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A new lactone from Senecio scandens
Biochemical Systematics and Ecology 35 (2007) 901e904 www.elsevier.com/locate/biochemsyseco
A new lactone from Senecio scandens Ji Shi a, Li Yang b, Chang-Hong Wang b, Gui-xin Chou b, Zheng-Tao Wang a,b,* a
Department of Pharmacognosy, China Pharmaceutical University, Nanjing 210038, China b Key Laboratory of Standardization of Chinese Medicines of Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China Received 14 November 2006; accepted 5 May 2007
Keywords: Senecio scandens; Compositae; Seneciolactone; Chemical constituents; Chemotaxonomy
1. Subject and sources Senecio plants (Compositae) are extensively used in single or formulated forms in Chinese traditional and folk medicine for antiinflammation, antibiosis, etc. There are about 100 species widely distributed in China with different morphological characteristics (Chen, 1999). Senecio scandens Buch.-Ham. ex D. Don, locally known as ‘‘Qianliguang’’, is one of the most popular species used as a Chinese medicinal herb but the chemical components of this species have not been fully disclosed to date. The aerial parts of this plant were collected from Rongan county, Guangxi province of PR China in April 2005 and the vouchers have been deposited in the Herbarium of the Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine. 2. Previous work Pyrrolizidine alkaloids and sesquiterpenes with a furanoeremophilane skeleton have been reported as the major components from the genus of Senecio (Bohlmann et al., 1977). Pyrrolizidine alkaloids (Batra and Rajagopalan, 1977), phenolic acids (Wang and Tu, 1980) and jacaranone glycosides (Tian et al., 2006) have been previously isolated from S. scandens. 3. Present study In the present study of S. scandens, a new lactone, (E)-seneciolactone (1), together with nine known compounds (2e10) were isolated and their structures determined based on spectral methods. The stereochemistry structures of seneciolactone (1) and (E)-cannabifolactone A (2) were firstly elucidated based on NOESY experiment. * Corresponding author. Shangai University of TCM, Institute of Chinese Materia Medica, 1 Cailun Road, Zhangjiang Hi-Tech Park, Shangai 201203, China. E-mail address: [email protected] (Z.-T. Wang). 0305-1978/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.bse.2007.05.001
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J. Shi et al. / Biochemical Systematics and Ecology 35 (2007) 901e904
The air-dried aerial parts of S. scandens (6.0 kg) were exhaustively extracted with 80% ethanol under reflux. The extract was evaporated in vacuum to yield a syrupy residue (200 g). The residue was suspended in water (3000 mL) and partitioned with petroleum ether (3000 mL 3), EtOAc (3000 mL 5) and n-BuOH (3000 mL 3) successively, to give the corresponding fractions (200 g, 300 g and 200 g), respectively. A portion (270 g) of the EtOAc extract was subjected to column chromatography on silica gel (200e300 mesh, 2 kg) using stepwise elution with CHCl3eMeOH (100:0, 50:1, 20:1, 10:1, and 1:1) to yield five