Determination of the absolute configuration of (+)-2,7(14),10- bisabolatrien-1-ol-4-one from Japanese cedar, Cryptomeria japonica

Article abstract of DOI:10.1271/bbb.66.1997

The absolute configuration of (+)-2,7(14),10-bisabolatrien-1-ol-4-one, a peculiar sesquiterpenol in the Japanese cedar, Cryptomeria japonica, was determined as (1S,6R)-2,7(14),10-bisabolatrien-1-ol-4-one by comparing the specific rotation values of crypto

Full text of DOI:10.1271/bbb.66.1997

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Determination of the Absolute Configuration of
(+)-2,7(14),10-Bisabolatrien- 1-ol-4-one from
Japanese Cedar, Cryptomeria japonica
Chul-Sa KIMa, Jun MORISAWAa, Nobuhiro NISHIYAMAa, Takehiro KASHIWAGIa, Shin-ich
TEBAYASHIa & Michio HORIIKEa
a Department of Bioresources Science, Faculty of Agriculture, Kochi University B200
Monobe, Nankoku 783-8502, Japan
Published online: 22 May 2014.
To cite this article: Chul-Sa KIM, Jun MORISAWA, Nobuhiro NISHIYAMA, Takehiro KASHIWAGI, Shin-ich TEBAYASHI & Michio
HORIIKE (2002) Determination of the Absolute Configuration of (+)-2,7(14),10-Bisabolatrien- 1-ol-4-one from Japanese
Cedar, Cryptomeria japonica , Bioscience, Biotechnology, and Biochemistry, 66:9, 1997-2000, DOI: 10.1271/bbb.66.1997
To link to this article: http://dx.doi.org/10.1271/bbb.66.1997
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Biosci. Biotechnol. Biochem., 66 (9), 1997–2000, 2002
Note
＋
Determination of the Absolute Conˆguration of ( )-2,7(14),10-Bisabolatrien-
1-ol-4-one from Japanese Cedar, Cryptomeria japonica
Chul-Sa KIM,† Jun MORISAWA, Nobuhiro NISHIYAMA, Takehiro KASHIWAGI
,
Shin-ich TEBAYASHI, and Michio HORIIKE
Department of Bioresources Science, Faculty of Agriculture, Kochi University, B200 Monobe,
Nankoku 783-8502, Japan
Received April 8, 2002; Accepted May 13, 2002
The absolute conˆguration of (
＋
)-2,7(14),10-bis-
abolatrien-1-ol-4-one, a peculiar sesquiterpenol in the
Japanese cedar, Cryptomeria japonica, was determined
methyl-5-(6-methylhepta-1,5-dien-2-yl)-3-(tetra-
hydropyran-2-yloxy)cyclohexene. After eliminating
the THP,9) (5
R
)-2-methyl-5-(6-methylhepta-1,5-dien-
2-yl)-2-cyclohexenol was oxidized with PDC to give
)-cryptomerione (6). The total yield was 8.4
as (1
paring the speciˆc rotation values of cryptomeriones re-
spectively converted from ( )-2,7(14),10-bisabolatrien-
1-ol-4-one and synthesized from (
S,6R)-2,7(14),10-bisabolatrien-1-ol-4-one by com-
(
R
z
＋
(Scheme 2). (
S)-Cryptomerione was synthesized
－
)-( )-carvone.
R
from ( )-carvone in the same way.
S
Key words: (1S,6R)-2,7(14),10-bisabolatrien-1-ol-4-
one; (+)-2,7(14),10-bisabolatrien-1-ol-4-
one; cryptomerione; Cryptomeria japoni-
ca
(+)-2,7(14),10-Bisabolatrien-1-ol-4-one was ˆrst
isolated by Nagashima and Tazaki as a new sesquiter-
penol from C. japonica,1) and various bioactivities of
this compound have recently been reported.2,3) The
absolute structure of this compound, however, has
not yet been proven, although its conˆguration at
C-1 and C-6 has been reported to be of trans form
1
＝
from the coupling constant value (
J
9.7 Hz) in H-
NMR date.1,3)
Scheme 1. Conversion from (+)-2,7(14),10-Bisabolatrien-1-ol-
4-one into Cryptomerione.
