Unusual isomeric corniculatolides from mangrove, Aegiceras corniculatum

Article abstract of DOI:10.1021/np200789s

Four new isomeric macrolides of combretastatin D-2 congeners named isocorniculatolide A (1), 11-O-methylisocorniculatolide A (2), 11-O-methylcorniculatolide A (3), and 12-hydroxy-11-O-methylcorniculatolide A (4), and the known corniculatolide A (5), arjunolic acid, and maslinic acid were isolated from the CHCl₃ extract of the bark of Aegiceras corniculatum. The structures of the new compounds (1-4) were elucidated by a combination of spectroscopic analysis (1-5), chemical modifications, and single-crystal X-ray analysis (1).

Full text of DOI:10.1021/np200789s

Note
pubs.acs.org/jnp
Unusual Isomeric Corniculatolides from Mangrove, Aegiceras
corniculatum
,
†
†
†
†
†
M. Gowri Ponnapalli,* S. CH. V. A. Rao Annam, Saidulu Ravirala, Sushma Sukki, Madhu Ankireddy,
and V. Raju Tuniki‡
†
Natural Product Chemistry, Indian Institute of Chemical Technology, Hyderabad, India, 500 607
‡
Centre for NMR and Structural Chemistry, Indian Institute of Chemical Technology, Hyderabad, India, 500 607
*
S Supporting Information
ABSTRACT: Four new isomeric macrolides of combretastatin D-2 congeners
named isocorniculatolide A (1), 11-O-methylisocorniculatolide A (2), 11-O-
methylcorniculatolide A (3), and 12-hydroxy-11-O-methylcorniculatolide A (4),
and the known corniculatolide A (5), arjunolic acid, and maslinic acid were isolated
from the CHCl extract of the bark of Aegiceras corniculatum. The structures of the
3
new compounds (1−4) were elucidated by a combination of spectroscopic analysis
(
1−5), chemical modifications, and single-crystal X-ray analysis (1).
Aegeceras corniculatum (syn. A. majus; family Aegecerataceae) is
a small tree or shrub that grows in the mangrove swamps of
Asia and Australia. It has been used traditionally to treat
1
asthma, diabetes, inflammation, and rheumatism. The earlier
2
pharmacological studies revealed cytotoxicity, itchytoxicity,
1
anti-inflammatory, antioxidant, and tyrosine phosphatase 1B
inhibitory activities of this plant. A number of saponins,
3
1
,3,4
triterpenes, sterols, and hydroquinones
have been pre-
viously reported from this plant. The metabolites that were
isolated from mangroves often possess unique structural
features and incorporate new or unusual assemblages of
Figure 1. Compounds isolated from Aegiceras corniculatum.
5
−8
functional groups.
In the course of our search for bioactive
C H O , suggesting 10 degrees of unsaturation. Its molecular
18
18
4
metabolites from Indian mangrove plants, the CHCl extract of
3
formula suggested the compound to be isomeric to
the bark of A. corniculatum afforded four new isomeric
macrolides of combretastatin D-2 congeners, named isocorni-
culatolide A (1), 11-O-methylisocorniculatolide A (2), 11-O-
methyl corniculatolide A (3), and 12-hydroxy-11-O-methyl-
9,10
corniculatolide A (5). The IR spectrum exhibited absorption
−1
−1
bands for hydroxy (3390 cm ) and carbonyl (1714 cm )
functionalities. It gave a monoacetate (1a) on acetylation with
acetic anhydride in pyridine, indicative of only one acylable
hydroxy group in the molecule.
9
,10
corniculatolide A (4), and the known corniculatolide A (5),
1
1
12
arjunolic acid, and maslinic acid. The D-series of
Compound 1 showed similar H and 13C NMR spectra
(Tables 1 and 2) to those of compound 5 (see Supporting
Information) with respect to chemical shifts and coupling
constants, while the overall spin systems for the macrolactone
1
1
3,14
combretastatins are reported only from Combretum caffrum
9
and Getonia fluoribunda (Combretaceae). Herein the isolation
and structure elucidation of the isolated metabolites 1−5
Figure 1) from the bark of A. corniculatum are reported. This is
(
1
1
and aromatic rings remain unchanged according to H− H
COSY and HMBC experiments (Figure 2). Minor differences
in the chemical shifts of the corresponding protons in
compound 1 and corniculatolide A show their close relation-
ship. The characteristic difference between these two could,
the first isolation of combretastatin D-2 congeners from A.
corniculatum.
