Three Novel Sesquiterpene Esters from Celastrus angulatus
Shaopeng Weia, Mingan Wangb, Jiwen Zhanga, Yong Qianc, Zhiqin Jia and Wenjun Wua,* aInstitute of Pesticide Science, Northwest Agricultural & Forestry University, Shaanxi 712100, China bCollege of Science, China Agricultural University, Beijing 100193, ChinacNature Standard Bio-technology Co. Ltd, Shanghai 201203, China
Received: January 6th, 2009; Accepted: March 10th, 2009
Three new sesquiterpene polyol esters with a β-dihydroagarofuran skeleton, NW12 (1), NW27 (2), and NW31 (4), together with a known compound, NW30 (3), were isolated from the root bark of Celastrus angulatus. Their chemical structures were elucidated by analyses of MS and NMR spectral data. Preliminary insecticidal and antitumor activities of these compounds were evaluated. Compounds 1-4 showed moderate stomach toxicity against Mythimna separata, and their KD50 values were
673.6, 1121.3, 1720.0 and 548.6 μg/g, respectively. Only 1 and 3 exhibited slight antitumor activity against human breast cancer cell line (Bcap-37), and their IC50 values were all above 50 μM.
Keywords: Celastrus angulatus, β-dihydroagarofuran sesquiterpene, insecticidal activity, antitumor activity.
Celastrus angulatus Maxim, a plant of the
Celastraceae family, is widely distributed and used in traditional Chinese medicine for rheumatism treatment and as an insecticide [1,2]. In previous studies, various β-dihydroagarofuran sesquiterpene polyol esters and alkaloids were isolated from the leaves and root bark of C. angulatus, and these compounds were shown to have an excellent stomach poison action against many species of Lepidoptera insects, such as Pieris rapae, Plutella xylostella and
Mythimna separata [3-8]. Besides insecticidal
activity, some of these compounds exhibited reverse multidrug resistance (MDR) effects, antitumor promotion (chemopreventive) and antitumor activities [9-13]. Fingerprint analysis based on LC/DAD/MS indicated that there are still lots of unknown β-dihydroagarofuran sesquiterpene compounds in the root bark extract of C. angulatus. To obtain a sufficient number of compounds for QSAR research, the chemical constituents from the root bark of C. angulatus were re-investigated guided by fingerprint analysis. These studies have led to the isolation from the root bark of this plant of three novel sesquiterpene polyol esters, NW12 (1), NW27 (2) and NW31 (4), together with a known compound, NW30 (3). In this paper, the isolation, structure
elucidation, insecticidal and antitumor activities of compounds 1-4 are presented.
NW12 (1) was analyzed for C37H52O13 by
HR-ESI-MS. The
IR spectrum revealed absorptions of
ester carbonyl at 1721 cm
-1and hydroxyl at 3420
cm
-1 The UV spectrum contained an aromatic moiety (λmax = 229 nm). The NMR spectral data suggestedthe presence of one acetate ester, one benzoate ester, two isobutanoate esters, one α-methylbutanoate ester
and two free hydroxyl groups. The 1H NMR
spectrum of compound 1 showed the presence of three tertiary methyl groups at δ 1.62 (s), 1.73 (s) and 1.78 (s). The signals observed at δ 5.53 (d, J = 3.5 Hz), 5.43 (m), 2.13 (m) and 2.00 (m), 2.58 (d, J = 3.0 Hz), 5.62 (dd, J = 3.5, 10.0 Hz), and 6.06 (d, J = 10.0 Hz) were assigned to the H-1, H-2, H-3, H-7, H-8 and H-9 protons based on the COSY spectrum of 1, and by comparison with the corresponding chemical shifts and coupling constants of Celangulatin C, which was previously isolated from the same plant [6]. The signals at δ 4.66 and 4.87 (d, J = 13.0 Hz) were also assigned to the methylene protons attached to the carbon atom bearing the primary ester group. The single signal observed at δ 5.25 was the H-6 proton as observed in the spectrum of Celangulatin C
No. 4
461 - 466
O OAc OMeBut OiBu OBz OH OH OiBu OAc OAc OFu O OAc OiBu OAc OH 1 2 3 CH3CH2CH C CH3 O iBu = CH3CH C O CH3 Fu = O C O Bz= C O H3C C O Ac= 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 OAc OAc OBz O OAc MeButO OAc OAc OAc OBz O OiBu OAc AcO 4 MeBut=
Figure 1: Structures of compounds 1~4.
