- Email: [email protected]
A new indole alkaloid from Ervatamia yunnanensis
Fitoterapia 81 (2010) 63–65
Contents lists available at ScienceDirect
Fitoterapia j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / f i t o t e
A new indole alkaloid from Ervatamia yunnanensis Yong-Sheng Jin a,1, Jing-Ling Du b,1, Hai-Sheng Chen b,⁎, Li Jin b, Shuang Liang b a b
Department of Organic Chemistry, College of Pharmacy, Second Military Medical University, Shanghai 200433, PR China Department of Phytochemistry, College of Pharmacy, Second Military Medical University, Shanghai 200433, PR China
a r t i c l e
i n f o
Article history: Received 15 March 2009 Accepted in revised form 17 July 2009 Available online 30 July 2009 Keywords: Ervatamia yunnanensis Tsiang Apocynaceae Indole alkaloid Ervataine
a b s t r a c t The stems of Ervatamia yunnanensis have afforded a new indole alkaloid, ervataine (1), whose structure was determined by spectroscopic analysis. Five known compounds, ibogaine (2) coronaridine (3), heyneanine (4), voacangine hydroxyindolenine (5) and coronaridine hydroxyindolenine (6), were also isolated. © 2009 Elsevier B.V. All rights reserved.
1. Introduction
2. Experimental
Ervatamia yunnanensis Tsiang is distributed in the Yunnan and Guangxi provinces of China, and its stem is used in Chinese folk medicine for the treatment of stomachache, dysentery, snakebites, rheumatic arthritis, hypertension and virus hepatitis [1,2]. Previous studies on this plant revealed the presence of indole alkaloids [3–7]. The alkaloid fraction from E. yunnanensis is endowed with significant antinociceptive activity [8], and some indole alkaloids from this plant were effective in the prevention and treatment of drug addiction [9]. We present here the isolation of a structurally unique new indole alkaloid, ervataine (1) and of five known compounds, ibogaine (2) [10], coronaridine (3) [11], heyneanine (4) [12–14], voacangine hydroxyindolenine (5) [15] and coronaridine hydroxyindolenine (6) [15] (Fig. 1).
2.1. General UV spectra were measured with a UV1600 (Shanghai Mapada Instruments Co., Ltd), and IR spectra were recorded on a Bruker Vector 22. HR-FAB-MS and ESI-MS were performed on a Waters Q-Tof micro mass spectrometer. 1H NMR, 13C NMR and 2D NMR spectra were recorded on a Bruker AVANCE II-600 spectrometer and chemical shifts are reported in parts per million relative to methanol-d4 (3.30 ppm for 1H and 49.0 ppm for 13C) or CDCl3 (7.27 ppm for 1H and 77.23 ppm for 13C). All solvents used were of analytical grade (Shanghai Chemical Co., Ltd.). Silica gel (100– 200 or 200–300 mesh, Qingdao Haiyang Chemical Co., Ltd.), sephadex LH-20 (Pharmacia Co., Ltd.), and macroporous resin AB-8 (Shanghai Mosu Tech. Co., Ltd.) were used for column chromatography. 2.2. Plant material
⁎ Corresponding author. Department of Phytochemistry, College of Pharmacy, Second Military Medical University, 325 GuoHe Road, Shanghai 200433, PR China. Fax: +86 21 65495819. E-mail addresses: [email protected] (Y.-S. Jin), [email protected] (H.-S. Chen). 1 These authors have contributed equally to this work. 0367-326X/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.fitote.2009.07.008
