- freely available
Molecules 2014, 19(2), 1603-1607; doi:10.3390/molecules19021603
Abstract: A new dicoumarinyl ether, 3-hydroxy-6-methoxy-7,7'-dicoumarinyl ether (1), was isolated from the roots of Stellera chamaejasme L, together with the known compound umbelliferone (2). Their structures were determined on the basis of spectroscopic techniques, including IR, NMR, and HR-ESI-MS.
Stellera chamaejasme L. (Ruixianglangdu in Chinese, family Thymelaeaceae), has been used in China as an important traditional medicine for the treatment of scabies, tinea, stubborn skin ulcers, chronic tracheitis, cancer, and tuberculosis [1,2]. Previous phytochemical studies of S. chamaejasme showed the presence of groups of biflavonoids, diterpenes, lignans, and coumarins [3,4,5,6,7,8,9,10,11,12]. In our continuous studies on the chemical constituents of S. chamaejasme, a new bicoumarin, 3-hydroxy-6-methoxy-7,7'-dicoumarinyl ether (1, Figure 1) was isolated, together with the known coumarin umbelliferone (2). Here, we report the isolation and structure elucidation of the new compound.
2. Results and Discussion
Compound 1 was obtained as a white, amorphous powder. HR-ESI-MS (negative) indicated a molecular formula of C19H12O7 by a pseudo molecular ion peak at m/z 351.0505 [M−H]−. The IR spectrum of 1 displayed absorptions of hydroxyl (3,448 cm−1), α,β-unsaturated lactone (1,724 cm−1), and phenyl (1,614, 1,580, and 1,456 cm−1) functionalities. In the 1H-NMR spectrum, vicinal pairs of signals typical of the H-3' and H-4' protons of an AX system at δH 6.31 (1H, d, J = 9.6 Hz, H-3') and 7.96 (1H, d, J = 9.6 Hz, H-4'), were observed, along with an ABX coupling pattern (δH 7.68 (1H, d, J = 8.6 Hz, H-5'), 7.10 (1H, dd, J = 8.6, 2.0 Hz, H-6') and 7.06 (1H, d, J = 2.0 Hz, H-8')), suggesting the presence of an 7-oxygenated coumarin moiety, which was further confirmed by the NOESY correlation of H-4' and H-5' (Figure 2).
The other unit was deduced to be a 3-hydroxy-6-methoxy-7-substituted- coumarin as follows: H-4 (δH 7.80) and H-5 (δH 7.24) showed a correlation in the NOESY experiment. Accordingly, cross-peaks between H-4 and C-5 (δC 109.9) and between H-5 and C-4 (δC 131.5) were evident in the HMBC experiment (Table 1). The correlation between the methoxy protons (δH 3.92) and H-5 in the NOESY spectrum indicated that the methoxy group was attached to C-6 (δC 146.6), which was further supported by the long-range correlation between the methoxy protons and C-6 in the HMBC spectrum. Compared with the known compound daphnoretin that was isolated from the same plant , the resonance of H-8' in 1 was shifted downfield by 0.22 ppm, and the H-8 one shifted upfield by 0.25 ppm, indicating that the two coumarin moieties were connected at C-7 and C-7' via an oxygen bridge, which was further supported by ESIMS/MS experiment of 1. The daughter ion peaks at m/z 206 and m/z 144 were derived from fission of the C-7'−O bond. Therefore, compound 1 was elucidated as 3-hydroxy-6-methoxy-7,7'-dicoumarinyl ether and named neodaphnoretin. The known compound was identified as umbelliferone (2) by comparison of its 1H- and 13C-NMR and MS data with published data.
