Two new compounds from Melodinus suaveolens

Article abstract of DOI:10.1080/14786419.2016.1205051

Two new compounds, 19-hydroxy-melodinine K (1) and melodiside (2), and 25 known compounds were isolated from leaves and twigs of Melodinus suaveolens. Their structures were elucidated based on 1- and 2-D NMR, FTIR, UV and MS spectroscopic data. 19-hydroxy-melodinine K showed cytotoxic activity against MDA-MB-231 breast, BCG-823 gastric, SW480 colon and Hela cancer cells.

Full text of DOI:10.1080/14786419.2016.1205051

Natural Product Research
Formerly Natural Product Letters
ISSN: 1478-6419 (Print) 1478-6427 (Online) Journal homepage: http://www.tandfonline.com/loi/gnpl20
Two new compounds from Melodinus suaveolens
Tian Dong Zhang, Bao Kun Zhu, Jun Ling, Qian Xu Yang, Xi Feng Teng & Meng
Wang
To cite this article: Tian Dong Zhang, Bao Kun Zhu, Jun Ling, Qian Xu Yang, Xi Feng Teng
& Meng Wang (2016): Two new compounds from Melodinus suaveolens, Natural Product
Research, DOI: 10.1080/14786419.2016.1205051
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Date: 31 July 2016, At: 13:45

Natural Product research, 2016
http://dx.doi.org/10.1080/14786419.2016.1205051
Two new compounds from Melodinus suaveolens
Tian Dong Zhanga, Bao Kun Zhua, Jun Linga, Qian Xu Yanga, Xi Feng Tengb and
Meng Wanga
ar&d, china tobacco Yunnan Industrial co. ltd, Kunming, china; bschool of traditional chinese Medicine,
Guangdong Pharmaceutical university, Guangzhou, china
ABSTRACT
ARTICLE HISTORY
received 18 January 2016
accepted 2 June 2016
Two new compounds, 19-hydroxy-melodinine K (1) and melodiside
(2), and 25 known compounds were isolated from leaves and twigs
of Melodinus suaveolens. Their structures were elucidated based on
1- and 2-D NMR, FTIR, UV and MS spectroscopic data. 19-hydroxy-
melodinine K showed cytotoxic activity against MDA-MB-231 breast,
BCG-823 gastric, SW480 colon and Hela cancer cells.
KEYWORDS
Melodinus suaveolens;
19-hydroxy-melodinine K;
melodiside; cytotoxicity
(1) 19-hydroxy-melodinine K;
(2) melodiside
1. Introduction
Plants of the genus Melodinus suaveolens Champ. ex Benth, family Apocynaceae, are woody
lianas or sometimes low shrubs naturally distributed in tropical or subtropical Asia and
Australia (Li et al. 1995). This genus has been shown to be a good source of monoterpenoid
indole alkaloids (Bernauer et al. 1969; Mehri et al. 1978, 1991; Rabaron et al. 1978; Baassou
et al. 1983, 1987; Mehri & Plat 1992; He et al. 1994; Zhang et al. 2003). Searches here for novel
and/or bioactive alkaloids have identified some representative skeletons and cytotoxic
CONTACT Xi Feng teng
xfteng78@163.com; Meng Wang
wangxiaomeng1310@sina.com
supplemental data for this article can be accessed http:dx.doi.org/10.1080/14786419.2016.1205051.
