A Cyclopeptide and a Tetrahydroisoquinoline Alkaloid from Ophiorrhiza nutans

Article abstract of DOI:10.1021/acs.jnatprod.7b00290

A new cyclopeptide, ophiorrhisine A (1), a new tetrahydroisoquinoline alkaloid, 7′,10-dide-O-methylcephaeline (2), two known β-carboline alkaloids, and four known tetrahydroisoquinoline alkaloids were isolated from Ophiorrhiza nutans (Rubiaceae). Compound 1 is a tetrapeptide possessing a 14-membered paracyclophane ring and a novel N,N,N-trimethyltyrosine residue in the side chain. The stereochemistry at the aryl-alkyl ether bond was different from that of other known 14-membered paracyclophanes. The structure of 2 was established by spectroscopic analysis and semisynthesis.

Full text of DOI:10.1021/acs.jnatprod.7b00290

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pubs.acs.org/jnp
A Cyclopeptide and a Tetrahydroisoquinoline Alkaloid from
Ophiorrhiza nutans
Tadayoshi Onozawa,† Mariko Kitajima,† Noriyuki Kogure,† Nichakan Peerakam,‡
Dammrong Santiarworn,§ and Hiromitsu Takayama*,†
†Department of Biofunctional Molecular Chemistry, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana,
Chuo-ku, Chiba 260-8675, Japan
‡Faculty of Pharmaceutical Science, Burapha University, Bangsaen, Chonburi Province 20131, Thailand
§Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand
S
* Supporting Information
ABSTRACT: A new cyclopeptide, ophiorrhisine A (1), a new
tetrahydroisoquinoline alkaloid, 7′,10-dide-O-methylcephaeline
(2), two known β-carboline alkaloids, and four known
tetrahydroisoquinoline alkaloids were isolated from Ophior-
rhiza nutans (Rubiaceae). Compound 1 is a tetrapeptide
possessing a 14-membered paracyclophane ring and a novel
N,N,N-trimethyltyrosine residue in the side chain. The
stereochemistry at the aryl−alkyl ether bond was different
from that of other known 14-membered paracyclophanes. The
structure of 2 was established by spectroscopic analysis and
semisynthesis.
Compound 1, named ophiorrhisine A, is a colorless solid
having the molecular formula C39H42N4O7 based on its
HRESIMS data (calcd 679.3132 [M + H]+; found m/z
679.3131 [M + H]+) (Figure 2). Its UV spectrum exhibited
absorptions at 205, 228, and 278 nm, indicating the presence of
phenyl and phenolic groups. The IR spectrum showed the
presence of hydroxy [3380 (br) cm−1], amine (3351 cm−1),
amide (1692 and 1656 cm−1), and carboxylate10 (1454 and
Ophiorrhiza plants belonging to Rubiaceae are known to
produce diverse monoterpenoid indole alkaloids such as
camptothecins1 having potent antitumor activity as well as β-
carboline-type alkaloids.2 Our studies on the constituents of
Ophiorrhiza plants distributed in Japan3 and Thailand4 have
resulted in the isolation of new camptothecin-related and/or β-
carboline-type alkaloids. In the course of our studies of new
biologically active natural products,5 a chemical investigation of
the alkaloids in Ophiorrhiza nutans collected in Thailand led to
the isolation of a new cyclopeptide, ophiorrhisine A (1), and a
new tetrahydroisoquinoline alkaloid, 7′,10-dide-O-methylce-
phaeline (2), together with two known indole alkaloids and
four known tetrahydroisoquinoline alkaloids. Herein, the
structure elucidation of these alkaloids is reported.