1
Preliminary H NMR analyses of compounds 1−5 revealed
structural similarity and indicated the presence of a rare
1
3
caffrane skeleton. Compound 1 was obtained as colorless
crystals, mp 200−202 °C. The HR-ESIMS of compound 1
displayed a protonated molecular ion [M + H]+ at m/z
Received: October 4, 2011
Published: February 8, 2012
299.1283 (calcd 299.1278) to deduce a molecular formula of
©
2012 American Chemical Society and
American Society of Pharmacognosy
275
dx.doi.org/10.1021/np200789s | J. Nat. Prod. 2012, 75, 275−279

Journal of Natural Products
Note
1
Table 1. H NMR Chemical Shifts of Compounds 1, 1a, 2, 3, 4, 5, and 5a (600 MHz, in CDCl )
3
1
1a
2
3
4
5
5a
δH (J, Hz)
4.06, m
position
δH (J, Hz)
δH (J, Hz)
δH (J, Hz)
δH (J, Hz)
δH (J, Hz)
δH (J, Hz)
2
3
4
6
7
4.06, m
4.05, m
4.05, m
2.52, t (6.8)
3.03, t (6.8)
7.25, d (8.3)
7.02, d (8.3)
6.85, d (8.3)
6.60, dd (8.3, 2.3)
2.48, t (6.7)
1.73, m
2.52, t (6.7)
3.02, t (6.7)
7.22 d (8.3)
7.03 d (8.3)
6.94 d (8.1)
6.69 dd (8.1, 1.8)
2.51 t (6.9)
1.76, m
2.53, t (6.7)
3.03, t (6.7)
7.23, d (8.5)
7.05, d (8.5)
6.83, d (8.1)
6.65, dd (8.1, 1.7)
2.49, t (6.8)
1.73, m
2.10, m
2.09, m
2.09, m
2.08, m
2.81, t (6.5)
7.29 d (8.3)
7.01 d (8.3)
6.81 d (8.1)
6.66, dd (8.1, 1.8)
2.85, m
2.80, m
2.81, m
2.79, t (6.6)
7.25, d (8.4)
7.01, d (8.4)
6.93, d (8.1)
6.65, dd (8.1, 2.1)
2.88, t (5.2)
2.27, m
7.29, d (8.3)
7.01, d (8.3)
7.30, d (8.4)
7.01, d (8.4)
6.83, d (8.1)
6.60, dd (8.1, 2.1)
2.84, m
1
1
1
1
1
1
1
2
2
3
5
6
7
8
9
0
6.35, s
2.80, m
2.24, m
2.26, m
2.25, m
3.58, t (6.7)
7.25, d (8.3)
7.02, d (8.3)
5.38, d (2.3)
5.57, br s
3.58, t (6.9)
7.22, d (8.3)
7.03, d (8.3)
5.53, d (1.8)
3.63, t (6.8)
7.23, d (8.5)
7.05, d (8.5)
5.38, d (1.7)
7.29, d (8.3)
7.05, d (8.3)
5.30, d (1.8)
7.29, d (8.3)
7.01, d (8.3)
4.85, s
7.30, d (8.4)
7.01, d (8.4)
5.29, d (2.1)
5.53, br s
7.25, d (8.4)
7.01, d (8.4)
5.42, d (1.8)
OH
5.76, br s
4.06, s
OMe
OAc
3.95, s
3.95, s
2.39, s
2.39, s
Table 2. 13C NMR Chemical Shifts of Compounds 1, 1a, 2, 3, 4, 5, and 5a (150 MHz,in CDCl3)
1
1a
2
3
4
5
5a
position
δC
δC
δC
δC
δC
δC
δC
2
173.1
38.6
173.1
38.5
173.1
38.6
63.9
28.6
63.9
28.6
63.9
28.6
63.9
28.6
3
4
5
6
7
8
1
1
1
1
1
1
1
1
1
1
2
32.3
32.4
32.4
33.9
33.9
33.9
33.9
137.9
130.6
123.7
155.9
149.2
142.7
115.3
122.1
131.5
28.2
137.7
130.5
123.7
155.9
153.1
139.4
117.0
122.7
137.0
28.4
137.5
130.5
123.9
156.2
151.7
146.4
112.1
121.4
132.2
28.2
137.4
131.0
123.6
154.5
151.1
146.1
113.2
120.8
133.1
26.9
137.6
130.9
123.4
154.5
153.9
133.1
149.0
107.7
136.3
27.3
137.9
131.1
123.5
154.2
149.0
142.5
114.9
121.5
132.6
27.0
137.7
131.0
123.4
154.4
153.1
139.2
114.2
121.2
136.6
27.3
0
1
2
3
4
5
6
7
8
9
0
26.3
26.8
26.7
32.7
32.3
32.7
32.3
62.2
61.9
62.1
173.9
131.0
123.6
111.6
56.1
173.3
130.9
123.4
105.7
61.3
173.9
131.1
123.5
112.6
173.5
131.0
123.4
122.4
130.6
123.7
115.4
130.5
123.7
122.7
130.5
123.9
116.2
56.2
OMe
OCOCH3
OCOCH3
169.2
20.8
169.3
20.8
1
1
were evident from the H− H COSY cross-peaks, viz., H-15/
H-16 and H-16/H-17. All the proton and carbon resonances
have been assigned on the basis of 2D-NMR interpretation
(
Table 3). Its HMBC spectrum exhibited a strong correlation
between the carbonyl carbon (C-2) and the 17-methylene,
which was crucial in assembling the macrolide portion of 1.
