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Two novel nortriterpenes from the roots of Phlomis umbrosa
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Chinese Chemical Letters 19 (2008) 1228–1230 www.elsevier.com/locate/cclet
Two novel nortriterpenes from the roots of Phlomis umbrosa Pu Liu a,*, Li Ying Li a, Rui Qi Niu a, Wei Ping Yin a, Tian Zeng Zhao b a
Chemical Engineering & pharmaceutical College, Henan University of Science and Technology, Luoyang 471003, China b Key Laboratory of Natural Products, Henan Academy of Sciences, Zhengzhou 450052, China Received 31 March 2008
Abstract Two novel 28-noroleanane-derived spirocyclic triterpenoids with unusual skeleton structures, phlomisone (1), phlomistetraol A (2), were isolated from the roots of Phlomis umbrosa. Their structures were elucidated by spectroscopic methods, including 1D, 2D nuclear magnetic resonance (NMR), high-resolution mass spectrometry (HR-MS). # 2008 Pu Liu. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved. Keywords: Phlomis umbrosa; Nortriterpenes
Phlomis umbrosa Turcz, one of the plants of the genus Phlomis (Lamiaceae), is a perennial herbaceous plant growing in northern China. Its rhizome has been used to treat cold, reduce swelling and staunch bleeding, and it has anti-inflammatory and detoxification properties [1,2]. Some triterpenoids, iridoid glycosides, phenylethanoid glycosides were separated from this plant [2–8]. As reported previously [9,10], we isolated four new nortriterpenoids and two phenylethanoid glycosides from the plant. Further studies on the chemical constituents of the rhizomes of this plant enabled us to isolate two novel nortriterpenoids with a rare skeleton. In this paper, we describe the isolation, structure elucidation of compounds 1–2. Compound 1, was obtained as an amorphous powder, ½a25 D +15.1 (c 1.13, MeOH). Its HRESI-MS exhibited a pseudomolecular ion [M+Na]+ at m/z 515.3338 (calcd. 515.3343), which was compatible with the molecular formula C29H48O6. The IR spectrum of compound 1 revealed the presence of hydroxy (3403 cm1). The 1H nuclear magnetic resonance (NMR) spectrum of compound 1 revealed five methyl groups [dH 1.19, 1.14, 1.08, 1.28, 1.31 (s, each 3H)]; four oxygenated methine proton signals [dH 4.50 (1H, m), 4.40 (d, 1H, J = 9.5 Hz), 4.54 (br, s, 1H), 4.75 (s, 1H)]; two oxygenated methylene proton signals [dH 4.46, 4.64 (d, each 1H, J = 11.1 Hz), 4.12, 4.27 (d, each 1H, J = 11.1 Hz)]; and an olefinic proton signal [dH 6.29 (br, s, 1H)]. Since the 13C NMR spectral data of this compound (Table 1) were similar to those of the known compounds from this plant[9], compound 1 was assumed to be a pentacyclic nortriterpene. The partial structure of the pentacyclic E ring was obtained from the HSQC and HMBC spectra, and combined to the triterpene skeleton by a spiro-carbon atom of dC 51.4. According to the HMBC spectral correlations, the hydroxyl groups deduced from the molecular formula could be located at C-2, C-3, C-18, C-19, C-23, and C-24: H-3 (d 4.40) to C-1, C-2, C-5, C-23, and C-24; H2-23 to C-3, C-4, C-5, and C-24; H-18 to C-13 and C-17; and H-19 to C-17, C-18, and
* Corresponding author. E-mail address: [email protected] (P. Liu). 1001-8417/$ – see front matter # 2008 Pu Liu. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved. doi:10.1016/j.cclet.2008.06.053
P. Liu et al. / Chinese Chemical Letters 19 (2008) 1228–1230 Table 1 NMR spectral data of compounds 1 and 2 (1H, 300MHz; No.