[6]. The 13C NMR DEPT spectrum of the parent
skeleton of 1 showed three methyl, two methylene, six methine, and four quaternary carbons. Their chemical shifts were very similar to those of Celangulatin C and the other 1,2,4,6,8,9,13-hepta- substituted-β-dihydroagarofuran sesquiterpene polyol esters [6,8].
From the HMQC spectrum of compound 1 and comparison with the corresponding carbon atom chemical shifts of Celangulatin C and the other β-dihydroagarofuran sesquiterpene polyol esters [6,8], the 13C NMR signals were assigned. Generally,
H-1, H-2, and H-6 in this class of compounds have axial, equatorial, and axial stereochemistry, respectively [8]. The coupling contants (J7,8 = 3.5 Hz, J8,9 = 10.0 Hz) between H-7 and H-8, and between
H-8 and H-9, suggested that H-7, H-8, and H-9 had equatorial, axial, and axial stereochemistry, respectively, which were confirmed by the cross peaks between H-1 and H-9 in the NOESY spectrum of 1, and the similar coupling pattern and constants in the 1H NMR spectrum of Celangulatin C [6].
One of the two free hydroxy groups was situated at C-4, and the second at C-6, as shown by the 1H NMR
chemical shift, because the normal value of H-6 is generally greater than or near to δ 6.00 when H-6 is esterified [8]. The ester group distributions were determined by the cross peaks between H-1 and the carbonyl at δ 169.5, H-2 and the carbonyl at δ 175.3, H-8 and the carbonyl at δ 175.8, H-9 and the
carbonyl at δ 165.9, and H-13 and the carbonyl at
δ 176.6 in the HMBC spectrum of 1. Thus, the
chemical structure of NW12 (1) was elucidated as 1β-acetoxy-8α,13-di-isobutanoyloxy-2β-(α-methyl) butanoyloxy-9β-benzoyloxy-4α,6α-dihydroxy-β-dihydroagarofuran.
NW27 (2) was analyzed for C35H46O13 by
HR-ESI-MS. Its IR spectrum exhibited the characteristic ester absorption at 1741 cm-1. The UV spectrum contained
an aromatic moiety (λmax = 230 nm). The 1H and 13C NMR spectral data suggested the presence of
four acetate esters, one α-methylbutanoate ester, and one benzoate ester. The 1H and 13C NMR data of the parent skeleton of 2 were very similar to
those of the reported Celahin-D [14], which
suggested that compound 2 contained a
1,2,6,8,9,13-hexasubstituted-β-dihydroagarofuran skeleton. Compound 2 was found to have the same stereochemistry for H-1, H-2, H-6, H-8 and H-9 as Celahin-D, because of the similar coupling patterns, coupling constants, and the cross peaks in the NOESY spectrum. The ester group distributions were determined by the cross peaks between H-1 and the carbonyl at δ 169.3, H-2 and the carbonyl at δ 170.0, H-6 and the carbonyl at δ 169.5, H-8 and the carbonyl at δ 175.3, H-9 and the carbonyl at δ 164.5, H-13 and the carbonyl at δ 170.6 in the HMBC spectrum of 2. Thus, the chemical structure of NW27 (2) was elucidated as 1β,2β,6α,13-tetra- acetoxy-8β-(α-methyl)butanoyloxy-9α-benzoyloxy-β-dihydroagarofuran.
