Novel Alkaloids from the Roots of Stemona sessilifolia

Novel Alkaloids from the Roots of Stemona sessilifolia

by Peng Wanga), Ai-Lin Liub), Zheng Anc), Zhi-Hong Lia), Guan-Hua Dub), and Hai-Lin Qin*a)

a) Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College(Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine,

Ministry of Education), Beijing 100050, P. R. China(phone: þ86-010-83172503; fax: þ86-010-63017757; e-mail: [email protected])

b) National Center for Pharmaceutical Screening, Institute of Materia Medica, Chinese Academy ofMedical Sciences & Peking Union Medical College, Beijing 100050, P. R. China

c) Department of Neurology, China–Japan Friendship Hospital, Beijing 100029, P. R. China

Four new Stemona alkaloids, sessilistemonamines A–C (1–3, resp.) and dihydrostemoninine (4),were isolated from the roots of Stemona sessilifolia. Their structures and relative configurations wereelucidated by means of in-depth 1D- and 2D-NMR-spectroscopic as well as mass-spectrometricexperiments; and the structure of 4 was solved by X-ray single-crystal diffraction. The stereoisomericcompounds 1–3 share an unprecedented tetracyclic decahydro-1H-furo[2’,3’:4,5]cyclopenta[1,2-b]pyr-rolo[1,2-a]azepine nucleus. Compounds 1 and 2 were found to be moderately active in terms ofacetylcholinesterase (AchE) inhibition, with IC50 values of 68.8�9.5 and 17.1�2.5 mm, resp.

Introduction. – The roots of Stemona sessilifoliaMiq. (Stemonaceae), as well as S.japonicaMiq. and S. tuberosa Lour., are used in China, Korea, Japan and some otherAsian countries as traditional herbal medicines to treat respiratory diseases such aspertussis and tuberculosis, and also as anthelmintic agents for domestic animals [1].Some Stemona alkaloids have also been reported to exhibit insecticidal and antitussiveactivities [2] [3]. Phytochemical studies of Stemonaceae have been focused so far onStemona alkaloids, and more than 80 such alkaloids have been reported in the literature[2] [4–6]. Pilli et al. classified these alkaloids into eight structurally distinct groups[6] [7], among which six share a common hydrated pyrrolo[1,2-a]azepine nucleus (A),one group being characterized by a hydrated pyrido[1,2-a]azepine system (B), the last(miscellaneous) group comprising five alkaloids lacking these two basic frameworks. Inhis latest review [2], Greger grouped the A-type alkaloids into three skeletal subtypesbased on biosynthetic considerations, including stichoneurine (tuberostemonine)-,protostemonine-, and croomine-derived variations distinguished by different carbonchains attached to C(9) of the pyrrolo[1,2-a]azepine nucleus.

Herein, we report the isolation, structure elucidation, and acetylcholinesterase(AchE)-inhibiting properties of four new pyrrolo[1,2-a]azepine-type or, according toGregerDs classification, stichoneurine (tuberostemonine)-type alkaloids from the rootextract of S. sessilifolia: the diastereoisomeric compounds sessilistemonamines A–C(1–3) and the stemonamide-type alkaloid dihydrostemoninine (4). The stereoisomericcompounds 1–3 were identified as (3S*,8aR*,9S*,9aR*,12S*,12aS*,12bR*)-,(3S*,8aR*,9R*,9aS*,12S*,12aR*,12bS*)-, and (3S*,8aR*,9R*,9aR*,12S*,12aS*,12bR*)-

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I 2007 Verlag Helvetica Chimica Acta AG, ZLrich

9-ethyl-12-hydroxy-12-methyl-3-[(2S,4S)-4-methyl-5-oxotetrahydrofuran-2-yl]decahy-dro-1H-furo[2’,3’:4,5]cyclopenta[1,2-b]pyrrolo[1,2-a]azepin-11(5H)-one, respectively,and compound 4 was found to correspond to (1’S*,2S*,3a’R*,4S*,8’S*,10a’S*,10b’R*)-1’-ethyl-4-methyl-8’-[(2S,4S)-4-methyl-5-oxotetrahydrofuran-2-yl]dodecahydro-5H-spiro[furan-2,2’-furo[3,2-c]pyrrolo[1,2-a]azepin]-5-one1).

