(+)-Episesaminone, a Sesamum indicum furofuran lignan. Isolation and hemisynthesis

Article abstract of DOI:10.1021/np9702953

Several lignans from Sesamum sp. contain an unusual oxygen insertion between their furano and aromatic rings. As part of our ongoing studies to clarify the biosynthetic pathway to the sesame lignans, the furanoketone, (+)-episesaminone, was isolated and fully characterized in part via hemisynthesis from (+)-sesamolin.

Full text of DOI:10.1021/np9702953

J . Nat. Prod. 1997, 60, 1189-1192
1189
(+)-Ep isesa m in on e, a Sesa m u m in d icu m F u r ofu r a n Lign a n . Isola tion a n d
Hem isyn th esis
Patrice A. Marchand, Massuo J . Kato,† and Norman G. Lewis*
Institute of Biological Chemistry, 467 Clark Hall, Washington State University, Pullman, Washington 99164-6340
Received J une 12, 1997X
Several lignans from Sesamum sp. contain an unusual oxygen insertion between their furano
and aromatic rings. As part of our ongoing studies to clarify the biosynthetic pathway to the
sesame lignans, the furanoketone, (+)-episesaminone, was isolated and fully characterized in
part via hemisynthesis from (+)-sesamolin.
During our ongoing studies directed toward defining
how (+)-sesamolin (1) biosynthesis occurs in Sesamum
indicum L. (Pedaliaceae),1 as well as that of related
lignans,2-6 the hitherto unknown tetrahydrofuran lig-
nan, (+)-episesaminone (2) (Figure 1), was isolated from
commercially available unroasted and unbleached seeds,
as well as from freshly harvested seed tissue. Its
structure was established via a combination of 1H-13C
NMR, IR, UV, and MS analyses and confirmed by total
F igu r e 1. Lignans from Sesamum indicum.
synthesis as follows: the presence of a conjugated
ketone in (+)-episesaminone (2) was suggested from its
IR (1647 cm-1) and UV (312 nm) absorbances and was
further supported from the resonance at 197.3 ppm in
its 13C-NMR spectrum, which revealed an aromatic
conjugated carbonyl group, with the latter confirmed by
was assigned to the oxybenzylic proton H-7 in a trans
configuration to H-8. Next, the multiplets centered at
4.28 and 4.10 ppm were correlated in the H-1H COSY
1
NMR spectrum and assigned to the three proton reso-
nances, viz. the protons of the methylene group at C-9′
and the methine proton at C-8′. In the same way, the
multiplets at 3.76-3.66 and 2.86 ppm were correlated
in the 2D 1H-1H spectrum and assigned to the hy-
droxymethyl group at C-9 and the methine proton at
C-8. Furthermore, 2D 13C-1H HETCOR NMR spectro-
scopic studies confirmed the furanoketone structure by
assignment of chemical shifts in the 13C-NMR spectrum
1
1
use of a H-13C 2D NMR HMBC experiment. The H-
NMR spectrum showed two aromatic o-carbonyl protons
at 7.56 ppm (1H, dd, J ) 8.1 Hz, J ) 1.7 Hz) and 7.45
ppm (1H, d, J ) 1.7 Hz). Additionally, the proton
resonances at 7.56 and 7.45 ppm, together with those
at 6.86 ppm (1H, d, J ) 8.1 Hz) and two methylenedioxy
protons downfield at 6.05 ppm, were indicative of a 3,4-
methylenedioxyphenyl (piperonyl) acetophenone system.