The dried whole plants of O. nutans were powdered and then
extracted with MeOH. The MeOH-soluble part of the extract
was separated by Sephadex LH-20 column chromatography
with MeOH/H2O. The 50% MeOH/H2O-soluble fraction was
purified by flash silica gel, reversed-phase, and amino-silica gel
chromatography to afford 1 and 2, together with the two
known indole alkaloids and four known tetrahydoisoquinoline
alkaloids: 5-carboxystrictosidine;6 lyaloside;7 demethylalangi-
side;8 alangiside;8 isoalangiside;8 and 10-O-demethylprotoeme-
tine.9 This is only the second demonstration that mono-
terpenoid indole alkaloids and monoterpenoid isoquinoline
alkaloids coexist in a plant species.8 Furthermore, from a
chemotaxonomical point of view, it is noteworthy that this is
the first isolation of tetrahydroisoquinoline alkaloids from the
genus Ophiorrhiza.
1
1387 cm−1) functionalities. The H NMR data acquired in
methanol-d4 (Table 1) showed signals for 18 aromatic protons
[δH 7.61 (2H, d), 7.37 (2H, dd), 7.29 (dd), 7.24 (2H, dd), 7.20
(2H, d), 7.15 (dd), 7.11 (dd), 6.86 (dd), 6.79 (dd), 6.77 (2H,
d), 6.75 (dd), 6.58 (2H, d)]; four α-amino methines [δH 5.03
(d), 4.67 (dd), 4.18 (dd), 3.95 (dd)]; one oxymethine [δH 5.77
(d)]; three methylenes [δH 3.45 (dd, J = 13.1, 6.2 Hz), 2.53
(dd, J = 13.1, 11.7 Hz); 3.07 (dd, J = 13.8, 3.4 Hz), 3.02 (dd, J
= 13.8, 9.6 Hz); 2.93 (dd, J = 13.8, 4.8 Hz), 2.66 (dd, J = 13.8,
9.6 Hz)]; and three equivalent N-methyls [δH 2.70 (9H, s)].
The 13C NMR data (Table 1) showed signals for four
deshielded carbons assignable to amide or hydroxycarbonyl
carbons (δC 178.4, 171.3, 167.0, 166.7); 24 aromatic carbons,
that is, two oxygenated tertiary aromatic carbons (δC 159.4,
158.0), four quaternary carbons (δC 140.5, 138.7, 135.1, 125.5),
and 18 tertiary carbons [δC 132.6, 131.5 (3C), 130.5 (2C),
129.4 (4C), 128.8, 127.6, 127.1 (2C), 122.5, 119.7, 117.0
(2C)]; eight tertiary carbons connected to oxygen or nitrogen
Received: April 3, 2017
© XXXX American Chemical Society and
American Society of Pharmacognosy
A
DOI: 10.1021/acs.jnatprod.7b00290
J. Nat. Prod. XXXX, XXX, XXX−XXX

Journal of Natural Products
Note
Figure 1. Structures of new compounds 1 and 2 and known alkaloids.
H-15 at δH 6.79 (dd, J = 8.3, 2.1 Hz) and H-16 at δH 6.86 (dd, J
= 8.3, 2.1 Hz), and between H-10 [δH 4.67 (dd, J = 11.7, 6.2
Hz)] and both H-11a [δH 3.45 (dd, J = 13.1, 6.2 Hz)] and H-
11b [δH 2.53 (dd, J = 13.1, 11.7 Hz)], together with the HMBC
correlations from both H-13 and H-16 to C-11 at δC 40.1. That
H-10 and H2-11 formed cross-peaks with the signal at δC 178.4
(C-34) indicated that this tyrosine unit possessed a carboxylic
group. In addition, the HMBC correlation between H-10 and
the amide carbonyl carbon at δC 171.3 (C-8) supported that the
tyrosine moiety was connected to a phenylalanine unit via an
amide linkage. The phenylalanine fragment was characterized
from the 1H−1H COSY correlations between H-7 [δH 4.18 (dd,
J = 9.6, 4.8 Hz)] and both H-29a [δH 2.93 (dd, J = 13.8, 4.8
Hz)] and H-29b [δH 2.66 (dd, J = 13.8, 9.6 Hz)] and from H-
31/31′ [δH 7.20 (2H, d, J = 6.9 Hz)] to H-33 [δH 7.11 (dd, J =
7.6, 7.6 Hz)] through H-32/32′, together with the HMBC
correlations from H-29 to both C-31/31′ [δC 130.5] and the
amide carbonyl carbon [δC 171.3 (C-8)] of the phenylalanine
unit. H-7 showed an HMBC cross-peak with the carbonyl
carbon of the β-hydroxyphenylalanine unit [δC 167.0 (C-5)].