C 75MHz; in C5D5N, d, ppm; J, Hz; HMBC: from H to C)
1 1
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 29 30
13
2
H d, J (Hz)
1.43, 2.33 m 4.50 m 4.40 d, 9.6 2.05 m 1.65, 1.88 m 1.50, 1.73 m 1.88 m 2.07 m 6.29 br, s
1.13, 1.90 m 1.55, 1.98 m 4.54 br, s 4.75 s 1.55, 1.77 1.73, 2.23 4.46, 4.64 4.14, 4.27 1.19 s 1.14 s 1.08 s 1.28 s 1.31 s
1229
m m d, 11.1 d, 11.1
13
C
48.2 69.4 79.9 48.2 49.0 19.5 34.2 40.3 48.5 38.7 24.1 119.1 144.1 44.4 27.2 28.3 51.4 73.6 82.6 43.0 38.7 29.2 69.5 64.6 17.9 18.3 23.6 29.7 22.4
HMBC 1, 4, 10, 25 1, 5, 23, 24
1
13
1.42, 2.35 m 4.49m 4.39 d, 9.6
48.3 69.4 80.0 48.2 48.9 19.5 34.1 40.3 48.5 38.7 23.9 119.6 143.3 44.5 28.1 38.0 49.6 74.5 49.7 44.8 81.3 39.6 69.6 64.6 17.8 18.1 23.4 29.3 24.8
H d, J (Hz)
2.05 m 1.66, 1.90 m 1.51, 1.75 m 1.86 m 10, 12, 13 10, 13
2.05 m 6.31 br, s
1.10, 1.84 m 1.47, 1.82 m 13, 14, 16, 19 16, 18, 29, 30
4.32 br, s 2.45, 1.37 d, 13.1
3, 4, 5, 24 3, 4, 5, 23 1, 5, 9, 10 7, 8, 9, 14 8, 14, 15 19, 20, 21, 30 19, 20, 21, 29
3.84 m 1.82 m 4.45, 4.64 d, 11.0 4.11, 4.24 d, 11.0 1.20 s 1.06 s 1.09 s 1.07 s 1.31 s
C
HMBC 1, 4, 10, 25 1, 5, 23, 24
10, 12, 13 10, 13
13, 14, 16, 19
21, 22, 29, 30 3, 4, 5, 24 3, 4, 5, 23 1, 5, 9, 10 7, 8, 9, 14 8, 14, 15 19, 20, 21, 30 19, 20, 21, 29
C-30. Furthermore, in the NOESY spectrum, the proton signal of H-2 correlated with that of H-24 and H-25; that of H3 correlated with H-23; that of H-18 correlated with H-27; and that of H-18 with H-19. Thus, the 4 hydroxyl groups should be assigned as 2a-, 3b-, 18b, and 19b-oriented configurations. The structure of compound 1 was designated as (2a,3b,17R,18b,19a)-19(18 ! 17)-abeo-28-norolean-12-ene-2,3,18,19, 23,24-hexaol (Fig. 1).
Fig. 1. Structures of compounds 1 and 2.
1230
P. Liu et al. / Chinese Chemical Letters 19 (2008) 1228–1230
+ Compound 2, was obtained as an amorphous powder, ½a25 D +15.6 (c 1.2, MeOH), revealed an [M+Na] ion at m/z + 515.3336 [M+Na] in the high-resolution positive Fourier transform mass spectrometer (FTMS) consistent with a molecular formula of C29H46O6 (calcd. for C29H48O6Na 515.3343). The 1H and 13C NMR spectra of 2 (Table 1) showed that its structure is closely related to that of 1, except for the positions of the hydroxyl group in ring E. The 1 H–1H COSY spectrum of 2 revealed a separated spin–spin system (H1-21/H2-22) in the E, and in the HMBC spectrum, the signal of H-21 (d 3.84) correlated with the carbon signals of C-22 (39.6), C-17, C-29 and C-30 indicated the hydroxyl group were located at positions C-21. The NOESY spectrum between dH 3.84 (m, 1H, H-21) and dH 1.31 (s, 3H, H-30) revealed the configuration of the C-21 hydroxyl group had an a-orientation in compound 2. Therefore, the structure of 2 was elucidated as (2a,3b,17R,18b,21a)-19(18 ! 17)-abeo-28-norolean-12-ene-2,3,18,21, 23,24hexaol (Fig. 1).