This was additionally supported by its mass spectrum,
which exhibited a base peak at m/z 149 and a fragment
ion at m/z 121, corresponding to acylium ion [ArCO+]
and piperonyl ion [Ar+] fragments, generated after
carbon-carbon bond cleavage at C-7′/C-8′ and C-7′/C-
1′, respectively.7 In an analogous manner, the second
piperonyl system was established by the proton reso-
nances at 6.95, 6.84, 6.76 (aromatic protons), and 5.94
ppm (OCH2O). This was further confirmed from its 13C-
NMR spectrum, using both DEPT and HMBC, to
determine the multiplicities and 3J coupling relation-
ships. That is, the methylenedioxy bridges at 5.94 and
6.05 ppm in the 1H-NMR spectrum were correlated with
the two OCH2O groups at 101.13 and 102.01 ppm,
respectively, thereby confirming the piperonyl structure
for both aromatic substituents in the 13C-1H HETCOR
NMR spectrum. The remaining assignments were
made using a combination of 1H, 1H-1H COSY, 13C
(DEPT mode), and 13C-1H HETCOR NMR spectroscopic
analyses, which established the tetrahydrofuran skel-
eton as follows: the doublet at 4.64 ppm (J ) 9.1 Hz)
1
relative to the corresponding H-NMR resonances (see
Experimental Section), in a manner analogous to that
used for other naturally occurring keto-lignans.8,9 Thus,
the methylenic multiplets at 4.28-4.10 ppm and 3.76-
3.66 ppm displayed correlations with the methylenic
carbon at 70.84 (C-9′) and the CH2OH group at 61.29
ppm (C-9), respectively, as did the multiplets at 4.18
and 2.86 ppm with the methine carbons at 49.98 ppm
(C-8′) and 52.26 ppm (C-8) in the DEPT 13C-NMR
spectrum. Additionally, the H-7 proton at 4.64 ppm was
correlated with the methine carbon (C-7) at 83.70 ppm,
thereby accounting for all of the resonances of the
tetrahydrofuran skeleton. Further support for this
structural determination was made by MS analysis,
which displayed a molecular ion at m/z 370, together
with fragment ions at m/z 203, 149, and 121 corre-
sponding to [ArC5H6O+], [ArCO+], and [Ar+], respec-
tively.7
Next, nuclear Overhauser enhancement difference
experiments established a cis stereochemistry between
the H-8 and H-8′ protons on the bridgehead carbons.
Furthermore, since no NOE was observed between the
H-7 and H-8 protons, these therefore had a trans
stereochemical relationship between them. Thus, (+)-
episesaminone (2) has the same overall stereochemistry
as that of magnolenin C (3) from Magnolia grandiflora10
(Figure 2). The absolute configuration of 2 at C-8′ was
* To whom correspondence should be addressed. Phone: 509-335-
2682. FAX: 509-335-7643. E-mail: lewisn@wsu.edu.
† Present address: Instituto de Quimica, Universidade de Sa˜o Paulo,
26077, 05599-970 Sa˜o Paulo SP, Brazil.
X Abstract published in Advance ACS Abstracts, November 1, 1997.
S0163-3864(97)00295-4 CCC: $14.00
© 1997 American Chemical Society and American Society of Pharmacognosy

1190 J ournal of Natural Products, 1997, Vol. 60, No. 11
Notes
shown in Scheme 1. Thus, oxidation of (+)-samin 7 with
pyridinium dichromate (PDC) under acidic conditions1,16
afforded the corresponding lactone, (+)-acuminatolide
81,17 in 78% yield. Subsequent condensation of 8 with
the Grignard reagent,18 obtained from bromosesamol (1-
bromo-3,4-(methylenedioxy)benzene), at room temper-
ature, followed by hydrolysis of the intermediate lactol
9, gave (+)-episesaminone (2) as shown (Scheme 1). The
synthetic product was identical in all respects to natu-
rally occurring (+)-episesaminone (2) (see Experimental
Section), except for the optical rotation value, i.e., [R]D
+120° (c 0.127, CHCl3) versus that of the natural
product 2 [[R]D +126.2° (c 0.127, CHCl3)]. Thus, since
(+)-samin 7 has a R configuration at C-8′,1,14 this
confirms the proposed stereochemical assignment of (+)-
episesaminone (2).
F igu r e 2. Lignan metabolites isolated from Magnolia gran-
diflora and Sesamum indicum, as well as from Streptomyces
cell cultures grown on sesame-seed media.
Last, in terms of the biosynthesis of (+)-episesami-
none (2), it can tentatively be proposed that it is formed
in vivo from (+)-sesamin (5) (Figure 2). Given that (+)-
episesaminone (2) can exist in its lactol form (see Figure
1) under basic conditions,10 only a single oxidation step
from (+)-sesamin 5 to 2 is required. Additionally, it
should be noted that its C-8′ S epimer, (-)-sesaminone
(4) (Figure 2) has been reported as present in Strepto-
myces IT-44 cell cultures grown on sesame-seed media.11
A possible explanation for its formation is that cis (+)-
episesaminone (2) is epimerized at C-8′ under prolonged
basic treatment to give the more stable trans form 4.