Results and Discussion. – 1. Extraction and Structure Elucidation. The crude EtOHextract of the roots of S. sessilifolia was re-extracted with petroleum ether to removelipophilic substances, and then partitioned between AcOEt and H2O. The aqueoussolution was extracted with BuOH, the organic extract was evaporated, and theresulting residue was purified by column chromatography to afford 1 (21.0 mg), 2(25.8 mg), 3 (8.3 mg), and 4 (trace).

Compound 1 was obtained as colorless prisms. Its molecular formula wasdetermined as C22H33NO5 on the basis of HR-FAB-MS (m/z 392.2453 ([MþH]þ ,calc. 392.2437)). EI-MS showed the base peak at m/z 292 ([M�C5H7O2]þ ), whichindicated that 1 was a Stemona alkaloid with a typical a-methyl-g-butyrolactone ringattached to C(3) [2] [6] [7]. The IR spectrum (KBr) of 1 showed characteristic OH(3431 cm�1) and lactone C¼O (1774 cm�1) absorptions. Detailed analysis of the 1H-and 13C-NMR spectra of 1 (Table 1), as well as 2D-NMR analyses (1H,1H-COSY,HMBC, NOE) established the complete structure and relative configuration of 1. The13C-NMR resonances at d(C) 177.6 (C(14)), 179.5 (C(21)), 87.3 (C(11)), and 83.5(C(18)) suggested the presence of two saturated lactones, as confirmed by the low-fieldresonances of two oxygenated methines at d(H) 4.63 (dd, J ¼ 4.5, 6.5 Hz, H�C(11))and 4.11 (ddd, J ¼ 5.5, 7.0, 10.0 Hz, H�C(18)). The 1H-NMR spectrum of 1 indicatedthe presence of three Me groups at d(H) 1.44 (s, Me(15)), 1.25 (d, J ¼ 7.0 Hz, Me(22)),and 0.97 (t, J ¼ 7.0 Hz, Me(17)), a unique feature not observed so far in previouslyreported Stemona alkaloids. ACH and a CH2 group next to an N-atom were discernible

CHEMISTRY & BIODIVERSITY – Vol. 4 (2007)524

1) Systematic names. In the formulae and discussion, arbitrary C-atom numbering is used.

at d(H) 3.23 (dt, J ¼ 7.0, 9.0 Hz, H�C(3)), 2.97 (dt, J ¼ 8.0, 15.5 Hz, Ha�C(5)), and3.35 (ddd, J ¼ 3.0, 9.5, 15.5 Hz, Hb�C(5)).

The 13C-NMR (DEPT) spectrum of 1 showed 22 C-atoms: two lactone C¼Ogroups at d(C) 177.6 (C(14)) and 179.5 (C(21)), three oxygenated C-atoms at d(C) 75.1(C(13)), 83.5 (C(18)), and 87.3 (C(11)), three C-atoms bearing a N-atom at d(C) 74.1(C(9a)), 66.8 (C(3)), and 40.7 (C(5)), three Me groups at d(C) 12.6 (C(17)), 14.8(C(22)), and 19.7 (C(15)), as well as seven additional methylenes and four methines.The 1H,1H-COSY experiment showed a spin system involving H�C(1), H�C(2),H�C(3), H�C(18), H�C(19), H�C(20) and H�C(22), suggesting a g-lactone ring at


Table 1. 1H- and 13C-NMR Spectroscopic Data of 1–3. At 500/125 MHz, resp, in CDCl3; d in ppm, J inHz. Arbitrary atom numbering.

