New axane and oppositane sesquiterpenes from Teclea nobilis.
ABSTRACT Two new isomeric axane and oppositane sesquiterpene derivatives, named teclenone A (1) and teclenone B (2), were isolated from the aerial parts of Teclea nobilis. Their structures have been established on the basis of (1)H and (13)C NMR spectral data, notably 2D NMR (1)H-(1)H COSY, (1)H-(13)C HMQC, (1)H-(13)C HMBC, and (1)H-(1)H NOESY experiments. This appears to be the first report of the rare axane and oppositane sesquiterpenes from the plant family Rutaceae.
- SourceAvailable from: Muhammad Ilias[Show abstract] [Hide abstract]
ABSTRACT: Five new furoquinoline alkaloids, namely tecleabine (1), tecleoxine (2), isotecleoxine (3), methylnkolbisine (4) and chlorodesnkolbisine (5) were isolated from the aerial parts of Teclea nobilis, together with seven known furoquinoline derivatives; one acridone alkaloid, and one known flavanone. The structures of the alkaloids 1-5 were established by 1D and 2D NMR spectral data, including COSY, HMQC and HMBC experiments, as well as HRMS.Phytochemistry 01/2004; 64(8):1405-11. · 3.05 Impact Factor
New Axane and Oppositane Sesquiterpenes from T eclea nobilis
Adnan J . Al-Rehaily,*,†M. Shamim Ahmad,†J aber S. Mossa,†and Ilias Muhammad‡
Department of Pharmacognosy, College of Pharmacy, P.O. Box 2457, King Saud University, Riyadh 11451, Saudi Arabia, and
National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy,
University of Mississippi, University, Mississippi 38677
Received December 28, 2001
Twonew isomeric axane and oppositane sesquiterpene derivatives, named teclenone A (1) and teclenone
B (2), were isolated from the aerial parts of Teclea nobilis. Their structures have been established on the
basis of1H and13C NMR spectral data, notably 2D NMR1H-1H COSY,1H-13C HMQC,1H-13C HMBC,
and1H-1H NOESY experiments. This appears to be the first report of the rare axane and oppositane
sesquiterpenes from the plant family Rutaceae.
Teclea nobilis Delile (Rutaceae), locally known as Al-
dhureim, is a shrub used in folk medicine as an analgesic
and antipyretic and also in the treatment of gonorrhea.1
Earlier phytochemical studies on this species2-4revealed
thepresenceof quinolineand furoquinolinealkaloids, while
limonoids, tetranortriterpenes, triterpenes, alkaloids, and
flavonoid glucosides were isolated from T. ouabanguiensis,
T. grandifolia, T. verdoorniana, and T. sudanica, respec-
tively.5-9In addition, the ethanol extract of T. nobilis was
reported tohave antipyretic and analgesic activities.10The
present investigation reports the isolation and structure
elucidation of two isomeric axane and oppositane sesqui-
terpene ketones, teclenone A (1) and teclenone B (2), from
the aerial parts of T. nobilis collected in the Southern
regions of Saudi Arabia.
TheMeCN fraction of then-hexaneextract was subjected
to flash chromatography, followed by centrifugal prepara-
tivethin-layer chromatography (seeExperimental Section),
to afford compounds 1 and 2 in yields of 0.003% and
0.0029%, respectively. Both of the compounds were ob-
tained as gums and found to be homogeneous on TLC.
Compound 1 was analyzed by HRMS for the molecular
formula C15H24O2. Its octahydro-1H-indenecarbon skeleton
was suggested on the basis of its1H and13C NMR spectral
data11-13(Table 1). Teclenone A (1) demonstrated the
presence of a carbonyl (νmax 1710 cm-1; δC-7 217.3), a
hydroxyl (νmax 3470 cm-1; δC-1 71.4), and an exocyclic
methylene (νmax1660 cm-1; δC-4145.3, δC-15112.7) groups.
The1H NMR spectrum of 1 exhibited signals for a tertiary
methyl (δ 0.90, s, H-14), an oxymethine (δ 3.64, dd, J )
11.8, 4.2 Hz, H-1), and an exocyclic methylene(δ 4.73, 4.64,
each s, H-15), while the13C NMR revealed twosinglets (δC
145.3, 49.9), three doublets (δC71.4, 59.9, 51.9), and four
triplets (δC32.1, 30.4, 27.3, 36.9), consistent with a 1-hy-
droxy-4(15)-methyleneoctahydroindene base skeleton.11-13
In addition, the1H NMR spectrum exhibited twosecondary
methyls (δ 1.02, 0.97, each d, J ) 6.9 Hz) and a methine
(δ 2.50, 1H, m), attributable to H-11-H-13, respectively.