The plant material was collected in May 2003 at Xishuangbanna, Yunnan province and identified by Wang Hong, Xishuangbanna tropical plant garden of Chinese Academy of Science. A voucher specimen (No. 200305-1) has been deposited
64
Y.-S. Jin et al. / Fitoterapia 81 (2010) 63–65
20 to yield compounds 2 (55 mg) and 5 (56 mg). The 60% EtOH eluate was subjected to silica gel CC eluting with a gradient of CHCl3–MeOH to give eight fractions (Fr. B1 to Fr. B8). Fr. B4 was rechromatographed on silica gel eluting with CHCl3/CH3OH (15:1) and then purified on Sephadex LH-20 to yield compounds 1 (18 mg), 4 (50 mg) and 6 (25 mg). The 30% EtOH eluate was subjected to silica gel CC eluting with a gradient of CHCl3–MeOH to give six fractions (Fr. C1 to Fr. C6). Fr. C1 was rechromatographed on silica gel eluting with CHCl3/ CH3OH (10:1) and then purified on Sephadex LH-20 to yield compound 3 (30 mg). Ervataine (1), obtained as white amorphous powder, mp 221–223 °C; UV max (MeOH): 225 (log ε 4.14), 278 (3.61) nm; IR bands (KBr): 3530, 1740, 1623 cm− 1; ESI-MS m/z: 309 [M + H] +; HRFABMS m/z: 309.1969[M + H] +, Calc. for C20H24N2O 308.19. For 1H and 13C NMR spectral data see Table 1. Ibogaine (2), obtained as white amorphous powder; ESIMS m/z: 311[M + H]+; For 1H and 13C NMR spectral data see Table 1. Coronaridine (3), obtained as a white powder, ESI-MS m/z: 361 [M + Na]+. 1H NMR and 13C NMR data were compared with the information in the literature [11], and it was identified as coronaridine. Heyneanine (4), isolated as white amorphous powder, ESIMS m/z: 377 [M + Na]+ 1, 1H NMR and 13C NMR data were compared with the information in the literatures [12–14], and it was identified as heyneanine. Voacangine hydroxyindolenine (5), separated as a white powder, ESI-MS m/z: 385 [M +H]+, 407 [M +Na]+, 1H NMR and 13C NMR data were compared with the information in the literature [15], and it was identified as voacangine hydroxyindolenine. Coronaridine hydroxyindolenine (6), obtained as a white powder, ESI-MS m/z: 377 [M + Na]+, 1H NMR and 13C NMR data was compared with the information in the literature [15], and it was identified as coronaridine hydroxyindolenine. 3. Results and discussion Fig. 1. Structures of compounds 1–6.
in the Herbarium of School of Pharmacy, Second Military Medical University, Shanghai. 2.3. Extraction and isolation The air-dried and powdered stems (5 kg) were extracted with 95% EtOH (10 L × 3) by reflux heating, and the percolate was concentrated in vacuum to yield an EtOH extract (400 g). The EtOH extract (400 g) was suspended in 2 L of water and acidified with 2% HCl aqueous solution to pH 3–4. The acidic mixture was centrifuged to give two layers. The upper layer (50 of 210 g) was subjected to column chromatography over macroporous resin AB-8 using a gradient solvent system EtOH/H2O to afford three fractions, 30%, 60% and 90% EtOH eluates. The 90% EtOH eluate was subjected to silica gel CC eluting with a gradient of CHCl3–MeOH to give six fractions (Fr. A1 to Fr. A6). Fr. A3 was rechromatographed on silica gel eluting with CHCl3/CH3OH (30:1) and then purified on Sephadex LH-