1
1
The H− H NOESY spectrum revealed the spatial
correlations between H-20 and H-16/H-17/H-19 (Figure 3).
1
13
1
1
1
1
From the H and C NMR, H− H COSY, and H− H
NOESY spectra, a computer-generated 3D structure was
obtained by using the molecular modeling program CS
CHEM 3D version 11 with MMFF force field calculations for
energy minimization in the Discovery Studio Module. The
calculated distances between H-20/H-19 (3.659 Å), H-20/H-
16 (2.191 Å), H-20/H-17 (2.653 Å), H-13/H-15 (2.579 Å),
Figure 2. Key COSY and HMBC correlations of compound 1.
however, be seen within the macrolactone structure due to the
possibility of lactone formation between C-2 and C-17 or vice
versa analogous to 5. The connectivities from C-15 to C-17
2
76
dx.doi.org/10.1021/np200789s | J. Nat. Prod. 2012, 75, 275−279

Journal of Natural Products
Note
1
1
1
1
1
Table 3. Key HMBC, H− H COSY, and H− H NOESY
10 sites of unsaturation. The H NMR spectrum of 2 resembles
Correlations of Compound 1
that of 1, except for the presence of an O-methyl group at δ
H
13
3
.95 (s, 3H) (Table 1). The C NMR values of all the carbons
position
HMBC
C2, C4, C5
COSY
NOESY
18
of 2 agreed closely with those of 1 except for the differences in
the chemical shifts of C-10, C-11, and C-12, which were
consistent with the presence of an O-methyl group. 2D-NMR
analysis (Table S2 and Figure S1) showed that 2 was the 11-O-
methyl derivative of 1.
The HR-ESIMS of compound 3 showed a sodiated
molecular ion peak at m/z 335.1251 ([M + Na] , calcd
35.1259). Its spectroscopic properties closely resemble those
of 5. It showed an O-methyl absorption at 2852 cm in its IR
spectrum, suggesting that it might be a methyl ether of 5. This
3
4
6
7
4
C2, C3, C5, C6, C18
C4, C7, C8, C18
C5, C6, C8, C19
C10, C11, C14
3
6
4
15
7
6
1
1
1
1
1
1
1
2
2
3
5
6
7
8
9
0
13
12
16
15, 17
16
19
18
C11, C15, C20
15
+
C13, C14, C16, C17, C20
C14, C15, C17
13
3
20
−1
C2, C15, C16
20
C4, C6, C8, C19
C5, C6, C8, C18
C10, C11, C13, C14, C15
3
was supported by the presence of an O-methyl group at δ 3.95
s, 3H) in its H NMR spectrum (Table 1). The coupling
20
1
(
15, 16, 17
1
patterns of aromatic protons in the H NMR spectrum
suggested that the methoxy group was situated at C-11.
NOESY spectrum of 3 revealed the correlation between the
methoxy protons and H-12. The 2D-NMR spectra (Table S2
and Figure S2) supported its structure as 11-O-methylcornicu-
latolide A.