fractions: Fr.1 (35 g) Fr.2 (40 g), Fr.3 (53 g), Fr.4 (41 g) and Fr.5 (78 g). Fr.1 was chromatographed on silica gel (200e300 mesh, 1000 g) with a petrol ethereEtOAc gradient system (10:1e2:1) to give five sub-fractions (sub Frs.1Ae1E). Sub Fr.1A was subjected to repeated column chromatography on silica gel by gradient elution with petroleum ethereEtOAc (5:1, 4:1, 3:1, 2:1) and purified by Sephadex LH-20 (CHCl3eMeOH (1:1)) to afford compound 1 (8 mg), (E)-cannabifolactone A (2, 10 mg) (Wu et al., 2002), 4methoxyphenylacetic acid (3, 10 mg) (Sadtler Research Laboratories Inc., 1969) and 2,5-dihydroxybenzeneacetic acid (4, 50 mg) (Yamaguchi et al., 1989), respectively. Sub Fr.1B (5 g) was subjected to repeated silica gel column chromatography (200e300 mesh) with a gradient of petroleum ethereEtOAc, followed by Sephadex LH-20 eluted with MeOH to yield jacaranone (5, 40 mg) (Bohlmann and Suwita, 1976), ethyl 2-(1-hydroxy-4-oxocyclohexa-2,5dienyl) acetate (6, 40 mg) (Bohlmann and Suwita, 1976), methyl 2-(1-hydroxy-4-oxocyclohexyl) acetate (7, 70 mg) (Bohlmann et al., 1981) and ethyl 2-(1-hydroxy-4-oxocyclohexyl) acetate (8, 20 mg) (Bohlmann et al., 1981). Fr.2 (20 g) was also subjected to repeated column chromatography on silica gel by gradient elution with petroleum ethereEtOAc (3:1, 1:1, 1:2, 0:1) to give 5-methoxybenzofuran-2(3H)-one (9, 27 mg) (Zbiral et al., 1965) and methyl 2-(1,4-dihydroxycyclohexyl)-acetate (10, 5.3 mg) (Wu et al., 2005). The structures of the known compounds (3e10) were elucidated by comparison of their UV, ESIMS/EIMS, 1H NMR, 13C NMR, HMBC and HMQC data with the published data. Compound 1 was obtained as a yellow powder. Mp. 80.4e82.5 C; UV lmax (MeOH): 197 nm, 362 nm; IR: 3420 cm1 (nOH), 1767 cm1 (nc]o), 1718 cm1 (nc]o), 1610 cm1, 1629 cm1, 1470 cm1 (nf).The molecular formula of 1 was assigned as C16H12O6, from HREIMS spectrometry (m/z 300.0637, calcd 300.0634). The absorptions at 1767 cm1 in the IR spectrum indicated the presence of a lactone structure. In the 13C NMR spectrum, 16 carbon signals were observed as one methyl, one methylene, six methines and eight quaternaries. From 1H NMR spectrum, we observed a typical ABX coupling system for a 1,2,4-trisubstituted aromatic ring [d7.08 (1H, d, J ¼ 8.6 Hz), 6.85 (1H, dd, J ¼ 8.6, 2.4 Hz), 7.84 (1H, d, J ¼ 2.4 Hz)], an a,a0 -disubstituted furan ring substituted at positions of [7.35 (1H, d, J ¼ 3.5 Hz), 6.85 (1H, d, J ¼ 3.5 Hz)] and a methyl group [d2.25 (3H, s)], respectively. The form of compound 1 was determined on the basis of a NOESY experiment, correlation between H-10 and H-12 was strong, but no correlation between H-10 and H-4 was observed, which indicated that the form was E type but not Z type, so the absolute structure of compound 1 was established as (E)-5-Hydroxy-3-[(5-acetoxymethyl-2-furanyl) methylene]2(3H)-benzofuranone (Fig. 1; Table 1).
O 17 H3C
15
16
13
14
O
12 O
11 HMBC
4
OH
10 3
5
NOESY
2
6 7
O
O
Fig. 1. Key HMBC and NOESY correlations for compound 1.
J. Shi et al. / Biochemical Systematics and Ecology 35 (2007) 901e904
903
Table 1 NMR spectral data of 1 (400 MHz, CDCl3) No.