Thus, the 2D structure of the 14-membered cyclopeptide
possessing a cyclophane architecture was clarified. The HMBC
correlations also confirmed the presence of an N,N,N-
trimethyltyrosine moiety. H-26/26′ [δH 6.77 (2H, d, J = 8.3
Hz)] showed COSY cross-peaks with H-27/27′ [δH 6.58 (2H,
d, J = 8.3 Hz)], and the former protons showed HMBC
correlations with the tertiary aromatic carbons at δC 131.5 (C-
26/26′), the oxygenated tertiary carbon at δC 158.0 (C-28), and
the secondary carbon at δC 33.1 (C-24), which indicated the
presence of a tyrosine residue. H-24a [δH 3.07 (dd, J = 13.8, 3.4
Hz)] and H-24b [δH 3.02 (dd, J = 13.8, 9.6 Hz)] showed
COSY cross-peaks with H-23 [δH 3.95 (dd, J = 9.6, 3.4 Hz)].
The noteworthy HMBC correlation between H-23 and the
three equivalent N-methyls [δC 52.6 (C-35)] confirmed the
presence of the N,N,N-trimethyltyrosine unit. HMBC correla-
tions between C-22 [δC 166.7] and H-4, H-23, and H2-24
showed that this tyrosine unit was attached to the macrocyclic
ring via an amide linkage. From the above results, the 2D
structure of 1 was determined.
Figure 2. Structure and selected COSY and HMBC correlations of
ophiorrhisine A (1).
[δC 86.4, 77.1, 57.9, 57.4, 55.5, 52.6 (3C)]; and three secondary
carbons [δC 40.1 (2C), 33.1]. These NMR values indicated that
1 is an alkaloidal peptide possessing four amino acid units
comprising two phenylalanine and two tyrosine residues.
Further analysis of the 2D NMR spectroscopic data of 1
(Table 1 and Figure 2) revealed that 1 also contained a
cyclopeptide consisting of a 14-membered cyclophane, a β-
hydroxyphenylalanine connected to a tyrosine fragment via an
aryl−alkyl ether bridge (vide infra), and an N,N,N-trimethyltyr-
osine residue.
In the 1H−1H COSY spectrum (Figure 2), correlations from
H-18/18′ [δH 7.61 (2H, d, J = 8.3 Hz)] to H-20 [δH 7.29 (dd, J
= 7.6, 7.6 Hz)] through H-19/19′ [δH 7.37 (2H, dd, J = 8.3, 7.6
Hz)] confirmed the presence of a phenyl moiety. H-3 [δH 5.77
(d, J = 2.1 Hz)] showed a cross-peak with H-4 [δH 5.03 (d, J =
2.1 Hz)] in the COSY spectrum, and HMBC correlations from
H-3 to C-17 (δC 140.5) and C-18/18′ (δC 127.1) revealed the
presence of the β-hydroxyphenylalanine unit. The HMBC
correlation between H-3 [δH 5.77] and C-1 [δC 159.4]