Compound 4 was analyzed as C H O (329.1373 m/z [M
1
9
20
5
+
1
+
H] by HR-ESIMS. Its H NMR spectrum closely resembles
that of 3, except for the presence of an additional hydroxy
1
1
group at C-12 (Table 1). Diagnostic H− H COSY, HSQC,
and HMBC correlations revealed that 4 was the hydroxylated
analogue of 11-O-methylcorniculatolide A. The structural
assignments of compound 4 were supported by comparison
1
13
of the spectroscopic data of 4 with those of 3. The H and C
NMR chemical shift values of 4 were fully consistent with those
of 3 except in the region from C-10 to C-14. This is in
accordance with the introduction of a hydroxy group at C-12,
which was further confirmed by 2D-NMR interpretation (see
Table S2 and Figure S2) to derive the structure of 4 as 12-
hydoxy-11-O-methylcorniculatolide A.
Figure 3. Key NOESY correlations of compound 1.
and H-4/H-6 (2.607 Å) are less than 4.00 Å; this is consistent
with the well-defined NOESY observed for each of these pairs.
Finally, the position of the lactone moiety between C-2 and
C-17 was supported by X-ray crystal structure determination
Interestingly, the H-20 signal in compounds 1−5 was
strongly shielded, because this proton is located above the
plane of the other aromatic ring. Dreiding models of 1 and 5
showed that the two aromatic rings are perpendicular to each
other, analogous to the D-series of combretastatins. The X-ray
crystal structure of 1 also further supported this observation.
Active fraction AEG-7 afforded arjunolic acid and maslinic
acid. These triterpenoids are responsible for the traditional use
of mangrove in the treatment of inflammatory diseases.
Another active fraction, AEG-3, afforded stigmasterol,
(Figure 4 and Table S1) to establish the structure of compound
1
as isocorniculatolide A.
1
corniculatolide A, an unidentified minor constituent ( H
NMR in SI as a mixture as well as pure form after separation),
and new compounds 1−4. The activity of this fraction may be
attributed to the presence of minor constituents that could not
be identified. Compounds 1−5 were found to be inactive in an
agar diffusion assay against the bacteria Staphylococcus aureus,
Bacillus subtilis, Micrococcus luteus, Escherichia coli, Klebsiella
pneumoniae, and the fungi Aspergillus niger, Aspergillus terreus,
and Aspergillus flavus.
Figure 4. ORTEP drawing of compound 1.
Biosynthetically, the isomers 1 and 5 are most probably
derived from phenylalanine. Partial reduction of the carboxylic
acid moiety seems to be the key step prior to the lactonization
in the proposed biosynthetic pathway (Scheme S1).
EXPERIMENTAL SECTION
■
General Experimental Procedures. Melting points were
determined on a Fischer-John micro melting point apparatus and
are uncorrected. IR spectra were recorded on a Nicolet-740 FT-IR
spectrophotometer. The NMR spectra were recorded with Bruker
Avance (300 MHz), Varian Inova (400 MHz), and Bruker Avance II
Compound 2 was obtained as colorless crystals. Its HR-
+
ESIMS showed an [M + H] ion at m/z 313.1445 (calcd
1
13
1
13
3
13.1434). When considered in conjunction with H and
C
(
600 MHz) for H and 75/100/150 MHz for C NMR spectra in
NMR data, this indicated a molecular formula of C H O with
CDCl with TMS as internal standard. Coupling constants are given in
1
9
20
4
3
2
77
dx.doi.org/10.1021/np200789s | J. Nat. Prod. 2012, 75, 275−279

Journal of Natural Products
Note
−
1
1
13
Hz. The ESIMS data were recorded on an Agilent 1100 MSD with an
ESI SL trap. The HR-ESIMS data were acquired on an Agilent 6510
Q-TOF and ESI probe. The UV−vis spectra were obtained using a
JASCO V-550 spectrophotometer. The X-ray diffraction measure-
ments were carried out at 298 K on a Bruker SMART APEX CCD
area detector system equipped with a graphite monochromator and
Mo Kα fine-focus sealed tube (λ = 0.71073 Å).
The bark of A. corniculatum was collected in March 2009 from the
Nizampatnam (latitude: 15°53′ N, longitude: 80°38′ E) coast of India
and identified by Prof. B. Kondala Rao, Department of Marine Living
Sources, Andhra University, Visakhapatnam. A voucher specimen (#
IIC-MG-107) has been deposited at the Herbarium of Natural Product
Chemistry, IICT.