F igu r e 3. Dimer 6 obtained by acid hydrolysis of sesamolin
1.
Sch em e 1. Hemisynthesis of (+)-Episesaminone (2)
from (+)-Sesamolin (1)
Exp er im en ta l Section
P la n t Ma t er ia ls. Seeds of S. indicum (unroasted
and unbleached) were either purchased from a local
produce store or obtained from ripe pods of mature S.
indicum plants grown in greenhouses at Washington
State University.
Gen er a l Exp er im en ta l P r oced u r e. Solvents were
either HPLC grade (CH3CN, MeOH, AcOH, CH2Cl2,
THF) or ACS grade (EtOAc, Hexanes) from Baker.
Tetrahydrofuran (THF) and methylene chloride (CH2-
Cl2) were distilled over LiAlH4-triphenylmethane and
CaH2, respectively. Column and analytical TLC sepa-
rations (Al Si G/UV 254) were performed using Si gel
60 (230-400 mesh) (Whatman). IR spectra were re-
corded on a Perkin-Elmer 1720-X FTIR spectrometer,
whereas NMR spectra were obtained using either
deduced as R ([R]D + 126.2°; c 0.127, CHCl3), given that
the previously reported S epimer,11 (-)-sesaminone (4)
had a negative optical rotation ([R]D - 25.0°; c 0.14,
MeOH).
1
Bruker AMX300 (for H, 13C, and 2D NMR) or Varian
To establish unambigously the proposed structure of
(+)-episesaminone (2), its hemisynthesis from (+)-
sesamolin (1),12 a readily available sesame-seed lignan
together with (+)-sesamin (5),13 was next developed. The
approach used was based on the known chemistry of
(+)-sesamolin (1), which can be hydrolyzed in H2SO4-
EtOH to give, as the major products, the dimer 6 (Figure
3) and lactol (+)-samin (7).14 Subsequent modification
of this hydrolytic procedure with 1 in acetate buffer (165
mM, pH 1.0) in EtOH gave three compounds: the
symmetrical dimer 6 (disaminyl ether) as the major
product, as well as smaller yields (10-20%) of the
required (+)-samin (7) and its corresponding ethoxy-
ether.15
Further refinement of the hydrolytic procedure, how-
ever, using DOWEX-50 X 2-200 exchange resin, NaOAc
buffer (165 mM, pH 1.0), and 10% HCl in CH3CN gave
7 in 65% yield (Scheme 1).
From lactol 7, the key step to afford (+)-episesami-
none (2) was a mono-Grignard addition to lactone 8 as
500VXR (for NOE measurements) spectrometers. All
spectra were recorded in CDCl3 using TMS as internal
reference, with chemical shifts (δ) expressed in parts
per million and coupling constants (J ) in Hertz. UV and
ORD spectra were recorded on a Perkin-Elmer Lambda
6 UV/vis spectrophotometer and a J ASCO 181 polarim-
eter at λ 289 nm (Na), respectively. HPLC separations
were carried out in the reversed-phase mode [Waters
C18 Nova-Pak, 150 × 3.9 mm i.d., 4 µm], eluted with
MeOH-H2O in a linear gradient of 3:7 f 7:3 over 60
min with detection at 280 nm. EIMS analyses were
carried out with an HPLC-MS (Integrity Waters), using
a reversed-phase column (Waters C18 Nova-Pak, 150 ×
2 mm i.d., 4 µm) eluted with a linear solvent gradient
A: H2O (3% v/v acetic acid) and B: CH3CN; as follows:
8:2 f 7:3 in 10 min, then 7:3 f 1:1 in 25 min; MS
analyses TIC (Total Intensity Chromatogram) were
performed from m/z 80 to 700 at a rate of 1 scan s-1
with an optimal temperature of the nebulizer at 80 °C
,

Notes
J ournal of Natural Products, 1997, Vol. 60, No. 11 1191
using (+)-sesamin (5) as a reference. Interpretation of
fragmentation patterns were calculated where Ar ) 3,4-
methylenedioxyphenyl.7 HRMS analyses employed a
VG 7070 EHF mass spectrometer at 70 eV.