© 2016 Informa uK limited, trading as taylor & Francis Group

2
T. D. ZHANG eT AL.
compounds from local Yunnan Melodinus spp. (Feng et al. 2009; Feng, Cai et al. 2010; Feng,
Li, Liu et al. 2010; Feng, Li, Wang et al. 2010; Cai et al. 2011, 2012; Zhang et al. 2016). Many
novel alkaloids were obtained from M. suaveolens distributed in theYunnan Province, China
(Liu et al. 2012, 2013). In our continual study of alkaloids with cytotoxicity, we paid attention
to titled plant from Guangdong Province, China. The present study describes the isolation,
structural determination and cytotoxic activities of two new compounds (1–2) together with
the 25 known ones, scandine (3), 10-hydroxy-scandine (4), scandine Nb-oxide (5), melodinine
T (6), meloscandonine (7), 19-epimeloscandonine (8), meloscine (9), 11-hydroxytabersonine
(10), 19-hydroxytabersonine (11), 11,19-dihydroxytabersonine (12), melodinine M (13),
venalstonine (14), 17α-hydroxyvenalstonine (15), melodinine L (16), 14α,15α-epoxykopsi-
nine (17), 19R-vindolinine (18), 19R-vindolinine Nb-oxide (19), 19S-vindolinine Nb-oxide (20),
stricticine (21), compactinervine (22), 11-methoxy-14,15-dehydro-16-epivincamine (23),
scandomelonine (24), scandomeline (25), 4′-hydroxy-2′,6′-dimethoxyphenol 1-O-β-D-(6-O-
syringoyl) glucopyranoside (26) and bergenin (27).
2. Results and discussion
The MeOH extract of M. suaveolens was partitioned between H2O and etOAc combination
with alkali treatment, and column chromatography on silica gel and C18 silica gel was used
to separate the alkaloidal fraction into 27 compounds.
Compound 1 exhibited a positive reaction with Dragendorff’s reagent. Its UV spectrum
showed absorption maxima characteristic of a β-anilinoacrylate chromophore (330 and
242 nm) (Moza et al. 1964), while the IR spectrum showed absorption bands due to OH and
NH (3398 and 3290 cm−1) and conjugated ester (1653 cm−1) functions. The molecular formula
C42H46N4O7 was established by HReSIMS m/z = 719.3443 [M + H]+, consistent with those of
bisindole. In the 1H NMR spectrum (Table S1) of 1, two singlets at δH 9.24 (1H) and 9.33 (1H)
suggested two NH groups of indole alkaloids. Two signals at δH 0.65 (3H, t, J = 7.2 Hz) and
1.00 (3H, d, J = 6.5 Hz) were assigned to two methyl groups CH3–18/18′, and singlets at δH
3.67 and 3.69 (each 3H, s) were perhaps assigned to two ester methoxyls. In the 13C NMR
spectrum of 1 (Table S1), 42 carbon resonances were observed. Of them, six quaternary
carbon resonances (δC 91.7, 92.8, 165.5, 166.8, 168.7 and 169.0) and two methoxy signals
(δC 50.9) were readily assigned to two β-anilinoacrylate moieties conjugated with a methyl
ester unit, respectively. According to the 13C NMR data, compound 1 could be divided into
two tabersonine units (Table S1) (Ziegler & Bennett 1973). The coupled protons at δH 4.84
(1H, d, J = 7.2 Hz, H-X) and 4.94 (1H, dd, J = 7.2, 3.5 Hz, H-Y), together with HMBC correlations
of δH 4.10 (1H, H-15)/δC 27.8 (C-19), 86.7 (C-Y) and 60.0 (C-X), revealed the connection of
C-X/Y/15, namely: C-3/14/15. In other unit, two singlets at δH 7.43 and 6.56 suggested the
presence of 10,11-bissubstituted indole ring A. The forth singlet showed HMBC correlation
to C-7′ (δC 55.8), suggesting it is assigned to H-9′. Likewise, δH 6.56 correlating with δC 131.1
(s, C-8′) could be assigned to H-12′. Further, up-fielded H-12 and its corresponding carbon
signal (δC 93.8) suggested oxy-substitute at its adjacent carbon C-11′. The coupling constant
(J = 6.3 Hz) of H-18′ indicated its neighbour carbon was substituted by hydroxyl, in combi-
nation with the HMBC correlations of δH 3.57 (19-OH′) and 1.00 (H-18′) with δC 66.3 (C-19′).
