNMR see Table 2. i3CNMR see Table 1.
Ginse~yne C triacetate [3a). The mixt. of 3 (13.6 mg). Ac,O
[M+H]+:
263.2011). HNMR
see
for
Ci7Ha702
Table 2. aCNMR see Table 1.
(20 ~11, Et,N (15 ~1) and 4-dimethylaminopyridine
(catalytic
Treatment of compound 4 with H,SO,. The mixt. of 4 (29 mg)
amount) in CH,CI, (3 ml) was stirred at room temp. for 1 hr. The
and 2%H,SO,-THF
(1:2f 4 ml was s&red at room temp. for
reaction mixt. was treated as usual, and purified by prep. HPLC,
eluted with hexane-Me&O
(4: 1) to give an oil @a, 16.6 mg). 20 hr and at 40 for 7 hr. The reaction mixt. was freed of THF
[or&, f 13.3 (CHCI,; c 1.49). IR v~~~iJcm-: 3028, 2932, 2260 under a stream of N, and added to satd NaHCO, soln (10 ml)
(C*), 1740 (C=O), 1642 (C=C), 970,914. UV nzzH nm (logs):
and extracted with EtOAc (10 ml x 2). The EtOAc layer was
200 (4.01), 220 (2.95),232 (298)s 244 (2.94), 258 (2.72). CIMS (iso- dried over MgSO, and coned under red. pres. The residue was
butane) 20 eV, m/z (rel. int.): 403 [M + H] + (26), 344 (58), 301(68), purified by prep. HPLC, eluted wth hexane-Me,CO (3: 1) to
give an amorphous powder (14 mg) which was identified as
283 [M-t-H-ZHOAc]+
(95), 241(66), 223 [MfH-3HOAc]+
(100). HNMR (500 MHz): r51.26-1.34(4H, m, H-12-H-13), 1.37 dihydropanaxacol (IO) by comparison with the physical data.
(2H, br q, J = 7 Hz, H-l I), 1.55 (2H, qui, J = 6 Hz, H-14), 2.03 (2H, UV kztrr nm (loge): 199 (3.56), 229 (2.77), 242 (2.71). 256 (2.50).
EIMS 70 eV, m/z (rel. int.): 280 [M] (O.OS),262 [M - H,O]+
6rq,5=6HsH-15),2.08,2.09and2.11(each3H,s,Ac),2.57(1H,
ddd, J=O.9, 6.1 and 17.6Hz, H-8a or H-8b), 2.62 (lH, ddd, J
(3.4), 244 [M-2H,O]+
(4.9), 159 (13), 104 (100). HNMR
=0.9, 6.0 and 17.6 Hz, H-8a or H-8b), 4.93 (lH, ddt, J= 1.2, 2.1 (500 MHz): 60.89 (3H, br t, J = 7 Hz, H-17),1.01 (3H, t, J = 7 HZ,
and 10.2 Hz, H-17a), 4.98 (lH, ddt, J = 1.52.1 and 17.1, H-17b), H-l), 1.26-1.41 (SH, m, H-13-H-161 1.43-1.55 (4H, m, H-ll-H5.05(1H,ddd,J=4.1,6.0and6.1Hz,H-9),5.10(1H,ddd,1=4,1,