1518, 1444, 1428, 1218, 1201 cm ; H, C, and 2D-NMR data (see
+
Tables 1, 2 and S2); HR-ESIMS m/z 335.1251 [M + Na] (calcd for
C H O Na, 335.1259).
19
20
4
12-Hydroxy-11-O-methylcorniculatolide A (4): C H O ; color-
less needles from a mixture of n-hexane and acetone (7:3); R 0.5
(hexane−acetone, 7:3); mp 244−245 °C; UV (CH OH) λ 275 nm
(ε 1795); IR (KBr) ν 3445, 2924, 1728, 1595, 1505, 1436, 1214
cm ; H, C, and 2D-NMR data (see Tables 1, 2 and S2); HR-
ESIMS m/z 329.1373 [M + H] (calcd for C H O Na,329.1388).
Corniculatolide A (5): C H O ; colorless needles from n-hexane
19
20
5
f
3
max
max
−
1
1
13
+
19
21
5
18
18
4
and acetone (8:2); R 0.45 (n-hexane−acetone, 7.5:2.5); mp 175−177
f
°C; UV (CH OH) λmax 278 nm; IR (KBr) νmax 3441, 2964, 1706,
3
−
1
1
13
1595, 1514, 1441, 1246, 1212 cm ; H and C NMR data (see
Tables 1, 2); HR-ESIMS m/z 299.1299 [M + H]+ (calcd for
The air-dried bark (5.0 kg) of A. corniculatum was ground to a fine
powder and was extracted with CHCl (10 L) in a Soxhlet apparatus
C
18
H
19
O
4
, 299.1283).
11-Acetoxycorniculatolide A (5a): C20H O ; IR (KBr) νmax 1765,
20 5
3
for 18 h to give the crude extract (32.0 g). The CHCl extract (31.0 g)
3
−1
1
13
was subjected to VLC on silica gel (230−400 mesh) and eluted with
mixtures of n-hexane and acetone−MeOH of increasing polarity to
give 30 fractions of 800 mL each. The identical fractions were pooled
based on the TLC profile. A total of nine main fractions (AEG-1−8)
were obtained and were tested for antimicrobial activity in an agar
diffusion assay. Fractions displaying significant activity were further
fractionated, using the methods described below. TLC profiles were
used to examine the pattern of significant components present in the
active fractions.
1730, 1594, 1505, 1433, 1258, 1216 cm ; H, and C NMR data (see
Tables 1, 2); HR-ESIMS m/z 341.1370 [M + H]+ (calcd for
C H O , 341.1384).
20 21 5
ASSOCIATED CONTENT
Supporting Information
■
*
S
Experimental Section: collection, extraction, and isolation;
1
13
spectral data of compounds 1−5; H/ C NMR, DEPT, and all
2D-NMR spectra for 1 to 4; H/ C NMR and DEPT spectra
of 5; H NMR of unidentified minor constituent and acetylated
compounds of 1 and 5; H NMR spectra of a mixture of
subfractions; X-ray data of 1. This material is available free of
charge via the Internet at http://pubs.acs.org.
1
13
Fraction AEG-3 (60 mg), a complex mixture of crude macrolides,
was obtained by gradient elution with n-hexane and acetone (8:2).
1
Repeated silica gel CC of this fraction gave four fractions (F −F ) and
1
1
4
revealed the presence of isomeric macrolide mixtures of 1 and 5 (20
mg); 2 and a minor constituent (2 mg); 3 and stigmasterol (10 mg);
and 4 and a minor constituent (4 mg).
Fractions F −F on subsequent silica gel CC afforded the
1
3
AUTHOR INFORMATION
metabolites 2 (1 mg), 3 (2 mg), and 4 (1 mg), minor constituents
■
*
(
<0.004 mg), and stigmasterol (7 mg). Our initial attempt to isolate
compound 1 was complicated by the presence of isomer 5, which
Corresponding Author
Tel/fax: +91-40-27160512. E mail: pmgowri@yahoo.com.
coeluted during chromatography. Fraction F was further chromato-
4
graphed on silica gel, eluting with (n-hexane−acetone, 88:12 step
Notes
gradient) to give fractions F -1, F -2, F -3, F -4, and F -5. Compound
The authors declare no competing financial interest.
4
4
4
4
4
1
, however, remained impure even after subsequent attempts to isolate
it using repeated silica gel CC of combined fractions F -1 and F -2.