Ripe P od Extr action . Mature (9-12 weeks’ growth)
S. indicum greenhouse grown plants were harvested,
with the intact seeds (50 g) carefully removed, and
immediately homogenized in a Waring blender contain-
ing MeOH (200 mL) and then extracted with hot MeOH
(50 °C, 3 × 200 mL). The resulting MeOH extracts (800
mL) were combined, filtered under reduced pressure
over a short path of sea sand, and the filtrate evaporated
to dryness in vacuo. The resulting residue was sub-
jected to column chromatography on Si gel (60 g) using
hexane-EtOAc 3:1 as solvent to give (+)-sesamolin (1)
(20 mg) and (+)-sesamin (5) (10 mg).9 Further elution
with hexane-EtOAc 1:1 gave two fractions; HPLC-MS
of the latter fraction gave a single component at the
same retention time as 2 with identical UV and MS
spectra to those of the synthetic (+)-episesaminone (2).
Isola tion of (+)-Ep isesa m in on e (2). Commercially
available S. indicum seeds (1.28 kg, unroasted) were
homogenized in a Waring blender containing MeOH (1
L) and extracted exhaustively with hot MeOH (11 × 1
L) at 50 °C. The resulting MeOH solubles (12 L) were
combined, cooled to 0 °C for 45 min, then filtered with
the filtrate concentrated in vacuo to give an oily residue.
This residue was suspended in MeOH-H2O (1:1, 150
mL), then sequentially extracted with hexanes (2 × 400
mL) and EtOAc (4 × 500 mL). The EtOAc solubles were
combined and concentrated (15 mL), to which MeOH
(150 mL) was next added. The resulting precipitate
(3.24 g) was removed by filtration to give a crude
mixture of (+)-sesamin (5) and (+)-sesamolin (1),9,19
with the filtrate concentrated to afford a yellow gum
(12.3 g). The latter was dissolved in a minimal amount
of EtOAc and applied to a Si gel column (300 g) eluted
with a hexane-EtOAc gradient (5:1 to 1:1; 150 mL
each). Fractions 6-7 (25 mL each) and 8-9 contained
(+)-sesamin (5) (536 mg)13 and (+)-sesamolin (1) (279
mg),9 respectively. Fractions 13-15 were evaporated
to dryness, reconstituted in CHCl3, then subjected to
preparative TLC eluted with 3% (v/v) MeOH in CHCl3
to give (+)-episesamin (2 mg) (C-7′ epimer of 5),7 (+)-
kobusin (1.5 mg),20 and a more polar fraction. The latter
was subjected to analytical HPLC separation [C18
reversed-phase, eluted with MeOH-H2O, linear gradi-
ent 3:7 f 7:3 in 60 min] to give (+)-piperitol (2 mg)21
and (+)-sesamolinol (1 mg).22 Fractions 17-20 (58 mg)
were pooled and purified by preparative TLC (CHCl3-
MeOH 5:1) to give two fractions, purification of which
by analytical HPLC as before gave (+)-sesamolinol (1.5
mg)22 and (+)-episesaminone (2) (1 mg), respectively.
Fractions 21-24 (88 mg) were chromatographed on Si
gel eluted with 5% (v/v) MeOH in CHCl3 to afford (+)-
pinoresinol (23 mg)23 and trans-ferulic acid (7 mg).
Hydrolysis of 1 to give the known (+)-samin 7,13
subsequent conversion to (+)-acuminatolide (8), and
complete physical and spectroscopic data of 7 and 8 are
described elsewhere.1
Dim er 6: IR (CHCl3) νmax 1503, 1443 (CdCAr), 1248
(C-O) cm-1; UV (CHCl3) λmax (log ꢀ) 243 (3.8), 288 (3.9),
337 (1.32) nm; mp 188-189 °C (MeOH), (lit.14 191-192
°C); [R]D +160.1° (c 1.37, CHCl3) (lit.14 [R]D +143° (c
1.74, CHCl3)); MS m/z 482 [M+] (5), 233 [C13H13O4+] (10),
203 [ArC5H6O+] (15), 189 (5), 163 (10), 150 [ArCHO+]
(95), 149 [ArCO+] (100), 135 [ArCH2+] (90), 121 [Ar+]
(20); HRMS 482.1581 (calcd for C26H26O9, 482.1517); 1H-
NMR δ 6.90-6.75 (m, 6H, H-2, H-5 and H-6), 5.96 (s,
4H, OCH2O), 5.29 (s, 2H, H-7′), 4.37 (d, J ) 8.4 Hz, 2H,
H-7), 4.38 (dd, J ) 9.2 Hz, J ) 7.8 Hz, 2H) and 4.05-
3.95 (m, 4H) and 3.58 (dd, J ) 9.2 Hz, J ) 7.8 Hz, 2H,
H-9 and H-9′), 3.05-2.95 (m, 2H, H-8′), 2.90-2.85 (m,
2H, H-8); 13C-NMR (DEPT mode) δ 148.06 (s, C-3),
147.39 (s, C-4), 134.63 (d, C-1), 119.78 (d, C-6), 108.25
(d, C-5), 106.65 (d, C-2), 102.96 (d, C-7′), 101.17 (t,
OCH2O), 87.06 (d, C-7), 71.44 (t, C-9), 69.43 (t, C-9′),
52.84, 52.77 (d, C-8 and C-8′) ppm.
