Three novel C-glycosidic ellagitannins, Rhoipteleanins H, I, and J, from Rhoiptelea chiliantha

Article abstract of DOI:10.1021/np980361g

Three novel C-glycosidic ellagitannins named rhoipteleanins H (1), I (2), and J (3) were isolated from the fruits and bark of Rhoiptelea chiliantha Diels et Hand.-Mazz. (Rhoipteleaceae), and the structures were elucidated on the basis of detailed spectroscopic analysis and chemical evidence. Rhoipteleanin H possesses a unique cyclopentenone carboxyl moiety, which is probably formed by oxidation and subsequent rearrangement of an aromatic ring of a usual C-glycosidic ellagitannin. Rhoipteleanin I is the first ellagitannin having a hydroxynaphthalene glucoside moiety. Rhoipteleanin J is a dimeric ellagitannin generated by dehydrative coupling between two molecules of a monomeric C-glycosidic ellagitannin and subsequent oxidation of an aromatic ring. From a chemotaxonomic viewpoint, presence of these characteristic ellagitannins in this plant provides a further support for the establishment of the order Rhoipteleales comprising Rhoipteleaceae as the only family.

Full text of DOI:10.1021/np980361g

J . Nat. Prod. 1999, 62, 425-429
425
Th r ee Novel C-Glycosid ic Ella gita n n in s, Rh oip telea n in s H, I, a n d J , fr om
Rh oiptelea ch ilia n th a
Zhi-Hong J iang, Takashi Tanaka, and Isao Kouno*
Faculty of Pharmaceutical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, J apan
Received August 14, 1998
Three novel C-glycosidic ellagitannins named rhoipteleanins H (1), I (2), and J (3) were isolated from the
fruits and bark of Rhoiptelea chiliantha Diels et Hand.-Mazz. (Rhoipteleaceae), and the structures were
elucidated on the basis of detailed spectroscopic analysis and chemical evidence. Rhoipteleanin H possesses
a unique cyclopentenone carboxyl moiety, which is probably formed by oxidation and subsequent
rearrangement of an aromatic ring of a usual C-glycosidic ellagitannin. Rhoipteleanin I is the first
ellagitannin having a hydroxynaphthalene glucoside moiety. Rhoipteleanin J is a dimeric ellagitannin
generated by dehydrative coupling between two molecules of a monomeric C-glycosidic ellagitannin and
subsequent oxidation of an aromatic ring. From a chemotaxonomic viewpoint, presence of these
characteristic ellagitannins in this plant provides a further support for the establishment of the order
Rhoipteleales comprising Rhoipteleaceae as the only family.
Rhoiptelea chiliantha Diels et Hand.-Mazz., a tree
distributed in southern China and northern Vietnam, is
the only species of the family Rhoipteleaceae. The system-
atic position of this monotypic family is still unclear, and
several opinions have so far been published on the basis
of morphological, anatomical, and palynological evidence.1
Our chemical research of this plant revealed the presence
of some characteristic secondary metabolites, that is,
triterpene-lignan esters,2 a rearranged ursane triterpene,3
a lupane triterpene and two triterpene caffeates,4 dimeric
ellagitannins,5,6 diarylheptanoids,7 and euphane-type trit-
erpene tridesmosides.8 The presence of these characteristic
metabolites chemotaxonomically supported the establish-
ment of the order Rhoipteleales.7,9 The dimeric ellagitan-
nins, isolated from the fruits as the major phenolic con-
stituents and named rhoipteleanins A-F,5,6 have unique
structures that were biogenetically formed by intermolecu-
lar oxidative C-C coupling of two molecules of monomers.
Numerous dimeric ellagitannins known before, except for
the C-glycosidic type, had been believed to be exclusively
biosynthesized by intermolecular C-O oxidative coupling
of pyrogallol rings;10 therefore, the isolation of the rhoipte-
leanins A-F suggested that the metabolism of hydrolyzable
tannins in this plant is unusual. Further investigation of
the minor polyphenolic metabolites of this plant led to the
isolation of three novel C-glycosidic ellagitannins named
rhoipteleanins H (1), from the fruits, and I (2) and J (3),
from the bark. This paper deals with the isolation and
structure elucidation of these compounds.
1,2,3,4,6-penta-O-galloyl-â-D-glucose;13 casuariin (7);11,12
pterocarinin A;14 2,3,4,6-bis-(S)-HHDP-D-glucose;15 and
alienanin B.16
Resu lts a n d Discu ssion
The MeOH extract of dried fruits was suspended in H2O
and extracted with ethyl ether and ethyl acetate, succes-
sively. The H2O layer was separated by a combination of
column chromatographies over MCI-gel CHP 20P, Sepha-
dex LH-20, and Bondapak ODS to afford rhoipteleanin H
(1) (0.004% based on the dry w) together with rhoiptelean-
ins A-G.5,6 The EtOH extract of the air-dried bark was
separated in a similar manner to afford rhoipteleanins I
(2)(0.006%) and J (3) (0.0007%), together with seven known
tannins: casuarinin (4);11,12 1-O-galloyl-2,3;4,6-bis-(S)-
4,4′,5,5′,6,6′-hexahydroxydiphenoyl(HHDP)-â-D-glucose;11
Rhoipteleanin H (1) was characterized as an ellagitannin
on the basis of its dark blue coloration with FeCl3 reagent
* To whom correspondence should be addressed. Tel: +81-95-847-1111,
ext 2517. Fax: +81-95-848-4387. E-mail: ikouno@net.nagasaki-u.ac.jp.