Reported in this paper is the absolute conˆguration
of (+)-2,7(14),10-bisabolatrien-1-ol-4-one that was
determined by its conversion to the known com-
pound, cryptomerione.
(+)-2,7(14),10-Bisabolatrien-1-ol-4-one (1) isolat-
ed from C. japonica3) was at ˆrst acetylated to 4-
acetoxycryptomerione (2) by conventional means.
Cryptomerione (3) was converted from 2 by de-
acetoxylation.4) These procedures did not aŠect the
conˆguration of the structures as shown in Scheme 1.
The total yield was 11.4
z
.
(R)-(„)-Carvone (4) was brominated by NBS to
give (
R
)-10-bromo-1(6),8-
p
-menthadien-2-one (5),5,6)
7)
and the carbonyl group of 5 was reduced by LiAlH4
to convert it to (4
2-ol. After protecting the hydroxyl group as a THP
ether,8) (4
)-10-bromo-2-(tetrahydropyran-2-yloxy)-
1(6),8-
R)-10-bromo-1(6),8-p-menthadien-
R
p
-menthadiene was reacted with 3-methyl-
Scheme 2. Synthesis of (
R)-Cryptomerione from (R)-Carvone.
2-butenylmagnesium bromide to produce (5R)-2-
†
To whom correspondence should be addressed. Fax: +81-888-64-5219; E-mail: cs-kim
＠
cc.kochi-u.ac.jp

1998
C.-S. KIM et al.
Table 1. Speciˆc Rotation Values for Each Cryptomerione
was chromatographed on a column of silica gel
(Wako C300), eluting with 5
z diethyl ether in
22
D
Cryptmerione
[
a]
(hexane)
hexane, to obtain 4-acetoxycryptomerione (61 mg) as
a colorless oil in a 91
z
yield. n2D2 1.497. [
a
]2D2+120
9
Cryptomerione from (+)-2,7(14),
10-bisabolatrien-1-ol-4-one
„25.8
9
＝
(c
＝
1.6, hexane). IR nmax (liquid ˆlm) cm„1: 1740
Cryptomerione from (
Cryptomerione from (
R
)-(„)-carvone
„25.7
+25.5
9
9
＝
＝
(acetoxy C O), 1685 (ketone C O), 1235 (C–O).
S
)-(+)-carvone
EIMS m z ): 173 (44), 148 (12), 145 (15), 69 (95),
(z
W
1
43 (74), 41 (100). H-NMR (CDCl3)
d
: 6.52 (1H, m,
7.7 and 1.6, H-4), 5.10 (1H,
m, H-10), 4.91 (1H, s, H-14a), 4.90 (1H, s, H-14b),
＝
J
H-3), 5.66 (1H, dd,
The speciˆc rotation values of the cryptomeriones
synthesized by each procedure are shown in Table 1.
Compound 3 converted from (+)-2,7(14),10-
bisabolatrien-1-ol-4-one had a speciˆc rotation of
＝
10.5, 7.7 and 3.3, H-5), 2.61 (1H,
13.1 and 3.3, H-6a), 2.45 (1H, dd,
2.87 (1H, ddd,
J
＝
＝
13.1
dd,
J
J
and 10.5, H-6b), 2.12 (2H, m, H-9), 2.07 (3H, s,
acetyl CH3), 2.04 (2H, m, H-8), 1.80 (3H, m, H-15),
1.68 (3H, s, H-12), 1.61 (3H, s, H-13). 13C-NMR
„25.8
the other hand, the speciˆc rotation of (
tomerione synthesized from ( )-(+)-carvone had the
9
, similar to that of 6 synthesized from 4. On
S
)-cryp-
＝
(CDCl3) d: 198.0 (s, C-1), 170.4 (s, C O), 147.1 (s,
S
same absolute value as that of 3, but the opposite
sign (Table 1). These results enabled us to conclude
that the absolute conˆguration of 3 converted from
(+)-2,7(14),10-bisabolatrien-1-ol-4-one was the same
C-7), 143.3 (d, C-3), 136.7 (s, C-2), 132.1 (s, C-11),
123.6 (d, C-10), 112.0 (t, C-14), 71.1 (d, C-4), 47.9
(d, C-5), 41.7 (t, C-6), 33.8 (t, C-8), 26.3 (t, C-9),
25.7 (q, C-12), 20.9 (q, acetyl CH3), 17.8 (q, C-13),
15.4 (q, C-15).