Ervataine (1), isolated as a white amorphous compound by preparative TLC, exhibited a [M + H]+ ion peak at m/z 309 in ESI-MS. The molecular formula was deduced as C20H24N2O on the basis of HRESI-MS data (m/z 309.1969 [M + H]+) and NMR data. The 1H NMR spectrum of 1 showed a typical splitting pattern of a 1,3,4-trisubstitued aromatic ring (δ 6.86, J = 2.4 Hz; 7.29, J = 2.4, 8.4 Hz; 7.08, J = 9.0 Hz), a singlet attributable to an aromatic methoxyl (δ 3.82, s), and the characteristic signals of an ethyl side chain (δ 0.88, J = 7.0 Hz; 1.51). 13C NMR demonstrated 20 carbon signals, including an indole moiety (δ 144.5, 108.8, 131.2, 101.1, 155.0, 111.1, 111.9, 131.6). By comparison of proton and carbon signals of 1 with those of 2, ibogaine, a known compound (Table 1), it could be deduced that the two compounds had the same skeleton. The sharp doublet at 4.49 ppm (J = 3.0 Hz) of 1 indicated that C-3 was connected to an atom with large electronegrativity. By D2O exchange experiment it was found that there was no presence of the NH broad singlet belonging to an indole chromophore in compound 1 but in compound 2. Comparison of the molecular formulas of 1 and 2, showed the lack of two protons in 1, where one extra unit of unsaturation was present. In addition, in the
Y.-S. Jin et al. / Fitoterapia 81 (2010) 63–65 Table 1 1 H NMR and Position
13
C NMR data of compounds 1 and 2 (CD3OD, 600 MHz). 1 δC (dept)
2 3 5
144.5(s) 93.2(d) 55.1(t)
6
34.0(t)
7 8 9 10 11 12 13 14 15 16 17
108.8 (s) 131.2(s) 101.1(d) 155.0(s) 111.1(d) 111.9(d) 131.6(s) 30.4(d) 25.5(t) 41.1(d) 22.6(t)
18 19 20 21 10- OCH3 a
65
12.3(q) 28.1(t) 42.8(d) 60.2(d) 56.5(q)
2 δH 4.49 (1H, 3.54 (1H, 3.07 (1H, 2.21 (1H, 1.50 a
δC (dept) d, J = 3.0 Hz) dt, J = 3.0, 14.4 Hz ) m) m)
6.86 (1H, d, J = 2.4 Hz) 7.29 (1H, dd, J = 2.4, 8.4 Hz) 7.08 (1H, d, J = 8.4 Hz) 2.07 (1H, 1.48 a 2.84 (1H, 3.19 (1H, 2.62 (1H, 0.88 (3H, 1.51 a 1.50 a 2.97 (1H, 3.82 (3H,
br.s) dd, J = 4.8, 10.8 Hz) m) m) t, J = 7.0 Hz)
s) s)
δH
144.4(s) 55.7(t) 50.9(t) 21.7(t) 109.0(s) 131.2(s) 101.3(d) 154.9(s) 111.1(d) 111.8(d) 131.9(s) 28.0(d) 23.2(t) 42.3(s) 33.2(t) 12.3(q) 28.9(t) 43.5(d) 59.2(d) 56.5(q)
6.87 (1H, d, J = 2.4 Hz) 6.65 (1H, dd, J = 2.4, 8.4 Hz) 7.08 (1H, d, J = 8.4 Hz)
0.91(3H, t, J = 7.2 Hz)
3.82(3H, s)
Signals were overlapped.
HMBC of 1, H-3 at δ 4.49 was correlated with C-5 at δ 55.1, C-15 at δ 25.5 and C-2 at δ 144.5, while H-19 at δ 1.51 was correlated with C-20 at δ 42.8 and C-15 at δ 25.5 (Fig. 2). Compound 1 could derive by the partial cyclization of compound 2, suggesting that C-3 of 1 may be linked with the nitrogen atom at indole chromophore, as confirmed by the detection of a HMBC correlation between H-3 and C-2, as well as by 13C NMR comparison with 2 [C-3 (Δδ = 37.5), C-14 (Δδ = 2.4), C-17 (Δδ = −10.6)]. Thus, 1, named ervataine, has an unprecedented cage-like connectivity. As an alternative constitution, a 3-hydroxyibogaine structure was also considered for the novel compound. The N-1/C-3 bond in the structure of ervataine is undoubtedly strained, but a 3D virtual structure of this compound could be constructed in a reasonable way using the Chem3D and Hyperchem programs. Moreover, the mass spectrum of indole alkaloids with secondary –OH, even tertiary –OH, usually gave the molecular ion peaks [M+ H]+; and only few have been reported to give a weaker dehydration peak [12,13,16] [M+ H-18]+. So, if the ion at m/z 309 could be due to a dehydration process, then the [M+ H]+ ion at m/z 327 should also be visible, something that
Fig. 2. Key HMBC correlations of compound 1.