10.1021/np980361g CCC: $18.00
© 1999 American Chemical Society and American Society of Pharmacognosy
Published on Web 02/27/1999

426 J ournal of Natural Products, 1999, Vol. 62, No. 3
J iang et al.
Ta ble 1. 1H NMR Data for Glucose and Cyclopentenone Moieties of Compounds 1-6 [in (CD3)2CO + D2O]
2
3
glucose
1
open chain
glycoside unit
unit A
unit B
4.15 (s)
4.61 (s)
5.48 (d 8)
5.51 (t 8)
4
5
6
1
2
3
4
5
6
5.42 (dd 3, 6)
4.98 (d 6)
6.10 (d 2)
5.59 (dd 2, 10) 5.81 (dd 2, 9)
5.38 (dd 4, 10) 5.41 (dd 3, 9)
5.01 (dd 4, 13) 4.91 (dd 3, 14) 3.82 (dd, 2, 13)
5.04 (d 2)
5.17 (t 2)
5.34 (t 2)
4.69 (d, 8)
3.56 (dd, 8, 9)
3.45 (t, 9)
3.41 (t, 9)
3.16 (ddd, 2, 5, 9) 5.91 (br s)
4.70 (br d 12)
5.63 (d 5)
5.64 (d 5)
4.70 (dd 2, 5)
5.48 (t 2)
5.50 (dd 2, 9)
5.37 (dd 3, 9)
4.90 (dd 3, 12) 4.95 (dd 3, 12) 4.59 (dd 3, 12)
4.68 (s)
4.79 (br s)
5.21 (t 2)
5.78 (dd 2, 8)
5.60 (dd 3, 8)
4.09 (s)
5.37 (s)
5.19 (d 6)
5.79 (dd 6, 8)
5.63 (d 7)
4.64 (dd 2, 5)
5.76 (br. s)
5.57 (t 4)
5.68 (br d 8)
4.70 (br d 12)
4.02 (d 13)
4.09 (d 14)
3.66 (dd, 5, 13)
4.26 (dd 2, 12) 3.62 (dd 3, 12) 4.11 (d 13)
4.07(d 12)
4.16 (d 12)
cyclopen-
tenone
1
5.32 (d, 3)
4.48 (s)
4.36 (s)
OCH3
3.76 (3H, s)
Ta ble 2. 13C NMR Data for Glucose and Cyclopentenone Moieties of Compounds 1-6 [in (CD3)2CO + D2O]
2
3
glucose
1
open-chain
pyranoside
unit A
unit B
4
5
6
1
62.8
79.3
67.0
73.4
69.7
64.7
40.4
79.5
74.4
73.2
71.1
64.4
103.2
74.1
77.3
70.7
77.4
62.4
68.3
77.4
72.7
75.2
73.0
63.6
47.5
83.6
78.0
71.6
71.6
65.9
67.8
77.4
70.3
74.6
71.6
65.0
38.3
81.2
74.9
73.3
71.3
64.5
46.2
81.1
76.4
70.1
72.0
64.5
2
3
4
5
6
cyclopen-
tenone
1
2
3
4
5
6
44.9
82.7
48.3
137.2
149.8
195.3
91.6
49.6
139.4
149.3
195.7
90.7
200.4
142.7
155.5
171.5
53.8
OCH3
tetrasubstituted double bond (cyclopentenone: Cp-4 and
-5), a conjugated ketone (Cp-3), a benzyl methine (Cp-1),
an oxygen-bearing quaternary carbon (Cp-2), a nonconju-
gated ester carbonyl (Cp-6), and a methoxyl group (Table
2). In the HSQC spectrum, the benzyl methine carbon (Cp-
1) was correlated with a proton signal at δ 5.32, and the
1H-1H COSY spectrum revealed a long-range coupling (J
) 3 Hz) of this methine proton with the glucose C-1 proton.
In the HMBC spectrum (Figure 1), both of these two
protons were correlated with the ketone carbon signal (Cp-
3) and the carbon signals due to the tetrasubstituted double
bond (Cp-4 and -5). In addition, long-range H-C couplings
of the benzyl methine proton signal (Cp-1) were also
observed with three aromatic carbons, the oxygen-bearing
quaternary carbon (Cp-2), and the nonconjugated ester
carboxyl carbon (Cp-6), which also correlated with the
methoxyl proton. The observation of these correlations
permitted us to construct a cyclopentenone ring possessing
a methoxycarbonyl group as shown in Figure 1, and this
was consistent with the molecular weight (966 dalton)
revealed by the negative ion FABMS, which showed the
[M - H]- peak at m/z 965.