13
2 3 4 5 5-OH 6 7 8 9 10 11 12 13 14 15 16 17
170.2 119.2 111.7 153.4
1
C NMR
117.4 111.1 148.0 122.3 122.0 152.9 120.9 114.5 152.9 57.3 173.2 21.1
H NMR
HMBC (H/C)
7.84 (1H, d, 2.4 Hz)
C-8, C-6
9.50 6.83 (1H, dd, 8.6, 2.4 Hz) 7.08 (1H, d, 8.6 Hz)
C-5, C-4, C-6 C-8, C-9, C-5
7.47
C-3, C-2, C-9, C-11
7.35 (1H, d, 3.5 Hz) 6.65 (1H, d, 3.5 Hz) 5.45 (2H)
C-14, C-13, C-16
2.25 (3H, s)
C-16
The structure of compound 2 was elucidated by comparison of its ESIMS, 1H NMR, 13C NMR with the literature (Wu et al., 2002), and the obvious NOE effect (Fig. 2) between H-10 and H-12 indicated that its absolute form was similar with that of compound 1, so the absolute form of compound 2 was also in E form. 4. Chemotaxonomic significance Previous phytochemical studies indicate that pyrrolizidine alkaloids and furanoeremophilane sesquiterpenoids are common in the genus of Senecio (Bohlmann et al., 1977). Batra and Rajagopalan (1977) reported two alkaloids senecionine and seneciphylline from S. scandens collected from Darjeeling, India. However, in our present study, only trace amount of pyrrolizidine alkaloid senkirkine and adonifoline were detected by LC/MS/MS, no senecionine and seneciphylline, as well as furanoeremophilanes were found which may be explained due to geographic diversity (data not shown). Another fact that should be commented is the isolation of benzofuranone lactones from S. scandens as cannabifolactone A with the same skeleton was also isolated in Senecio cannabifolius Less. (Wu et al., 2002) collected from northeastern China. Quinol esters and its corresponding tetrahydroquinol esters have been reported from Senecio clevelandii collected from California (Bohlmann et al., 1981); Senecio minutus collected from Spain (Torres et al., 2000), Senecio
OH O
OH
O
O
Fig. 2. Selected NOE correlations for compound 2.
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J. Shi et al. / Biochemical Systematics and Ecology 35 (2007) 901e904
imparipinnatus and Senecio confusus from Mexico (Mericli et al., 1989). In the present research two quinol esters (5 and 6) and their tetrahydro-analogs (7 and 8) were isolated from S. scandens for the first time. Accordingly, it could be suggested that pyrrolizidine alkaloids, benzofuranone lactone and quinol esters are characteristic for this species. Acknowledgements This research was financially supported by the Natural Science Foundation of China (NSFC), a key program for Prof. Zheng-Tao Wang (No. 30530840). References Batra, V., Rajagopalan, T.R., 1977. Curr. Sci. 46, 141. Bohlmann, F., Knoll, K.H., Zdero, C., Mahanta, P.K., Greaz, M., Suwita, A., Ehlera, A., Le Van, N., Abraham, W.R., Natu, A.A., 1977. Phytochemistry 16, 965. Bohlmann, F., Suwita, A., 1976. Chem. Ber. 109, 2014. Bohlmann, F., Zdero, C., Robert, M.K., Robinson, H., 1981. Phytochemistry 20, 2425. Chen, Y.-L., 1999. Flora Reipublicae Popularis Sinicae, vol. 77. Science Press, Beijing. 225e271. Mericli, A.H., Mericli, F., Jakupovic, J., Bohlmann, F., Dominguez, X.A., Vega, H.S., 1989. Phytochemistry 28, 1149. Sadtler Research Laboratories Inc., 1969. Nuclear Magnetic Resonance Spectra [s], vols. 4e6. 2001Me4000M 3, 192. Torres, P., Grande, C., Anaya, J., Grande, M., 2000. Fitoterapia 71, 91. Tian, X.-Y., Wang, Y.-H., Yang, Q.-Y., Liu, X., Fang, W.-S., Yu, S.-S., 2006. J. Asian Nat. Prod. Res. 8, 125. Wang, X.-F., Tu, D.-J., 1980. Acta Pharm. Sin. 15, 503. Wu, B., Wu, L.-J., Wang, L.-Q., 2002. J. Asian Nat. Prod. Res. 4, 315. Wu, B., Lin, F.-H., Gao, H.-Y., Wu, L.-J., Kim, C., 2005. Chin. Tradit. Herb. Drugs 36, 1447. Yamaguchi, S., Koda, N., Yamamoto, H., 1989. Clin. Chem. 35, 1806. Zbiral, E., Menard, E.L., Muller, J.M., 1965. Helv. Chim. Acta 48, 404.