|NO.||δH Mult (J = Hz)||δC||HMBC||NO.||δH Mult (J = Hz)||δC||HMBC|
|2||157.8 s||3'||6.31 d (9.6)||115.0 d||2', 10'|
|3||137.5 s||4'||7.96 d (9.6)||144.4 d||2', 5', 9'|
|4||7.80 s||131.5 d||2, 3, 5, 9||5'||7.68 d (8.6)||130.6 d||4', 7', 9'|
|5||7.24 s||109.9 d||4, 6, 7, 9||6'||7.10 dd (8.6, 2.0)||114.3 d||8', 10'|
|6||146.6 s||7'||161.1 s|
|7||151.2 s||8'||7.06 d (2.0)||104.9 d||6', 7'|
|8||6.90 s||103.7 d||6, 7, 9, 10||9'||156.5 s||10'|
|9||149.0 s||10'||115.5 s|
|10||111.6 s||6-OCH3||56.7 q|
|2'||160.7 s||3.92 s||6|
Melting points were measured on a Thermal Values analytical microscope and are uncorrected. IR spectra were recorded on a FI−IR 200SXY spectrophotometer (Nicolet, Madison, WI, USA). The high resolution-electrospray ionization-mass spectra (HR-ESI-MS) were acquired with a Micromass Q−TOF mass spectrometer (Waters Corporation, Carlsbad, CA, USA). NMR spectra were measured (1H at 600 MHz and 13C at 150 MHz) with TMS as the internal standard on a DD2 600 NMR instrument (Agilent, Santa Clara, CA, USA). Silica gel G254 and H (Qingdao Sea Chemical Factory, Qingdao, China) were used for TLC and column chromatography, respectively.
3.2. Plant Material
The roots of S. chamaejasme were collected in Kunming, Yunnan Province, China, in October, 2010. The plant was identified by Le Cai (Yunnan University). A voucher specimen (LJ-RXLD1008) was deposited with the Zhejiang University City College.
3.3. Extraction and Isolation
Air-dried powdered roots (3.0 kg) of S. chamaejasme were extracted exhaustively with 95% aq. EtOH (2 L) at r.t. for four times (7 days for each time). After concentration in vacuo, a crude extract (360 g) was obtained, which was suspended in H2O (1 L), and the suspension was extracted three times successively with petroleum ether, EtOAc and BuOH (1 L). The EtOAc fraction (160 g) was subjected to column chromatography (CC) with a PE/EtOAc gradient system of increasing polarity (9:1, 8:2, 7:3, 6:4, 5:5) as eluent to give six fractions (Fr. 1–6). Fr. 3 was rechromatographed on a SiO2 column with CHCl3/MeOH (98:2→95:5) to give compounds 1 (34 mg) and 2 (23 mg).
Neodaphnoretin (1) was obtained as white, amorphous powder, mp 133–135 °C, from CHCl3−MeOH (97:3). IR (KBr) cm−1: 3,448, 1,724, 1,614, 1,580, 1,456; 1H-NMR (CD3COCD3) δ: see Table 1; 13C-NMR (CD3COCD3) δ: see Table 1; HR-ESI-MS: m/z [M−H]− 351.0505 (calcd. for C19H11O7, 351.0505).
Umbelliferone (2) was obtained as colorless crystals, mp 222–224 °C, from MeOH; 1H-NMR (CD3OD) δ: 7.83 (1H, d, J = 9.4 Hz), 7.44 (1H, d, J = 8.5 Hz), 6.79 (1H, dd, J = 8.5, 2.0 Hz), 6.70 (1H, d, J = 2.0 Hz), 6.17 (1H, d, J =9.4 Hz); 13C-NMR (CD3OD) δ: 162.3, 161.8, 155.8, 144.6, 129.2, 113.1, 111.6, 102.0.
A new dicoumarinyl ether, 3-hydroxy-6-methoxy-7,7'-dicoumarinyl ether (1) was isolated from the EtOH extract of the roots of Stellera chamaejasme L together with the known compound umbelliferone (2).
Supplementary materials can be accessed at: http://www.mdpi.com/1420-3049/19/2/1603/s1.
This work was supported by National Science Foundation of China under Grant [No. 81302668]; Zhejiang Provincial Natural Science Foundation of China under Grant [LQ12H30003]; and Hangzhou Science and Technology Information Institute of China under Grant [20120633B31].
Xiang-Rong Li and Jie Li organized the study. Qian Shen, and Li-Ting Chen carried out the extraction and isolation. Jie Li and Chen-Hao Bao interpreted the results and helped write the manuscript.