The HMBC correlations of H-3 with δC 115.2 (s, C-10′) and δC 161.6 (s, C-11′) and 120.1 (d,
C-9′) suggested linkage of two units by bonds of C-3/C-10′. Unfortunately, there were no
additional HMBC correlations between both the units. However, 22 unsaturation degrees of

NATURAL PRODUCT ReSeARCH
3
Figure 1. structures of new compounds 1–2.
1 implied presence of another ring. Analysis of chemical shifts of C-3/14/10′/11′ further
disclosed presence of a furan ring (Kam et al. 1993) inconsistent with molecular model. The
13C NMR data suggested that 1 was similar to melodinine K (Feng, Li, Wang et al. 2010) except
for a methylene (δC 35.0) in melodinine K was replaced by a methine (δC 66.3) in 1. The ROeSY
correlations of H-19/H-15 suggested that the both of them were at α-orientation. The cou-
pling constants of H-3, H-14 and H-15 suggested that the relative configuration of 1 was the
same as that of conophyllidine and melodinine K. The structure of compound 1 was estab-
lished, therefore, as shown in Figure 1.
Compound 2 was isolated as a white powder. The FTIR spectra of 2 exhibited absorption
bands for OH (3342 cm−1), and ester carboxylic group (1712 cm−1) and benzene ring (1616
and 1520 cm−1). Its UV spectrum showed the characteristic absorption bands at 246 and
323 nm. The positive HReSI spectrum showed a sodiated molecular ion peak at m/z =
1
577.1530 [M + Na]+, with a molecular formula of C25H30O14Na. The H NMR spectrum of 2
displayed two pair of aromatic signals at δH 7.06 (s, 2H) and 6.99 (s, 2H), which demonstrated
two 1, 3, 4, 5-tetrasubstituted aromatic rings (Shao et al. 2004). Its 1H NMR spectrum (Figure
S6) also exhibited two singlets due to five methoxyl groups at δH 3.80 (s, 3H) and δH 3.70 (s,
12H), respectively. The above information, together with the observation of a methyl ester
signal (δC 165.6 (s), 52.2 (q)), indicated the presence of two 4-hydroxy-3,5-dimethoxy benzoic
units in the molecule. Furthermore, a glucosyl unit (δC 101.7, 76.4, 74.2, 74.0, 70.5 and 63.8)
was observed in the 13C NMR spectrum of 2. In addition, HMBC correlations were observed
between the anomeric proton signal at δH 5.09 (1H, d, J = 7.2 Hz) with δC 137.9 (C-4′), and
between δH 4.43 and 4.19 (H-6) with δC 165.4 (C-7′′). So 2 was determined as shown in Figure
1 and named as melodiside. The J value (7.2 Hz) of the anomeric proton of the sugar moieties
revealed the β-configuration of the glucosyl residue. The identification of the sugar residue
was continued by hydrolysis with 10% HCl to afford D-glucose which was confirmed by
comparison with authentic samples and determination of their optical rotation values
([ꢀ]20 = +19.5°) (eskander et al. 2005)
D
Other compounds 3–27 were identified by comparison of their NMR spectroscopic data
with the literature. Compounds 1–27 were evaluated for their cytotoxicity against four

4
T. D. ZHANG eT AL.
human cancer cell lines. Only 1 showed moderate cytotoxicity against MDA-MB-231, BCG-
823, SW480 and Hela cell lines, with IC50 values of 1.43, 1.84, 4.96 and 2.15 μM, respectively,
while by comparison, cisplatin gave IC50 values of 4.43, 11.84, 15.33 and 16.56 μM. The other
compounds were found to be inactive under these conditions.