12),1.74(2H,m,H-2),2.53,2.16and2.11(eachbrOH),2.55(1H,
5.5 and 7.7 Hz, H-10), 5.33 (lH, d-like, J=9 Hz, H-la), 5.53 (lH,
ddd,J= 1.0,6.5and 17.3 H~H-8b),2.~(lH,ddd,J=l.O,5.7and
d-like,J=17Hz,H-lb),5.79(1H,ddt,J=6.6,10.2and
17.1H2,
17.3 Hz, H-8a), 3.59 (IH, br td, J=6 and 4 Hz, H-10) 364 (lH, br
H-16), X30-5.90 (lH, m, H-21, 5.90 (HI, br d, J=6Hz, H-3). td, J=Band 4Hz, H-9),4.36(lH, br t,J=6Hz, H-3). 13CNMR
t3C NMR (125 MHz): S20.81,2&88 and 20.9 (each q, Ac), 21.9 (t, (125 MHz): 69.4(q, C-l), 14.1 (q, C-17), 22.7 (t, C-16), 25.1 (t, CC-8), 24.9,28.6 and 28.8 (each t, C-12-C-14), 30.4 (t, C-l i), 33.6 (t,
15), 25.7 (t, C-8), 29.3 (t, C-13), 29.6 (t, C-12), 30.8 (t, C-21, 31.9 (t,
C-15), 64.5 (d, C-31, 66.4, 71.5, 76.3 and 77.0 (each s, C-4-C-7,
C-14),33.7(&C-l 11.64.1(d,C-3), 66.7(s,C-6),69.7(s,C-5),72.3(d,
overlapping with solvents signal), 71.0 (4 C-9), 73.0 (d, C-10), C-lo), 73.2 (d, C-91, 77.3 (s, C-4), 77.5 (s, C-7).
114.4(1, C-17), 119.5 (t, C-l), 132.2(&C-2), 138.8(d,C-16), 169.4,
Synthesis of 7-oeten-l-al
(14) from 1,8-nonadiene (II)
170.1 and 170.4 (each s, AC).
(i) 8-nonen-1,2-diol(l2)jkomcompound 11[14]. The mixt. of60%
Gi~senoy~e C aceta~~de (3b). The mixt. of 3 (2Omg), 2,2~-methy~o~ho~e-~-o~de
(3 ml), Ha0 (5 ml), and Me,CO
dimethoxypropane (1 ml), and p_TsOH . Hz0 (4.5 mg) was stir(2 ml) and 100 mg of 0~0, m 10 ml t-BuOH was added to 11
red at room temp. for 15 min. The reaction mixt. was added to (1.22 g) at 0. The reaction mixt. was stirred at room temp. for
satd NaHCO, soln (lOml), and extracted with EtOAc (1Ornl 12 hr. A slurry of Na,S,O, (1 g), magnesium silicate (12 g
x 3). The EtOAc layer was washed with satd NaCl soln (10 ml) magnesol), and H,O (8 ml) was added, and the magnesol was
and dried over MgSO,, and coned under red. pres.
filtered, The filtrate was neutralized to pH 7 with 0.5 M H,SO,,
The residue was purified by prep. HPLC, efuted with
freed of Me&O under red. pres.. and pH was further adjusted to