1 2 31H 13C 1H 13C 1H 13C

CH2(1) 1.66–1.71 (m) 3.4 1.80–1.86 (m), 28.9 1.83–1.90 (m), 42.51.40–1.45 (m) 1.74–1.81 (m)

CH2(2) 1.77–1.81 (m, Ha), 25.4 1.80–1.86 (m), 26.4 1.81–1.89 (m, Ha), 24.11.46–1.50 (m, Hb) 1.40–1.45 (m) 1.50–1.54 (m, Hb)

H�C(3) 3.23 (dt, J¼7.0, 9.0) 66.8 3.49 (dt, J¼7.5, 9.0) 62.0 3.16 (dt, J¼7.0, 9.0) 67.9CH2(5) 3.35 (ddd,

J¼3.0, 9.5, 15.5, Hb),40.7 3.38 (br. d,

J¼16.0, Ha),43.5 2.83 (ddd,

J¼2.5, 6.5, 13.5, Hb),44.8

2.97 (dt,J¼8.0, 15.5, Ha)

2.89 (br. t,J¼14.0, Hb)

2.41–2.48 (m, Ha)

CH2(6) 1.92–1.97 (m), 29.6 2.00–2.04 (m, Hb), 22.0 1.84–1.91 (m), 29.71.37–1.42 (m) 1.39–1.42 (m, Ha) 1.08–1.15 (m)

CH2(7) 1.66–1.71 (m), 24.2 1.50–1.55 (m), 23.3 1.70–1.78 (m), 30.61.50–1.55 (m) 1.15–1.21 (m) 1.57–1.65 (m)

CH2(8) 1.66–1.71 (m, Hb), 26.9 1.74–1.76 (m), 28.4 1.62–1.66 (m), 26.00.94–0.97 (m, Ha) 1.28–1.29 (m) 0.87–0.95 (m)

H�C(9) 1.54–1.58 (m) 56.3 2.00–2.04 (m) 55.1 1.86–1.91 (m) 52.8C(9a) 74.1 73.7 80.5H�C(10) 1.92–1.97 (m) 46.7 2.14–2.20 (m) 44.0 1.96–1.98 (m) 47.4H�C(11) 4.63 (dd, J¼4.5, 6.5) 87.3 5.18 (dd, J¼6.5, 8.5) 82.7 4.97 (t, J¼6.0) 83.9H�C(12) 3.08 (d, J¼6.5) 48.4 2.36 (d, J¼8.5) 59.0 2.62 (d, J¼6.5) 57.7C(13) 75.1 74.8 77.2C(14) 177.6 178.3 178.4Me(15) 1.44 (s) 19.7 1.58 (s) 20.2 1.87 (s) 20.9CH2(16) 1.38–1.42 (m) 22.7 1.39–1.43 (m), 18.4 1.69–1.73 (m), 18.9

1.28–1.29 (m) 1.54–1.59 (m)Me(17) 0.97 (t, J¼7.0) 12.6 0.97 (t, J¼7.0) 15.1 0.98 (t, J¼7.0) 12.4H�C(18) 4.11 (ddd,

J¼5.5, 7.0, 10.0)83.5 4.10 (ddd,

J¼5.5, 7.5, 11.0)84.4 4.43 (dt,

J¼5.0, 10.0)77.6

CH2(19) 2.33–2.38 (m, Hb), 34.4 2.32–2.34 (m), 34.6 2.41–2.48 (m, Ha), 35.61.47–1.52 (m, Ha) 1.50–1.54 (m) 1.55–1.62 (m, Hb)

H�C(20) 2.57–2.63 (m) 34.8 2.54–2.61 (m) 34.8 2.64–2.72 (m) 35.5C(21) 179.5 179.6 179.3Me(22) 1.25 (d, J¼7.0) 14.8 1.25 (d, J¼7.0) 14.9 1.30 (d, J¼7.0) 15.013-OH 2.42 (br. s) 2.10 (br. s) 2.17 (br. s)