3. Experimental
3.1. General experimental procedures
UV spectra were obtained using a Shimadzu UV-2401A spectrophotometer (Shimadzu Corp.,
Kyoto, Japan). Scanning IR spectroscopy was performed on a Tenor 27 spectrophotometer
using KBr pellets. eSI and HReSI mass spectroscopy were performed on Bruker HCT/esquire
and API QSTAR Pulsar 1 spectrometer (Applied Biosystems, Ltd., Warrington, UK). 1D- and
2D- NMR spectra were obtained on Bruker DRX-500 and AM-400 MHz spectrometers (Bruker
BioSpin GmBH, Rheinstetten, Germany) with TMS as an internal standard. Column chroma-
tography (CC) was performed on silica gel (200–300 mesh, Qingdao Haiyang Chemical Co.,
Ltd, Qingdao, China) and C18-silica gel (20–45 μm, Fuji Silysia Chemical Ltd.). Fractions were
monitored by TLC on silica gel plates (GF254, Qingdao Haiyang Chemical Co., Ltd.) and
spots were visualised with Dragendorff’s reagent spray. Medium pressure liquid chroma-
tography (MPLC) was employed using a Buchi pump system coupled with C18-silica gel-
packed glass columns (15 × 230 and 26 × 460 mm). High-performance liquid chromatography
(HPLC) was performed using a Waters 1525eF pump (Waters Corp., Milford, MA, USA) coupled
with a HPLC Sunfire and Xbridge C18 columns (250 × 19 mm) and Cosmosil C18 columns
(250 × 20 mm). The HPLC system employed a Waters 2998 photodiode array detector and a
Waters fraction collector III (Waters Corp.).
3.2. Plant material
Leaves and twigs of M. suaveolens Champ. ex Benth were collected in July 2012 in Zhongshan,
Guangdong Province, P.R. China, and identified by Dr. Xi-Feng Teng. A voucher specimen
(Cai120706) was deposited in the State Key Laboratory of Phytochemistry and Plant Resources
in West China, Kunming Institute of Botany, Chinese Academy of Sciences.
3.3. Extraction and isolation
After being dried and powdered, 11 kg of M. suaveolens leaves and twigs were extracted
with MeOH (3 × 50 L) at room temperature, and the solvent were removed in vacuo. The
residue was dissolved in 0.3% aqueous hydrochloric acid (v/v), basified with 5% aqueous
ammonia to pH 8–9 and partitioned with etOAc (3 × 3 L). The etOAc phase (21 g) was sub-
jected to CC over silica gel (300 g) and eluted with a CHCl3–acetone gradient (from 1:0 to
2:1, v/v) to produce seven fractions (I–VII). Fraction I (1.5 g) was purified by C18 MPLC with a
MeOH–H2O gradient (from 1:1 to 4:1, v/v) to yield subfractions I-1~6. Compound 3 (121 mg)
was crystallised from subfractions I-5 and fraction II (1.2 g) from methanol. Subfraction I-2
(193 mg) was purified on a Cosmosil preparative C18 HPLC column with a gradient of MeOH–
H2O (50:50–70:30, v/v) to yield 17 (7 mg). Subfraction I-4 (55 mg) was further subjected to
same HPLC column using a MeOH–H2O (70:30–80:20, v/v) gradient eluent to yield 14 (6 mg).

