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Helvetica Chimica Acta – Vol. 92 (2009)
Herticins A and B, New Sesquiterpenes from Hertia intermedia
by Shazia Yasmeen a ), Naheed Riaz b ), Amna Bibi c ), Nighat Afza a ), Abdul Malik* c ), and
Rasool Bukhsh Tareen d )
a
) Pharmaceutical Research Center, PCSIR Laboratories Complex Karachi, Karachi-75280, Pakistan
b
) Department of Chemistry, The Islamia University of Bhawalpur, Pakistan
c
) International Center for Chemical and Biological Sciences, HEJ Research Institute of Chemistry,
University of Karachi, Karachi-75270, Pakistan
(phone: þ 92-21-4824926; fax: þ 92-21-4819018; e-mail: abdul.malik@iccs.edu,
shazrasheed@yahoo.com)
d
) Department of Botany, University of Baluchistan, Baluchistan, Pakistan
Herticins A (¼ (8aH)-10b-hydroxyeremophilenolide; 1) and B (¼ (8aH)-6a,10b-dihydroxyeremophilenolide; 2), two new sesquiterpenes, have been isolated from the AcOEt-soluble fraction of the
MeOH extract of Hertia intermedia (whole plant). Their structures were assigned from 1H- and 13C-NMR
spectra (DEPT) and 2D-NMR analyses (COSY, NOESY, and HMBC experiments) in combination with
HR-MS experiments and comparison with literature data of related compounds.
Introduction. – The genus Hertia belongs to the family Compositae, tribe
Senecioneae. The twelve species of Hertia are distributed all over South and North
Africa and South West Asia [1]. Hertia intermedia is also known as Othonnopsis
intermedia. It is found in Baluchistan commonly in Quetta, Koeie, Chaman, KanozaiMoorga, and Wazir. It is also found in Kurram and regions below Parachinar. These are
small shrubs with pretty yellow flowers [2]. A literature survey revealed that no
phytochemical or biological studies have so far been carried out on this plant. The
methanolic extract of the whole plant of H. intermedia showed significant toxicity in the
brine shrimp lethality test [3] [4]. On further fractionation, major toxicity was observed
in the AcOEt-soluble fraction which prompted us to investigate the chemical
constituents of this fraction. As a result, we have isolated two new sesquiterpenes
named herticins A (¼ (8aH)-10b-hydroxyeremophilenolide; 1) and B (¼ (8aH)6a,10b-dihydroxyeremophilenolide; 2), respectively.
Results and Discussion. – The MeOH extract of the whole plant was divided into
fractions soluble in hexane, AcOEt, BuOH, and H2O. Column chromatography of the
2009 Verlag Helvetica Chimica Acta AG, Zrich
Helvetica Chimica Acta – Vol. 92 (2009)
405
AcOEt-soluble fraction provided two new eremophilenolide type sesquiterpenes
named as herticins A (¼ (8aH)-10b-hydroxyeremophilenolide; 1) and B (¼ (8aH)6a,10b-dihydroxyeremophilenolide; 2), respectively.
Herticin A (1) was obtained as a white solid. The IR spectrum exhibited the OH
group (3607 and 3468 cm1) and a,b-unsaturated g-lactone bands (1756 and
1645 cm1). The molecular formula of 1 was established as C15H22O3 on the basis of
HR-EI-MS showing an Mþ peak at m/z 250.3334 (calc. 250.3378). The molecular
formula was confirmed by the 13C-NMR (BB and DEPT) spectra (Table 1), which
showed 15 signals: three Me, five CH2 , two CH, and five quaternary C-atoms. The
fragment peak at m/z 232 ([M H2O]þ ) in the EI-MS spectrum revealed the presence
of one OH group, which was confirmed by a quaternary C-atom at d(C) 75.0. The Hatom appearing at d(H) 5.07 (ddq, J ¼ 10.5, 4.8, 1.5, 1 H) showed coupling to the Catom at d(C) 77.2 in the HMQC experiment, and was assigned to the secondary OH
group integrated in a lactone ring. Three Me groups appeared in the 1H-NMR spectrum
at d(H) 1.79 (d, J ¼ 1.5), 0.98 (s), and 0.81 (d, J ¼ 6.4). The Me group at d(H) 1.79
showed interaction in the HMBC with C(11) (d(C) 120.6), C(7) (d(C) 161.2), and
C(12) (d(C) 175.1) suggesting a Me-substituted a,b-unsaturated lactone. One of the
CH2 groups appeared at d(H) 2.13 (dd, J ¼ 13.0, 4.8, 1 H) and 1.94 (dd, J ¼ 13.0, 10.5,
1 H). Another CH2 group gave rise to two doublets at d(H) 2.64 (d, J ¼ 13.8, 1 H) and
2.42 (d, J ¼ 13.8, 1 H). In the HMBC, significant correlations were observed between
the CH2 group appearing at d(H) 1.94 and 2.13 with the C-atoms C(5) (d(C) 44.9),
C(10) (d(C) 75.0), C(8) (d(C) 77.2), and C(7) (d(C) 161.2); the Me group appearing at
d(H) 0.98 correlated with the C-atoms C(4) (d(C) 33.5), C(6) (d(C) 31.7), C(5) (d(C)
44.9), and C(10) (d(C) 75.0). The 1H- and 13C-NMR data were comparable to the
eremophilenolide class of sesquiterpenes [5 – 7]. A literature search revealed that the
data is almost superimposible to 10b-hydroxyeremophilenolide [8]. The optical
rotation observed for 1 ([a]D ¼ þ 165 (c ¼ 0.470, CHCl3 )) was, however, different from
that of 10b-hydroxyeremophilenolide ([a]D ¼ 169 (c ¼ 0.470, CHCl3 )), indicating
that herticin A (1) is a stereoisomer of 10b-hydroxyeremophilenolide. The signal for
Me attached to C(5) was shifted downfield, which indicated that the A/B ring system
could not be trans fused, thus confirming a 10b-OH group [9]. The absence of a
NOESY correlation between HC(8) and the Me group attached to C(5) and the
coupling constant of HC(8) and HC(9) [1] provided evidence for their relative
trans-orientation (Fig.). Hence, herticin A (1) was assigned the structure (8aH)-10bhydroxyeremophilenolide, i.e., compound 1 ist the C(8)-epimer of the known natural
product 10b-hydroxyeremophilenolide (see Formulae).