The assignments of spectral data and stereochemistry for
1 were established by extensive 2D NMR experiments
involving the analysis of its1H-1H COSY,1H-13C HMQC,
and gradient1H-13C HMBC spectra.
The HMBC experiment established the placement of the
hydroxyl, carbonyl, and methyl groups at the C-1, C-7, and
C-14 positions, respectively, by3J correlations between the
signals at δ 3.64 (H-1), δC-936.9, and δC-1418.0; δ 2.53
(H-5), δC-171.4, δC-330.4, δC-7217.3, δC-1418.0, and δC-15
112.7. In addition, the HMBC established the assignments
of the C-4 and C-6 carbons by
between δ 3.25 (H-6), δC-4145.3, and δC-7217.3, as well
as correlations between H-15 (δ 4.73 and 4.64), δC-330.4,
and δC-559.9. Finally, placement of the C-6 isobutanone
substituent was established by cross-peaks between δ 2.50
(H-11), δC-12 18.4, δC-13 17.7, and C-7; the latter was
correlated to C-6. On the basis of the foregoing data the
gross structure was established as shown (1).
The relative stereochemical assignments of carbons C-1,
C-5, C-6, and C-10 were resolved using the1H-1H NOESY
experiments (Figure1). Theseshowed correlations between
δ 3.64 (H-1), 3.25 (H-6), and 2.03 (H-9B), indicating that
the protons are cis to each other and ?-oriented. On the
other hand, H-5 showed cross-peaks with H-12 (δ 1.02),
H-13 (δ 0.97), and H-9A (δ 1.42), suggesting that the
protons are cis to each other and placed at the opposite
side (R-oriented) of the molecule. In addition, H-5 (δ 2.53)
showed correlations with H-14 (δ 0.90), thereby confirming
that compound 1 has a cis-fused octahydro-1H-indene
(axane) ring junction. Thus, the hydroxyl at C-1, H-5, and
C-10 methyl groups were placed at the R-face of the
* Towhom correspondence should be addressed. Tel: + 966-1-467-7258.
Fax: + 966-1-467-7245. E-mail: email@example.com.
†King Saud University.
‡National Center for Natural Products Research, Thad Cochran Research
1374J . Nat. Prod. 2002, 65, 1374-1376
10.1021/np0106485 CCC: $22.00 © 2002 American Chemical Society and American Society of Pharmacognosy
Published on Web 08/22/2002
molecule, opposite the ?-oriented methine protons H-1 and
H-6. On the basis of the foregoing data, the relative
stereochemistry was assigned as shown in Figure 1.
The1H and13C NMR spectral data of 2 (C15H24O2) were
in close agreement with those observed for 1?-hydroxy-
4(15)-oppositene derivative 3 [1R-(1-methoxy-2-methylpro-
cept for the presence of a carbonyl group at C-7 instead of
themethoxyl substituent. Furthermore, a closecomparison
of the1H and13C NMR spectra of 2 with 1 and those of
led tothe conclusion that, indeed, 2 was a 7-oxoderivative
of 3. Thus, the structure and stereochemistry of 2 were
unambiguously established by detailed 2D NMR studies,
including COSY, HMQC, HMBC, and NOESY experiments.
The13C NMR spectrum revealed theanticipated desheiding
of C-1 to δ 78.9 and sheiding of C-5, C-14, and C-15 to δC
54.0, δC12.4, and δC106.9, respectively (versus δC-171.4,
δC-5 59.9, δC-14 18.0, and δC-15 112.7 for 1), due to the
presenceof theC-1?-hydroxyl group, and agrees with those
previously reported for 311(δC-179.3, δC-555.5, δC-1412.3,
and δC-15107.2) and related oppositane derivatives. Two
significant differences were noted from the NOESY spec-
trum of 2, when compared with 1 (Figure 1). The NOESY
of 2 showed correlations between δ 3.62 (H-1), δ 2.09 (H-
3A), and δ 2.57 (H-5), indicating that the protons are cis
to each other and R-oriented. On the other hand, H-6 (δ
3.17) showed a cross-peak with H-14 (δ 0.67); the latter
correlated with H-3B (δ 2.26), indicating that they are cis
to each other and ?-oriented. As a result, the hydroxyl
group at C-1 was placed at the ?-face of the molecule and
opposite the R-oriented methine protons H-1 and H-5.