Polyacetylenes from Panax ginseng

pH 2. The soln was saturated with NaCl, and extracted with
EtOAc (20 ml x 3). The EtOAc layer was dried over MgSO,, and
purified by prep. HPLC, eluted with hexane-Me&O (2: 1) to
give an oil 12 (220 mg). IR YE: cm-: 3400 (br OH), 2932,164O
(C=C), 1462, 914. HNMR (400 MHz): 61.23-1.50 (8H, m, H3-H-6), 2.01 (2H, br qt, J = 1.7 and 17.0 Hz, H-7), 3.20 (2H, br,
OH-1 and OH-2), 3.39 (lH, dd, J=7.8 and 11.2H2, H-l), 3.60
(lH,dd,J=2.9and
11.2 Hz,H-1),3.65(1H,m,H-2),4.91 (lH,ddt,
J= 1.2, 1.7 and 10.2 Hz, H-9), 4.97 (lH, dq, J = 1.7 and 17.0 Hz,
H-9), 5.78 (lH, ddt, J=6.6, 10.2 and 17.0 Hz, H-8). sCNMR
(100 MHz): 625.5,28.8 and 29.2 (each t, C-4-C-6), 33.1 (t, C-3 or
C-7), 33.7 (t. C-7 or C-3), 66.8 (t, C-l), 72.4 (d, C-2), 114.3 (b,C-9),
139.0 (d, C-8). FAB-MS (positive, neat), m/z: 159 [M + H]+, 141
123 [M + H -2H,O]+;
HR-FABMS m/z
[M+H-HzO]+,
159.1382 (Calcd for CgH,,O, [M+H]+: 159.1385).
(ii) 7-octenal(13)from compound 12. The mixt. of 12 (53 mg),
THF (1 ml), Hz0 (1 ml), and NaIO, (280mg) was stirred at
room temp. for 30 min. The reaction mixt. was added to satd
NaCl soln (2Oml) and extracted with EtOAc (20mlx 3). The
EtOAc layer was dried over MgSOI, and coned under red pres.
The residue was purified by prep. HPLC, eluted with
hexane-C,H, (1: 1) to give an oil (13, 19 mg). Irvin
cm-:
2932, 1722 (C=O), 1640 (C=C), 996,914. H NMR (400 MHz):
S1.3c1.47 (4H, m, H-4 and H-5), 1.64 (2H, qui, J=7 Hz, H-3),
2.06 (2H, br qt, J= 1.5 and 6.6 Hz, H-6), 2.42 (2H, td, J= 1.9 and
7.3 Hz, H-2), 4.94 (lH, ddt, J= 1.5, 2.0 and 10.5 Hz, H-8), 5.00
(lH,ddt, J=1.5,2.0and 17.1 Hz,H-8), 5.79(1H,ddt, J=6.6,10.5
and 17.1 Hz, H-7), 9.76 (lH, t, J= 1.9 Hz, H-l). CNMR
(100 MHz): 622.0 and 28.6 ( x 2) (each t, C-3-C-S), 33.5 (t, C-6),
43.9 (b,C-2), 114.5 (t, C-8), 138.7 (d, C-7), 202.7 (d, C-Q FAB-MS
@ositive,m-nitrobenzyl alcohol)m/z: 127 [M +H]+, 109 [M +H
-H,O]+;
HR-EIMS m/z 126.1065 (Calcd for CsHIdO [Ml:
126.1045).
(iii) I-octen-1-ol (14) from comj7ofmd 13. The mixt. of 13
(18 mg), and NaBH, (36 mg) in MeOH (7 ml) was stirred at room
temp. for 40 min. The reaction mixt. was added to satd NaCl soln
(10 ml), and extracted with EtOAc (20 ml x 3). The EtOAc layer
was dried over MgSO,, and coned under red. pres. to give an oil
(14, 14 mg). IR ~2:~ cm-: 3400 (br OH), 1640 (C=C), 914.
H NMR (400 MHz): 8 1.29-1.43 (6H, m, H-3-H-5), 1.57 (2H, br
qui, J=7 Hz, H-2), 2.06 (2H, br q, J=7 Hz, H-6), 3.64 (2H, t, J
=7 Hz, H-l), 4.93 (lH, ddt, J=1.2, 2.2 and 10.2 Hz, H-8), 5.00
(lH, dq, J= 1.7 and 17.1 Hz., H-8), 5.81 (lH, ddt, J=6.6,10.2 and
17.1 Hz, H-7). 13CNMR (100 MHz): b25.6,28.8 and 28.9 (each t,
C-3-C-5), 32.8 (t, C-2), 33.7 (t, C-6), 63.1 (t, C-l), 114.3 (t, C-8),
139.1 (d, C-7); EIMS 70 eV, m/z (rel. int.): 110 [M-H,O]+
(16).
Preparation ofcompound 14_fromcompound 1. The preparation
of 3 from 1 followed the above method. The mixt. of 3 (17 mg),
THF (0.6 ml), Hz0 (0.6 ml), and NaIO, (148 mg) was stirred at
room temp. for 20 min. The reaction mixt. was added to satd
NaCl soln (lOml), and extracted by EtOAc (2Omlx 3). The
EtOAc layer was dried over MgSO,, and coned under red. pres.
The residue was added to NaBH, (15 mg), and MeOH (7 ml),
stirred at room temp. for 20 min. The reaction mixt. was added to

3333

satd NaCl soln (10 ml), and extracted with EtOAc (20 ml x 3).
The EtOAc layer was dried over MgSO,, and coned under red.
pres. to give a pale yellow oil (13 mg) which was identified as 14
by GC-MS [column: DB-1, 15 m x 0.53 mm; carrier gas: He at
19 mlmin-; temp.: programmed 50-250 at lo min- , injection temp.: 200; sep. inl.: 250]. R, 4.3 min.
Acknowledgements-The

authors are grateful to Dr K. Sugama,

Mr K. Kano and Mrs N. Kobayashi for H and CNMR and
mass spectral measurements. We also thank Dr M. Okada for
the plant material.
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