C(3), which was confirmed by HMBC correlations between H�C(3) and both C(18)and C(19), and between H�C(18) and C(2) (Fig. 1). Another g-lactone ring wasidentified by the 1H,1H-COSY correlation between H�C(11) and H�C(12), and bythe long-range HMBC correlations between H�C(11) and C(9a), C(12), C(13), C(14)and C(16), as well as between H�C(12) and C(1), C(9a), C(10), C(11), C(13), andC(14), respectively. The Et group was unequivocally located at C(10), based on HMBCcorrelations between Me(17) and both C(16) and C(10). The OH group attached toC(13) was revealed by the chemical shifts of the signals at d(H) 1.44 (s, Me(15)) andd(C) 75.1 (C(13)). The HMBC experiment was also used to elucidate other relevantconnectivities (Fig. 1).

The relative configuration of 1 was established by NOE difference spectra (Fig. 2).Significant NOE correlations were observed between H�C(11) and H�C(12),H�C(12) and Ha�C(5), H�C(3) andMe(15). Therefore, the cis relationship betweenH�C(11) and H�C(12), and the a-orientation of H�C(11), H�C(12), and Me(15)could be deduced. The observation that no NOE correlations were observed betweenH�C(12) and H�C(10), H�C(11) and H�C(9) revealed the b-orientation of bothH�C(10) and H�C(9). Moreover, the NOE correlations between H�C(18) andHb�C(5), and between H�C(18) and H�C(20) suggested b-orientation of H�C(18)and H�C(20), which is common in most Stemona alkaloids with an a-methyl-g-butyrolactone ring at C(3) [2] [6] [7].

Compound 2 was obtained as colorless plates. Its molecular formula wasdetermined as C22H33NO5, identical to 1, on the basis of HR-EI-MS (m/z 391.2384(Mþ ; calc. 391.2359)). Similar to 1, an EI-MS fragment at m/z 292 and IR absorptionsat 3427, 1765, and 1751 cm�1 were observed. The 1H-, 13C-, and 2D-NMR spectra of 2were very similar to those of 1, with the same 22 carbon resonances, including fourquaternary C-atoms, seven CH, eight CH2, and three Me groups (Table 1). Theseobservations suggested that 2 had the same constitution as 1, as further confirmed byclosely similar 1H,1H-COSY, HSQC, and HMBC spectra. Detailed analysis of the NOEdata (Fig. 2) established that 2 was a diastereoisomer of 1, with inverted configurationat C(9a), C(10), C(11), and C(12). NOE Correlations of H�C(11) with H�C(9) andH�C(12), and of H�C(12) with Hb�C(5) indicated b-orientation of these H-atoms, aswell as of the C(9a)�C(12) bond. The NOE correlation of H�C(18) with Me(15)suggested a-orientation of Me(15). Since no correlation between H�C(12) andH�C(10) was observed, the Et group was placed in b-orientation. As a result of thealmost rectangular arrangement of rings A and B, H�C(18) showed an NOEcorrelation with Ha�C(5), but not with Hb�C(5).


Fig. 1. Selected HMBC correlations of 1

Compound 3 was obtained as colorless prisms. Its molecular formula was alsodetermined as C22H33O5N on the basis of HR-EI-MS (m/z 391.2370 (Mþ ; calc.391.2359)). EI-MS displayed the same fragment atm/z 292 as for 1 and 2 ; however, thisfragment was far less prominent in 3, m/z 276 being the base peak. The IR absorptionsat 3438 and 1759 cm�1 were similar as those for 1 and 2. A detailed investigation of the1H-, 13C-, and 2D-NMR (DEPT, HSQC, 1H,1H COSY, HMBC) spectra suggested thatcompound 3 was an epimer of 1, with inverted configuration at C(10). In the NOEdifference spectra of 3 (Fig. 2), starting from a conventional a-orientation of H�C(3),as found in most Stemona alkaloids (including 1 and 2), correlations of H�C(11) withH�C(12), of H�C(10) with H�C(12), of H�C(3) with H�C(12), and of H�C(3)with Me(15) indicated their a-orientation. Since no such correlations were foundbetween H�C(9) and H�C(11) and H�C(12), H�C(9) was placed in b-orientation.