NATURAL PRODUCT ReSeARCH
5
Subfraction I-6 (42 mg) was further subjected to sunfire C18 HPLC column using a MeCN–H2O
(40:60–55:45, v/v) gradient eluent to yield 11 (6 mg). Fraction III (5.2 g) was separated on a
C18 MPLC column with a gradient of MeOH–H2O (40:60–75:25, v/v) to yield subfraction III-
1~6. Subfraction III-1 (77 mg) was further purified on a sunfire C18 HPLC column with a gra-
dient of MeCN–H2O (35:65–55:45, v/v) to afford 7 (21 mg), 8 (6 mg) and 6 (17 mg). Subfraction
III-3 (320 mg) was further preparatively purified on a sunfire C18 HPLC column with a gradient
MeCN–H2O (35:45–50:37, v/v) to afford subfraction III-3–1~6. Subfraction III-3–1 (34 mg) was
purified on a sunfire C18 HPLC column with a gradient MeOH–H2O (50:50–55:45, v/v) to yield
12 (7 mg) and 1 (6 mg). Compounds 21 (17 mg) and 15 (4 mg) were obtained from subfrac-
tion III-3–2 (39 mg) on a Xbridge preparative C18 column with a gradient MeOH–H2O (50:50–
60:40, v/v). Subfraction III-3–3 (52 mg) was purified on a sunfire C18 MPLC column with a
MeOH–H2O gradient eluent (from 50 to 65%, v/v) to yield 13 (11 mg). Alkaloids 3 (6 mg) and
23 (4 mg) were purified on a sunfire C18 MPLC column from subfraction III-3–4. Subfraction
III-3–6 was further separated on the Xbridge C18 column with a gradient MeOH–H2O (50:50–
65:35, v/v) to yield 17 (7 mg) and 18 (3 mg). Subfraction III-5 (58 mg) was purified by sunfire
C18 HPLC with a MeOH–H2O gradient (from 60:40 to 80:20, v/v) to yield 25 (4 mg), 10 (4 mg)
and 1 (3 mg). Subfraction III-6 (34 mg) was further separated on a semi-preparative sunfire
C18 HPLC column with a gradient MeOH–H2O (70:30–75:25, v/v) to yield 24 (7 mg) and 25
(11 mg). Fraction IV (2.9 g) was purified on a C18 MPLC column with a MeOH–H2O gradient
(from 1/1 to 4/1, v/v) to yield subfracti′on IV-1~4. Subfraction IV-2 (74 mg) further was applied
to a silica gel column using a petroleum ether–acetone gradient eluent (from 3:1–2:1, v/v)
to yield subfraction IV-2–1~2. Subfraction IV-2–1 (51 mg) was further separated on a pre-
parative C18 HPLC column with a gradient MeOH–H2O (30:70–60:40, v/v) to afford 16 (6 mg)
and 22 (11 mg). Same column [MeOH–H2O (25:75–40:60, v/v)] was used to purify subfraction
IV-2–2 to obtain 5 (4 mg), 20 (5 mg) and 19 (7 mg). Subfraction IV-2 (46 mg) was further
separated on a sunfire C18 preparative column with a gradient MeOH–H2O (30:70–60:40, v/v)
to produce 4 (6 mg). Fraction V (2.5 g) was purified on C18 column with a MeCN–H2O gradient
eluent (from 13:87 to 25:75, v/v) to yield 9 (3 mg) and 2 (11 mg). Compounds 26 (11 mg)
and 27 (14 mg) were crystallised from fractions VI and VII from methanol, respectively.
3.3.1. 19-Hydroxy-melodinine K (1)
White powder:[ꢀ]20 = −146(c, 0.30, CH3OH); UV (CH3OH) λmaxMeOH nm (log ε): 330 (4.34), 242
D