NW31 (4) was analyzed for C34H44O13 by
HR-ESI-MS. Its IR spectrum exhibited the characteristic ester absorption at 1741 cm-1. The UV spectrum contained an aromatic moiety (λmax = 230nm). The 1H and 13C NMR spectral data suggested the presence of
four acetate esters, one benzoate ester, and one isobutanoate ester. The 1H and 13C NMR data of the
parent skeleton of 4 were similar to those of 2, which suggested that compound 4 contained a 1,2,6,8,9,13-hexasubstituted-β-dihydroagarofuran skeleton. Based on the COSY, HMQC spectra of 4, and the NMR data of 2 and other sesquiterpene esters [14], the 1H
and 13C NMR signals were assigned and 4 was found
to have the same stereochemistry for H-1, H-2, H-6, H-8 and H-9 as 2 because of the similar coupling patterns, coupling constants, and the cross peaks in the NOESY spectrum. The ester group distributions were determined by the cross peaks between H-1 and the carbonyl at δ 169.2, H-2 and the carbonyl at δ 169.9, H-6 and the carbonyl at δ 169.5, H-8 and the carbonyl at δ 170.5, H-9 and the carbonyl at δ 164.5,
and H-13 and the carbonyl at δ 175.7 in the
HMBC spectrum of 4. Thus, the chemical structure of NW31 (4) was elucidated as 1β,2β,6α,8β- tetra-acetoxy-9α-benzoyloxy-13-isobutanoyloxy-β-dihydroagarofuran.
NW30 (3) was the known compound 1β,2β,6α,13- tetraacetoxy-8β-isobutanoyloxy-9α-furancarbonyl-oxy-4α-hydroxy-β-dihydroagarofuran, based on UV,
IR, HR-ESI-MS, 1H and 13C NMR spectroscopic
evidence [6].
The insecticidal activities of compounds 1~4 against 4th instar larvae of Mythimna separata were evaluated by the leaf disc method. The results showed that the KD50 values for compounds 1-4 were 673.6, 1121.3,
1720.0 and 548.6 μg/g, respectively. It was very interesting that compound 3 exhibited much weaker activity than the other compounds. The stereochemistry of the ester groups at C-1, C-2, C-6, C-8 and C-9 are similar, and the difference between them are the substitution groups at C-8, C-9 and C-13, whereas the activity of 4 is more than three times that of 2. The substitution groups at C-13 of 2 and 3 are all acetate esters, and these two compounds exhibited much weaker insecticidal activity than the other compounds. This suggested that the acyl group at C-13 contributes much to the insecticidal activity. These data confirmed further that the type and stereochemistry of the ester groups at C-8, C-9 and C-13 have a characteristic influence on the
insecticidal activity of β-dihydroagarofuran sesquiterpene polyol esters [6-8].
In vitro antitumor activities of compounds 1~4
against human colon (HT-29), breast (Bcap-37) and lung (NCI-H460) cancer cell lines were evaluated by the SRB method [15]. The results showed that only compounds 1, 3 and celangulatin C exhibited slight cytotoxic activity against Bcap-37 (IC50 > 50μM).
Comparison of the structural characteristic of 1, 3, and celangulatin C with the other two compounds, showed that the protons at C-4 of the active compounds are all substituted by hydroxyl groups. These suggested that the hydroxyl group at C-4 is crucial to the antitumor activity of this type of compound. All the compounds showed no obvious antiproliferative activities against the other two cell lines. These results suggested cell type selectivity for the tested compounds.
Table 1: The insecticidal and antitumor activities of compounds 1-4.
Compounds Insectcidal activity KD50, μg/g Antitumor activity IC50, μM 1 673.6 54.6 2 1121.3 － 3 1720.0 109.8 4 548.6 － celangulatin C 265.5 85.2 Vincristine sulfate not tested 28.1
Insecticidal activity was tested against 4th instar larvae of M. separata.
Antitumor activity was tested against human breast cancer cell (Bcap-37).
Experimental
Plant material: The root bark of C. angulatus was
collected in Qinling mountain, Taibai County, Shaanxi Province, People’s Republic of China, in October 2006, and authenticated by Prof. Hua Yi of the College of Life Sciences, Northwest Agricultural & Forestry University. The voucher specimens (samples no. NWAU2006-A18) were deposited at the College of Life Sciences, Northwest Agricultural & Forestry University.