The structures of sessilistemonamines A–C (1–3) are exclusive to all known groupsin PilliDs classification system [6] [7]. They contain a novel tetracyclic decahydro-1H-furo[2’,3’:4,5]cyclopenta[1,2-b]pyrrolo[1,2-a]azepine nucleus. On the other hand, inGregerDs system [2], they belong to the stichoneurine (tuberostemonine)-typealkaloids, being characterized by a linkage between C(12) and C(9a).

Compound 4 was obtained as colorless prisms. Its structure and relativeconfiguration was unambiguously elucidated by X-ray crystallography, a perspectiveview of 4 being shown in Fig. 3. Comparison of the structure of 4 with stemoninine, analkaloid isolated from S. sessilifolia [8], revealed that 4 is the 12,13-dihydro derivativeof the latter. Consequently, 4 was named dihydrostemoninine. Because of the limitedamount of 4 available, no spectroscopic and spectrometric data were recorded.

2. Biological Studies. The amount of hydrolyzed acetylcholine (Ach) is related tothe activity of AchE under certain conditions. When Ach is exposed to acetylcholineesterase (AchE), the amount of hydrolyzed Ach can be calculated from the amount ofremaining Ach, which reflects the activity of AchE [9].

Sessilistemonamines A–C (1–3, resp.) were tested for their AchE-inhibitingproperties, huperzine A being used as positive control. Their IC50 values are shown inTable 2. As one can see, compounds 1 and 2 were moderately active, with IC50 values of68.8�9.5 and 17.1�2.5 mm, respectively. In contrast, sessilistemonamine C (3) did notshow any activity. Since compounds 1–3 are stereoisomers, the observed differences inthe inhibition of AchEmust be solely due to different spatial configurations. Whereas 1and 2 showed activities in the same order of magnitude, compound 3, with only one(instead of four) altered stereogenic center(s) relative to 1, was completely inactive.

Fig. 2. Key NOE correlations of 1–3


Clearly, further structure–activity relationships for compounds 1–3 would beinteresting to investigate. This is the first report of AchE-inhibiting Stemona alkaloids.

Experimental Part

General. M.p.: XT4–100x microscopic melting-point apparatus; uncorrected. Optical rotations:Perkin-Elmer 343 digital polarimeter. IR Spectra: Nicolet IMPACT-400 FT-IR spectrometer; in cm�1.1H- and 13C-NMR spectra: Varian Inova-500 apparatus; chemical shifts d in ppm rel. to residual CHCl3(d(H) 7.26, d(C) 77.0 ppm). EI-, HR-EI, and HR-FAB-MS: Autospec UltimaETOF mass spectrometer;in m/z.Plant Material. The roots of S. sessilifolia were obtained from Ding Xian market, Hebei Province,

P. R. China, in June 2005. The plant material was identified by Prof. Lin Ma (Institute of MateriaMedica), and a voucher specimen (No. pc337-07) was deposited at the Department of Natural MedicinalChemistry, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking UnionMedical College, Beijing, P. R. China.Extraction and Isolation. The dried, ground roots (24.4 kg) of S. sessilifolia were extracted with 95%

EtOH at reflux. After evaporation of the solvent, a dark residue was obtained, which was taken up in85% aq. EtOH, and extracted with petroleum ether (PE; b.p. 60–908) to remove lipophilic substances.The ethanolic phase was evaporated, and the resulting residue was partitioned between AcOEt and H2O.The aq. phase was finally extracted with BuOH (3� ), and the BuOH-soluble extract (113 g) wassubjected to column chromatography (CC) (SiO2; CHCl3/MeOH 100 :0!100 :10). The fraction (30 g)eluted with CHCl3 was further purified by CC (SiO2; PE/AcOEt gradient) to afford compounds 1(21.0 mg), 3 (8.3 mg), and 4 (trace). The above BuOH-soluble fraction (28 g) eluted with CHCl3/MeOH50 :1 was further chromatographed (SiO2; PE/AcOEt gradient) to afford 2 (25.8 mg).