The CD spectrum of 1 showed a positive Cotton effect
at 239 nm and a negative one at 267 nm, indicating that
the atropisomerism of the HHDP group had the S-config-
uration.18 The NOESY spectrum showed the cross-peaks
between H-1 and H-2, and between H-2 and H-3, and no
proton was correlated with the benzyl methine proton (Cp-
1). On the assumption that this compound was derived
from 4, examination using a Dreiding model and computer-
aided molecular modeling (CAChe system) indicated that
the benzyl methine proton (Cp-1) must be â oriented for
construction of both six-membered (including glc-1, -2 and
Cp-4, -5) and 10-membered lactone rings (including
F igu r e 1. Selected HMBC correlations (HfC) observed for 1.
and reddish brown coloration with NaNO2-AcOH re-
agent.17 The 1H NMR spectrum exhibited a two-proton
aromatic singlet signal (δ 7.20) due to a galloyl group, three
one-proton aromatic singlets (δ 6.91, 6.60, and 6.43), and
aliphatic proton signals attributable to six methines, a
methylene, and a methoxyl group (Table 1). The similarity
of the chemical shifts and coupling pattern of the five
aliphatic methine and methylene protons to those of
casuarinin (4),11,12 suggested the presence of an open-chain
glucose. The 13C NMR spectrum showed five conjugated
ester carboxyl signals [δ 169.1, 168.8 (×2), 166.8, and 163.2]
and signals arising from four pyrogallol rings, one of which
is attributable to the galloyl group. The HMBC spectrum
showed correlations of these ester carbons with the glucose
and aromatic protons, confirming the connectivity of ester
linkages, including the location of the galloyl group at
glucose C-5, as shown in Figure 1. The correlations also
revealed the presence of an HHDP group attached to C-4
and C-6 positions of the open-chain glucose moiety. The
remaining carbon signals indicated the presence of a

Ellagitannins from Rhoiptelea
J ournal of Natural Products, 1999, Vol. 62, No. 3 427
F igu r e 2. Selected HMBC correlations (HfC) observed for 2.
Sch em e 1. Biogenesis of Rhoipteleanin H (1).
The atropisomerism of the HHDP groups in 2 was
chemically confirmed by alkaline hydrolysis (2% NaOMe-
MeOH) of 2a , yielding methyl trimethoxybenzoate (2b),
dimethyl hexamethoxydiphenate 2c ([R]D -32.5°, CHCl3),20
and 2d . The negative specific rotation value of 2c indicated
the S-configuration of the biphenyl bond. In addition, the
atropisomerism of the C-substituted HHDP (BPH) group
was also deduced to be in the S-series from the observation
of a positive Cotton effect at 237 nm and a negative one
at 264 nm in the CD spectrum of 2. Thus, the structure
ofrhoipteleanin I was established to be as shown in
formula 2.
glc-2, -3 and Cp-1, -5). Configuration of the quaternary
carbon (Cp-2) of the cyclopentenone ring could not be
confirmed clearly; however, the absence of NOE between
the Cp-1 proton and the methoxyl group suggested an R
orientation of the methoxycarbonyl group.
From these results, the structure of rhoipteleanin H was
proposed to be represented by the formula 1. This com-
pound was presumed to be formed by oxidation of a
pyrogallol ring attached to the glucose C-1 of 4 followed
by benzylic acid-type rearrangement and methylation
(Scheme 1).
Although complex tannins comprising a C-glycosidic
ellagitannin unit and a flavan-3-ol unit were found in the
J uglandaceae,21 Fagaceae,19,22 Myrtaceae,23 Combretace-
ae,24 and Theaceae,25 rhoipteleanin I (2) represents a new
type of tannin in which a naphthalene glycoside unit is
connected to an ellagitannin unit through a carbon-carbon
linkage.
Rhoipteleanin I (2) showed a dark blue coloration with
1
1% FeCl3 reagent. The H and 13C NMR spectra (Tables 1
and 2) exhibited aliphatic signals arising from a glycosid-
4
ically linked â-glucopyranose with C1-conformation and a
fully acylated polyalcohol moiety. The signals due to the
polyalcohol moiety were similar to those of the stachyurin
unit in stenophyllanin B (5), a complex tannin isolated from
Quercus species (Fagaceae),19 suggesting the presence of a
C-1 substituted stachyurin unit in 2. This was supported
by the appearance of the signals due to five ester carbonyl
carbons and five pyrogallol-type aromatic rings in the 13C
NMR spectrum and confirmed by the HMBC correlations
(Figure 2) between the oxygen-bearing aliphatic protons
and the ester carbonyl carbons, and between the ester
carbonyl carbons and aromatic protons.
The remaining 10 aromatic carbon signals suggested the
presence of a dioxygenated naphthalene moiety. The
coupling pattern of the aromatic protons [one singlet at δ
6.79, two broad doublets at δ 8.24 and 8.26 (d, J ) 9 Hz),
and two double-triplets at δ 7.41 and 7.47 (J ) 1 and 9
Hz)] indicated that this naphthalene moiety is 1,2,4-
trisubstituted. The negative FABMS spectrum of 2 showed
an [M - H]- ion peak at m/z 1239, and a methyl ether 2a
obtained by methylation with Me2SO4-K2CO3 exhibited
the [M + Na]+ ion peak at m/z 1487 in the positive FABMS.