suggested that the hydroxy group in the β-hydroxyphenylala-
nine residue was connected to a tyrosine unit via an aryl−alkyl
ether bond. The tyrosine moiety was identified from the
1H−1H COSY cross-peaks between H-13 at δH 7.15 (dd, J =
8.9, 2.1 Hz) and H-14 at δH 6.75 (dd, J = 8.9, 2.1 Hz), between
The relative configuration was elucidated via NOESY
experiments in DMSO-d6 (Figure 3). NOESY correlations of
B
DOI: 10.1021/acs.jnatprod.7b00290
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Journal of Natural Products
Note
Table 1. NMR Spectroscopic Data (600 MHz) of Ophiorrhisine A (1)
a
a
b
b
position
δC
type
C
δH (J in Hz)
δC
δH (J in Hz)
1
159.4,
157.7
2
3
86.4,
57.9,
CH
CH
C
5.77, d (2.1)
85.5
56.6
5.77, s
4
5.03, d (2.1)
4.96, d (9.6)
5
167.0,
164.8
6
NH
CH
C
8.15, br s
4.27, m
7
55.5,
4.18, dd (9.6, 4.8)
52.7
8
171.3,
168.8
9
NH
CH
CH2
7.20, m
10
11
57.4,
40.1,
4.67, dd (11.7, 6.2)
3.45, dd (13.1, 6.2)
2.53, dd (13.1, 11.7)
56.2
c
4.28, m
3.16, dd (12.4, 6.2)
2.42, dd (12.4, 11.7)
12
135.1,
131.5,
119.7,
122.5,
132.6,
140.5,
127.1,
129.4,
128.8,
C
134.4
130.6
118.3
120.5
131.3
139.6
125.8
127.8
127.1
13
CH
CH
CH
CH
C
7.15, dd (8.9, 2.1)
6.75, dd (8.9, 2.1)
6.79, dd (8.3, 2.1)
6.86, dd (8.3, 2.1)
6.96, br d (8.3)
6.61, dd (8.3, 2.1)
6.71, dd (8.3, 2.1)
6.80, d (8.3)
14
15
16
17
18/18′
19/19′
20
CH
CH
CH
NH
C
7.61, 2H, d (8.3)
7.61, 2H, d (8.3)
7.37, 2H, dd (8.3, 7.6)
7.29, dd (7.6, 7.6)
7.33, 2H, dd (8.3, 7.6)
7.24, dd (7.6, 7.6)
8.42, d (9.6)
21
22
166.7,
77.1,
33.1,
165.0
74.2
31.0
23
CH
CH2
3.95, dd (9.6, 3.4)
3.07, dd (13.8, 3.4)
3.02, dd (13.8, 9.6)
4.18, d (10.2)
24
3.03, d (12.4)
2.85, dd (12.4, 10.2)
25
125.5,
131.5,
117.0,
158.0,
40.1,
C
124.1
130.1
115.6
26/26′
27/27′
28
CH
CH
C
6.77, 2H, d (8.3)
6.58, 2H, d (8.3)
6.72, 2H, d (8.3)
6.57, 2H, d (8.3)
156.6
c
29
CH2
2.93, dd (13.8, 4.8)
2.66, dd (13.8, 9.6)
2.93, dd (13.8, 4.8)
2.66, dd (13.8, 9.6)
30
138.7,
130.5,
129.4,
127.6,
178.4,
C
137.7
127.8
129.1
125.9
172.8
50.9
31/31′
32/32′
33
CH
CH
CH
C
7.20, 2H, d (6.9)
7.18, 2H, m
7.24, 2H, m
7.05, m
7.24, 2H, dd (7.6, 6.9)
7.11, dd (7.6, 7.6)
34
35
52.6,
CH3
2.70, 9H, s
2.60, 9H, s
a
b
c
Measured in methanol-d4. Measured in DMSO-d6. Overlapped with DMSO-d6 signal.