Syn th esis of (+)-Ep isesa m in on e (2). A suspension
of magnesium turnings (5.2 mg, 1.2 equiv) and 1-bromo-
3,4-(methylenedioxy)benzene (1.1 equiv, 23.5 mL) in dry
THF (5 mL) was heated under argon until reflux began,
this being maintained for 3 h. The resulting suspension
was cooled to room temperature and added dropwise to
a solution of 8 (44 mg, 0.177 mmol) in dry THF (50 mL).
After being stirred for 12 h, the solvent was removed
in vacuo, with the resulting residue subjected to column
chromatography (hexane-EtOAc, 3:1 then 1:1) to give
2 (18.4 mg, yield 29%, conversion 47% based on starting
material) and unreacted starting material 8 (18 mg).
The [R]D (120°; c 0.127, CHCl3), MS, HRMS, 1H and 13C
NMR, IR, and UV spectra were identical with naturally
occurring (+)-episesaminone (2) except for the optical
rotation value, i.e., [R]D +120° (c 0.127, CHCl3) versus
that of the natural product 2 {[R]D +126.2° (c 0.127,
CHCl3) see above}.
(+)-E p isesa m in on e (2). (+)-[3R-(3R,4R,5â)]-1,3-
Benzodioxol-5-yl[1-(1,3-benzodioxol-5-yl)-2-(hydroxy-
methyl)tetrahydro-1H,3H-3-furanyl]methanone: IR
(CHCl3) νmax 3600-3200 (OH), 1647 (CdO), 1604, 1505,
1444, 1409 (CdC Ar), 1251 (C-O) cm-1; UV (MeOH)
λmax (log ꢀ) 230 (4.76), 280 (3.75), 312 (2.87) nm; [R]D
+126.2° (c 0.127, CHCl3); MS m/z 370 [M+] (38), 352
[M - H2O+] (5), 243 (5), 203 [ArC5H6O+] (25), 194 (40),
176 (48), 152 (50), 150 [ArCHO+] (45), 149 [ArCO+]
(100), 121 [Ar+] (40); HRMS m/z 370.1044 (calcd for
1
C20H18O7, 370.1053); H-NMR δ 7.56 (1H, dd, J ) 8.1
Hz, J ) 1.7 Hz, H-6′), 7.45 (1H, d, J ) 1.7 Hz, H-2′);
6.95 (1H, d, J ) 1.65 Hz, H-2), 6.86 (1H, d, J ) 8.1 Hz,
H-5′), 6.84 (1H, dd, J ) 7.94 Hz, J ) 1.65 Hz, H-6), 6.76
(1H, d, J ) 7.94 Hz, H-5), 6.05 (2H, s, OCH2-O), 5.94
(2H, s, OCH2-O), 4.64 (1H, d, J ) 9.1 Hz, H-7), 4.28
(1H, m, H-9′eq), 4.10 (2H, m, H-9′ax + H-8′), 3.76 (1H,
m) and 3.66 (1H, m, H-9), 2.86 (1H, m, H-8); 13C-NMR
(DEPT mode) δ 197.30 (s, C-7′), 152.18 (s, C-4′), 148.44
(s, C-3′), 147.98 (s, C-4), 147.45 (s, C-3), 134.42 (s, C-1),
131.14 (s, C-1′), 124.93 (d, C-6′), 119.08 (d, C-6), 108.30
(d, C-5), 108.09 (d, C-2′), 107.93 (d, C-5′), 107.14 (d, C-2),
102.01 (t, OCH2O), 101.13 (t, OCH2O), 83.70 (d, C-7),
70.84 (t, C-9′), 61.29 (t, C-9), 52.26 (d, C-8), 49.98 (d,
C-8′) ppm.