Acknowledgment The project was supported by the fund for Doctor of Henan University of Science and Technology. Reference [1] Dictionary of Chinese Materia Medica, Jiangsu New Medical College, Shanghai Scientific and Technical Publishing House, Shanghai, 1977, p. 2665. [2] S.J. Guo, L.M. Gao, D.L. Cheng, Pharmazie 56 (2) (2001) 178. [3] J. Zhao, X.W. Yang, H.Z. Fu, R.Z. Li, Z.C. Lou, Zhongcaoyao (Chin. Tradit. Herbal Drugs, in Chinese) 30 (2) (1999) 90. [4] Y.L. Yang, S.J. Guo, K. Sun, Lanzhou Daxue Xuebao, (J. Lanzhou Univ. Nat. Sci., in Chinese) 40 (2) (2004) 67. [5] C.Z. Zhang, C. Li, S.L. Feng, J.G. Shi, Phytochemistry 30 (12) (1991) 4156. [6] M. Toshio, Y. Ryouko, U. Akira, Phytochemistry 43 (2) (1996) 475. [7] K.Y. Jung, J.C. Do, K.H. Son, Saengyak Hakhoechi 27 (2) (1996) 87. [8] B.S. Chung, J.W. Kim, J.C. Kim, Y.H. Kim, Saengyak Hakhoechi 14 (1) (1983) 5. [9] P. Liu, Z. Yao, H.Q. Li, H.Q. Duan, Helv. Chim. Acta 90 (2) (2007) 601. [10] P. Liu, Y. Takaishi, H.Q. Duan, Chin. Chem. Lett. 18 (2) (2007) 155.
Chinese Chemical Letters 19 (2008) 1228–1230 www.elsevier.com/locate/cclet
Two novel nortriterpenes from the roots of Phlomis umbrosa Pu Liu a,*, Li Ying Li a, Rui Qi Niu a, Wei Ping Yin a, Tian Zeng Zhao b a
Chemical Engineering & pharmaceutical College, Henan University of Science and Technology, Luoyang 471003, China b Key Laboratory of Natural Products, Henan Academy of Sciences, Zhengzhou 450052, China Received 31 March 2008
Abstract Two novel 28-noroleanane-derived spirocyclic triterpenoids with unusual skeleton structures, phlomisone (1), phlomistetraol A (2), were isolated from the roots of Phlomis umbrosa. Their structures were elucidated by spectroscopic methods, including 1D, 2D nuclear magnetic resonance (NMR), high-resolution mass spectrometry (HR-MS). # 2008 Pu Liu. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved. Keywords: Phlomis umbrosa; Nortriterpenes
Phlomis umbrosa Turcz, one of the plants of the genus Phlomis (Lamiaceae), is a perennial herbaceous plant growing in northern China. Its rhizome has been used to treat cold, reduce swelling and staunch bleeding, and it has anti-inflammatory and detoxification properties [1,2]. Some triterpenoids, iridoid glycosides, phenylethanoid glycosides were separated from this plant [2–8]. As reported previously [9,10], we isolated four new nortriterpenoids and two phenylethanoid glycosides from the plant. Further studies on the chemical constituents of the rhizomes of this plant enabled us to isolate two novel nortriterpenoids with a rare skeleton. In this paper, we describe the isolation, structure elucidation of compounds 1–2. Compound 1, was obtained as an amorphous powder, ½a25 D +15.1 (c 1.13, MeOH). Its HRESI-MS exhibited a pseudomolecular ion [M+Na]+ at m/z 515.3338 (calcd. 