Extraction and isolation: The dried and pulverized
root bark (2 kg) of C. angulatus was extracted with toluene under reflux. The extracted material (120 g) was adsorbed onto a D101 macroporous resin column (6.5×150 cm) and eluted with MeOH-H2O (5:5, 6:4,
7:3 and 8:2); 100 fractions of ca. 500 mL each were collected. After analysis with LC/DAD/MS, fractions containing unknown sesquiterpene polyol esters were selected for further isolation. NW12 (1, 36 mg), NW27 (2, 56 mg), NW30 (3, 45 mg) and NW31
(4, 42 mg) were obtained by RP-HPLC from fractions No.20, 35, 42 and 43, respectively.
General experimental procedures: Melting points
were measured on a Yanagimoto apparatus and are uncorrected. Optical rotations were measured on a Perkin-Elmer 341 polarimeter. IR spectra were determined on an IR-450 instrument (KBr plate). 1H
NMR, 13C NMR, DEPT, COSY, HMQC, HMBC, and
NOESY spectra were recorded on a Bruker Avance 500 MHz NMR Spectrometer with CDCl3 as solvent
and TMS as internal standard. HR-ESI-MS were obtained on a Bruker Apex II mass spectrometer. A Finnigan LCQ Advantage MAX LC/MS, equipped with a Surveyor DAD detector and a Waters Spherisorb C18 column (4.6×250 mm, 5 μm), was used to analyze the samples. Compounds were purified using a Shimadzu 6AD HPLC apparatus with
a C18 preparative column (20×250 mm, 10 μm),
MeOH-H2O (60: 40) as eluent, and a UV detector at
230 nm.
Insecticidal activity: Leaf discs of known area were
treated with known amounts of the test samples dissolved in acetone (acetone and celangulin C were used as control). The 4th instar larvae of M. separata
were fed with the discs for 12 h (repeated 10 times for each sample). After 24 h, the numbers of knocked-down larvae (symptoms: the larvae were narcotized and could not move; the bodies were immobilized and very soft; and response disappeared completely) were recorded, and the toxicity was ascertained by estimating the median knock-down dose (KD50 value)
of the test sample [8].
In vitro cytotoxicity: In vitro cytotoxicity was
evaluated against human colon (HT-29), human breast (Bcap-37) and human lung (NCI-H460) cell lines, as described previously [15]. The test compounds were dissolved in DMSO (10 mg/mL) and diluted with cell culture medium to 6 required concentrations (100, 50, 25, 12.5, 6.25 and 3.12 μg/mL). The final concentration of DMSO was less than 1% of the total volume. At this concentration, DMSO was found to be nontoxic to the cells tested. The cells were exposed to drugs for 72 h. Cell growth was assayed using Sulforhodamine B (SRB). The optical density (OD) was read at 490 nm. All cytotoxicity tests were performed 3 times in quadruplicate. The IC50 values
were calculated from the curves constructed by plotting cell survival (%) versus compound concentration (μM). Vincristine sulfate was used as positive control. Compound 1 MP: 170-172ºC. [α]D:+8.0 (c 0.50, CH3OH). IR (KBr): 3420(OH), 1721(CO), 1468, 1369, 1277, 949 cm-1.
UV/Vis λmax (MeOH): 229 nm.