Ack n ow led gm en t. The authors wish to thank the
National Science Foundation (MCB-9219586), and the
Arthur M. and Kate Eisig-Tode Foundation (to P.A.M.)
for generous support of this study, as well as to FAPESP
(M.J .K.) for providing a travel grant, Dr. W. F. Siems
(Department of Chemistry, Washington State Univer-
sity) for high resolution mass spectra and Dr. J . Zajicek
for helpful discussions.

1192 J ournal of Natural Products, 1997, Vol. 60, No. 11
Notes
(13) Davenport, J . B.; Sutherland, M. D. Aust. J . Chem. 1954, 7, 384-
386.
(14) Haslam, E.; Haworth, R. D. J . Chem. Soc. 1955, 827-833.
(15) Fukuda, Y.; Isobe, M.; Nagata, M.; Osawa, T.; Namiki, M.
Heterocycles 1986, 24, 923-926.
Refer en ces a n d Notes
(1) Marchand, P. A.; Zajicek, J ., Lewis, N. G. Can. J . Chem. 1997,
75, 840-849.
(2) Davin, L. B.; Wang, H.-B.; Crowell, A. L.; Bedgar, D. L.; Martin,
D. M.; Sarkanen S.; Lewis. N. G. Science 1997, 275, 362-366.
(3) Dinkova-Kostova, A. T.; Gang, D. R.; Davin, L. B.; Bedgar, D.
L.; Chu, A.; Lewis, N. G. J . Biol. Chem. 1996, 271, 29473-29482.
(4) Chu, A.; Dinkova, A.; Davin, L. B.; Bedgar D. L.; Lewis. N. G.
J . Biol. Chem. 1993, 268, 27026-27033.
(16) Corey, E. J .; Su, W.-G. J . Am. Chem. Soc. 1987, 109, 7534-
7536.
(17) J akupovic, J .; Pathak, V. P.; Bohlmann, F.; King, R. M.;
Robinson, H. Phytochemistry 1987, 26, 803-807.
(18) Ishibashi, H.; Su So, T.; Okochi, K.; Sato, T.; Nakamura, N.;
Nakatani, H.; Ikeda, M. J . Org. Chem. 1991, 56, 95-102.
(19) Adriani, W. Z. Unters. Lebensmittel 1928, 56, 187-194.
(20) Iida, T.; Nakano, M.; Ito, K. Phytochemistry 1982, 21, 673-675.
(21) Brieskorn, C. H.; Huber, H. Tetrahedron Lett. 1976, 26, 2221-
2224.
(5) Gang, D. R.; Dinkova-Kostova, A. T.; Davin, L. B.; Lewis, N. G.
ACS Symp. Ser. 1997, 658, 58-89.
(6) Davin, L. B.; Lewis, N. G. ACS Symp. Ser. 1994, 562, 202-246.
(7) Pelter, A.; Ward, S.; Rao, E. V.; Sastry, K. V. Tetrahedron 1976,
32, 2783-2788.
(8) Kinjo, J .; Higuchi, H.; Fukui, K.; Nohara, T. Chem. Pharm. Bull.
1991, 39, 2952-2955.
(9) Banerji, A.; Sarkar, M.; Ghosal, T.; Pal, S. C.; Shoolery, J . N.
Tetrahedron 1984, 40, 5047-5052.
(22) Osawa, T.; Nagata, M.; Namiki, M.; Fukuda, Y. Agric. Biol.
Chem. 1985, 49, 3351-3352.
(23) Fonseca, S. F.; Nielsen, L. T.; Ruveda, E. A. Phytochemistry 1979,
18, 1703-1708.
(10) Rao, K. V.; Wu, W.-N. Lloydia 1978, 41, 56-62.
(11) Chiung, Y.-M.; Hayashi, H.; Matsumoto, H.; Otani, T.; Yoshida,
K.-I.; Huang, M.-Y.; Chen, R.-X.; Liu, J .-R.; Nakayama, M.
J . Antibiot. 1994, 47, 487-491.
(12) Takano, S.; Ohkawa, T.; Tamori, S.; Satoh, S.; Ogasawara, K.
J . Chem. Soc., Chem. Commun. 1988, 189-191.
NP9702953