A new lactone from Senecio scandens Ji Shi a, Li Yang b, Chang-Hong Wang b, Gui-xin Chou b, Zheng-Tao Wang a,b,* a
Department of Pharmacognosy, China Pharmaceutical University, Nanjing 210038, China b Key Laboratory of Standardization of Chinese Medicines of Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China Received 14 November 2006; accepted 5 May 2007
Keywords: Senecio scandens; Compositae; Seneciolactone; Chemical constituents; Chemotaxonomy
1. Subject and sources Senecio plants (Compositae) are extensively used in single or formulated forms in Chinese traditional and folk medicine for antiinflammation, antibiosis, etc. There are about 100 species widely distributed in China with different morphological characteristics (Chen, 1999). Senecio scandens Buch.-Ham. ex D. Don, locally known as ‘‘Qianliguang’’, is one of the most popular species used as a Chinese medicinal herb but the chemical components of this species have not been fully disclosed to date. The aerial parts of this plant were collected from Rongan county, Guangxi province of PR China in April 2005 and the vouchers have been deposited in the Herbarium of the Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine. 2. Previous work Pyrrolizidine alkaloids and sesquiterpenes with a furanoeremophilane skeleton have been reported as the major components from the genus of Senecio (Bohlmann et al., 1977). Pyrrolizidine alkaloids (Batra and Rajagopalan, 1977), phenolic acids (Wang and Tu, 1980) and jacaranone glycosides (Tian et al., 2006) have been previously isolated from S. scandens. 3. Present study In the present study of S. scandens, a new lactone, (E)-seneciolactone (1), together with nine known compounds (2e10) were isolated and their structures determined based on spectral methods. The stereochemistry structures of seneciolactone (1) and (E)-cannabifolactone A (2) were firstly elucidated based on NOESY experiment. * Corresponding author. Shangai University of TCM, Institute of Chinese Materia Medica, 1 Cailun Road, Zhangjiang Hi-Tech Park, Shangai 201203, China. E-mail address: [email protected] (Z.-T. Wang). 0305-1978/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.bse.2007.05.001
902
J. Shi et al. / Biochemical Systematics and Ecology 35 (2007) 901e904
The air-dried aerial parts of S. scandens (6.0 kg) were exhaustively extracted with 80% ethanol under reflux. The extract was evaporated in vacuum to yield a syrupy residue (200 g). The residue was suspended in water (3000 mL) and partitioned with petroleum ether (3000 mL 3), EtOAc (3000 mL 5) and n-BuOH (3000 mL 3) successively, to give the corresponding fractions (200 g, 300 g and 200 g), respectively. A portion (270 g) of the EtOAc extract was subjected to column chromatography on silica gel (200e300 mesh, 2 kg) using stepwise elution with CHCl3eMeOH (100:0, 50:1, 20:1, 10:1, and 1:1) to yield five fractions: Fr.1 (35 g) Fr.2 (40 g), Fr.3 (53 g), Fr.4 (41 g) and Fr.5 (78 g). Fr.1 was chromatographed on silica gel (200e300 mesh, 1000 g) with a petrol ethereEtOAc gradient system (10:1e2:1) to give five sub-fractions (sub Frs.1Ae1E). Sub Fr.1A was subjected to repeated column chromatography on silica gel by gradient elution with petroleum ethereEtOAc (5:1, 4:1, 3:1, 2:1) and purified by Sephadex LH-20 (CHCl3eMeOH (1:1)) to afford compound 1 (8 mg), (E)-cannabifolactone A (2, 10 mg) (Wu et al., 2002), 4methoxyphenylacetic acid (3, 10 mg) (Sadtler Research Laboratories Inc., 1969) and 2,5-dihydroxybenzeneacetic acid (4, 50 mg) (Yamaguchi et al., 1989), respectively. Sub Fr.1B (5 g) was subjected to repeated silica gel column chromatography (200e300 mesh) with a gradient of petroleum ethereEtOAc, followed by Sephadex LH-20 eluted with MeOH to yield jacaranone (5, 40 mg) (Bohlmann and Suwita, 1976), ethyl 2-(1-hydroxy-4-oxocyclohexa-2,5dienyl) acetate (6, 40 mg) (Bohlmann and Suwita, 1976), methyl 2-(1-hydroxy-4-oxocyclohexyl) acetate (7, 70 mg) (Bohlmann et al., 1981) and ethyl 2-(1-hydroxy-4-oxocyclohexyl) acetate (8, 20 mg) (Bohlmann et al., 1981). Fr.2 (20 g) was also subjected to repeated column chromatography on silica gel by gradient elution with petroleum ethereEtOAc (3:1, 1:1, 1:2, 0:1) to give 5-methoxybenzofuran-2(3H)-one (9, 27 mg) (Zbiral et al., 1965) and methyl 2-(1,4-dihydroxycyclohexyl)-acetate (10, 5.3 mg) (Wu et al., 2005). The structures of the known compounds (3e10) were elucidated by comparison of their UV, ESIMS/EIMS, 1H NMR, 13C NMR, HMBC and HMQC data with the published data. Compound 1 was obtained as a yellow powder. Mp. 80.4e82.5 C; UV lmax (MeOH): 197 nm, 362 nm; IR: 3420 cm1 (nOH), 1767 cm1 (nc]o), 1718 cm1 (nc]o), 1610 cm1, 1629 cm1, 1470 cm1 (nf).The molecular formula of 1 was assigned as C16H12O6, from HREIMS spectrometry (m/z 300.0637, calcd 300.0634). The absorptions at 1767 cm1 in the IR spectrum indicated the presence of a lactone structure. In the 13C NMR spectrum, 16 carbon signals were observed as one methyl, one methylene, six methines and eight quaternaries. From 1H NMR spectrum, we observed a typical ABX coupling system for a 1,2,4-trisubstituted aromatic ring [d7.08 (1H, d, J ¼ 8.6 Hz), 6.85 (1H, dd, J ¼ 8.6, 2.4 Hz), 7.84 (1H, d, J ¼ 2.4 Hz)], an a,a0 -disubstituted furan ring substituted at positions of [7.35 (1H, d, J ¼ 3.5 Hz), 6.85 (1H, d, J ¼ 3.5 Hz)] and a methyl group [d2.25 (3H, s)], respectively. The form of compound 1 was determined on the basis of a NOESY experiment, correlation between H-10 and H-12 was strong, but no correlation between H-10 and H-4 was observed, which indicated that the form was E type but not Z type, so the absolute structure of compound 1 was established as (E)-5-Hydroxy-3-[(5-acetoxymethyl-2-furanyl) methylene]2(3H)-benzofuranone (Fig. 1; Table 1).
O 17 H3C
15
16
13
14
O
12 O
11 HMBC
4
OH
10 3
5
NOESY
2
6 7
O
O
Fig. 1. Key HMBC and NOESY correlations for compound 1.
J. Shi et al. / Biochemical Systematics and Ecology 35 (2007) 901e904
903
Table 1 NMR spectral data of 1 (400 MHz, CDCl3) No.