515.3343), which was compatible with the molecular formula C29H48O6. The IR spectrum of compound 1 revealed the presence of hydroxy (3403 cm1). The 1H nuclear magnetic resonance (NMR) spectrum of compound 1 revealed five methyl groups [dH 1.19, 1.14, 1.08, 1.28, 1.31 (s, each 3H)]; four oxygenated methine proton signals [dH 4.50 (1H, m), 4.40 (d, 1H, J = 9.5 Hz), 4.54 (br, s, 1H), 4.75 (s, 1H)]; two oxygenated methylene proton signals [dH 4.46, 4.64 (d, each 1H, J = 11.1 Hz), 4.12, 4.27 (d, each 1H, J = 11.1 Hz)]; and an olefinic proton signal [dH 6.29 (br, s, 1H)]. Since the 13C NMR spectral data of this compound (Table 1) were similar to those of the known compounds from this plant[9], compound 1 was assumed to be a pentacyclic nortriterpene. The partial structure of the pentacyclic E ring was obtained from the HSQC and HMBC spectra, and combined to the triterpene skeleton by a spiro-carbon atom of dC 51.4. According to the HMBC spectral correlations, the hydroxyl groups deduced from the molecular formula could be located at C-2, C-3, C-18, C-19, C-23, and C-24: H-3 (d 4.40) to C-1, C-2, C-5, C-23, and C-24; H2-23 to C-3, C-4, C-5, and C-24; H-18 to C-13 and C-17; and H-19 to C-17, C-18, and
* Corresponding author. E-mail address: [email protected] (P. Liu). 1001-8417/$ – see front matter # 2008 Pu Liu. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved. doi:10.1016/j.cclet.2008.06.053
P. Liu et al. / Chinese Chemical Letters 19 (2008) 1228–1230 Table 1 NMR spectral data of compounds 1 and 2 (1H, 300MHz; No.
C 75MHz; in C5D5N, d, ppm; J, Hz; HMBC: from H to C)
1 1
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 29 30
13
2
H d, J (Hz)
1.43, 2.33 m 4.50 m 4.40 d, 9.6 2.05 m 1.65, 1.88 m 1.50, 1.73 m 1.88 m 2.07 m 6.29 br, s
1.13, 1.90 m 1.55, 1.98 m 4.54 br, s 4.75 s 1.55, 1.77 1.73, 2.23 4.46, 4.64 4.14, 4.27 1.19 s 1.14 s 1.08 s 1.28 s 1.31 s
1229
m m d, 11.1 d, 11.1
13
C
48.2 69.4 79.9 48.2 49.0 19.5 34.2 40.3 48.5 38.7 24.1 119.1 144.1 44.4 27.2 28.3 51.4 73.6 82.6 43.0 38.7 29.2 69.5 64.6 17.9 18.3 23.6 29.7 22.4
HMBC 1, 4, 10, 25 1, 5, 23, 24
1
13
1.42, 2.35 m 4.49m 4.39 d, 9.6
48.3 69.4 80.0 48.2 48.9 19.5 34.1 40.3 48.5 38.7 23.9 119.6 143.3 44.5 28.1 38.0 49.6 74.5 49.7 44.8 81.3 39.6 69.6 64.6 17.8 18.1 23.4 29.3 24.8
H d, J (Hz)
2.05 m 1.66, 1.90 m 1.51, 1.75 m 1.86 m 10, 12, 13 10, 13
2.05 m 6.31 br, s
1.10, 1.84 m 1.47, 1.82 m 13, 14, 16, 19 16, 18, 29, 30
4.32 br, s 2.45, 1.37 d, 13.1
3, 4, 5, 24 3, 4, 5, 23 1, 5, 9, 10 7, 8, 9, 14 8, 14, 15 19, 20, 21, 30 19, 20, 21, 29
3.84 m 1.82 m 4.45, 4.64 d, 11.0 4.11, 4.24 d, 11.0 1.20 s 1.06 s 1.09 s 1.07 s 1.31 s
C
HMBC 1, 4, 10, 25 1, 5, 23, 24
10, 12, 13 10, 13
13, 14, 16, 19
21, 22, 29, 30 3, 4, 5, 24 3, 4, 5, 23 1, 5, 9, 10 7, 8, 9, 14 8, 14, 15 19, 20, 21, 30 19, 20, 21, 29
C-30. Furthermore, in the NOESY spectrum, the proton signal of H-2 correlated with that of H-24 and H-25; that of H3 correlated with H-23; that of H-18 correlated with H-27; and that of H-18 with H-19. Thus, the 4 hydroxyl groups should be assigned as 2a-, 3b-, 18b, and 19b-oriented configurations. The structure of compound 1 was designated as (2a,3b,17R,18b,19a)-19(18 ! 17)-abeo-28-norolean-12-ene-2,3,18,19, 23,24-hexaol (Fig. 1).