as that of (R)-(„)-cryptomerione. Therefore, the ab-
solute conˆguration of (+)-2,7(14),10-bisabolatrien-
1-ol-4-one isolated from Japanese cedar was evaluat-
Cryptomerione (3). After 2 (61 mg, 0.22 mmol)
ed as (1
would not have changed during the convertion of
(+)-2,7(14),10-bisabolatrien-1-ol-4-one into )-
(„)-cryptomerione. This result is based on the deter-
S
,6
R
), because the conˆguration at C-6
and zinc powder (60 mg, 0.92 mmol) had been mixed
with acetic acid (1.5 ml), the mixture was stirred and
heated under re‰ux for 5 h. The mixture was them
diluted with water and extracted with diethyl ether.
The diethyl ether layer was washed with saturated so-
dium bicarbonate water and then dried over anhy-
drous Na2SO4. After removing the solvent under
reduced pressure, the crude product was chro-
(
R
minations of similar sesquiterpenoids to (1S,6R)-
2,7(14),10-bisabolatrien-1-ol-4-one in C. japonica
.
Experimental
matographed on a silica gel column, eluting with 2
z
GC-MS data for all compounds were measured
with a Shimadzu QP2000 mass spectrometer. GC
analyses were done with a Shimadzu GC-14A
instrument ˆtted with a fused silica column (HR1701,
diethyl ether in hexane, to obtain a residue (20 mg).
This residue was puriˆed by HPLC (YMC-Pac
SII-06, 300 mm
with 0.5 ethanol in hexane (4 ml min ‰ow rate) to
give cryptomerione (6 mg) as a colorless oil in a
×
10 mm i.d., S-5 mm, 60 Å), eluting
z
W
×
0.25
med from 200
10
m
m thickness, 25 m 0.2 mm i.d.) and program-
C (2-min hold) to 250 C at a rate of
C min. Infrared spectra were taken into a
9
9
z 9
12.5 yield. [a (c 0.6, hexane). IR nmax
]2D2„25.8
＝
(liquid ˆlm) cm„1: 1680 (C O). EIMS m z
(
z
): 218
＝
9
W
W
Shimadzu FT-IR4300 instrument as a liquid ˆlm. 1H-
and 13C-NMR data for all compounds were measured
with a JEOL Lambda 400 spectrometer at 400 MHz,
using TMS as an internal standard. Letters s, d, t, q,
and m represent singlet, doublet, triplet, quartet, and
multiplet, respectively, and coupling constants are
given in Hz. Speciˆc rotation values were recorded
with a Horiba High Sensitive Polarimeter SEPA-200.
(1), 148 (13), 135 (11), 109 (21), 69 (57), 67 (14), 53
(15), 41 (100), 39 (27). 1H-NMR (CDCl3)
d
: 6.75 (1H,
6.8 and 1.5, H-10), 4.85
(1H, s, H-14a), 4.82 (1H, s, H-14b), 2.69 (1H, ddt,
＝
J
m, H-3), 5.09 (1H, tq,
＝
＝
15.9,
J
13.6, 10.2 and 4.0, H-5), 2.59 (1H, ddd,
3.7 and 1.5, H-4a), 2.46 (1H, dtm, 18.3 and 4.4,
15.9 and 13.2, H-4b), 2.27
18.3 and 11.0, H-6b), 2.11 (2H, m,
H-9), 2.05 (2H, m, H-8), 1.79 (3H, dt, 2.4 and
1.0, H-13), 1.61 (3H, s,
: 199.8 (s, C-1), 150.7 (s,
J
J
＝
＝
J
H-6a), 2.35 (1H, dd,
＝
J
(1H, ddm,
J
＝
＝
J
d
4-Acetoxycryptomerione
(
2
). The mixture of
1.4, H-15), 1.68 (3H, d,
(+)-2,7(14),10-bisabolatrien-1-ol-4-one (57 mg,
0.25 mmol), acetic anhydride (1.5 ml) and triethyl-
amine (1.5 ml) was stirred at room temperature for
3 h. The mixture was then poured into ice-cooled
water and extracted with diethyl ether. The ethereal
H-12). 13C-NMR (CDCl3)
C-7), 144.6 (d, C-3), 135.3 (s, C-2), 131.9 (s, C-11),
123.7 (d, C-10), 109.1 (t, C-14), 43.5 (t, C-6), 41.1 (d,
C-5), 34.2 (t, C-8), 31.7 (t, C-4), 26.6 (t, C-9), 25.6
(q, C-12), 17.7 (q, C-13), 15.7 (q, C-15).