did not occur in ervataine. Based on spectroscopic evidence, structure 1 seems the most plausible for ervataine. Acknowledgements This study was supported by the National Natural Science Foundation of China (20272081, 20872178) and Shanghai Leading Academic Discipline Project (No. B906). We are grateful to one of the reviewers for the suggestion of the alternative 3-hydroxyibogaine structure for ervataine. References [1] Institute of Bonica of Kunming, Flora Yunnanica. Beijing: Science Press; 1983. p. 478. [2] Yu Y, Gao JM, Liu JK. Yunnan Zhiwu Yanjiu 1999;21:399. [3] Liu G, Liu X, Feng XZ. Planta Med 1988;54:519. [4] Yu Y, Gao JM, Liu JK. Chin Chem Lett 1999;10:575. [5] Luo XG, Chen HS, Zhang WD, Xu YX, Huang M, Liu J, Liu WY, et al. Dier Junyi Daxue Xuebao 2002;23:662. [6] Liang S, Luo XG, Chen HS, Zhang XD, Huang M, Liu WY. Chin Chem Lett 2006;17:783. [7] Luo XG, Chen HS, Liang S, Huang M, Xuan WD, Jin L. Chin Chem Lett 2007;18:697. [8] Chen MY, Zhou LH, Zhang XD, Luo XG, Chen HS, Huang M. Yaoxue Shijian Zazhi 2006;24:203. [9] Xuan WD, Chen HS, Yuan ZX, Zhang XD, Huang M. Dier Junyi Daxue Xuebao 2006;27:92. [10] Yu DQ, Yang JS. Chemical analytical manual (the second edition), the seventh fascicle: NMR spectra analysis. Beijing: Chemical Industry Press; 2001. p. 818. 836. [11] Okuyama E, Gao LH, Yamazaki M. Chem Pharm Bull 1992;40:2075. [12] Kam TS, Sim KM. J Nat Prod 2002;65:669. [13] Govindachari TR, Joshi BS, Saksena AK, Sathe SS, Viswanathan N. Tetrahedron Lett 1965;43:3873. [14] Perera P, Sandberg F, van Beek TA, Verpoorte R. Planta Med 1984;50:251. [15] Alberto M, Matias R, Gabriel F, Antoniao G. J Nat Prod 1996;59:185. [16] Cong PZ, Su KM. Chemical analytical manual (the second edition), the ninth fascicle: mass spectrum analysis. Beijing: Chemical Industry Press; 2001. p. 686–700.
Contents lists available at ScienceDirect
Fitoterapia j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / f i t o t e
A new indole alkaloid from Ervatamia yunnanensis Yong-Sheng Jin a,1, Jing-Ling Du b,1, Hai-Sheng Chen b,⁎, Li Jin b, Shuang Liang b a b
Department of Organic Chemistry, College of Pharmacy, Second Military Medical University, Shanghai 200433, PR China Department of Phytochemistry, College of Pharmacy, Second Military Medical University, Shanghai 200433, PR China
a r t i c l e
i n f o
Article history: Received 15 March 2009 Accepted in revised form 17 July 2009 Available online 30 July 2009 Keywords: Ervatamia yunnanensis Tsiang Apocynaceae Indole alkaloid Ervataine
a b s t r a c t The stems of Ervatamia yunnanensis have afforded a new indole alkaloid, ervataine (1), whose structure was determined by spectroscopic analysis. Five known compounds, ibogaine (2) coronaridine (3), heyneanine (4), voacangine hydroxyindolenine (5) and coronaridine hydroxyindolenine (6), were also isolated. © 2009 Elsevier B.V. All rights reserved.
1. Introduction
2. Experimental
Ervatamia yunnanensis Tsiang is distributed in the Yunnan and Guangxi provinces of China, and its stem is used in Chinese folk medicine for the treatment of stomachache, dysentery, snakebites, rheumatic arthritis, hypertension and virus hepatitis [1,2]. Previous studies on this plant revealed the presence of indole alkaloids [3–7]. The alkaloid fraction from E. yunnanensis is endowed with significant antinociceptive activity [8], and some indole alkaloids from this plant were effective in the prevention and treatment of drug addiction [9]. We present here the isolation of a structurally unique new indole alkaloid, ervataine (1) and of five known compounds, ibogaine (2) [10], coronaridine (3) [11], heyneanine (4) [12–14], voacangine hydroxyindolenine (5) [15] and coronaridine hydroxyindolenine (6) [15] (Fig. 1).
