~ P e r g a m o n
Phytochemistry, Vol. 46, No. 8, pp. 1375-1377, 1997
© 1997 Elsevier Science Ltd. All rights reserved
Printed in Great Britain
A 2-ACYLCYCLOHEXANE-1,3-DIONE FROM VIROLA OLEIFERA
NEUCiRIO R. AZEVEDO, SUZANA C. SANTOS, EURiPEDES G. DE MIRANDA and PEDRO H. FERRI*
Instituto de Quimica, Universidade Federal de Goi/ts, C. P. 131, Campus Samambaia, 74001-970 Goifinia, GO, Brazil
(Received 4 April 1997)
Key Word Index--Virola oleifera; Myristicaceae; leaves; polyketide; oleiferinone; 3,6fl-dihy-
droxy-2-(13-phenyltridecanoyl)-2-cyclohexen- 1-one; 2-acylarylcyclohexane- 1,3-dione.
Abstraet--A novel arylalkanone derivative, oleiferinone, has been isolated from the chlorophyll-free hexane
fraction of the 95% ethanol extract from leaves of Virola oleifera. Its structure was deduced as 3,6fl-dihydroxy-
2-(13-phenyltridecanoyl)-2-cyclohexen-l-one, on the basis of the NMR techniques. © 1997 Elsevier Science
Virola oleifera, ucuOba-branca, is endemic to the
Atlantic Forest in the south-eastern region of Brazil
and has been used in traditional 'caiqara' medicine in
order to relieve gastric-intestinal disorders, as a
wound-healing anti-inflammatory, and to stimulate
memory and cerebral intelligence . Previous chemi-
cal investigations of leaves from this species have
shown the presence of lignan-7-ols, oleiferins A-C, a
lignan-7-one (oleiferin-D), a 2,7'-cyclolignan-7-ol
(oleiferin-E), besides the known compounds, galbacin,
(+)-aristolignin and (+)-eupomatenoid-8 , two
7,7'-cyclolignans, verrucosin and galbulin, and oto-
bafenol in the arils,
austrobailignan-6 and arylalkanones in the kernels .
In other studies , the absolute configurations for
oleiferins A-C were established from acid-catalysed
Friedel-Crafts-type cyclization and comparison of the
spectral data, and optical rotations for known 2,7'-
cyclolignans. Herein, we now report on the isolation
and characterization of an arylalkanone, oleiferinone
(1), from the chlorophyll-free hexane fraction of the
95% ethanol extract from the leaves of V. oleifera.
and otobain, methyl-
RESULTS AND DISCUSSION
The chlorophyll-free hexane fraction of the 95%
ethanol extract from the leaves was separated by vac-
uum liquid chromatography . After continuous pre-
parative TLC separation, compound 1 was isolated as
a pale amorphous yellow solid, mp 59.5-60 °. It had a
molecular formula of C25H360 4 ([M] + at m/z 400),
as determined by E1 mass spectrometry, and its IR
* Author to whom correspondence should be addressed.
~~,., L J 12
spectrum contained absorptions due to hydroxyl
groups at 3420 cm -t, conjugated carbonyl (1665
cm -1) and a conjugated chelated carbonyl group at
1546 cm-~; its long-chain nature was revealed by the
presence of bands at 2918, 2847, 1465 and 724 cm -~.
The UV spectrum exhibited maxima at 233 and 271
nm (log ~ 4.08 and 4.14, respectively), indicating the
presence of the cyclic polyketone group, 'fl-triketone'.
Adding base caused enhancement of the peak at 271
nm and disappearance of the peak at 233 nm, similar
to those of acylcyclohexane-l,3-diones . The t3C
NMR decoupled spectrum (Table l) showed 25 lines
in agreement with the molecular formula. DEPT pulse
sequences allowed the determination of the hydro-
genation pattern of each carbon, revealing five unsatu-
rated non-hydrogenated carbons, including enol and
two keto carbonyls [6 195.0, 197.2 and 205.7], five
unsaturated and one saturated methine, and 14 satu-
rated methylenes. The ~H NMR spectrum contained
the signal of a H-bonded hydroxyl proton at excep-
tionally large downfield shift [6 18.30 (1H, sl, OH-
3)], consistent with the proposed six-membered ring
structure , signals of an unsubstituted phenyl group
[6 7.02-7.20 (5H, m)], benzylic methylene signals [6
N. R. AZEVEDO et al.
Table 1. tH and nCNMR assignments for compound 1
C ~3C HETCOR COSY*
~ "-" :
,., ,.., ~.~ 3'
29.1, 29.2(2), 29.3,
15', 19' 128.1
16', 18' 128.2
* Observed 1H-1H correlations are connected by arrows.