This result suggested that there is one phenolic hydroxyl
group on the naphthalene moiety in addition to 15 phenolic
hydroxyl groups of the pyrogallol rings in 2. The positions
of the hydroxyl and glucopyranosyl groups were determined
to be located at C-1′ and C-4′, respectively, on the basis of
the HMBC experiment shown in Figure 2. Furthermore,
because the H-1 of the stachyurin unit was correlated to
the C-1′, C-2′, and C-3′ of the naphthalene moiety (Figure
2), the location of stachyurin unit was determined to be at
the C-2′ position of the naphthalene moiety.
Rhoipteleanin J (3) was also characterized as an ellagi-
tannin by coloration with FeCl3 and NaNO2-AcOH re-
1
agent. In the aliphatic region of the H NMR spectrum, a
methine singlet (δ 4.48) and two sets of signals arising from
two polyalcohol moieties (units A and B) were observed
(Table 1). The 1H and 13C NMR (Table 2) spectral com-
parison showed that chemical shifts and coupling pattern
of the unit A were similar to those of 4, except for the small
J H-4,H-5 value. The signals due to the remaining polyalco-
hol moiety (unit B) seem to be related to those of psidinin
C (6).23 In the aromatic region, the 1H NMR spectrum
exhibited a two-proton singlet (δ 7.09) due to a galloyl
group and seven one-proton aromatic singlets, and the 13C
NMR spectrum revealed the presence of eight pyrogallol
rings along with 10 ester carbonyl signals. These spectro-
scopic data indicated that 3 is a dimeric ellagitannin
consisting of two C-glycosidic ellagitannin units. This was
supported by the negative ion FABMS, which showed the
[M-H]- peak at m/z 1823.
Partial hydrolysis of 3 in hot water afforded casuariin
(7),11,12 indicating the presence of a casuarinin unit (unit
A) in the molecule of 3. The remaining part of the molecule
(unit B) was determined by following spectroscopic obser-
vation: first, analysis of the 13C NMR and HMBC spectra
showed a galloyl group at the glucose C-5′ position and an
HHDP group at the C-4′ and C-6′ positions (Figure 3). Next,
the 13C NMR chemical shifts of the signals due to a methine
(Cp-1), a tetrasubstituted double bond (Cp-2, -3), a conju-

428 J ournal of Natural Products, 1999, Vol. 62, No. 3
J iang et al.
chemotaxonomic marker of J uglandaceae, the occurrence
of rhoipteleanin I (2) having a juglone-related glucoside
moiety in the molecule also supported the relationship
between the Rhoipteleaceae and J uglandaceae, although
the glycosides with nonconjugated form have not been
isolated from this plant so far.
Exp er im en ta l Section
Gen er a l Exp er im en ta l P r oced u r es. Optical rotations
were measured with a J ASCO DIP-370 digital polarimeter.
Column chromatography was performed with Sephadex LH-
20 (25-100 µm, Pharmacia Fine Chemical Co. Ltd.), MCI-gel
CHP 20P (75-150 µm, Mitsubishi Chemical Industries, Ltd.),
Bondapak ODS (Waters), and Chromatorex ODS (Fuji Silysia).
Thin-layer chromatography was performed on precoated Si gel
60 F254 plates (0.2 mm thick, Merck) with C6H6-HCOOEt-
HCOOH (1:7:1 or 1:7:2 v/v) and precoated cellulose F254 plates
(0.1 mm thick, Merck) with 2% HOAc, and spots were detected
by UV illumination and by spraying with 2% ethanolic FeCl3
reagent. Analytical HPLC was performed on a Tosoh ap-
paratus equipped with a CCPM solvent delivery system, UV-
8000 spectrometer (280 nm) and a Cosmosil 5C18-AR (Nacalai
Tesque Inc.) column (4.6 mm i.d. × 250 mm) (mobile phase,
CH3CN-50 mM H3PO4, gradient elution from 5 to 30% CH3-
CN for 30 min; flow rate, 0.8 mL/min). The CD spectra were
measured with a J ASCO J -720w apparatus. Negative FABMS
were recorded on a J EOL J MX DX-303 spectrometer with
F igu r e 3. Selected HMBC correlations (HfC) observed for 3.
