Isolation and absolute stereochemistry of optically active sydonic acid from Glonium sp. (Hysteriales, Ascomycota)

Article abstract of DOI:10.1271/bbb.80535

Optically active sydonic acid (1) was isolated for the first time from a culture broth of Glonium sp. The absolute stereochemistry was established to be (S) by comparing the circular dichroism (CD) spectrum with that of (+)-curcutetraol after conversion i

Full text of DOI:10.1271/bbb.80535

Biosci. Biotechnol. Biochem., 73 (1), 203–204, 2009
Note
Isolation and Absolute Stereochemistry of Optically Active Sydonic Acid
from Glonium sp. (Hysteriales, Ascomycota)
Shinji KUDO, Takanori MURAKAMI, Junsuke MIYANISHI, Kazuaki TANAKA,
y
Noboru TAKADA, and Masaru HASHIMOTO
Faculty of Agriculture and Life Science, Hirosaki University, 3-Bunkyo-cho, Hirosaki 036-8561, Japan
Received August 4, 2008; Accepted September 9, 2008; Online Publication, January 7, 2009
[doi:10.1271/bbb.80535]
Optically active sydonic acid (1) was isolated for the
1
6
3
A. sydowi4
HOOC
OH
producer
[α]D
G. sp.
+2.73°
2.30
first time from a culture broth of Glonium sp. The
absolute stereochemistry was established to be (S) by
comparing the circular dichroism (CD) spectrum with
that of (+)-curcutetraol after conversion into (+)-
sydonol (2).
20
0°
1.0
(S)
7
c
OH
Sydonic acid (1)
(both in MeOH)
158-159°C
(both from benzene)
mp
85-86°C
LiAlH4, THF, reflux
Key words: sydonic acid; optically active form; circular
dichroism (CD) spectrum
OH
A. sp6
+7.2°
1.0
HO
HO
prep. from 1
producer
[α]D
20
(S)
+8.6°
1.0
c
Several bisabolane-type phenolic sesquiterpenes have
been isolated from such sources as herb plants,1) marine
sponge,2) marine bacteria,3) and fungi,4,5) Some of
them exhibited interesting biological activities. In the
course of our studies of metabolites from fungi with
unique ecologies, we disclosed a bisabolane, (+)-sydonic
acid (1), from Glonium sp. (Hysteriales, Ascomycota)
found in beech (Fagus crenata) from the Shirakami area.
Although the optical rotation value of 1 has been reported
to be zero, the sample obtained in the present study was
found to be optically active. The absolute stereochem-
istry of its C7 position was established to be (S)-configu-
ration after converting into (+)-sydonol and comparing
the CD spectrum with that of (S)-(+)-curcutetraol.
The ethyl acetate extract obtained from 3.0 liters of a
culture broth of Glonium sp. was subjected to silica gel
column chromatography. The subsequent recrystalliza-
tion from benzene gave 1 (30 mg) as fine needles.6) The
1H- and 13C-NMR spectral and MS analyses indicated
that the sample thus obtained was identical to sydonic
acid (1) as shown in Fig. 1, and those spectral data
matched well with data in the literature.4) Sydonic acid
(1) was isolated from the fungus Aspergillus sydowi in
OH
(both in MeOH)
Sydonol (2)
1
3
OH
bacterium CNH-7413
+5.24°
producer
20
[α]D
11
(S)
6
7
c
0.74
(MeOH)
OH
OH
Curcutetraol (3)
Fig. 1. Structures and Some Physical Data for Sydonic Acid (1),
Sydonol (2) and Curcutetraol (3).
Fig. 2. CD Spectrum of 2 (0.15 mM in MeOH).
1978. Although the optical rotation value of 1 was
20
reported to be zero (c 1.0, MeOH), it was ½ꢀꢀD
¼
þ2:73ꢁ (c 2.30, MeOH) in our case. This difference was
critical when considering the accuracy of the measure-
ment at such a concentration. Furthermore, the melting
point of our sample was 85–86 ꢁC which is much lower
than that in the literature (158–159 ꢁC, from benzene).
These discrepancies suggested that 1 isolated from
Glonium sp. was an optically active form, while that
produced by Aspergillus sydowi was the racemate.
Unfortunately, the crystals of optically active 1 were
very fine and not suitable for an X-ray diffraction
analysis, so we could not investigate its absolute
stereochemistry directly.
trum in acetone-d6 was identical with the data for 2
isolated from Aspergillus sp.7,8) The optical rotation
value for 2 thus obtained was ½ꢀꢀD ¼ þ8:6ꢁ (c 1.0,
20
MeOH) which accorded well with that in the literature
20
(½ꢀꢀD ¼ þ7:2ꢁ (c 1.0, MeOH)).7)
Although the absolute configuration of 2 has not been
reported, the CD spectrum of 2 prepared in the present
study (Fig. 2) resembled that of (+)-curcutetraol (3), an
11-hydroxy analogue of 2, isolated from marine bacteria
by Lindel et al.3) They established the absolute config-
uration of the stereogenic center of 3 to be S based on a
comparison of the experimental CD spectrum with that
obtained by quantum mechanics calculations. Asami’s
asymmetric total synthesis has recently confirmed that.9)
Reduction of 1 with LiAlH4 in THF readily provided
sydonol (2) as oil in a 91% yield. The 13C-NMR spec-
y
To whom correspondence should be addressed. Tel/Fax: +81-172-39-3782; E-mail: hmasaru@cc.hirosaki-u.ac.jp
Abbreviations: CD, circular dichroism