2.1. General UV spectra were measured with a UV1600 (Shanghai Mapada Instruments Co., Ltd), and IR spectra were recorded on a Bruker Vector 22. HR-FAB-MS and ESI-MS were performed on a Waters Q-Tof micro mass spectrometer. 1H NMR, 13C NMR and 2D NMR spectra were recorded on a Bruker AVANCE II-600 spectrometer and chemical shifts are reported in parts per million relative to methanol-d4 (3.30 ppm for 1H and 49.0 ppm for 13C) or CDCl3 (7.27 ppm for 1H and 77.23 ppm for 13C). All solvents used were of analytical grade (Shanghai Chemical Co., Ltd.). Silica gel (100– 200 or 200–300 mesh, Qingdao Haiyang Chemical Co., Ltd.), sephadex LH-20 (Pharmacia Co., Ltd.), and macroporous resin AB-8 (Shanghai Mosu Tech. Co., Ltd.) were used for column chromatography. 2.2. Plant material
⁎ Corresponding author. Department of Phytochemistry, College of Pharmacy, Second Military Medical University, 325 GuoHe Road, Shanghai 200433, PR China. Fax: +86 21 65495819. E-mail addresses: [email protected] (Y.-S. Jin), [email protected] (H.-S. Chen). 1 These authors have contributed equally to this work. 0367-326X/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.fitote.2009.07.008
The plant material was collected in May 2003 at Xishuangbanna, Yunnan province and identified by Wang Hong, Xishuangbanna tropical plant garden of Chinese Academy of Science. A voucher specimen (No. 200305-1) has been deposited
64
Y.-S. Jin et al. / Fitoterapia 81 (2010) 63–65
20 to yield compounds 2 (55 mg) and 5 (56 mg). The 60% EtOH eluate was subjected to silica gel CC eluting with a gradient of CHCl3–MeOH to give eight fractions (Fr. B1 to Fr. B8). Fr. B4 was rechromatographed on silica gel eluting with CHCl3/CH3OH (15:1) and then purified on Sephadex LH-20 to yield compounds 1 (18 mg), 4 (50 mg) and 6 (25 mg). The 30% EtOH eluate was subjected to silica gel CC eluting with a gradient of CHCl3–MeOH to give six fractions (Fr. C1 to Fr. C6). Fr. C1 was rechromatographed on silica gel eluting with CHCl3/ CH3OH (10:1) and then purified on Sephadex LH-20 to yield compound 3 (30 mg). Ervataine (1), obtained as white amorphous powder, mp 221–223 °C; UV max (MeOH): 225 (log ε 4.14), 278 (3.61) nm; IR bands (KBr): 3530, 1740, 1623 cm− 1; ESI-MS m/z: 309 [M + H] +; HRFABMS m/z: 309.1969[M + H] +, Calc. for C20H24N2O 308.19. For 1H and 13C NMR spectral data see Table 1. Ibogaine (2), obtained as white amorphous powder; ESIMS m/z: 311[M + H]+; For 1H and 13C NMR spectral data see Table 1. Coronaridine (3), obtained as a white powder, ESI-MS m/z: 361 [M + Na]+. 1H NMR and 13C NMR data were compared with the information in the literature [11], and it was identified as coronaridine. Heyneanine (4), isolated as white amorphous powder, ESIMS m/z: 377 [M + Na]+ 1, 1H NMR and 13C NMR data were compared with the information in the literatures [12–14], and it was identified as heyneanine. Voacangine hydroxyindolenine (5), separated as a white powder, ESI-MS m/z: 385 [M +H]+, 407 [M +Na]+, 1H NMR and 13C NMR data were compared with the information in the literature [15], and it was identified as voacangine hydroxyindolenine. Coronaridine hydroxyindolenine (6), obtained as a white powder, ESI-MS m/z: 377 [M + Na]+, 1H NMR and 13C NMR data was compared with the information in the literature [15], and it was identified as coronaridine hydroxyindolenine. 3. Results and discussion Fig. 1. Structures of compounds 1–6.