13
2 3 4 5 5-OH 6 7 8 9 10 11 12 13 14 15 16 17
170.2 119.2 111.7 153.4
1
C NMR
117.4 111.1 148.0 122.3 122.0 152.9 120.9 114.5 152.9 57.3 173.2 21.1
H NMR
HMBC (H/C)
7.84 (1H, d, 2.4 Hz)
C-8, C-6
9.50 6.83 (1H, dd, 8.6, 2.4 Hz) 7.08 (1H, d, 8.6 Hz)
C-5, C-4, C-6 C-8, C-9, C-5
7.47
C-3, C-2, C-9, C-11
7.35 (1H, d, 3.5 Hz) 6.65 (1H, d, 3.5 Hz) 5.45 (2H)
C-14, C-13, C-16
2.25 (3H, s)
C-16
The structure of compound 2 was elucidated by comparison of its ESIMS, 1H NMR, 13C NMR with the literature (Wu et al., 2002), and the obvious NOE effect (Fig. 2) between H-10 and H-12 indicated that its absolute form was similar with that of compound 1, so the absolute form of compound 2 was also in E form. 4. Chemotaxonomic significance Previous phytochemical studies indicate that pyrrolizidine alkaloids and furanoeremophilane sesquiterpenoids are common in the genus of Senecio (Bohlmann et al., 1977). Batra and Rajagopalan (1977) reported two alkaloids senecionine and seneciphylline from S. scandens collected from Darjeeling, India. However, in our present study, only trace amount of pyrrolizidine alkaloid senkirkine and adonifoline were detected by LC/MS/MS, no senecionine and seneciphylline, as well as furanoeremophilanes were found which may be explained due to geographic diversity (data not shown). Another fact that should be commented is the isolation of benzofuranone lactones from S. scandens as cannabifolactone A with the same skeleton was also isolated in Senecio cannabifolius Less. (Wu et al., 2002) collected from northeastern China. Quinol esters and its corresponding tetrahydroquinol esters have been reported from Senecio clevelandii collected from California (Bohlmann et al., 1981); Senecio minutus collected from Spain (Torres et al., 2000), Senecio
OH O
OH
O
O
Fig. 2. Selected NOE correlations for compound 2.
904
J. Shi et al. / Biochemical Systematics and Ecology 35 (2007) 901e904
imparipinnatus and Senecio confusus from Mexico (Mericli et al., 1989). In the present research two quinol esters (5 and 6) and their tetrahydro-analogs (7 and 8) were isolated from S. scandens for the first time. Accordingly, it could be suggested that pyrrolizidine alkaloids, benzofuranone lactone and quinol esters are characteristic for this species. Acknowledgements This research was financially supported by the Natural Science Foundation of China (NSFC), a key program for Prof. Zheng-Tao Wang (No. 30530840). References Batra, V., Rajagopalan, T.R., 1977. Curr. Sci. 46, 141. Bohlmann, F., Knoll, K.H., Zdero, C., Mahanta, P.K., Greaz, M., Suwita, A., Ehlera, A., Le Van, N., Abraham, W.R., Natu, A.A., 1977. Phytochemistry 16, 965. Bohlmann, F., Suwita, A., 1976. Chem. Ber. 109, 2014. Bohlmann, F., Zdero, C., Robert, M.K., Robinson, H., 1981. Phytochemistry 20, 2425. Chen, Y.-L., 1999. Flora Reipublicae Popularis Sinicae, vol. 77. Science Press, Beijing. 225e271. Mericli, A.H., Mericli, F., Jakupovic, J., Bohlmann, F., Dominguez, X.A., Vega, H.S., 1989. Phytochemistry 28, 1149. Sadtler Research Laboratories Inc., 1969. Nuclear Magnetic Resonance Spectra [s], vols. 4e6. 2001Me4000M 3, 192. Torres, P., Grande, C., Anaya, J., Grande, M., 2000. Fitoterapia 71, 91. Tian, X.-Y., Wang, Y.-H., Yang, Q.-Y., Liu, X., Fang, W.-S., Yu, S.-S., 2006. J. Asian Nat. Prod. Res. 8, 125. Wang, X.-F., Tu, D.-J., 1980. Acta Pharm. Sin. 15, 503. Wu, B., Wu, L.-J., Wang, L.-Q., 2002. J. Asian Nat. Prod. Res. 4, 315. Wu, B., Lin, F.-H., Gao, H.-Y., Wu, L.-J., Kim, C., 2005. Chin. Tradit. Herb. Drugs 36, 1447. Yamaguchi, S., Koda, N., Yamamoto, H., 1989. Clin. Chem. 35, 1806. Zbiral, E., Menard, E.L., Muller, J.M., 1965. Helv. Chim. Acta 48, 404.