1H NMR (500 MHz, CDCl 3): δ 1.62 (3H, s, H-12), 1.73(3H, s, H-15), 1.78(3H, s, H-14), 2.00, 2.13(2H, m, H-3), 2.58 (1H, d, J = 3.5 Hz, H-7), 4.66, 4.87 (2H, dd, J = 13.5 Hz, H-13), 5.25 (1H, s, H-6), 5.43 (1H, m, H-2), 5.53 (1H, d, J = 3.5 Hz, H-1), 5.62 (1H, dd, J = 3.5,10.0 Hz, H-8), 6.06 (1H, d, J = 10.0 Hz, H-9); OMeBut 2.43 (1H, m), 1.65, 1.55 (2H, m), 1.18 (3H, d, J = 7.5 Hz), 0.88 (3H, t, J = 7.5 Hz); OBz 7.85 (2H, d, J = 6.5 Hz),7.56 (1H,t, J = 6.5 Hz), 7.41 (2H, t, J = 6.5 Hz); OiBu 2.84(1H, m), 2.38 (1H, m), 1.34 (6H, d,J = 6.5 Hz), 0.96 (6H, d,J = 6.5 Hz); OAc 1.52 (3H, s). 13C NMR (125 MHz CDCl 3): δ 24.3 (CH3), 26.4 (CH3), 30.1 (CH3), 41.5 (CH2), 50.7(C), 53.7(CH), 62.1 (CH2), 66.9 (CH), 72.2 (C), 73.9 (CH), 75.1 (CH), 75.5 (CH), 77.0 (CH), 84.6 (C), 91.6 (C); OMeBut 175.3 (CO), 41.6 (CH), 26.6(CH2), 16.8 (CH3), 1.4 (CH3); OBz 165.9 (CO), 133.5 (CH), 129.5 (2CH), 128.7 (2CH), 129.2 (C); OiBu 175.8(CO), 175.9 (CO), 34.4 (CH), 34.2 (CH), 19.2 (CH3), 19.2 (CH3), 18.7 (CH3), 18.6 (CH3); OAc 169.5 (CO), 20.5 (CH3).
HR-ESI-MS: m/z [M + NH4] + calcd for C37H56NO13:
722.3752; found: 722.3748. Compound 2 MP: 163-165ºC. [α]D:-20.0 (c 0.50, CH3OH). IR (KBr): 3420(OH), 1741(CO), 1366, 1369, 1272,826 cm-1.
UV/Vis λmax (MeOH): 230 nm.
1H NMR (500 MHz, CDCl 3): δ 1.15 (3H, d, J = 7.6 Hz, H-12), 1.44 (3H, s, H-15), 1.60 (3H, s, H-14), 2.32 (1H, d, J = 2.8 Hz, H-7), 2.40 (1H, m, H-4), 2.50, 1.79 (2H, m, H-3), 5.06, 4.62 (2H, dd, J = 12.8 Hz, H-13), 5.33 (1H, d, J = 2.8 Hz, H-8), 5.55 (1H, s, H-9), 5.60 (1H, m, H-2), 5.72 (1H, d, J = 3.6 Hz, H-1), 6.39 (1H, s, H-6); OMeBut 2.45 (1H, m), 1.81, 1.58 (2H, m), 1.25 (3H, d, J = 7.2 Hz), 0.97 (3H, t, J = 7.6 Hz); OBz 8.00 (2H, d, J = 7.2 Hz),7.57 (1H, t, J=7.2 Hz), 7.45 (2H, t, J = 7.2 Hz); OAc 2.27 (3H, s), 2.11 (3H, s), 2.09 (3H, s), 1.44 (3H, s). 13C NMR (125 MHz CDCl 3): δ 16.4 (CH3), 25.8 (CH3), 30.2 (CH3), 30.9 (CH2), 32.6(CH), 52.2 (C), 53.1 (CH), 65.7 (CH2), 69.0 (CH), 71.6 (CH), 73.8 (CH), 74.5 (CH), 76.4 (CH), 81.6 (C), 89.7 (C);
OMeBut 175.3 (CO), 41.0 (CH), 26.5 (CH2), 16.7
(CH3), 11.5 (CH3); OBz 164.5 (CO), 133.7 (CH),
128.4 (2CH), 130.0 (2CH), 130.1 (C); OAc 170.6 (CO), 21.3 (CH3), 170.0 (CO), 21.3 (CH3), 169.5
(CO), 21.1 (CH3), 169.3 (CO), 20.3 (CH3).