in the Herbarium of School of Pharmacy, Second Military Medical University, Shanghai. 2.3. Extraction and isolation The air-dried and powdered stems (5 kg) were extracted with 95% EtOH (10 L × 3) by reflux heating, and the percolate was concentrated in vacuum to yield an EtOH extract (400 g). The EtOH extract (400 g) was suspended in 2 L of water and acidified with 2% HCl aqueous solution to pH 3–4. The acidic mixture was centrifuged to give two layers. The upper layer (50 of 210 g) was subjected to column chromatography over macroporous resin AB-8 using a gradient solvent system EtOH/H2O to afford three fractions, 30%, 60% and 90% EtOH eluates. The 90% EtOH eluate was subjected to silica gel CC eluting with a gradient of CHCl3–MeOH to give six fractions (Fr. A1 to Fr. A6). Fr. A3 was rechromatographed on silica gel eluting with CHCl3/CH3OH (30:1) and then purified on Sephadex LH-
Ervataine (1), isolated as a white amorphous compound by preparative TLC, exhibited a [M + H]+ ion peak at m/z 309 in ESI-MS. The molecular formula was deduced as C20H24N2O on the basis of HRESI-MS data (m/z 309.1969 [M + H]+) and NMR data. The 1H NMR spectrum of 1 showed a typical splitting pattern of a 1,3,4-trisubstitued aromatic ring (δ 6.86, J = 2.4 Hz; 7.29, J = 2.4, 8.4 Hz; 7.08, J = 9.0 Hz), a singlet attributable to an aromatic methoxyl (δ 3.82, s), and the characteristic signals of an ethyl side chain (δ 0.88, J = 7.0 Hz; 1.51). 13C NMR demonstrated 20 carbon signals, including an indole moiety (δ 144.5, 108.8, 131.2, 101.1, 155.0, 111.1, 111.9, 131.6). By comparison of proton and carbon signals of 1 with those of 2, ibogaine, a known compound (Table 1), it could be deduced that the two compounds had the same skeleton. The sharp doublet at 4.49 ppm (J = 3.0 Hz) of 1 indicated that C-3 was connected to an atom with large electronegrativity. By D2O exchange experiment it was found that there was no presence of the NH broad singlet belonging to an indole chromophore in compound 1 but in compound 2. Comparison of the molecular formulas of 1 and 2, showed the lack of two protons in 1, where one extra unit of unsaturation was present. In addition, in the
Y.-S. Jin et al. / Fitoterapia 81 (2010) 63–65 Table 1 1 H NMR and Position
13
C NMR data of compounds 1 and 2 (CD3OD, 600 MHz). 1 δC (dept)
2 3 5
144.5(s) 93.2(d) 55.1(t)
6
34.0(t)
7 8 9 10 11 12 13 14 15 16 17
108.8 (s) 131.2(s) 101.1(d) 155.0(s) 111.1(d) 111.9(d) 131.6(s) 30.4(d) 25.5(t) 41.1(d) 22.6(t)
18 19 20 21 10- OCH3 a
65
12.3(q) 28.1(t) 42.8(d) 60.2(d) 56.5(q)
2 δH 4.49 (1H, 3.54 (1H, 3.07 (1H, 2.21 (1H, 1.50 a
δC (dept) d, J = 3.0 Hz) dt, J = 3.0, 14.4 Hz ) m) m)
6.86 (1H, d, J = 2.4 Hz) 7.29 (1H, dd, J = 2.4, 8.4 Hz) 7.08 (1H, d, J = 8.4 Hz) 2.07 (1H, 1.48 a 2.84 (1H, 3.19 (1H, 2.62 (1H, 0.88 (3H, 1.51 a 1.50 a 2.97 (1H, 3.82 (3H,
br.s) dd, J = 4.8, 10.8 Hz) m) m) t, J = 7.0 Hz)
s) s)
δH
144.4(s) 55.7(t) 50.9(t) 21.7(t) 109.0(s) 131.2(s) 101.3(d) 154.9(s) 111.1(d) 111.8(d) 131.9(s) 28.0(d) 23.2(t) 42.3(s) 33.2(t) 12.3(q) 28.9(t) 43.5(d) 59.2(d) 56.5(q)
6.87 (1H, d, J = 2.4 Hz) 6.65 (1H, dd, J = 2.4, 8.4 Hz) 7.08 (1H, d, J = 8.4 Hz)
0.91(3H, t, J = 7.2 Hz)
3.82(3H, s)
Signals were overlapped.