gated ketone (Cp-4), and an aliphatic quaternary carbon
(Cp-5) were almost identical to those of the cyclopentenone
ring of 6 (Table 2). Presence of the partial structure similar
to that of 6 was comfirmed by the HMBC experiment
(observed at J CH ) 4, 6, 8, 10, and 12 Hz, Figure 3): a long-
range correlation of the methine (δ 4.48, Cp-1) with the
glucose C-1′ (unit B) revealed connectivitiy of the cyclo-
pentenone ring to glucose C-1′. In addition, a series of
correlations through the glucose H-3′ (unit B)-3′-ester
carbonyl carbon (δ 166.6)-an aromatic proton of a pyro-
gallol ring (δ 6.55)-an aromatic carbon (δ 111.0)-the Cp-1
proton-2′-ester carbonyl carbon (δ 168.3) confirmed the
presence of a macrocyclic lactone ring. The remaining
galloyl residue (GA) was shown to be attached to the
glucose C-1′ (unit B) through a C-C bond, because the
glucose H-1′ (unit B) was correlated with C-2 (δ 124.1) and
C-3 (δ 148.5) of the galloyl group (GA), and an aromatic
proton (δ 7.20) was coupled with the glucose C-1′ (4J ) and
a carboxyl group (δ 165.6) (Figure 3). An ether linkage
between the C-3 hydroxy group of the galloyl residue and
the quaternary carbon (Cp-5) of the cyclopentenone ring
was deduced from the appearance of the C-3 signal of the
galloyl residue at lower field (δ 148.5) compared to that of
usual galloyl group (δ 145.7). Furthermore, the orientation
of the glucose H-1 and methine proton (Cp-1) of the
cyclopentenone ring was presumed to be R and â, respec-
tively, because the NOESY spectrum showed NOE cor-
relation between glucose H-1 and H-3 and no correlation
peaks with the Cp-1 proton. Computer-aided molecular
modeling indicated that the alternative configuration of the
Cp-1 methine carbon, although it was a distorted structure
with strong strain, required the NOE between the methine
proton and both of the glucose H-1 and H-2 (2.2-2.5 Å).
1
glycerol as a matrix. H and 13C NMR spectra were obtained
with Varian Unity plus 500 and Varian Gemini 300 spectrom-
eters operating at 500 and 300 MHz for 1H, and 125 and 75
MHz for 13C, respectively; chemical shifts are reported in parts
per million on the δ scale with TMS as the internal standard,
and coupling constants are in Hertz. HMQC (J CH)140 Hz),
HMBC (nJ CH optimized for 4, 6, 8, 10, and 12 Hz) and NOESY
(mixing time 0.50 s) experiments were performed using
standard Varian pulse sequences. Computer-aided molecular
modeling was done by Mechanics version 3.7 of CAChe system
(CAChe Scientific).
P la n t Ma t er ia ls. Fruits and bark of R. chiliantha were
collected in Huaping, Guangxi, China. A voucher specimen has
been deposited in the Laboratory of Plant Chemotaxonomy,
China Pharmaceutical University, Nanjing.
Isola tion . The air-dried fruits (495 g)6 were extracted with
MeOH and then 70% Me2CO. The extracts were combined, and
the organic solvent was evaporated under reduced pressure.
The resulting aqueous solution was partitioned with Et2O and
EtOAc successively to afford the Et2O extract (24.0 g), the
EtOAc extract (9.0 g), and the aqueous extract (26.4 g). The
H2O layer was chromatographed on MCI-gel CHP 20P [0-100%
MeOH-Me2CO-H2O (1:1)] to give five fractions: fraction 1
(1.6 g), fraction 2 (3.8 g), fraction 3 (2.0 g), fraction 4 (4.1 g)
and fraction 5 (4.9 g). fraction 5 was further subjected to
Sephadex LH-20 chromatography [60-100% MeOH and then
Me2CO-H2O (1:1)] and Bondapak ODS (0-40% MeOH) to
afford rhoipteleanin H (1) (26 mg).
The air-dried bark (5.7 kg)2 was extracted with 95% EtOH.
The extract (570 g) was partitioned in a manner similar to
that described for the fruits to give an Et2O layer (402 g),
EtOAc layer (45 g), and H2O layer (123 g). The EtOAc layer
was subjected to MCI-gel CHP 20P chromatography (0-100%
MeOH), and the fractions eluted with 20-60% MeOH were
separated by column chromatography over Sephadex LH-20
(40-100% MeOH) to afford casuarinin (4)(12.3 g), 1-O-galloyl-
2,3;4,6-bis-(S)-HHDP-â-D-glucose (685 mg), and 1,2,3,4,6-penta-
O-galloyl-â-D-glucose (123 mg). The H2O layer was subjected
to Sephadex LH-20 column chromatography. After washing
the column with H2O, elution of 40-100% MeOH yielded four
fractions: fraction 1 (12.4 g), fraction 2 (14.0 g), fraction 3 (8.6
g), and fraction 4 (13.2 g). Fraction 2 was separated by
Chromatorex ODS (0-50% MeOH) chromatography to give
casuariin (7) (194 mg) and pterocarinin A (2.1 g). Chromatog-
raphy of fraction 3 over MCI-gel CHP 20P (0s50% MeOH) and
1
Because partial hydrolysis of 3 gave 7 and the H NMR
chemical shift indicated acylation of the C-5 hydroxyl group
of the casuarinin unit (unit A), it was strongly suggested
that the carboxyl group of the galloyl residue attached to
the C-1′ position of the unit B was linked to the C-5
hydroxyl group of the unit A. In addition, atropisomerism
of three biphenyl bonds was determined to be all S in
configuration from appearance of a large positive Cotton
effect at 236 nm and a negative one at 267 nm in the CD
spectrum. On the basis of these results, the structure of
rhoipteleanin J was proposed as that shown in formula 3.