HR-ESI-MS: m/z [M + NH4] +calcd for C35H50NO13:
692.3277; found: 692.3269. Compound 3 MP: 93-95ºC. [α]D:+29.0 (c 0.50, CH3OH). IR (KBr): 3440(OH), 1715(CO), 1375, 1270, 1115, 890 cm-1.
UV/Vis λmax (MeOH): 231 nm.
1H NMR (500 MHz, CDCl 3): δ 1.47 (3H, s, H-15), 1.57 (3H, s, H-14), 1.63(3H, s, H-12), 2.21, 1.96 (2H, m, H-3), 2.29 (1H, d, J = 2.8 Hz, H-7), 5.02, 4.63 (2H, dd, J = 12.8 Hz, H-13), 5.27 (1H, m, H-8), 5.47 (1H, d, J = 2.8 Hz, H-9), 5.53 (1H, dd, J = 2.8, 4.0 Hz, H-2), 5.55 (1H, d, J = 4.0 Hz, H-1),6.51 (1H, s, H-6); OFu 8.01 (1H, s), 7.44 (1H, d, J = 2.0 Hz), 6.72 (1H, d, J=2.0 Hz); OiBu 2.65 (1H, m), 1.25 (6H, d,J = 6.5 Hz); OAc 2.30 (3H, s), 2.15 (3H, s), 2.13(3H, s), 1.65 (3H, s). 13C NMR (125 MHz CDCl 3): δ 24.3 (CH3), 25.4 (CH3), 29.4 (CH3), 41.8 (CH2), 53.2 (CH), 53.8 (CH), 65.6 (CH2), 67.7 (CH), 69.7 (C), 70.4 (CH), 72.5 (CH), 74.9 (CH), 76.0 (CH), 83.2 (C), 91.3 (C); OiBu 175.8 (CO), 33.8 (CH), 18.8 (CH3), 18.7 (CH3); OFu 160.8 (CO), 148.9 (CH), 144.0 (CH), 117.7 (C), 109.6 (CH); OAc 170.5 (CO), 21.5 (CH3), 169.7 (CO), 21.1 (CH3), 169.7 (CO), 21.0 (CH3), 169.4 (CO), 20.4 (CH3).
HR-ESI-MS: m/z [M + NH4] + calcd for C32H46NO15:
684.2867; found: 684.2866. Compound 4 MP: 160-162ºC. [α]D:-6.0 (c 0.50, CH3OH). IR (KBr): 3420(OH), 1737(CO), 1367, 1229, 1187, 980 cm-1.
UV/Vis λmax (MeOH): 230 nm.
1H NMR (500 MHz, CDCl 3): δ 1.16 (3H, d, J = 7.2 Hz, H-12), 1.47(3H, s, H-15), 1.57 (3H, s, H-14), 2.35 (1H, m, H-7), 2.40 (1H, m, H-4), 2.49, 1.78 (2H, m, H-3), 5.06, 4.62 (2H, dd, J = 12.8 Hz, H-13), 5.31 (1H, d, J = 1.6 Hz, H-8), 5.57 (1H, s, H-9), 5.60 (1H, m, H-2), 5.72 (1H, d, J = 2.4 Hz, H-1), 6.37 (1H, s, H-6); OBz 8.01 (2H, d, J = 7.5 Hz),7.58 (1H, t, J = 7.5 Hz), 7.44 (2H, t, J = 7.5 Hz); OiBu 2.65 (1H, m), 1.25 (6H, d, J = 7.0Hz); OAc 2.26 (3H, s), 2.11 (3H, s), 2.09 (3H, s), 1.47 (3H, s). 13C NMR (125 MHz CDCl 3): δ 16.8 (CH3), 25.7 (CH3), 30.2 (CH3), 30.9 (CH2), 32.6 (CH), 52.3 (C), 53.0 (CH), 65.6 (CH2), 69.0 (CH), 71.5 (CH), 73.7 (CH), 74.6 (CH), 76.5 (CH), 81.5 (C), 89.7 (C); OBz 164.5 (CO), 133.7 (CH), 130.1 (CH), 128.3 (2CH), 129.1 (C); OiBu 175.7 (CO), 33.9 (CH), 18.8 (2CH3);
OAc 170.5 (CO), 21.2 (CH3), 169.9 (CO), 21.2
(CH3), 169.5 (CO), 21.0(CH3), 169.2(CO), 20.2
(CH3).