204
S. KUDO et al.
The 1H-NMR spectrum in dimethysulfoxide-d6 was identical to that
HOOC
OH
reported. 13C-NMR (125 MHz, CD3OD) ꢁ: 22.86, 22.90, 22.98, 28.82,
28.99, 40.43, 43.57, 77.88, 118.60, 121.50, 127.77, 131.58, 138.00,
156.91, 169.86. ESIMS (rel. int.) m=z: 267.1601 (18, calcd. for
C
15H23O4 [MH]þ, 167.1596), 249.1488 (100, calcd. for C15H21O3
4
[M ꢂ (OH)]þ, 249.1485).
Reduction of 1 to produce sydonol (2). A suspension of 1 (7.5 mg,
28 mmol) and LiAlH4 (1.4 mg, 38 mmol) in THF (1.0 ml) was refluxed
for 2 h. After cooling to 0 ꢁC, 10% tartaric acid solution (0.2 ml) was
added. The mixture was stirred at room temperature for 1 h and then
filtered through a Celite pad. The filtrate was concentrated in vacuo,
and the residue thus obtained was purified by silica gel column
chromatography (hexane:AcOEt = 75:25) to give sydonol (2, 6.5 mg,
91%) as an oil. 1H-NMR (400 MHz, in acetone-d6) ꢁ: 0.82 (6H, d,
J ¼ 6:6 Hz), 1.14 (2H, m), 1.35 (2H, m), 1.49 (1H, nonatet,
J ¼ 6:6 Hz), 1.62 (3H, s), w1.79, 1.91 (each 1H, ddd, J ¼ 4:9, 11.7,
13.7 Hz), 4.02 (1H, t, J ¼ 5:9 Hz), 4.52 (2H, d, J ¼ 5:9 Hz), 5.24 (1H,
br), 6.75 (2H, m), 7.04 (1H, d, J ¼ 8:4 Hz), 9.70 (1H, br). ESIMS (rel.
Fig. 3. Carbenium Ion Derived from 1.
Since the achiral C11 hydroxy group of 3 was expected
to scarcely contribute to the CD spectrum, the close CD
curve of 2 suggested the same chirality as that of 3.
Consequently, 1 isolated from Glonium sp. in this study
was concluded to be the (S)-isomer. The similar optical
rotation values for 2 and 3 might provide additional
proof.
Since optically active benzyl alcohols readily race-
mize under mild conditions, we needed to consider the
racemization of 1 during its isolation from fungi.
However, no reduction of the optical rotation value
was apparent when we dissolved optically active 1 in
aqueous CH3CN (1:1) and left at room temperature
for 12 h in the presence of camphorsulfonic acid
(3.0 mg/ml). Thus, racemization of 1 during its isolation
hardly occured. The electron-withdrawing carboxylic
acid function at the C3 position probably destabilized
benzyl cation 4, as shown in Fig. 3, which prevented
the C7 hydroxyl group from elimination. Accordingly,
we conclude that Aspergillus sydowi produced 1 in a
racemic form, in contrast to Glonium sp.
int.) m=z: 235.1709 (100, calcd. for
C
15H23O2 [MH ꢂ H2O]þ,
235.1698). The 13C NMR spectrum in acetone-d6 in CDCl3 was in
good accordance with the reported data.7)