layer was washed with 1
N HCl and subsequently with
saturated sodium bicarbonate water, before being
dried over anhydrous Na2SO4. After removing the
solvent under reduced pressure, the crude product
(R)-10-Bromo-1(6),8-p-menthadien-2-one
(5).
After replacing the air with N2 gas in a ‰ask, NBS
(13.5 g, 130 mmol) and benzoylperoxide (500 mg) in

Determination of the Absolute Conˆguration of (+)-2,7(14),10-Bisabolatrien-1-ol-4-one
1999
benzene (50 ml) were loaded into the ‰ask. While
stirring the solution under re‰ux, ( )-(„)-carvone
(7.5 g, 50 mmol) in benzene (100 ml) was added and
left to stand for 3 h. After partition between benzene
and water, the benzene layer was dried over anhy-
drous Na2SO4 and the solvent removed. The resulting
residue was chromatographed on silica gel, eluting
(130 mg) as a colorless oil in a 29.8
z
yield based on
R
5. n2D2 1.5041. [
a
]2D2„25.7
9(c
＝
＝
1.9, hexane). IR nmax
(liquid ˆlm) cm„1: 1680 (C O). EIMS m z
z
( ): 218
＝
W
(M+,1), 148 (12), 135 (11), 109 (21), 69 (74), 67 (12),
1
53 (15), 41 (100), 39 (27). H-NMR (CDCl3)
d
: 6.75
6.8 and 1.5, H-10),
4.85 (1H, s, H-14a), 4.82 (1H, s, H-14b), 2.69 (1H,
＝
J
(1H, m, H-3), 5.09 (1H, tq,
＝ ＝
13.6, 10.2 and 4.0, H-5), 2.59 (1H, ddd, J
with 5
oil (3.26 g) of (
one in a 28.5
yield. n2D2
hexane). IR nmax (liquid ˆlm) cm„1: 1675 (C O).
EIMS m z ): 149 (21), 121 (14), 107 (32), 105 (16),
z
diethyl ether in hexane, to give a yellowish
)-10-bromo-1(6),8- -menthadien-2-
1.5438. [ 3.0,
]2D4„19
ddt,
J
＝
R
p
a
15.9, 3.7 and 1.5, H-4a), 2.46 (1H, dtm,
J
18.3 and
＝
(
c
＝
＝
4.4, H-6a), 2.35 (1H, dd,
J
＝
15.9 and 13.2, H-4b),
z
9
＝
2.27 (1H, ddm,
J
18.3 and 11.0, H-6b), 2.11 (2H,
＝
(z
m, H-9), 2.05 (2H, m, H-8), 1.79 (3H, dt,
J
2.4 and
1.0, H-13), 1.61 (3H, s,
: 199.8 (s, C-1), 150.7 (s,
W
＝
J
93 (11), 91 (15), 82 (100), 79 (23), 77 (13), 65 (11), 55
(14), 54 (59), 53 (23), 51 (12), 43 (10), 41 (45), 39 (64).
1.4, H-15), 1.68 (3H, d,
H-12). 13C-NMR (CDCl3)
d
1H-NMR (CDCl3)
d
: 6.76 (1H, m, H-6), 5.31 (1H, s,
C-7), 144.6 (d, C-3), 135.3 (s, C-2), 131.9 (s, C-11),
123.7 (d, C-10), 109.1 (t, C-14), 43.5 (t, C-6), 41.1 (d,
C-5), 34.2 (t, C-8), 31.7 (t, C-4), 26.6 (t, C-9), 25.6
(q, C-12), 17.7 (q, C-13), 15.7 (q, C-15).