In our previous paper,7 the establishment of the order
Rhoipteleales (comprising Rhoipteleaceae as the only fam-
ily) and the taxonomic affinities of this order to J uglan-
dales, Fagales, and Myricales were proposed chemotaxo-
nomically. The isolation of the characteristic ellagitannins,
rhoipteleanins H-J , from this plant provides further
support for the systematic position of this monotypic family.
Because juglone-related glucosides are well known as the

Ellagitannins from Rhoiptelea
J ournal of Natural Products, 1999, Vol. 62, No. 3 429
Sephadex LH-20 (60-90% MeOH) yielded rhoipteleanins I (2)
(324 mg) and J (3) (40 mg), together with two known ellagi-
tannins, 2,3;4,6-bis-(S)-HHDP-D-glucose (646 mg) and aliena-
nin B (295 mg).
1H NMR [500 MHz, (CD3)2CO + D2O] δ 7.20 (1H, s, 5-substi-
tuted galloyl), 7.09 (2H, s, 5′-galloyl-2, 6), 6.95 (1H, s, 4′, 6′-
HHDP-3), 6.91 (1H, s, 4, 6-HHDP-3), 6.62 (1H, s, 4′, 6′-HHDP-
3′), 6.57 (1H, s, 4, 6-HHDP-3′), 6.55 (1H, s, 3′-PH-3), 6.44 (1H,
s, 2, 3-BPH-3′); 13C NMR [125 MHz, (CD3)2CO + D2O] δ 170.4
(2, 3-BPH-7′), 170.0 (4, 6-HHDP-7′), 168.7 (4′, 6′-HHDP-7′),
168.3 (2′-ester carbonyl), 168.2 (4, 6-HHDP-7), 167.1 (4′, 6′-
HHDP-7), 166.6 (3′-PH-7), 166.1 (5′-galloyl-7), 165.6 (5-
substituted galloyl-7), 165.4 (2, 3-BPH-7), 148.5 (5-substituted
galloyl-3), 147.3, 146.4, 145.2, 144.9, 144.46, 144.34, 143.6 (4,
6-HHDP-4, 4′, 6, 6′; 4′, 6′-HHDP-4, 4′, 6, 6′; 3′-PH-4, 6;
5-substituted galloyl-4, 5; BPH-4, 4′, 6, 6′), 145.7 (5′-galloyl-3,
5), 139.3 (5′-galloyl-4), 138.84, 136.81, 136.6, 136.4, 135.7,
135.5, 134.8 (4, 6-HHDP-5, 5′; 4′, 6′-HHDP-5, 5′; 3′-PH-5, BPH-
5, 5′), 127.44, 127.36, 126.1, 125.9, 125.5, 124.6 (4, 6-HHDP-
2, 2′; 4′, 6′-HHDP-2, 2′; 3′-PH-2, BPH-2′), 124.1 (5-substituted
galloyl-2), 120.46, 120.43 (5′-galloyl-1; 2, 3-BPH-2), 117.0,
116.7, 116.2, 116.1, 115.7, 115.6, 115.0 (4, 6-HHDP-1, 1′; 4′,
6′-HHDP-1, 1′; BPH-1, 1′; 5-substituted galloyl-1), 116.7 (2,
3-BPH-3), 112.1 (5-substituted galloyl-6), 111.0 (3′-PH-1), 110.3
(5′-galloyl-2, 6), 109.0 (4′, 6′-HHDP-3), 108.7 (4, 6-HHDP-3),
108.4 (4′, 6′-HHDP-3′), 107.8 (3′-PH-3), 107.3 (4, 6-HHDP-3′),
104.8 (2, 3-BPH-3′); CD (4.1 × 10-5M, EtOH) ∆ꢀ267 -23.3, ∆ꢀ236
58.8; anal. calcd for C81H52O50‚8H2O; C 49.40%; H 3.48%; found
C 49.49%, H 3.42%.
R h oip t elea n in
H
(1). tan amorphous powder; [R]15
D
-26.7°(c 0.4, MeOH); negative FABMS m/z 965 [M - H]-; 1H
NMR [500 MHz, (CD3)2CO + D2O] δ 7.20 (2H, s, galloyl), 6.91
(1H, s, 4, 6-HHDP-H-3), 6.60 (1H, s, 4, 6-HHDP-H-3′), 6.43
(1H, s, PH-3). 13C NMR [125 MHz, (CD3)2CO+D2O] δ 169.1
(HHDP-7′), 168.8 [2C, HHDP-7, C-substituted galloyl (PH)-
7], 166.8 (galloyl-7), 163.2 (Cp-7), 146.3 (PH-6), 146.0 (galloyl-
3, 5), 145.7 (PH-4), 145.3 × 2, 144.8, 144.6 (HHDP-4, 4′, 6, 6′),
139.8 (galloyl-4), 136.8 (HHDP-5), 136.1 (HHDP-5′), 135.3 (PH-
5), 126.4, 125.1 (HHDP-2, 2′), 124.4 (PH-2), 120.2 (galloyl-1),
116.1 (HHDP-1), 115.5 (HHDP-1′), 110.5 (PH-1), 110.2 (galloyl-
2, 6), 108.5 (HHDP-3), 107.3, 107.2 (HHDP-3′, PH-3); CD (5.1
× 10-5M, EtOH) ∆ꢀ267 -10.9, ∆ꢀ239 31.7; anal. calcd for
C
42H30O27‚9/2 H2O, C 48.15%; H 3.75%. found: C 48.07%, H
3.67%.