Fig. 3. X-Ray crystal structure of 4

Table 2. Acetylcholinesterase Inhibition by Compounds 1–3. For details, see Exper. Part.

Compound IC50 [mm]

1 68.8�9.52 17.1�2.53 >100Huperzine Aa) 0.021�0.016

a) Positive control.

Sessilistemonamine A (¼ (3S*,8aR*,9S*,9aR*,12S*,12aS*,12bR*)-9-Ethyl-12-hydroxy-12-methyl-3-[(2S,4S)-4-methyl-5-oxotetrahydrofuran-2-yl]decahydro-1H-furo[2’,3’:4,5]cyclopenta[1,2-b]pyrrolo[1,2-a]azepin-11(5H)-one ; 1). Colorless prisms (PE/AcOEt). M.p. 193–1948. [a]20D ¼ þ117 (c¼0.075,MeOH). IR (KBr): 3431, 2935, 2873, 1774, 1657, 1460, 1385, 1200, 1101, 1016, 928. 1H- and 13C-NMR: seeTable 1. EI-MS: 375 (5), 374 (32), 293 (44), 292 (100), 276 (50), 235 (24), 234 (30), 136 (69). HR-FAB-MS: 392.2453 ([MþH]þ , C22H34NOþ

5 ; calc. 392.2437).Sessilistemonamine B (¼ (3S*,8aR*,9R*,9aS*,12S*,12aR*,12bS*)-9-Ethyl-12-hydroxy-12-methyl-3-

[(2S,4S)-4-methyl-5-oxotetrahydrofuran-2-yl]decahydro-1H-furo[2’,3’:4,5]cyclopenta[1,2-b]pyrrolo[1,2-a]azepin-11(5H)-one ; 2). Colorless plates (PE/AcOEt). M.p. 252–2548. [a]20D ¼ �29 (c¼0.055, MeOH).IR (KBr): 3427, 2968, 2935, 1765, 1751, 1460, 1375, 1306, 1198, 1130, 1011, 928. 1H- and 13C-NMR: seeTable 1. EI-MS: 392 (6, [MþH]þ ), 391 (22, Mþ ), 375 (63), 374 (75), 293 (48), 292 (85), 277 (58), 276(100), 235 (66), 234 (75), 137 (36), 136 (82). HR-EI-MS: 391.2384 (Mþ , C22H33NOþ

5 ; calc. 391.2359).Sessilistemonamine C (¼ (3S*,8aR*,9R*,9aR*,12S*,12aS*,12bR*)-9-Ethyl-12-hydroxy-12-methyl-3-

[(2S,4S)-4-methyl-5-oxotetrahydrofuran-2-yl]decahydro-1H-furo[2’,3’:4,5]cyclopenta[1,2-b]pyrrolo[1,2-a]azepin-11(5H)-one ; 3). Colorless prisms (PE/AcOEt). M.p. 221–2228. [a]20D ¼ �157 (c¼0.05,MeOH). IR (KBr): 3438, 2935, 1759, 1631, 1348, 1203, 1028. 1H- and 13C-NMR: see Table 1. EI-MS:391 (3,Mþ ), 375 (13), 374 (46), 293 (3), 292 (16), 277 (16), 276 (100), 235 (12), 234 (15), 136 (41). HR-EI-MS: 391.2370 (Mþ , C22H33NOþ

5 ; calc. 391.2359).X-Ray Crystal Structure of Dihydrostemoninine (¼ (1’S*,2S*,3a’R*,4S*,8’S*,10a’S*,10b’R*)-1’-Ethyl-