＝ ＝
1.2, H-9b), 4.01 (2H, dd, J
H-9a), 5.06 (1H, d,
J
2.9 and 1.1, H-10), 3.03 (1H, m, H-4), 2.68 (1H,
＝ ＝
16.1, 3.9 and 1.7, H-5a), 2.58 (1H, dtq, J
ddd,
18.0, 4.4 and 1.4, H-3a), 2.39 (1H, dd,
13.2, H-5b), 2.34 (1H, ddq, 18.3, 13.4 and 2.4,
H-3b), 1.80 (3H, m, H-7). 13C-NMR (CDCl3)
J
＝
J
16.1 and
J
＝
9
(S)-Cryptomerione. [a (c 1.9, hexane).
]2D2+25.5
＝
IR nmax (liquid ˆlm) cm„1: 1680 (C O). EIMS m z
＝
d
:
W
198.9 (s, C-2), 146.8 (s, C-8), 144.0 (d, C-6), 135.6 (s,
C-1), 115.6 (t, C-9), 43.1 (t, C-3), 38.1 (d, C-4), 35.0
(t, C-10), 31.5 (t, C-5), 15.7 (q, C-7).
(
z
): 218 (M+, 1), 148 (12), 135 (11), 109 (21), 69
1
(74), 67 (12), 53 (15), 41 (100), 39 (27). H-NMR
＝
6.8
(CDCl3)
d
: 6.75 (1H, m, H-3), 5.09 (1H, tq,
J
and 1.5, H-10), 4.85 (1H, s, H-14a), 4.82 (1H, s, H-
＝
13.6, 10.2 and 4.0, H-5), 2.58
(R)-Cryptomerione (
6
). 5 (2.66 g, 11.6 mmol) was
)-10-bromo-1(6),8-
14b), 2.69 (1H, ddt,
(1H, ddd,
dtm,
J
＝
15.9, 3.7 and 1.5, H-4a), 2.47 (1H,
reduced by LiAlH4 to give (4
R
p
-
J
menthadien-2-ol (2.54 g) according to the established
procedure,7) the hydroxyl group of the product
(693 mg) then being protected as a THP ether
(740 mg).8) A solution of 3-bromo-2-methyl-2-butene
(745 mg, 5 mmol) in dry THF (9 ml) was slowly
added over 10 min to magnesium (375 mg) while stir-
J
＝
18.3 and 4.4, H-6a), 2.35 (1H, dd,
J
＝
15.9
＝
and 13.2, H-4b), 2.27 (1H, ddm,
J
18.3 and 11.0,
H-6b), 2.11 (2H, m, H-9), 2.05 (2H, m, H-8), 1.79
＝
＝
1.0,
(3H, dt,
J
2.4 and 1.4, H-15), 1.68 (3H, d,
J
H-13), 1.61 (3H, s, H-12). 13C-NMR (CDCl3)
d
:
199.8 (s, C-1), 150.7 (s, C-7), 144.6 (d, C-3), 135.3 (s,
C-2), 131.9 (s, C-11), 123.7 (d, C-10), 109.1 (t, C-14),
43.5 (t, C-6), 41.1 (d, C-5), 34.2 (t, C-8), 31.7 (t,
C-4), 26.6 (t, C-9), 25.6 (q, C-12), 17.7 (q, C-13),
15.7 (q, C-15).
ring and keeping at „259C under N2 gas. After ter-
minating the exothermic reaction, the reactant was
added to dry THF (6 ml) containing the THP ether
(472 mg) and cuprous bromide (30 mg) while stirring
9
for 30 min at „25 C. The solution was diluted with
saturated ammonium chloride water and then ex-
tracted with diethyl ether. The organic layer was
washed with saturated sodium bicarbonate water and
subsequently with saturated aqueous NaCl, before
being dried over anhydrous Na2SO4. After removing
the solvent, the residue was puriˆed by silica gel
Acknowledgments
We are grateful to Drs. Hayato Shinohara and
Toshio Kono (Kochi Prefectural Industrial Technol-
ogy Center) for providing the cedar wood. We thank
the Center for Joint Research and Development at
Kochi University for measuring the NMR spectral
data.
column chromatography, eluting with 5
z
diethyl
ether in hexane, to give a colorless oil (441 mg) of a
mixture of four diastereomers. After eliminating
THP9) from the diastereomers, the product (320 mg)
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