R h oip t elea n in
I
(2): tan amorphous powder, [R]15
D
+22.8° (c 0.3, MeOH); negative FABMS m/z 1239 [M - H]-,
1H NMR [500 MHz, (CD3)2CO + D2O] δ 8.26 [1H, br d, J )
8.9 Hz, naphthalene unit (NP) H-5], 8.24 (1H, br d, J ) 9.3
Hz, NP-H-8), 7.47 (1H, dt, J ) 1, 9 Hz, NP-H-7), 7.41 (1H,
dt, J ) 1, 9 Hz, NP-H-6), 7.17 (2H, s, galloyl), 6.79 (1H, s,
NP-H-3), 6.77 (1H, s, HHDP-6), 6.60 [1H, s, C-substituted
HHDP (BPH)-6′], 6.59 (1H, s, HHDP-3′); 13C NMR [125 MHz,
(CD3)2CO + D2O] δ 169.4 (BPH-7′), 169.0 (HHDP-7′), 168.5
(HHDP-7), 168.0 (BPH-7), 166.1 (galloyl-7), 147.6 (NP-4), 145.9
(galloyl-3, 5, BPH-4′), 145.4 (NP-1), 145.1, 145.0 (HHDP-4, 4′),
145.9, 144.4, 144.3, 143.2, 143.1 (BPH-6, 6′; HHDP-6, 6′, BPH-
4), 139.2 (galloyl-4), 138.6 (BPH-5), 136.6 (HHDP-5), 135.97
(HHDP-5′), 135.7 (BPH-5′), 127.4, 126.7 (HHDP-2, 2′, NP-9,
10), 126.3 (NP-7), 126.0 (NP-6), 124.7 (BPH-2′), 123.5 (NP-2),
122.9 (NP-5), 122.2 (NP-8), 120.8, 120.6 (BPH-2, galloyl-1),
119.3 (BPH-3), 116.5 (BPH-1′), 115.7 (BPH-1), 115.6 (HHDP-
1), 115.2 (HHDP-1′), 111.9 (NP-3), 110.0 (galloyl-2, -6), 108.5
(HHDP-3), 107.1 (HHDP-3′), 105.95 (BPH-3′); CD (2.1 ×
10-5M, EtOH) ∆ꢀ264 -13.0, ∆ꢀ237 44.8; anal. calcd for C57H44O32‚
4H2O, C 52.14%; H 3.99; found: C 52.00%, H 4.00%.
P a r tia l Hyd r olysis of 3. A solution of 3 (1 mg) in H2O (1
mL) was heated (80 °C) for 48 h. HPLC analysis of the mixture
showed a peak at tR 10.1 min, which corresponded to 7.
Ack n ow led gm en t. The authors are grateful to Dr. T.
Fujioka and Dr. K. Mihashi for MS measurement of rhoipte-
leanin J . This work was supported by a Grant-in-Aid for
Scientific Research (no. 07672273) from the Ministry of Educa-
tion, Science, Sports and Culture of J apan.
Refer en ces a n d Notes
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219-224.
Meth yla tion of 2. A mixture of 2 (50 mg), Me2SO4 (2.0 mL),
and anhydrous K2CO3 (2.0 g) in dry Me2CO (20 mL) was
heated under reflux for 5 h. The inorganic material was
removed by filtration, and the filtrate, after concentration, was
applied to a Si gel column. Elution with C6H6-Me2CO (95:5)
yielded the hexadecamethylate 2a (38 mg) as a white amor-
(4) J iang, Z.; Tanaka, T.; Kouno, I. Phytochemistry 1995, 40, 1223-1226.
(5) J iang, Z.; Tanaka, T.; Kouno, I. J . Chem. Soc., Chem. Commun. 1995,
1467-1468.
(6) Tanaka, T.; J iang, Z.; Kouno, I. Chem. Pharm. Bull. 1997, 45, 1915s
1921.