H-3 [δH 5.77 (s)]/H-4 [δH 4.96 (d, J = 9.6 Hz)]/NH-6 [δH
8.15 (br s)]/H-14 [δH 6.61 (dd, J = 8.3, 2.1 Hz)], and of H-10
[δH 4.28 (m)]/H-11b [δH 2.42 (dd, J = 12.4, 11.7 Hz)]/H-13
[δH 6.96 (br d, J = 8.3 Hz)] revealed that these protons were on
the same side of the 14-membered ring. The relative
configuration of the β-hydroxyphenylalanine residue (H-3/H-
4) was deduced from the 1H−1H NMR coupling constants and
the 13C NMR chemical shifts. H-3 was observed as a doublet in
methanol-d4 with a small coupling constant of J3,4 = 2.1 Hz and
as a singlet [δH 5.77 (s)] in DMSO-d6, respectively, indicating
that H-3 and H-4 were syn-oriented. In addition, the chemical
shift of C-3 in 1 (δC 86.4 in methanol-d4, δC 85.5 in DMSO-d6)
confirmed that compound 1 possessed an L-threo β-
hydroxyphenylalanine residue12 (3R*, 4S*). From these results
and biosynthesis considerations, it was presumed that
compound 1 consisted of L-amino acid moieties and its
absolute configuration was 3R, 4S, 7S, 10S, and 23S.
Compound 1 is an analogue of the known 14-membered
paracyclophane xylopyrine C,11 with the characteristic functions
including a carboxylate group at C-10, an N,N,N-trimethy-
lammonium group at C-23, and a hydroxy group at C-28.
Compound 2, 7′,10-dide-O-methylcephaeline, is a colorless
unstable solid, and in solution it darkened readily, indicating the
presence of a catechol moiety. Compound 2 had a molecular
formula of C26H34N2O4 from the HRESIMS data (calcd
439.2597 [M + H]+; found m/z 439.2615 [M + H]+) (Figure
4). Its UV spectrum exhibited absorptions at 207, 227 (sh), and
287 nm, which demonstrated the presence of tetrahydroiso-
quinoline moieties.
The 1H NMR data acquired in methanol-d4 (Table 2)
showed signals for a methoxy group [δH 3.81 (3H, s)], an ethyl
group [δH 0.93 (3H, dd, J = 7.6, 7.6 Hz), 1.70 (m), 1.13 (m)],
and four one-proton aromatic singlets [δH 6.77 (s), 6.64 (s),
6.52 (s), 6.49 (s)]. The 13C NMR data (Table 2) showed
signals for 12 aromatic carbons, including four oxygenated
tertiary aromatic carbons (δC 147.8, 145.8, 144.9, 144.7), four
quaternary aromatic carbons (δC 131.2, 131.2, 126.8, 126.3), six
carbons connected to oxygen or nitrogen (δC 63.7, 62.3, 56.3,
53.8, 53.0, 41.6), and eight aliphatic carbons (δC 42.9, 41.3,
C
DOI: 10.1021/acs.jnatprod.7b00290
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Journal of Natural Products
Note
Table 2. NMR Spectroscopic Data (600 MHz, Methanol-d4)
of 7′,10-Dide-O-methylcephaeline (2)
position
1
δC
type
CH2
δH (J in Hz)
37.0,
2.62, m
1.13, m
2
3
4
37.7,
42.9,
62.3,
CH
CH
CH2
1.57, ddd (11.7, 11.0, 11.0)
1.39, m
3.07, dd (11.7, 3.4)
2.10, dd (11.7, 11.7)
3.02, dd (11.0, 5.5)
2.50, ddd (11.0, 11.0, 4.1)
3.07, m
6
7
53.8,
29.5,
CH2
CH2
2.67, d (14.5)
7a
8
126.3,
112.8,
147.8,
145.8,
112.6,
131.2,
63.7,
C
CH
C
6.64, s
6.77, s
9
10
11
11a
11b
12
C
CH
C
CH
CH2
3.11, d (13.1)
1.70, m
Figure 3. Key NOESY correlations of ophiorrhisine A (1) (DFT calcd
structure, Spartan ‘16, B3LYP, 6-31*).