4
4
ACKNOWLEDGMENTS
■
Surprisingly, an enriched solution of 1 in a mixture of n-hexane and
acetone was crystallized to obtain pure compound 1 (4 mg). Fraction
F4-5 was crystallized from a mixture of n-hexane and acetone to afford
compound 5 (10 mg) as colorless crystals. The triterpenoids arjunolic
acid (30 mg) and maslinic acid (10 mg) were also isolated from
another active fraction (AEG-7) obtained by VLC.
This work was supported by a Grant-in-Aid from the
Department of Science and Technology, New Delhi, India.
We thank Dr. J. S. Yadav, Director of IICT, for constant
encouragement. S.CH.V.A.R.A. is pleased to thank the CSIR for
awarding SRF. We thank Dr. N. Mohal, Vice President and
Head of Chemistry, Izenbio, India, for valuable suggestions and
Dr. G. N. Sastry for providing energy minimization calculations.
Acetylation of compounds 1 and 5. Compound 1 or 5 (each 2
mg) was dissolved in a mixture of C H N (0.2 mL) and Ac O (0.2
5
5
2
mL), and the solution was left overnight at ambient temperature. After
usual workup, the product was purified by recrystallization from n-
hexane to afford 1a (2 mg) and 5a (2 mg), respectively.
DEDICATION
■
Isocorniculatolide A (1): C H O ; colorless needles from a
18
18
4
Dedicated to Professor S. R. Anjaneyulu Ammanamanchi for
his pioneering research in the area of natural products.
mixture of n-hexane and acetone (7:3); R 0.5 (n-hexane−acetone,
f
7
.5:2.5); mp 202−203 °C; UV (CH OH) λ 279 nm (ε 2739); IR
3
max
−1 1
(
KBr) ν 3390, 2963, 1714, 1594, 1518, 1427, 1271, 1218 cm ; H,
max
1
3
REFERENCES
C, and 2D-NMR data (see Tables 1−3 and Figures 2, 3); HR-ESIMS
■
+
m/z 299.1283 [M + H] (calcd for C H O , 299.1278).
(1) Bandaranayake, W. M. Traditional and Medicinal Uses of
Mangroves. Mangroves and Salt Marshes 1998, 2, 133−148.
(2) Xu, M.; Deng, Z.; Li, M.; Li, J.; Fu, H.; Proksch, P.; Lin, W. J. Nat.
Prod. 2004, 67, 762−766.
18
19
4
1
1-Acetoxyisocorniculatolide A (1a): C H O ; IR (KBr) ν
20 20 5 max
1 1 13
−
1
760, 1730, 1594, 1504, 1435, 1255, 1190 cm ; H, and C NMR
data (see Tables 1, 2); HR-ESIMS m/z 341.1371 [M + H] (calcd for
+
C H O , 341.1384).
(3) Talat, R.; Ahsana, D.; Shamsher, A.; Sabira, N.; Muhammad, I. C.
J. Ethno. Pharm. 2008, 118, 514−521.
20
21
5
1
1-O-Methylisocorniculatolide A (2): C H O ; colorless needles
19 20 4
from acetone; R 0.5 (n-hexane−acetone, 8:2); mp 134−136 °C; UV
(4) Talat, R.; Ahsana, D.; Sabira, N.; Shamsher, A.; Muhammad, I. C.
J. Ethno. Pharm. 2008, 120, 248−254.
f
(
1
1
CH OH) λ 278 nm (ε 1856); IR (KBr) ν 2928, 1729, 1516,
3 max max
−1
1
13
438, 1416, 1259, 1208 cm ; H, C, and 2D-NMR data (see Tables
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2000, 63, 344−346.
+
, 2 and S2); HR-ESIMS m/z 313.1445 [M + H] (calcd for
C H O ,313.1434).
(6) Wang, J.-D.; Zhang, W.; Li, Z.-Y.; Xiang, W.-S.; Guo, Y.-W.;
Krohn, K. Phytochemistry 2007, 68, 2426−2431.
(7) Konishi, T.; Konoshima, T.; Maoka, T.; Fujiwara, Y. Tetrahedron
Lett. 2000, 41, 3419−3422.
19
21
4
1
1-O-Methylcorniculatolide A (3): C H O ; colorless needles
19 20 4
from acetone; R 0.45 (n-hexane−acetone, 8:2); mp 142−145 °C; UV
f
(
CH OH) λ 278 nm (ε 2482); IR (KBr) ν 2963, 1714, 1594,
3 max max
2
78
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