Furthermore, the NOESY showed no correlation between
H-5 and H-14, thereby suggesting that 2 has a trans ring
junction. Finally, compounds 1 and 2 were evaluated for
in vitro antibacterial (Staphylococcus aureus, methicillin-
resistant S. aureus, and Pseudomonus aeruginosa), anti-
fungal (Candida albicans and Cryptococcus neoformans),
and antimalarial (Plasmodium falciparum D6 and W2
clones) activities and found to be inactive in these assays.
This appears tobe the first report of teclenone A (1) and
teclenone B (2) from a natural source, as well as the first
report of the rare axane and oppositane sesquiterpenes
from theplant family Rutaceae. Oppositanesesquiterpenes
had previously been reported from Torillus japonica
(Umberiferae)5and the liverwort Chiloscyphus pallescens
(Hepaticae),14and axane sesquiterpenes from the sponge
Axinella cannabina.15Axanes and oppositanes are formed
by rearrangement of germacrane D, and their biogenetic
pathway has recently been suggested by Bu ¨low and Ko ¨nig
(2000).13Thus, 4-cycloaxeneand 4-cyclooppositene13appear
tobe the biogenetic precursors of axane and oppositol type
compounds 1 and 2, respectively. It is intriguing to note
that teclenoneA (1) has thesamestereochemistry as 4(15)-
cycloaxene13at the chiral centers C-5 and C-10, the latter
carrying an R (relative stereochemistry) methyl group,
while the oppositane derivatives from higher plants, in-
cluding Torillus japonica11-13and Dysoxylum variable,16
are epimeric at C-10.
E xperimental Section
General E xperimental Procedures. UV spectra were
recorded in MeOH, using a Shimadzu UV-1601PC spectro-
photometer, and IR spectra were obtained in a thin film on a
Perkin-Elmer 5808 spectrophotometer. TheNMR spectra were
recorded on a Bruker AvanceDRX 500 instrument at 500 MHz
(1H) and at 125 MHz (13C) in CDCl3, using TMS as internal
standard. Multiplicity determinations (DEPT) and 2D NMR
spectra (gradient DQF-COSY, HMQC, gradient HMBC, and
NOESY) were run using the standard Bruker pulse program.
HRMS wereobtained by direct injection using Bruker Bioapex-
T able 1.
1H and13C NMR Data for Teclenone A (1) and Teclenone B (2)
3.64 dd (11.8, 4.2)a
C-2, C-9, C-10, C-14
C-1, C-4, C-10
3.62 dd (11.3, 4.6)
C-2, C-5, C-9, C-10, C-14
C-1, C-4, C-10
30.4 t C-1, C-2, C-4
30.2 t C-1, C-2, C-4
54.0 d2.53 d (10.9) C-1, C-3, C-4, C-6, C-7,
C-10, C-14, C-15
C-4, C-5, C-7, C-8
2.57 d (11.1)C-1, C-4, C-6, C-7, C-10,
C-4, C-5, C-7, C-86
3.25 ddd (10.3, 10.9, 6.8)51.9 d
3.17 ddd (10.1, 11.1, 6.6) 47.8 d
27.2 t1.81 m
C-5, C-7, C-9, C-101.59 m
C-6, C-7, C-9, C-10
36.9 tC-1, C-5, C-6, C-8, C-10,
37.8 t C-1
2.03 m1.79 m
1.02 d (6.9)c
0.97 d (6.9)c
4.73 s, 4.64 s
C-7, C-12, C-13
C-7, C-11, C-13
C-7, C-11, C-12
C-1, C-5, C-9
1.10 d (6.8)c
1.08 d (6.8)c
4.76 s, 4.38 s
C-7, C-12, C-13
C-1, C-5, C-9, C-10
aCoupling constants (J values in Hz) arein parentheses.bMultiplicities of carbon signals weredetermined by DEPT (135°) experiments.
F igure 1. Key 2D NMR1H-1H HOESY correlations (dashed lines)
for compounds 1 and 2.