HR-ESI-MS: m/z [M + NH4] +calcd for C34H48NO13:
678.3120; found: 678.3129.
Acknowledgments - These projects were financed
by the National Key S&T Research Foundation of China (No. 2003CB114404) and the National Natural Science Foundation of China (No.20672087).
References
[1] Cheng CY, Huang PH. (1999)Flora Reipublicae Popularis Sinicae, Vol. 45, No. 3, Science Press, Beijing,China. 7–128.
[2] Ji ZQ, Hu ZN, Liu GQ, Wu WJ. (2004) Advances in research of insecticidal components of Celastrus angulatus (Celastraceae).
Acta Botanica Boreali-Occidentalia Sinica, 24, 748-753.
[3] Wakabayashi N, Wu WJ, Waters RM, Redfern RE, Mills Jr GD, Demilo AB, Lusby WR, Andrzejewski D. (1988) Celangulin: a
nonalkaloidal insect antifeedant from Chinese bittersweet, Celastrus angulatus. Journal of Natural Products, 51, 537-542.
[4] Wu WJ, Tu YQ, Liu HX, Zhu JB. (1992) Celangulins II, III, and IV: new insecticidal sesquiterpenoids from Celastrus angulatus.
Journal of Natural Products, 55, 1294-1298.
[5] Liu JK, Han XW, Jia ZJ, Ju Y, Wang HQ. (1991) Two sesquiterpene alkaloids from Celastrus angulatus.Phytochemistry, 30,
3437-3440.
[6] Ji ZQ, Wu WJ, Yang H, Shi BJ, Wang MA. (2007) Four novel insecticidal sesquiterpene esters from Celastrus angulatus. Natural
Product Research, 21, 334-342.
[7] Wang MA, Wu WJ,Zhu JB, Ji ZQ, Zhou WM. (2006)Two new insecticidal sesquiterpene polyol esters from Celastrus angulatus.
Natural Product Research, 20, 653-658.
[8] Wu WJ, Wang MA, Zhu JB, Zhou WM, Hu ZN, Ji ZQ. (2001) Five new insecticidal sesquiterpenoids from Celastrus angulatus.
[9] Takaishi Y, Ohshima S, Nakano K, Tomimatsu T, Tokuda H, Nishino H, Iwashima A. (1993) Structures of sesquiterpene polyol esters from Celastrus stephanotiifolius with potential tumor-promotion inhibitory activity. Journal of Natural Products, 56, 815-824.
[10] Yin WP, Zhao TZ, Gao LJ, Zou DP, Kang JX. (1999) A novel sesquiterpene polyol ester from Celastrus angulatus and its
antitumor activities. Chinese Chemical Letters, 10, 487-490.
[11] Kim SE, Kim YH, Lee JJ, Kim YC. (1998) A new sesquiterpene ester from Celastrus orbiculatus reversing multidrug resistance in cancer cells. Journal of Natural Products, 61, 108-111.
[12] Kim SE, Kim HS, Hong YS, Kim YC, Lee JJ. (1999) Sesquiterpene esters from Celastrus orbiculatus and their structure-activity relationship on the modulation of multidrug resistance. Journal of Natural Products, 62, 697-700.
[13] Wang KW, Pan YJ. (2006) A novel sesquiterpene polyol ester from the Celastrus rosthornianus with anti-tumor activities, Natural
Product Communications, 1, 537-539.
[14] Huang HC, Shen CC, Chen CF, Wu YC, Kuo YH. (2000) A novel agarofuran sesquiterpene, Celahin D from Celastrus hindsii
Benth. Chemical & Pharmaceutical Bulletin, 48, 1079-1080.
[15] Kim JY, Koo HM, Kim DS. (2001) Development of C-20 modified betulinic acid derivatives as antitumor agents. Bioorganic &