(3.97); IR (KBr) νmax 3398, 3290, 1653, 1648, and 1435 cm−1;The 1H NMR (500 MHz) (acetone-d6)
δH 9.24 (1H, s, H-1), 9.33 (1H, s, H-1′), 7.43 (1H, s, H-9′), 6.96 (1H, t, J = 7.4 Hz, H-11), 6.91 (1H,
d, J = 7.3 Hz, H-12), 6.56 (1H, s, H-12′), 6.54 (1H, t, J = 7.4 Hz, H-10), 6.05 (1H, d, J = 7.4 Hz, H-9),
5.86 (1H, overlap, H-14′), 5.84 (1H, overlap, H-15′), 4.94 (1H, dd, J = 7.2, 3.5 Hz, H-14), 4.84 (1H,
d, J = 7.2 Hz, H-3), 4.10 (1H, dd, J = 3.5, 7.0 Hz, H-15), 3.69 (3H, s, C′OOMe′), 3.67 (3H, s, COOMe),
3.57 (1H, d, J = 6.0 Hz, 19′-OH), 3.55 (1H, dq, J = 6.0, 6.3, H-19′), 3.46 and 3.10 (each 1H, m,
H-5), 3.01 and 2.42 (each 1H, d, J = 14.5 Hz, H-17′), 2.97 (1H, s, H-21′), 2.93 and 2.74 (eac 1H,
m, H-3′), 2.89 and 2.92 (each 1H, m, H-5′), 2.65 (1H, s, H-21), 2.68 and 2.57 (each 1H, d,
J = 15.5 Hz, H-17), 2.08 and 1.74 (each 1H, m, H-6), 1.95 and 1.54 (each 1H, m, H-6′), 1.07 and
0.76 (each 1H, qd, J = 14.6, 7.2 Hz, H-19), 1.00 (3H, d, J = 6.3 Hz, H-18′), 0.65 (3H, t, J = 7.2 Hz,
H-18); 13C NMR (125 MHz) spectroscopic data (acetone-d6) δC 169.0 (s, CO2Me), 168.7 (s,
C′O2Me), 166.8 (s, C-2′), 165.5 (s, C-2), 161.6 (s, C-11′), 146.5 (s, C-13′), 144.6 (s, C-13), 139.0 (s,
C-8), 131.1 (d, C-15′), 131.1 (s, C-8′), 128.4 (d, C-11), 126.7 (d, C-14′), 122.1 (d, C-9), 121.2 (d,
C-12), 120.1 (d, C-9′), 115.2 (s, C-10′), 110.3 (d, C-10), 93.8 (d, C-12′), 92.8 (s, C-16′), 91.7 (s,

6
T. D. ZHANG eT AL.
C-16), 86.7 (d, C-14), 70.0 (d, C-15), 67.2 (d, C-21′), 66.3 (d, C-21/19′), 60.0 (d, C-3), 55.8 (s, C-7′),
55.2 (s, C-7), 51.4 (t, C-5), 51.1 (t, C-3′), 50.9 (q, CO2Me, C′O2Me), 47.5 (s, C-20′), 46.5 (t, C-5′),
46.2 (t, C-6′), 45.6 (s, C-20), 43.1 (t, C-6), 28.5 (t, C-17′), 27.8 (t, C-19), 23.4 (t, C-17), 19.5 (q,
C-18′), 7.5 (q, C-18); Positive eSIMS m/z 719 [M + H]+; and HReSIMS m/z 719.3443 [M + H]+
(calcd. for C42H47N2O7, 719.3445).
3.3.2 Melodiside (2)
White powder:[ꢀ]20 = −57 (c, 0.22, CH3OH); UV (CH3OH) λmaxMeOH nm (log ε): 212 (4.12), 246
D
(3.42), and 323 (3.34); IR (KBr) νmax 3343, 1712, 1616 and 1520 cm−1; The 1H NMR (400 MHz)
(DMSO-d6) δH 7.06 (2H, s, H-2′, 6′), 6.99 (2H, s, H-2′′, 6′′), 5.08 (1H, d, J = 7.2 Hz, H-1′), 4.43 (1H,
d, J = 15.0 Hz, H-6), 4.19 (1H, dd, J = 15.0, 7.6 Hz, H-6), 3.80 (3H, s, COOCH3), 3.70 (12H, s,
3′,5′,3′′,5′′-OCH3), 3.44 (1H, m, H-5), 3.25 (2H, m, H-3, 2), 3.20 (1H, m, H-4); 13C NMR spectro-
scopic data (DMSO-d6) δC 165.6 (s, C-7′), 165.3 (s, C-7′′), 152.4 (s, C-3′,5′), 147.4 (s, C-3′′, 5′′),
140.7 (s, C-4′′), 137.9 (s, C-41′), 124.6 (s, C-4′), 119.1 (s, C-1′′), 106.7 (d, C-2′, 6′, 2′′, 6′′), 101.7
(d, C-1), 76.4 (d, C-3), 74.2 (d, C-5), 74.0 (d, C-2), 70.5 (d, C-4), 63.8 (t, C-6); 56.2 (q, 3′/5′-OCH3),
55.9 (q, 3′′/5′′-OCH3), 52.2 (q, 7′-OCH3); positive eSIMS m/z 577 [M + Na]+; and HReSIMS m/z
577.1530 [M + Na]+ (calcd. for C25H30O14Na, 577.1533).