24.5,
1.13, m
13
11.5,
41.3,
CH3
CH2
0.93, 3H, dd (7.6, 7.6)
2.06, dd (12.4, 11.0)
1.45, dd (12.4, 11.7)
4.03, d (11.0)
3.18, ddd (11.7, 6.1, 5.5)
2.92, m
α
1′
3′
53.0,
41.6,
CH
CH2
4′
29.3,
CH2
2.73, m
2.62, m
4′a
5′
6′
7′
8′
126.8,
116.4,
144.9,
144.7,
113.8,
131.2,
56.3,
C
CH
C
6.49, s
Figure 4. Structure, selected COSY and HMBC correlations, and
differential NOE in 7′,10-dide-O-methylcephaeline (2).
C
CH
C
6.52, s
8′a
-OMe
CH3
3.81, 3H, s
37.7, 37.0, 29.5, 29.3, 24.5, 11.5). These spectroscopic data are
similar to those of 10-O-demethylprotoemetine,9 a coexisting
alkaloid. The signal for the C-1′ formyl proton in the latter was
absent, and instead, signals for an extra tetrahydroisoquinoline
moiety was present in the spectrum of 2. The 2D NMR
spectroscopic data of 2 (Figure 4) indicated that the 2D
structure should be similar to emetine,13 but there were
plates (Fuji Silysia Chemical, Tokyo, Japan). Column chromatog-
raphy: silica gel 60 (70−230 mesh, Merck, Tokyo, Japan), silica gel
60N [40−50 mm (for flash chromatography), Kanto Chemical,
Tokyo, Japan], Chromatorex NH (100−200 mesh, Fuji Silysia
Chemical, Tokyo, Japan), Cosmosil 75C18-OPN (Nacalai tesque,
Kyoto, Japan), Sephadex LH-20 (GE Healthcare Japan, Tokyo, Japan),
and DIAION HP20 (Mitsubishi Chemical, Tokyo, Japan). Medium-
pressure liquid chromatography (MPLC): C.I.G. prepacked column
CPS-HS-221-05 (silica gel, Kusano Kagakukikai, Tokyo, Japan), Ultra
Pack NH-40A (amino-silica gel, Yamazen, Osaka, Japan), and Ultra
Pack ODS-A-40A (ODS, Yamazen, Osaka, Japan).
Plant Material. Ophiorrhiza nutans was collected from the
northern part of Thailand (Queen Sirikit Botanic Garden, Chiang
Mai, and Chiang Rai) in August to December 2007 and identified by
one of the authors, D.S., on the basis of the specimens deposited in
Queen Sirikit Botanic Garden and Chiang Mai University Herbarium.
A voucher specimen (No. 2007003) was deposited in the Faculty of
Pharmacy, Chiang Mai University.
The whole plants of O. nutans (321.9 g, dry weight) were powdered
and then extracted with 90% MeOH (3 L, 2 × 2.5 L) to give a MeOH
extract (49.9 g) after evaporation of the solvent. The MeOH-soluble
part of the extract (26.4 g) was separated by Sephadex LH-20 column
chromatography with a MeOH/H2O gradient to give 12 fractions (fr.
1−4 were eluted with 50% MeOH/H2O, fr. 5−7 with 75% MeOH/
H2O, fr. 8−11 with MeOH, and fr. 12 with acetone). Fr. 3 (11.72 g)
was purified by silica gel chromatography with a MeOH/CHCl3
gradient. Fr. 5 was separated by repeated chromatography, including
1
remarkable differences in the H and 13C NMR spectra. These
spectra showed only one methoxy signal. The NOE correlation
of OMe/H-8 suggested that the methoxy group was located at
C-9. To establish the structure and the absolute configuration,
2 was treated with trimethylsilyldiazomethane TMSCHN2 to
1
afford a methylated compound whose H NMR, ESIMS, and
the specific rotation data were identical with those of emetine.13
Accordingly, the structure of 2 was defined as 7′,10-dide-O-
methylcephaeline.