Figure. Key NOESY correlations for 1 and 2
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Helvetica Chimica Acta – Vol. 92 (2009)
Table 1. 1H- and 13C-NMR Data, and HMBC Correlations of Compound 1 (in CDCl3 ; d in ppm, J in Hz)
d( H )
CH2(1)
CH2(2)
CH2(3)
HC(4)
C(5)
CH2(6)
C(7)
HC(8)
CH2(9)
C(10)
C(11)
C(12)
Me(13)
Me(14)
Me(15)
1.47 – 1.51
1.30 – 1.36
1.17 – 1.21
1.42 – 1.45
d(C ) HMBC ( H ! C )
(m), 1.71 – 1.74 (m)
(m), 1.57 – 1.61 (m)
(m), 1.38 – 1.41 (m)
(m)
36.5
22.3
29.7
33.5
44.9
2.64 (d, J ¼ 13.8), 2.42 (d, J ¼ 13.8)
31.7
161.2
5.07 (ddq, J ¼ 10.5, 4.8, 1.5)
77.2
2.13 (dd, J ¼ 13.0, 4.8), 1.94 (dd, J ¼ 13.0, 10.5) 40.9
75.0
120.6
175.1
1.79 (d, J ¼ 1.5)
8.3
0.98 (s)
14.7
0.81 (d, J ¼ 6.4)
16.0
C(3), C(5), C(9)
C(10), C(4)
C(1), C(4), C(5)
C(2), C(10), C(6), C(15)
C(4), C(5), C(7), C(8), C(10), C(11)
C(9), C(7), C(10)
C(5), C(7), C(8), C(10)
C(7), C(11), C(12)
C(4), C(5), C(6), C(10)
C(3), C(4), C(5)
Herticin B (2) was also obtained as a white solid and exhibited bonds for OH (3529,
3419, and 3214 cm1) and an a,b-unsaturated g-lactone (1756 and 1645 cm1). The
broad band and DEPT 13C-NMR spectra displayed 15 signals: three Me, four CH2 ,
three CH, five quaternary C-atoms (Table 2). The molecular formula of 2 was
established as C15H22O4 from its HR-EI-MS showing an Mþ peak at m/z 266.3326 (calc.