3.4. Cytotoxicity assay
Four human cancer cell lines, MDA-MB-231 breast, BCG-823 gastric, SW480 colon and Hela,
were used for cytotoxic assays. Cells were cultured in RPMI-1640 (Sigma–Aldrich, St. Louis,
MO, USA) or DMeM medium (Hyclone, Logan, UT, USA), supplemented with 10% foetal bovine
serum (Hyclone) in 5% CO2 at 37 °C. Cytotoxicity assays were performed according to the
MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) method in 96-well micro
plates. Briefly, 100 μL of adherent cell types were seeded into each well of 96-well cell culture
plates and allowed to adhere for 12 h before the addition of test compounds. Suspended
cell types were seeded at an initial density of 1 × 105 cells/mL just before drug addition. each
tumor cell line was exposed to a test compound at concentrations of 0.04, 0.2, 1.0, 5.0 and
25.0 μM in DMSO in triplicate for 48 h, with cisplatin (Sigma–Aldrich) as the positive control.
After treatment, cell viability was assessed, cell growth graphed and IC50 values calculated
by Reed and Muench’s method (Reed & Muench 1938).
4. Conclusions
Alkaloidal fraction of M. suaveolens afforded two new compounds, 19-hydroxy-melodinine
K (1) and melodiside (2), and 25 known compounds. 19-hydroxy-melodinine K showed cyto-
toxic activity against cancer cells, which was consistent with this type skeleton as previously
reported in the genus. This type of bisindole could stimulate future phytochemical
studies.
Acknowledgements
The authors are grateful to the members of the analytical group in the State Key Laboratory of
Phytochemistry and Plant Resources in West China, Kunming Institute of Botany Chinese Academy of
Sciences, for the spectral measurements.

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Funding
This work was supported by Yunnan province key new product development project [grant number
2015BA006]; and Key project of China National Tobacco Corporation [grant number 110201402042].
References
Baassou S, Mehri HM, Rabaron A, Plat M. 1983. (+)Melonine and NB-oxy melonine, a new indoline
skeleton. Tetrahedron Lett. 24:761–762.
Baassou S, Mehri H, Plat M. 1987. Alkaloids of Melodinus celastroides. Isolation of four new alkaloids.
Ann Pharm Fr. 45:49–56.
Bernauer K, englert G, Vetter W, Weiss eK. 1969. Constitution of Melodinus alkaloid (+)-meloscine,
(+)-epimeloscine and (+)-scandine. 1. Alkaloid from Melodinus scandens Forst. Helv Chim Acta.
52:1886–1905.
Cai XH, Jiang H, Li Y, Cheng GG, Liu YP, Feng T, Luo XD. 2011. Cytotoxic indole alkaloids from Melodinus
fusiformis and M. morsei. Chin J Nat Med. 9:259–263.
Cai XH, LiY, LiuYP, Li XN, Bao MF, Luo XD. 2012. Alkaloids from Melodinus yunnanensis. Phytochemistry.
83:116–124.
eskander J, Lavaud C, Abdel-khalik SM, Soliman HSM, Mahmoud II, Long C. 2005. Saponins from the
leaves of Mimusops laurifolia. J Nat Prod. 68:832–841.
Feng T, Cai XH, Li Y, Wang YY, Liu YP, Xie MJ, Luo XD. 2009. Melohenines A and B, two unprecedented
alkaloids from Melodinus henryi. Org Lett. 11:4834–4837.