References and Notes
1) Ono, M., Morinaga, H., Matsuoka, C., Ikeda, T., Okawa, M.,
Kinjo, J., and Nohara, T., New bisabolane-type sesquiterpenes
from the aerial parts of Lippia dulcis. Chem. Pharm. Bull., 53,
1175–1177 (2005).
2) Peng, J., Franzblau, S. G., Zhang, F., and Hamann, M. T., Novel
sesquiterpenes and a lactone from the Jamaican sponge Myrme-
kioderma styx. Tetrahedon Lett., 43, 9699–9702 (2002).
3) Mulhaupt, T., Kaspar, H., Otto, S., Reichert, M., Bringmann, G.,
¨
and Lindel, T., Isolation, structural elucidation, and synthesis of
curcutetraol. Eur. J. Org. Chem., 334–341 (2005).
Experimental
Isolation of (+)-sydonic acid. Glonium sp. collected from the
Shirakami area of Aomori prefecture in 2007 was cultured in a potato-
sucrose medium [3.0 liters, prepared from a potato extract (from 600 g
potato), 60 g of sucrose, and water] at 25 ꢁC for 28 d on a rotary shaker
(110 rpm). After filtration, the culture broth was extracted with ethyl
acetate (2.0 liters) and concentrated in vacuo. The residue thus
obtained was subjected to silica gel column chromatography (AcOEt/
hexane = 20:80) to give a crude sample (35 mg). Recrystallization
from benzene gave pure sydonic acid (1, 30 mg) as needles.4) The
melting point (mp) and optical rotation values are given in Fig. 1. IR
(KBr) cmꢂ1: 3400, 2955, 1670, 1560, 1425, 1385, 1300, 1H-NMR
(400 MHz, in CD3OD) ꢁ: 0.81 (6H, d, J ¼ 6:5 Hz), 1.13 (2H, m), 1.18
(1H, m), 1.33 (1H, m), 1.47 (1H, m), 1.59 (3H, s), 1.77 (ddd, J ¼ 4:8,
11.6, 13.7 Hz), 1.94 (1H, ddd, J ¼ 4:5, 12.2, 13.7 Hz), 7.25 (1H, d,
J ¼ 7:9 Hz), 7.36 (1H, d, J ¼ 1:6 Hz), 7.43 (1H, dd, J ¼ 1:6, 7.9 Hz).
4) Hamasaki, T., Nagayama, K., and Hatsuda, Y., Two new
metabolites, sydonic acid and hydroxysydonic acid from Asper-
gillus Sydowi. Agric. Biol. Chem., 42, 37–40 (1978).
5) Ishikawa, Y., Morimoto, K., and Hamasaki, T., Flavoglaucin,
a
metabolite of Eurotium chevalieri, its antioxidation and
synergism with tocopherol. JAOCS, 61, 1864–1868 (1984).
6) So far, we have not found any remarkable biological activity of 1.
7) Nukina, M., Sato, Y., Ikeda, M., and Sassa, T., Sydonol, a new
fungal morphogenic substance produced by an unidentified
Aspergillus sp. Agric. Biol. Chem., 45, 789–790 (1981).
8) The solvent used for the 1H-NMR analysis was not described in
ref. 7.
9) Zhang, C., Ito, S., Hosoda, N., and Asami, M., First asymmetric
total synthesis of (+)-curcutetraol. Tetrahedon Lett., 49, 2552–
2554 (2008).