Notes J ournal of Natural Products, 2002, Vol. 65, No. 9 1375
FTMS with electro-spray ionization (ESI). EIMS were meas-
ured using an E.I. Finnigan model 4600 quadruple system or
a Shimadzu QP500 GC/mass spectrometer. Optical rotations
were recorded in CHCl3 at ambient temperature, using a
Perkin-Elmer 241 MC polarimeter. TLC analyses werecarried
out on silica gel G 254 plates, with the solvent system
n-hexane-EtOAc (1:1). For flash column chromatography,
silica gel 60 (40 µm) was used with n-hexane-EtOAc mixtures
as solvent system. Centrifugal preparative TLC (CPTLC) was
performed using a Chromatotron (Harrison Research Inc.
model 7924) on 1 or 2 mm silica gel PF254 disks, with a N2
flow rate of 2-4 mL min-1. The isolated compounds were
visualized by spraying with 5% anisaldehyde-H2SO4 and
heating the plates to 100 °C.
Plant Material. Theaerial parts of T. nobilis werecollected
in March 1999, from Al-Namas, Saudi Arabia. A voucher
specimen (#14050) was deposited at the Herbarium of the
Medicinal, Aromatic and Poisonous Plants Research Center,
King Saud University, Riyadh, Saudi Arabia.
E xtraction and Isolation. The ground aerial parts of T.
nobilis (1.15 kg) were successively extracted with n-hexane,
followed by EtOH, in a Soxhlet for 72 h (yields 46 and 85 g,
respectively). The gummy residue of the n-hexane extract,
obtained after evaporation in vacuo, was partitioned between
n-hexane(300 mL) and MeCN (4 × 100 mL) presaturated with
each other. Flash chromatography of the MeCN residue (22
g) over silica gel (450 g), using EtOAc (1% f 10%) in n-hexane
as solvent, yielded 200 fractions (each 150 mL), which were
pooled into 25 fractions according to their TLC patterns.
Fraction 10 (1.27 g) was subjected to CPTLC (Chromatotron,
2 mm silica gel disk), using CHCl3as solvent, which afforded
three fractions (A-C). Fraction B (70 mg) was purified by a
silica gel column, with n-hexane-EtOAc (9.5:0.5) as solvent,
to yield 1 (34.5 mg), while fraction C (213 mg) was subjected
to CPTLC (Chromatotron, 1 mm silica gel disk), using CHCl3
as solvent, which afforded 2 (31.4 mg).
T eclenone A [1r-(1-Oxo-2-methylpropyl)-3ar-methyl-
7-methyleneoctahydroinden-4r-ol] (1): gum; [R]D +28.9°
(c 1.5, CHCl3); UV (MeOH) λmax (log ?) 229 (3.16) 285 (2.40)
nm; IR (CHCl3) νmax3470, 3090, 2980, 2960, 2890, 1710, 1660,
1485, 1070, 920 cm-1;1H and13C NMR, see Table 1; EIMS
m/z 236 [M]+(0.2), 193 (1), 165 (8), 147 (52), 121 (12), 105 (19),
91 (17), 83 (57), 79 (12), 71 (12), 43 (100); HRMS m/z 259.3359
[M + Na]+(calcd for C15H24O2Na, 259.3396).
T eclenone B [1r-(1-Oxo-2-methylpropyl)-3a?-methyl-
7-methyleneoctahydroinden-4?-ol] (2): gum; [R]D +75.8°
(c 1.8, CHCl3); UV (MeOH) λmax(log ?) 231 (2.60), 279 (2.10),
280 (sh) (2.10); IR (CHCl3) νmax3450, 3090, 2990, 2950, 2900,
1710, 1660, 1475, 1065, 895 cm-1;1H and13C NMR, see Table
1; EIMS m/z 236 [M]+(0.2), 193 (2), 165 (13), 147 (88), 121
(20), 105 (29), 91 (22), 83 (14), 79 (15), 71 (17), 43 (100); HRMS
m/z 259.3373 [M + Na]+(calcd for C15H24O2Na, 259.3396).
Acknowledgment.The authors thank Dr. S. Abidin,
College of Pharmacy, King Saud University, for identification
of the plant material, Ms. Sharon Sanders, Mr. Charlie
Dawson, Ms. Miranda Logan, and Mr. J ohn Trott, NCNPR,
University of Mississippi, for technical assistance, and Mr.
Frank M. Wiggers, for recording NMR spectra, and Dr. D.
Chuck Dunbar, for HRMS.
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1376 J ournal of Natural Products, 2002, Vol. 65, No. 9Notes