Triterpenoids from Owenia cepiodora

Article abstract of DOI:10.1016/S0031-9422(98)00307-0

The limonoid, 28-deoxonimbolide, and three protolimonoids, 24S,25- dihydroxytirucall-7-en-3-one, 3-oxo-tirucalla-7, 24-dien-21-al and 21,24R- epoxy-25-hydroxytirucall-7-en-3-one were isolated from the leaves and bark of Owenia cepiodora.

Full text of DOI:10.1016/S0031-9422(98)00307-0

Phytochemistry Vol. 49, No. 8, pp. 2457±2460, 1998
1998 Published by Elsevier Science Ltd. All rights reserved
Printed in Great Britain
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0
031-9422/98/$ - see front matter
PII: S0031-9422(98)00307-0
TRITERPENOIDS FROM OWENIA CEPIODORA
DULCIE A. MULHOLLAND*, MARIA KOTSOS, HAMDANI A. MAHOMED
and DAVID A. H. TAYLOR
Natural Products Research Group, Department of Chemistry, University of Natal, Durban, 4041,
South Africa
(
Received 16 March 1998; accepted in revised form March 1998)
Key Word IndexÐOwenia cepiodora; Meliaceae; Melioideae; 28-deoxonimbolide, 24S,25-
dihydroxytirucall-7-en-3-one; 3-oxo-tirucalla-7,24-dien-21-al; 21,24R-epoxy-25-hydroxytiru-
call-7-en-3-one.
AbstractÐThe limonoid, 28-deoxonimbolide, and three protolimonoids, 24S,25-dihydroxytirucall-7-en-3-
one, 3-oxo-tirucalla-7, 24-dien-21-al and 21,24R-epoxy-25-hydroxytirucall-7-en-3-one were isolated from
the leaves and bark of Owenia cepiodora. # 1998 Published by Elsevier Science Ltd. All rights reserved
INTRODUCTION
RESULTS AND DISCUSSION
The Meliaceae family produces a class of com-
The ring C opened limonoid, 28-deoxonimbolide
pounds called limonoids. Limonoids are tetranortri- (1) was isolated from the leaves of Owenia cepio-
terpenoids with a b- substituted furan ring at dora. The compound has been isolated previously
C±17a. Rings A±D of the triterpenoid skeleton may from the leaves of Azadirachta indica (neem) [9].
be oxidized and rearrangements may occur giving Melia and Azadirachta are very similar chemically
di€erent types of limonoids. The type of limonoid and contain ring C-oxidized limonoids of the
produced by a species has been used for taxonomic nimbin class. These compounds were thought to
purposes [1]. Owenia is a genus of the Meliaceae distinguish Melia and Azadirachta from the rest of
found only in Australia and has been placed in the the Meliaceae family [1], although one other
tribe Trichileae of the subfamily Melioideae. Seed example of a ring C opened limonoid had been
of Owenia acidula and Owenia venosa have been found previously in the Trichilieae tribe of which
examined previously and have yielded the limonoid Owenia is also a member: the isolation of heude-
6
a-acetoxyhavanensin acetate and the triterpenoid bolin from Trichilia heudelotti [10]. This second
a-isobutyryl-7a-deacetylglabretal [2]. Glabretal- report con®rms that ring-C opened limonoids are
3
type compounds are an interesting by-product of not restricted to Melia and Azadirachta.
limonoid metabolism and have been isolated from Three triterpenoids were isolated from the hexane
Aglaia [3], Guarea [4], Owenia [2], Turraea [3], and extract of the bark of O. cepiodora. The ®rst com-
Dysoxylum [5±7], species. In the classi®cation of pound was identi®ed as 24S,25-dihydroxytirucall-7-
Pennington and Styles [8], these genera belong to en-3-one (2). This compound has not been reported
di€erent tribes of the subfamily Melioideae. previously, although the 3b-hydroxy derivative (2C)
However, in spite of the thorough investigation of has been described [11]. C±3 occurred at d 216.1
Melia and Azadirachta in recent years, glabretal- con®rming the presence of a ring A ketone, H±7
type compounds have not been found in the Meliaea occurred at d 5.28 and C±7 and C±8 at d 117.8 and
tribe of the Melioideae subfamily. The limonoid 6a- d 145.9, respectively. Resonances occurred at d 73.2
1
3
acetoxydeoxyhavanensin is a common limonoid and and d 78.6 in the C NMR spectrum and these
hence its presence in the Owenia examined pre- were assigned to C±25 and C±24, respectively.
viously is not of taxonomic signi®cance.
The leaves and bark of Owenia cepiodora F. yielded the 24-acetate, (2A); forced acetylation of
Muell. were investigated in order to determine their 2 led to the 24,25-diacetate (2B), and NaBH
chemical composition. reduction yielded the known compound 3b,24S,25-
H±24 occurred at d 3.32. Standard acetylation of 2
4
trihydroxytirucall-7-ene (2C). The stereochemistry
at C-24 of the 3/3-hydroxy derivative 2C was
determined by the lanthanide complex method of
*
Author to whom correspondence should be addressed.
2457