Conflicts of Interest
The authors declare no conflict of interest.
- Xu, Z.H.; Qin, G.W.; Li, X.Y.; Xu, R.S. New biflavanones and bioactive compounds from Stellera chamaejasme L. Acta Pharm. Sin. 2001, 36, 668–671. [Google Scholar]
- Zhang, C.; Zhou, S.S.; Feng, L.Y.; Zhang, D.Y.; Lin, N.M.; Zhang, L.H.; Pan, J.P.; Wang, J.B.; Li, J. In vitro anti-cancer activity of chamaejasmenin B and neochamaejasmin C isolated from the root of Stellera chamaejasme L. Acta Pharmacol. Sin. 2013, 34, 262–270. [Google Scholar] [CrossRef]
- Niwa, M.; Takamizawa, H.; Tatematsu, H.; Hirata, Y. Piscicidal constituents of Stellera. chamaejasme L. Chem. Pharm. Bull. 1982, 30, 4518–4520. [Google Scholar] [CrossRef]
- Niwa, M.; Tatematsu, S.; Liu, G.Q.; Hirata, Y. Isolation and structures of two new C-3/C-3'-biflavanones, neochamaejasmin A and neochamaejasmin B. Chem. Lett. 1984, 539–542. [Google Scholar]
- Niwa, M.; Liu, G.Q.; Tatematsu, S.; Hirata, Y. Chamaechromone, a novel rearranged biflavonoid from Stellera. chamaejasme L. Tetrahedron Lett. 1984, 25, 3735–3738. [Google Scholar] [CrossRef]
- Tatematsu, H.; Kurokawa, M.; Niwa, M.; Hirata, Y. Piscicidal constituents of Stellera. chamaejasme L. II. Chem. Pharm. Bull. 1984, 32, 1612–1613. [Google Scholar] [CrossRef]
- Liu, G.Q.; Tatematsu, H.; Kurokawa, M.; Niwa, M.; Hirata, Y. Novel C-3/C-3''-biflavanones from stellera chamaejasme L. Chem. Pharm. Bull. 1984, 32, 362–365. [Google Scholar] [CrossRef]
- Niwa, M.; Otsuji, S.; Tatematsu, S.; Liu, G.Q.; Chen, S.F.; Hirata, Y. Stereostructures of two biflavanones from Stellera. chamaejasme L. Chem. Pharm. Bull. 1986, 34, 3249–3251. [Google Scholar] [CrossRef]
- Jiang, Z.H.; Tanaka, T.; Sakamoto, T.; Kouno, I.; Duan, J.A.; Zhou, R.H. Biflavanones, diterpenes, and coumarins from the roots of Stellera. chamaejasme L. Chem. Pharm. Bull. 2002, 50, 137–139. [Google Scholar] [CrossRef]
- Yang, G.H.; Liao, Z.X.; Xu, Z.Y.; Zhang, H.P.; Chen, D.F. Antimitotic and antifungal C-3/C-3'-biflavanones from Stellera. chamaejasme. Chem. Pharm. Bull. 2005, 53, 776–779. [Google Scholar] [CrossRef]
- Asada, Y.; Sukemori, A.; Watanabe, T.; Malla, K.J.; Yoshikawa, T.; Li, W.; Kolike, K.; Chen, C.H.; Akiyama, T.; Qian, K.; et al. Stelleralides A-C, novel potent anti-HIV daphnane-type diterpenoids from Stellera. chamaejasme L. Org. Lett. 2011, 13, 2904–2907. [Google Scholar] [CrossRef]
- Li, J.; Zhao, W.; Hu, J.L.; Cao, X.; Yang, J.; Li, X.R. A new C-3/C-3''-biflavanone from the roots of Stellera. chamaejasme L. Molecules 2011, 16, 6465–6469. [Google Scholar]
- Feng, B.M.; Pei, Y.H.; Han, B. Research on chemical constituents of Stellera. chamaejasme L. J. Shenyang Pharm. Univ. 2000, 17, 258–259. [Google Scholar]
- Sample Availability: Available from the authors.
© 2014 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).