266.3372). In the EI-MS, strong peaks at m/z 266 (Mþ ), 248 ([M H2O]þ ), and 230
([M 2 H2O]þ ) were observed, suggesting the presence of two OH groups in the
molecule. Beside the signal for an additional oxygenated C-atom appearing at d(C)
71.3, the 1H- and 13C-NMR spectra were nearly identical with those of compound 1,
which disclosed that compound 2 is a hydroxylated derivative of compound 1. The HTable 2. 1H- and 13C-NMR Data, and HMBC Correlations of Compound 2 (in CDCl3 ; d in ppm, J in Hz)
CH2(1)
CH2(2)
CH2(3)
HC(4)
C(5)
HC(6)
C(7)
HC(8)
CH2(9)
C(10)
C(11)
C(12)
Me(13)
Me(14)
Me(15)
d( H )
d(C )
HMBC ( H ! C )
1.33 – 1.36 (m), 1.73 – 1.77 (m)
1.21 – 1.24 (m), 1.57 – 1.61 (m)
1.16 – 1.20 (m), 1.29 – 1.31 (m)
1.26 – 1.28 (m)
35.9
22.1
29.5
33.3
46.3
71.3
160.7
76.1
41.4
C(3), C(5), C(10), C(9)
C(10), C(4)
C(1), C(4), C(5)
C(2), C(10), C(6), C(15)
C(7), C(9),C(10)
C(5), C(7), C(8), C(10)
76.0
122.0
174.6
8.6
10.5
16.0
C(7), C(11), C(12)
C(4), C(5), C(6), C(10)
C(3), C(5)
4.60 (s)
5.31 (ddq, J ¼ 10.5, 4.7, 1.4)
2.25 (dd, J ¼ 13.2, 4.7),
1.98 (dd, J ¼ 13.2, 10.5)
1.85 (d, J ¼ 1.4)
1.20 (s)
0.81 (d, J ¼ 5.6)
C(4), C(5), C(7), C(8), C(10), C(11), C(14)
Helvetica Chimica Acta – Vol. 92 (2009)
407
atom appearing as a ddq at d(H) 5.31 (J ¼ 10.5, 4.7, 1.4, 1 H) was assigned to the Hatom a to the lactone O-atom. The H-atom of a secondary OH group at d(H) 4.60
appeared as a singlet in the 1H-NMR spectrum. In the HMBC, it showed correlations
with C(11) (d(C) 122.0), C(7) (d(C) 160.7), C(8) (d(C) 76.1), C(5) (d(C) 46.3), and
C(14) (d(C) 10.5), allowing us to place this OH group at C(6). The 1H- and 13C-NMR
data of compound 2 showed similarity to that of 6b,10b-dihydroxyeremophilenolide
[10]. The two compounds differ in their melting point and optical rotation. Thus, the
two compounds differ in their configuration. The absence of a NOESY correlation
between HC(8) and the Me group attached to C(5) and the coupling constant of
HC(8) and HC(9) [1] confirmed that this compound has the same configuration at
C(8) as compound 1. The downfield chemical shift (d(H) 1.20) of the Me group
attached to C(5) confirmed a cis-fused A/B ring system. The absence of a NOESY
interaction between HC(6) and HC(8) allowed us to assign a orientation for the
OH group at C(6). Thus herticin B (2) was assigned to be (8aH)-6a,10b-dihydroxyeremophilenolide.
Experimental Part
General. Column chromatography (CC): silica gel (SiO2 ; 230 – 400 mesh; Merck). Thin-layer
chromatography (TLC): SiO2 60 F 254 plates (Merck). Optical rotations: Jasco DIP-360 digital
polarimeter. IR spectra: Jasco 302-A spectrophotometer, in CHCl3 or MeOH solns.; in cm1. NMR
spectra: Bruker instrument; d in ppm, J in Hz. EI- and HR-EI-MS: Jeol JMS-DA-500 mass
spectrometers; in m/z (rel. %).
Plant Material. The whole plant material of H. intermedia Boiss was collected from Baluchistan
(Pakistan) in May 2006 and identified by R. B. T., Plant Taxonomist, Department of Botany, University
of Baluchistan, where a voucher specimen (HI-36-06) has been deposited.
Extraction and Isolation. The air dried whole plant (28 kg) was exhaustively extracted with MeOH
(3 50 l) at r.t. The combined MeOH extracts were concentrated, and the residue (750 g) was divided
into hexane (135 g), AcOEt (150 g), BuOH (68 g), and H2O (38 g) soluble fractions. The AcOEt soluble
fraction was subjected to CC (SiO2 ; hexane/AcOEt, AcOEt, AcOEt/MeOH, of increasing polarity). The
fractions from hexane/AcOEt 75 : 25 were combined and subjected to CC (SiO2 ; hexane/AcOEt 85 : 15)
to yield 1 (13 mg) and (2) (9 mg) from the top and tail fractions, resp.
Herticin A (¼ (8aH)-10b-Hydroxyeremophilenolide; (4aR,5S,8aS,9aR)-4a,5,6,7,8,8a,9,9a-Octahydro-8a-hydroxy-3,4a,5-trimethylnaphtho[2,3-b]furan-2(4H)-one; 1). White solid. M.p. 184 – 1868.
1
13
[a] 26
C- NMR: Table 1. EID ¼ þ 165 (c ¼ 0.470, CHCl3 ). IR (KBr): 3607, 3468, 1756, 1645. H- and
MS: 250 (3, Mþ ), 232 (39, [M H2O]þ ), 126 (34), 125 (72), 97 (70). HR-EI-MS: 250.3334 (Mþ,
C15H22O þ3 ; calc. 250.3378).
Herticin B (¼ (8aH)-6a,10b-Dihydroxyeremophilenolide; (4S,4aS,5S,8aS,9aR)-4a,5,6,7,8,8a,9,9aOctahydro-4,8a-dihydroxy-3,4a,5-trimethylnaphtho[2,3-b]furan-2(4H)-one; 2). White solid. M.p. 79 –
1
13
838. [a] 26
C- NMR:
D ¼ þ 104 (c ¼ 0.06, MeOH). IR (KBr): 3529, 3419, 3214, 1756, 1645. H- and
Table 1. EI-MS: 266 (3, Mþ ), 248 (6, [M H2O]þ ), 230 (3, [M 2 H2O]þ ), 141 (25), 123 (55), 97 (100),
55 (80). HR-EI-MS: 266.3326 (Mþ, C15H22O þ3 ; calc. 266.3372).
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Received July 24, 2008