Feng T, Cai XH, Liu YP, Li Y, Wang YY, Luo XD. 2010. Melodinines A−G, monoterpenoid indole alkaloids
from Melodinus henryi. J Nat Prod. 73:22–26.
Feng T, Li Y, Liu YP, Cai XH, Wang YY, Luo XD. 2010. Melotenine A, a cytotoxic monoterpenoid indole
alkaloid from Melodinus tenuicaudatus. Org Lett. 12:968–971.
Feng T, Li Y, Wang YY, Cai XH, Liu YP, Luo XD. 2010. Cytotoxic indole alkaloids from Melodinus
tenuicaudatus. J Nat Prod. 73:1075–1079.
He YL, Chen WM, Feng XZ. 1994. Melomorsine, a new dimeric indoline alkaloid from Melodinus morsei.
J Nat Prod. 57:411–414.
Kam TS, Loh KY, Wei C. 1993. Conophylline and conophyllidine: new dimeric alkaloids from
Tabernaemontana divaricata. J Nat Prod. 56:1865–1871.
Li PT, Leeuwenberg AJM, Middleton DJ. 1995. Apocynaceae. Flora of China. 16:2.
LiuYP, LiY, Cai XH, Li XY, Kong LM, Cheng GG, Luo XD. 2012. Melodinines M–U, cytotoxic alkaloids from
Melodinus suaveolens. J Nat Prod. 75:220–224.
Liu YP, Zhao YL, Feng T, Cheng GG, Zhang BH, Li Y, Cai XH, Luo XD. 2013. Melosuavines A–H, cytotoxic
bisindole alkaloid derivatives from Melodinus suaveolens. J Nat Prod. 76:2322–2329.
Mehri H, Plat M. 1992. The Structure of scandomelidine, bisindole alkaloid from Melodinus scandens.
J Nat Prod. 55:241–244.
Mehri MH, Rabaron A, Sevenet T, Plat MM. 1978. Plants of new caledonia. 26. Alkaloids of Melodinus
balansae var pacivenosus. Phytochemistry. 17:1451–1452.
Mehri H, Baassou S, Plat M. 1991. 10, 10’-Methylene-bis[(+)Na-norvallesamidine], Nb,
Nb’-methylene-[bis(+)meloninium] dichloride, Nb’-chloromethylcelastrome-linium chloride and
Nb’-chloromethylcelastromelidinium chloride-dimeric alkaloids, possible artifacts in extraction of
Melodinus celastroides compounds. J Nat Prod. 54:372–379.
Moza BK, Trojánek J, Bose AK, Das KG, Funke P. 1964. The structure of lochnericine and lochnerinine.
Tetrahedron Lett. 5:2561–2566.
Rabaron A, Mehri MH, Sevenet T, Plat MM. 1978. Plants of new caledonia. 50. alkaloids of Melodnus
celastroides. Phytochemistry. 17:1452–1453.
Reed LJ, Muench H. 1938. A simple method of estimating fifty percent endpoints. Am J Hyg. 27:493–497.
Shao ZY, Zhu DY, GuoYW. 2004. Oldhamioside, a new phenolic glucoside from Daphniphyllum oldhamii.
Chin Chem Lett. 15:52–54.
Zhang YW, Yang R, Cheng Q, Ofuji K. 2003. Henrycinols A and B, two novel indole alkaloids isolated
from Melodinus henryi Craib. Helv Chim Acta. 86:415–419.

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T. D. ZHANG eT AL.
Zhang PZ, Zhang YM, Gu J, Zhang GL. 2016. Two new alkaloids from Melodinus hemsleyanus Diels. J
Nat Prod. 30:162–167.
Ziegler Fe, Bennett GB. 1973. Claisen rearrangement in indole alkaloid synthesis. Total synthesis of
(+-)-tabersonine. J Am Chem Soc. 95:7458–7464.