2
458
D. A. MULHOLLAND et al.
Nakanishi et al. [12±14]. Complexation [4:1 ratio, J = 11.4 Hz) and d 3.42 (dd, J = 11.4,2.4 Hz). The
substrate: Eu(dpm)
] of 2C in dry chloroform molecular formula indicated a ring was necessary in
3
provided a CD spectrum DE + 4.5 at 314 nm indi- the side chain. Thus structure (4) is proposed.
cating the C±24 hydroxy group to have the S- Acetylation was unsuccessful con®rming the
con®guration [11].
The second compound was identi®ed as 3-oxo-tir-
absence of a primary hydroxy group at C±21. The
1
H NMR spectrum for bourjotinolone A (5) [16]
2.9
ucalla-7,24-dien-21-al (3) and has been isolated pre- showed H±24 as
a
doublet at
d
1
viously from Simarouba amera [15]. Reduction of (J23b,24a=9.0 Hz) and the H NMR spectrum for
the two carbonyl groups with NaBH
b,21-diol (3A) as expected.
The third compound was identi®ed as 21,24R-
4
yielded the sapelin C (6) [17] showed H±24 as a doublet at d
2.9 (J23b,24a=10.0 Hz). In (4), H±24 appears as a
3
doublet of doublets signal (J23b,24a=10.5 Hz,
J23b,24a=2.4 Hz) at d 3.10. These coupling constants
suggest the con®guration at C±24 of (4) to be R, as
epoxy-25-hydroxytirucall-7-en-3-one (4) and has not
been reported previously although the 23a-hydroxy
analogue, bourjotinolone A(5) has been isolated
from Flindersia bourjotiana [16]. Mass spectrometry
1
3
in bourjotinolone A (5) and sapelin C(6). The
NMR data for bourjotinolone A (5) [18], is given in
C
1
3
Table 1 for comparison purposes.
indicated a molecular formula of C H O .
C
NMR spectra were similar to (2), with a keto group
3
0
48
3
7
at C±3 (d 216.9) and D -double bond (d 117.9,
EXPERIMENTAL
1
45.8). C±24 had been shifted from d 78.6 in (2) to
d 84.3 and C±25 from d 73.2 to d 72.1. The C±21
Dried leaves (250 g) and bark (121 g) of
methyl carbon resonance had been replaced by a Owenia cepiodora F. Muell. (Voucher Specimen
methylene carbon resonance at d 70.6. The H ±21 UND.HAM 8) were collected in Rockhampton,
doublet which occurred at d 0.85 in (2) was Australia. The leaves were crushed and extracted
replaced by a pair of resonances at d 4.02 (d, with hexane and CHCl . The CHCl extract yielded,
3
3
3