Fig. 1. Structures of compounds 1 and 2.
1230
P. Liu et al. / Chinese Chemical Letters 19 (2008) 1228–1230
+ Compound 2, was obtained as an amorphous powder, ½a25 D +15.6 (c 1.2, MeOH), revealed an [M+Na] ion at m/z + 515.3336 [M+Na] in the high-resolution positive Fourier transform mass spectrometer (FTMS) consistent with a molecular formula of C29H46O6 (calcd. for C29H48O6Na 515.3343). The 1H and 13C NMR spectra of 2 (Table 1) showed that its structure is closely related to that of 1, except for the positions of the hydroxyl group in ring E. The 1 H–1H COSY spectrum of 2 revealed a separated spin–spin system (H1-21/H2-22) in the E, and in the HMBC spectrum, the signal of H-21 (d 3.84) correlated with the carbon signals of C-22 (39.6), C-17, C-29 and C-30 indicated the hydroxyl group were located at positions C-21. The NOESY spectrum between dH 3.84 (m, 1H, H-21) and dH 1.31 (s, 3H, H-30) revealed the configuration of the C-21 hydroxyl group had an a-orientation in compound 2. Therefore, the structure of 2 was elucidated as (2a,3b,17R,18b,21a)-19(18 ! 17)-abeo-28-norolean-12-ene-2,3,18,21, 23,24hexaol (Fig. 1).
Acknowledgment The project was supported by the fund for Doctor of Henan University of Science and Technology. Reference [1] Dictionary of Chinese Materia Medica, Jiangsu New Medical College, Shanghai Scientific and Technical Publishing House, Shanghai, 1977, p. 2665. [2] S.J. Guo, L.M. Gao, D.L. Cheng, Pharmazie 56 (2) (2001) 178. [3] J. Zhao, X.W. Yang, H.Z. Fu, R.Z. Li, Z.C. Lou, Zhongcaoyao (Chin. Tradit. Herbal Drugs, in Chinese) 30 (2) (1999) 90. [4] Y.L. Yang, S.J. Guo, K. Sun, Lanzhou Daxue Xuebao, (J. Lanzhou Univ. Nat. Sci., in Chinese) 40 (2) (2004) 67. [5] C.Z. Zhang, C. Li, S.L. Feng, J.G. Shi, Phytochemistry 30 (12) (1991) 4156. [6] M. Toshio, Y. Ryouko, U. Akira, Phytochemistry 43 (2) (1996) 475. [7] K.Y. Jung, J.C. Do, K.H. Son, Saengyak Hakhoechi 27 (2) (1996) 87. [8] B.S. Chung, J.W. Kim, J.C. Kim, Y.H. Kim, Saengyak Hakhoechi 14 (1) (1983) 5. [9] P. Liu, Z. Yao, H.Q. Li, H.Q. Duan, Helv. Chim. Acta 90 (2) (2007) 601. [10] P. Liu, Y. Takaishi, H.Q. Duan, Chin. Chem. Lett. 18 (2) (2007) 155.