HMBC of 1, H-3 at δ 4.49 was correlated with C-5 at δ 55.1, C-15 at δ 25.5 and C-2 at δ 144.5, while H-19 at δ 1.51 was correlated with C-20 at δ 42.8 and C-15 at δ 25.5 (Fig. 2). Compound 1 could derive by the partial cyclization of compound 2, suggesting that C-3 of 1 may be linked with the nitrogen atom at indole chromophore, as confirmed by the detection of a HMBC correlation between H-3 and C-2, as well as by 13C NMR comparison with 2 [C-3 (Δδ = 37.5), C-14 (Δδ = 2.4), C-17 (Δδ = −10.6)]. Thus, 1, named ervataine, has an unprecedented cage-like connectivity. As an alternative constitution, a 3-hydroxyibogaine structure was also considered for the novel compound. The N-1/C-3 bond in the structure of ervataine is undoubtedly strained, but a 3D virtual structure of this compound could be constructed in a reasonable way using the Chem3D and Hyperchem programs. Moreover, the mass spectrum of indole alkaloids with secondary –OH, even tertiary –OH, usually gave the molecular ion peaks [M+ H]+; and only few have been reported to give a weaker dehydration peak [12,13,16] [M+ H-18]+. So, if the ion at m/z 309 could be due to a dehydration process, then the [M+ H]+ ion at m/z 327 should also be visible, something that
Fig. 2. Key HMBC correlations of compound 1.
did not occur in ervataine. Based on spectroscopic evidence, structure 1 seems the most plausible for ervataine. Acknowledgements This study was supported by the National Natural Science Foundation of China (20272081, 20872178) and Shanghai Leading Academic Discipline Project (No. B906). We are grateful to one of the reviewers for the suggestion of the alternative 3-hydroxyibogaine structure for ervataine. References [1] Institute of Bonica of Kunming, Flora Yunnanica. Beijing: Science Press; 1983. p. 478. [2] Yu Y, Gao JM, Liu JK. Yunnan Zhiwu Yanjiu 1999;21:399. [3] Liu G, Liu X, Feng XZ. Planta Med 1988;54:519. [4] Yu Y, Gao JM, Liu JK. Chin Chem Lett 1999;10:575. [5] Luo XG, Chen HS, Zhang WD, Xu YX, Huang M, Liu J, Liu WY, et al. Dier Junyi Daxue Xuebao 2002;23:662. [6] Liang S, Luo XG, Chen HS, Zhang XD, Huang M, Liu WY. Chin Chem Lett 2006;17:783. [7] Luo XG, Chen HS, Liang S, Huang M, Xuan WD, Jin L. Chin Chem Lett 2007;18:697. [8] Chen MY, Zhou LH, Zhang XD, Luo XG, Chen HS, Huang M. Yaoxue Shijian Zazhi 2006;24:203. [9] Xuan WD, Chen HS, Yuan ZX, Zhang XD, Huang M. Dier Junyi Daxue Xuebao 2006;27:92. [10] Yu DQ, Yang JS. Chemical analytical manual (the second edition), the seventh fascicle: NMR spectra analysis. Beijing: Chemical Industry Press; 2001. p. 818. 836. [11] Okuyama E, Gao LH, Yamazaki M. Chem Pharm Bull 1992;40:2075. [12] Kam TS, Sim KM. J Nat Prod 2002;65:669. [13] Govindachari TR, Joshi BS, Saksena AK, Sathe SS, Viswanathan N. Tetrahedron Lett 1965;43:3873. [14] Perera P, Sandberg F, van Beek TA, Verpoorte R. Planta Med 1984;50:251. [15] Alberto M, Matias R, Gabriel F, Antoniao G. J Nat Prod 1996;59:185. [16] Cong PZ, Su KM. Chemical analytical manual (the second edition), the ninth fascicle: mass spectrum analysis. Beijing: Chemical Industry Press; 2001. p. 686–700.