2.56 (t, J = 7.9 Hz, H-13')], or-methylene signals of a
ketone [3 2.90 (1H, ddd, J = 6.5, 8.5 and 16 Hz, H-
2'a), 6 3.03 (1H, ddd, J --- 6.5, 8.5 and 16 Hz, H-2'b)],
signals of homobenzylic methylene and fl-methylene
protons of ketone [3 1.60 (4H, m, H-3' and H-IT)],
and signals of alkyl polymethylene chain [3 1.26 (16H,
sl, H-4'-H-11')]. Additionally, the substructure
• CH2"CH2"CH(OH)" incorporating a fl-triketone
system was established through a homonuclear COSY
spectrum. The methylene signal at ~ 2.74 (2H, m, H-
4) was coupled with the diastereotopic protons at 6
2.32 (1H, m, H-5~) and 6 1.75 (IH, ddt, J= 11, 13
and 14 Hz, H-5fl), which itself was coupled with the
oxygenated methine signal at 3 3.95 (IH, dd, J = 5.5
and 13 Hz, H-6~), indicating that the isolated com-
pound has the 2-acylcyclohexane-1,3-dione system .
uC-~H HETCOR and further JH-JH COSY cor-
relations allowed assignments of the carbon resonance
and the connectivity between the above-mentioned
partial substructure (Table 1). Interestingly, the spin-
system of H-2'a/b in 1 displayed two distinct signals
(6 2.90 and ~ 3.03), indicating that free rotation of the
side-chain is hindered, as a consequence of a hydrogen
bond between the enolic proton and the carbonyl
group. However, no direct evidence for the alternative
positions of the enolic double bond is available. The
relative stereochemistry of compound 1 was deter-
mined by the ~H NMR spectrum. The large coupling
constant (J = 13 Hz) between H-5 axial and H-6
indicates that OH-6 is equatorial. The EI mass spec-
trum was in agreement with the structure proposed
from the ~H and ~3C analyses. It exhibited the
[C~C(OH)CHECHECH(OH)~OCOCH2CH2] + frag-
ment at m/z 183, accompanied by characteristic base
peak at m/z 91. Hence, based on the accumulated
evidence, the structure of oleiferinone, 1, was eluci-
dated as 3,6fl-dihydroxy-2-(13-phenyltridecanoyl)-2-
acylcyclohexen-l-one. While acyl- and acylaryl-res-
orcinols or phloroglucinols-type arylalkanones are
well known in various species of Virola, Knema and
Myristica [9, 10], compound 1 is distinguished by a 2-
acylarylcyclohexane-1,3-dione system, which has been
rarely reported in plants . However, 2-acyl-
cyclohexane-l,3-diones have been isolated from the
larval mandibular glands of some Lepidoptera 
and have a wide range of activity as kairomones .
Similar synthetic compounds have been described as
insecticidal, fungicidal and possessing antibiotic
General. Mp: uncorr. IH and 13C NMR: 300 and
75.5 MHz, respectively, using TMS as int. standard.
IR: KBr pellet. ELMS: 70 eV.
Plant material. Leaves of V. oleifera (Schott) A. C.
Smith were collected by Dr Gentil Gody (Reserva
Florestal Atl~ntica, Ubatuba, SP, Brazil) in May
1990, and authenticated by Dr Jorge Tamashiro
(Departamento de Botfinica, Universidade Estadual
de Campinas-UNICAMP, Campinas, SP, Brazil). A
voucher specimen is deposited in the Herbarium of
Isolation. In order to eliminate chlorophylls and
other colouring matter, air-dried powdered leaves
were extracted with 95% EtOH. The deep green leaf
extract (24 g) was dissolved in MeOH and H20 was
added in order to reach a 7:3 ratio. The resulting
soln was filtered off over a layer of prewashed Celite.
Hexane was used to partition the MeOH-H20 soln,
yielding a yellowish fr. The chlorophyll-free hexane
fr. (2.7 g) was fractionated by vacuum LC  over
silica gel H (40 #m) using hexane and hexane-EtOAc
mixts of increasing polarity, to yield 1 (6 mg).
hexen-l-one (1). Pale amorphous yellow solid, mp
59.5-60 ° (hexane). IR Vmax cm-~: 3420, 2918, 2847,
1665, 1546, 1465, 1404, 1114, 755, 724, 704. UV
2~ °n nm (log e): 233 (4.08), 271 (4.14); +NaOH: 265
(4.2). IH NMR (300 MHz, CCL) 3:1.26 (16H, sl, H-
4'-H-II'), 1.60 (4H, m, H-3' and H-IT), 1.75 (IH,
ddt, J = 11, 13 and 14 Hz, H-5fl), 2.32 (1H, m, H-5ct),
2.56 (2H, t, J = 7.9 Hz, H-IT), 2.74 (2H, m, H-4),
2.90 (1H, ddd, J = 6.5, 8.5 and 16 Hz, H-2'a), 3.03
(1H, ddd, J = 6.5, 8.5 and 16 Hz, H-2"b), 3.71 (1H, sl,
OH-6), 3.95 (1H, dd, J = 5.5 and 13 Hz, H-6ct), 7.02-
7.20 (5H, m, Ar-H), 18.30 (1H, s, OH-3). 13C NMR
(75.5 MHz, CCh): Table 1. ElMS m/z (rel. int.): 400
[M] + (30), 183 (40), 91 (100), 69 (30), 55 (60).
CNPq (Conselho Nacional de Desenvolvimento Cien-
tifico e Tecnolrgico) and FUNAPE (Funda95o de
Apoio ~t Pesquisa-UFG), Brazil, is gratefully acknowl-
support from the
A 2-Acylcyclohexane-1,3-dione from Virola oleifera Download full-text
edged. Thanks are also due to Dr G. Godoy, who
made the material available, Dr J. Tamashiro for the
botanical identification, Mrs Paula Pilli and Mrs
S6nia Cris6stomo (UNICAMP) for the measurements
of Ill, 13C NMR, IH-IH COSY and 13C-IH HETCOR
spectra, and Dr A. J. Ribeiro da Silva, UFRJ for the
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