Compound 1 was evaluated for cytotoxicity toward the
human cancer cell lines A549, HT29, and HCT116, but no
cytotoxicity was detected (IC50 > 15 μM).
EXPERIMENTAL SECTION
■
1
General Experimental Procedures. H and 13C NMR spectra:
JEOL JNM ECZ at 600 MHz (1H) or 150 MHz (13C), respectively.
UV: JASCO V-560. ESIMS: JEOL JMS T100GCV. HRESIMS: JEOL
JMS-T100LP AccuTOF LC-plus. ECD: JASCO J-720WI. TLC:
precoated silica gel 60 F254 plates (0.25 mm thick) and precoated
RP-18 F254 plates (Merck, Tokyo, Japan); precoated amino-silica gel
D
DOI: 10.1021/acs.jnatprod.7b00290
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Journal of Natural Products
Note
silica gel flash column chromatography (MeOH/CHCl3 gradient) or
ODS open column chromatography, to afford demethylalangiside
(179.6 mg), alangiside (183.3 mg), and isoalangiside (3.4 mg). Fr. 9
was purified by ODS chromatography (60% H2O/MeOH) to give 5-
carboxystrictosidine (922.2 mg). Fr. 4 (10.76 g) from Sephadex LH-20
column chromatography was purified by DIAION HP20 column
chromatography with a H2O/MeOH gradient. The fraction eluted
with MeOH was separated by repeated chromatography, including
amino-silica gel open column chromatography (MeOH/CHCl3
gradient) or MPLC (ODS, 40% H2O/MeOH), to afford ophiorrhisine
A (1, 10.2 mg) and lyaloside (1.0 mg). The fraction eluted with
MeOH was purified by repeated chromatography, including silica gel
flash chromatography (NH4OH/MeOH/CHCl3 gradient) or amino-
silica gel open column chromatography (15% MeOH/CHCl3), to give
7′,10-dide-O-methylcephaeline (2, 7.5 mg) and 10-O-demethylpro-
toemetine (3.9 mg).
(d) Arbain, D.; Handayani, D.; Allen, Y.; Sargent, M. V. ACGC Chem.
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Chem. Soc., Perkin Trans. 1 1998, 2537−2540. (f) Arbain, D.; Byrne, L.
T.; Dachriyanus; Evrayoza, N.; Sargent, M. V. Aust. J. Chem. 1997, 50,
1111−1112. (g) Arbain, D.; Byrne, L. T.; Dachriyanus; Sargent, M. V.
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3062, 1692, 1656, 1576, 1540, 1531, 1514, 1489, 1454, 1387, 1222,
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ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.jnat-
prod.7b00290.
■
S
Photographs of Ophiorrhiza off. nutans Cl. ex Hk. f. and
NMR spectra for ophiorrhisine A (1) and 7′,10-dide-O-
methylcephaeline (2) (PDF)
AUTHOR INFORMATION
Corresponding Author
*E-mail: takayamah@faculty.chiba-u.jp.
ORCID
Hiromitsu Takayama: 0000-0003-3155-2214
Notes
The authors declare no competing financial interest.
■
(6) Ferrari, F.; Mesana, I.; Botta, B.; De Mello, J. F. J. Nat. Prod.
1982, 49, 1150−1151.
ACKNOWLEDGMENTS
This work was supported by JSPS KAKENHI Grant Numbers
26293023, 16H05094, and 17H03993.
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1485−1489.
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1228−1239.
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(9) Itoh, A.; Tanahashi, T.; Tabata, M.; Shikata, M.; Kakite, M.;
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(10) Silverstein, R. M.; Webster, F. X.; Kiemle, D. J. Spectrometric
Identification of Organic Compounds, 7th ed.; John Wiley & Sons, Inc.:
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DOI: 10.1021/acs.jnatprod.7b00290
J. Nat. Prod. XXXX, XXX, XXX−XXX