Triterpenoids from Owenia cepiodora
2459
1
3
Table 1. C NMR data for compounds (2), (3), (4) and
Acetylation of 2 with Ac O/pyridine/dimethyl-
2
(
3
5) (75 MHz, CDCl )
aminopyridine yielded 24S,25-diacetoxy-tirucall-7-
1
en-3-one (2B). H NMR: d 0.78 (3H, s), 0.84 (3H,
Carbon
(2)
(3)
(4)
38.5 t
(5)
38.6 t
d, J = 6.0 Hz, H
1
1
3
±21), 0.98 (3H, s), 1.02 (3H, s),
.09 (3H, s), 1.23 (3H, s), 1.42 (3H, s), 1.46 (3H, s),
.94 (3H, s, OAc), 2.09 (3H, s, OAc), 2.73 (1H, td,
1
2
3
4
5
6
7
8
9
38.5 t
38.3 t
34.8 t
216.7 s
47.8 s
55.2 d
24.3 t
118.3 d
145.2 s
52.2 d
35.0 s
17.7 t
31.9 t
43.3 s
50.9 s
33.6 t
29.2 t
48.2 d
21.5 q
12.7 q
48.2 d
205.8 d
26.9* t
25.9* t
123.5 d
132.5 s
17.8 q
24.5 q
25.6 q
22.8 q
27.2 q
34.9 t
216.0 s
47.8 s
53.1 d
24.3 t
117.8 d
145.9 s
52.3 d
34.9 s
18.2 t
32.9 t
43.4 s
51.1 s
34.0 t
28.2* t
48.4 d
21.5 q
12.7 q
35.9 d
18.2 q
28.4* t
33.6 t
78.6 d
73.2 s
24.5 q
26.5 q
23.1 q
21.9 q
27.4 q
34.9 t
216.9 s
47.8 s
52.3 d
24.3 t
17.9 d
45.8 s
48.4 d
35.0 s
18.2 t
32.9 t
43.1 s
51.3 s
33.9 t
27.2 t
43.2 d
21.6 q
12.7 q
35.6 d
70.6 t
27.0 t
21.2 t
84.3 d
72.1 s
24.5 q
25.8 q
23.5 q
22.4 q
27.5 q
35.0 t
216.8 s
47.9 s
52.4 d
24.4 t
118.1 d
145.7 s
48.5 d
35.1 s
18.2 t
33.0 t
43.3 s
51.3 s
34.0 t
27.4 t
44.8 d
21.6 q
12.8 q
37.5 d
70.1 t
36.5 t
64.6 d
86.5 d
74.2 s
24.0 q
28.5 q
24.6 q
22.3 q
27.5 q
J = 6.6, 14.4 Hz, H±2ax), 5.10 (1H, dd, J = 2.7,
9.9 Hz, H±24), 5.30 (1H, m, H±7).
Reduction of 2 with NaBH yielded 3b,24S,25-
4
1
trihydroxy-tirucall-7-ene (2C). H NMR. d 0.72
(3H, s, H ±19), 0.80 (3H, s, H ±18), 0.84 (3H, s,
3
3
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
H
3
±30), 0.86 (3H, d, J = 6.0 Hz, H
s H ±29, H ±28), 1.14 (3H, s, H ±26), 1.20 (3H, s,
±27), 3.25 (1H, dd, J = 4.5, 10.8 Hz, H±24), 3.33
3
±21), 0.95 (6H,
3
3
3
H
3
(
1H, m, H±3a, W1/2=12.0 Hz).
3-Oxo-tirucalla-7,24-dien-21-al
(3)
(678 mg),
+
HRMS M at m/z 438.3487 (C30H46O requires
438.3498). H NMR: d0.81 (3H, s), 0.97 (3H, s),
0.99 (3H, s), 1.02 (3H, s), 1.08 (3H, s), 1.54 (3H, s),
2
1
1
5
.65 (3H, s), 2.71 (1H, td, J = 6.3, 14.4 Hz, H-2ax),
.05 (1H, m H±24), 5.30 (1H, m, H±7), 9.47 (1H, d,
Nacl
�1
H±21, J = 5.4 Hz). IR lmax cm : 1730, 1680.
Reduction of 3 with NaBH yielded 3b,21-dihy-
droxy-tirucalla-7,24-diene (3A), mp 136±1388 (lit.
4
1
1
38±1398 [12]). H NMR: d 0.72 (3H, s), 0.81 (3H,
s), 0.84 (3H, s), 0.95 (3H, s), 0.97 (3H, s), 1.60 (3H,
s), 1.69 (3H, s), 3.22 (1H, dd, H±3a, J = 4.5,
10.8 Hz), 3.58 (1H, dd, J = 4.8, 11.1 Hz, H±21a),
*
Values for the same compound may be interchanged.
3
.71 (1H, dd, J = 3.0, 11.1 Hz, H±21b), 5.08 (1H,
m, H±24), 5.25 (1H, m, H±7).
1,24R-Epoxy-25-hydroxytirucall-7-en-3-one (4)
after repeated CC over silica gel (Merck 9385), the
limonoid 28-deoxonimbolide (1). The hexane extract
of the ground bark a€orded three triterpenoids,
2
+
(
48 3
1.0 g), HRMS M at m/z 456.3609 (C30H O
1
requires 456.3603). H NMR: d 0.77 (3H, s), 0.98
2
4S,25-dihydroxytirucall-7-en-3-one
(2),
3-oxo-
(
(
3H, s), 1.02 (3H, s), 1.03 (3H, s), 1.09 (3H, s), 1.13
6H, s), 2.73 (1H, td, J = 6.6, 14.4 Hz, H±2ax),
.10 (1H, dd, J = 2.4, 10.5 Hz, H±24), 3.43 (1H, dd,
tirucalla-7,24-dien-21-al (3) and 21,24R-epoxy-25-
hydroxytirucall-7-en-3-one (4). The structures of the
compounds were determined using 2D NMR and
3
J = 2.4, 11.4 Hz, H±21a), 4.02 (1H, d, J = 11.4 Hz,
H±21b), 5.29 (1H, m, H±7). IR lmax cm : 3420,
1700.
1
MS techniques. H NMR spectra were recorded
using a Varian Gemini 300 NMR spectrometer in
NaCl
�1
1
3
CDCl
in Table 1.
8-Deoxonimbolide
52.2178, requires 452.2181). The structure was
3
. C NMR data for (2), (3), and (4) are given
AcknowledgementsÐWe are grateful to Mrs J. King
for providing the plant material and the University
of Natal Research Fund for funding this project.
MK and HAM were funded by Foundation for
Research Development post graduate bursaries. We
thank Dr P Bosho€ of the Cape Technikon for
mass spectral data.
2
(1)
C
27
H
32
O
6
(found
4
con®rmed by comparison of physical data against
literature values [9].
2
4S,25-Dihydroxytirucall-7-en-3-one (2) (616 mg),
HRMS m/z 458.3746 (C H O requires 458.3760).
3
0
50
3
1
H NMR (300 MHz, CDCl
3H, d, J = 6.0 Hz, H
3
): d 0.78 (3H, s), 0.85
(
3
±21), 0.97 (6H, s, 2 ÂCH
3
),
1
.02 (3H, s), 1.08 (3H, s), 1.14 (3H, s), 1.19 (3H, s),
.73 (1H, td, J = 5.7, 15.4 Hz, H±2ax), 3.32 (1H,
REFERENCES
2
NaCl
�1
m, H±24), 5.28 (1H, m H±7). IR lmax cm : 3450,
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2
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2
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