4-methyl-8’-[(2S,4S)-4-methyl-5-oxotetrahydrofuran-2-yl]dodecahydro-5H-spiro[furan-2,2’-furo[3,2-c]pyrrolo[1,2-a]azepin]-5-one; 4)2). Colorless prism (PE/AcOEt). The structure was solved on a MACDIP 2030K X-ray diffractometer using MoKa radiation (l¼0.71073 Q) at 295 K. The structure wassolved by direct methods using SHELXL-97. Crystal data and refinement details: formula C22H33NO5,Mr ¼ 391.5; monoclinic; space group P21, a ¼ 11.101(2), b ¼ 7.998(2), c ¼ 12.196(2) Q, b¼100.35(3)8 ;V ¼ 1065.2(4) Q3;Dcalc¼1.221 g/cm3, Z¼2; mMo¼0.086 mm�1; crystal dimensions 0.15�0.20�0.60 mm;2qmax¼500; Nint¼2372, Nobs ( jF j 2�s jF j 2)¼2368; R¼0.0683, Rw¼0.1633.Acetylcholinesterase-Inhibition Assay. The assay was performed according to a literature method [9].

Briefly, a mixture of 7 mm acetylcholine (Ach; 20 ml) and test sample (at a given concentration; 10 ml)was added to the preformed acetylcholinesterase (AchE) system (20 ml) in culture wells. The wells wereincubated for 1 h at 378, treated with a mixture of 1m H2NOH·HCl (35 ml) and 3.5m NaOH (35 ml),followed by addition of a soln. of HCl/H2O 1 :2 (40 ml), 10% FeCl3 soln. (40 ml). Then, the UV/VISabsorbance of each probe was measured at 530 nm. The wells without sample, and without Ach andsample, were taken as neg. control and blank, resp.; and huperzine A, purchased from NingboPharmaceutical Factory of Chinese Traditional Medicine, was used as pos. control. The S50% inhibitoryconcentrationD, IC50 , was calculated from the contrast values.

REFERENCES

[1] National Pharmacopoeia Committee, SChinese PharmacopoeiaD, Chemical Industry Press, Beijing,2005, Chapt. 1, p. 88 (in Chinese).

[2] H. Greger, Planta Med. 2006, 72, 99.[3] E. Kaltenegger, B. Brem, K. Mereiter, H. Kalchhauser, H. KThlig, O. Hofer, S. Vajrodaya, H.

Greger, Phytochemistry 2003, 63, 803; P. Mungkornasawakul, S. G. Pyne, A. Jatisatienr, D. Supyen,C. Jatisatienr, W. Lie, A. T. Ung, B. W. Skelton, A. H. White, J. Nat. Prod. 2004, 67, 675; H. S. Chung,P. M. Hon, G. Lin, P. P. But, H. Dong, Planta Med. 2003, 69, 914.

[4] T. Sastraruji, A. Jatisatienr, S. G. Pyne, A. T. Ung, W. Lie, M. C. Williams, J. Nat. Prod. 2005, 68,1763.


2) The crystallographic data of 4 have been deposited with the Cambridge Crystallographic DataCentre as supplementary publication number CCDC-604535. Copies of the data can be obtained,free of charge, at http://www.ccdc.cam.ac.uk/data request/cif.

[5] R. W. Jiang, P. M. Hon, Y. T. Xu, Y. M. Chan, H. X. Xu, P. C. Shaw, P. P. But, Phytochemistry 2006,67, 52.

[6] R. A. Pilli, G. B. Rosso, M. C. F. de Oliveira, in SThe AlkaloidsD, Ed. G. A. Cordell, Elsevier, NewYork, 2005, Vol. 62, Chapt. 2, p. 77.

[7] R. A. Pilli, M. C. F. Oliveira, Nat. Prod. Rep. 2000, 17, 117.[8] D. Cheng, J. Guo, T. T. Chu, E. Roder, J. Nat. Prod. 1988, 51, 202.[9] A. L. Liu, G. H. Du, Comput. Appl. Chem. 2003, 20, 547 (in Chinese).

Received November 8, 2006


Novel Alkaloids from the Roots of Stemona sessilifolia

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