(7) J iang, Z.; Tanaka, T.; Hirata, H.; Fukuoka, R.; Kouno, I. Phytochem-
istry 1996, 43, 1049-1054.
phous powder; [R]15 +14.2° (c 0.3, CHCl3); positive FABMS
D
(8) J iang, Z.; Tanaka, T.; Hirata, H.; Fukuoka, R.; Kouno, I. Tetrahedron
1997, 53, 16999-17008.
m/z: 1487 [M + Na]+, 1465 (M + H)+; 1H NMR [300 MHz,
CDCl3] δ 7.88, 8.17 (each 1H, d, J ) 9 Hz, NP-H-5, 8), 7.24,
7.36 (each 1H, t, J ) 9 Hz, NP-H-6, 7), 7.34 (2H, s, galloyl-
H), 6.93, 6.71, 6.64, 6.60 (each 1H, s), 5.79 (1H, dd, J ) 2, 9
Hz, H-4), 5.46 (1H, dd, J ) 3, 9 Hz, H-5), 5.08 (1H, d, J ) 2
Hz, H-3), 5.02 (1H, s, H-2), 4.95 (1H, dd, J ) 3, 14 Hz, H-6),
4.83 (1H, s, H-1), 4.75 (1H, d, J ) 8 Hz, glucopyranose H-1),
4.22 (1H, d, J ) 14 Hz, H-6), 4.12, 3.99 (×3), 3.95 (×2), 3.93
(×2), 3.90, 3.87, 3.85, 3.69, 3.64, 3.61, 3.46, 3.44 (each s, total
16 CH3).
(9) Hutschinson, J . The Families of Flowering Plants, 2nd ed.; Claren-
don: Oxford, 1959.
(10) Haslam, E.; Cai, Y. Nat. Prod. Rep. 1994, 11, 41-65.
(11) Okuda, T.; Yoshida, T.; Ashida, M.; Yazaki, K. J . Chem. Soc., Perkin
Trans. 1 1982, 1765-1772.
(12) Nonaka, G.; Sakai, T.; Tanaka, T.; Mihashi, K.; Nishioka, I. Chem.
Pharm. Bull. 1990, 38, 2151-2156.
(13) Nishizawa, M.; Yamagishi, T.; Nonaka, G.; Nishioka, I. J . Chem. Soc.,
Perkin Trans. 1 1982, 2963-2968.
(14) Nonaka, G.; Ishimaru, K.; Azuma, R.; Ishimatsu, M.; Nishioka, I.
Chem. Pharm. Bull. 1989, 37, 2071-2077.
(15) Schmidt. O. T.; Wu¨rtele, L.; Harreus, A. J ustus Liebigs Ann. Chem.
1965, 690, 150-162
Meth a n olysis of 2a . Compound 2a (33 mg) was treated
with 2% sodium methoxide in MeOH (5 mL) at room temper-
ature for 6 days. The mixture was neutralized with Amberlite
IR120B (H+ form) and, after concentration, separated by Si
gel column chromatography with C6H6-Me2CO (97:3-91:9,
v/v) and then CHCl3-MeOH-H2O (9:1:0.1-8:2:0.2, v/v) to
yield methyl trimethoxybenzoate (2b) (3 mg), dimethyl (S)-
hexamethoxydiphenate (2c) (5 mg) [R]15D -32.5° (c 0.3, CHCl3),
and 2d (2.4 mg). Compound 2d : a white amorphous powder,
(16) Nonaka, G.; Sakai, T.; Mihashi, K.; Nishioka, I. Chem. Pharm. Bull.
1991, 39, 884-888.
(17) Bate-Smith, E. C. Phytochemistry 1972, 11, 1153-1156.
(18) Okuda, T.; Yoshida, T.; Hatano, T.; Koga, T.; Tho, N. Tetrahedron
Lett. 1982, 23, 3937-3940.
(19) Nonaka, G.; Nishimura, H.; Nishioka, I. J . Chem. Soc., Perkin Trans.
1 1985, 163-168.
(20) Ikeya, Y.; Taguchi, H.; Yoshioka, I.; Kobayashi, H. Chem. Pharm.
Bull. 1979, 27, 1383-1394.
(21) Tanaka, T.; Kirihara, S.; Nonaka, G.; Nishioka, I. Chem. Pharm. Bull.
1993, 41, 1708-1716.
[R]15 +69.9° (c 0.2, MeOH); positive FABMS m/z 939 [M +
D
1
Na]+; H NMR [300 MHz, CDCl3 + CD3OD (8:1)] δ 8.30, 8.09
(22) Ishimaru, K.; Nonaka, G.; Nishioka, I. Chem. Pharm. Bull. 1987, 35,
602-610.
(each 1H, d, J ) 9 Hz, NP-H-5, 8), 7.56, 7.48 (each 1H, t, J )
9 Hz, NP-H-6, 7), 7.42 (1H, s), 6.62 (1H, s, NP-H-3), 5.32
(1H, d, J ) 1 Hz, H-1), 4.90 (1H, d, J ) 8 Hz, glucopyranose
H-1), 4.74 (1H, dd, J ) 1, 7 Hz, H-2), 4.10, 4.03, 3.97, 3.96,
3.84, 3.72, 3.64, 3.60 (each 3H, s, OCH3).
(23) Tanaka, T.; Ishida, N.; Ishimatsu, M.; Nonaka, G.; Nishioka, I. Chem.
Pharm. Bull. 1992, 40, 2092-2098.
(24) Lin, T. C.; Tanaka, T.; Nonaka, G.; Nishioka, I.; Young, T. J . Chem.
Pharm. Bull. 1991, 39, 1144-1147.
(25) Han, L.; Hatano, T.; Yoshida, T.; Okuda, T. Chem. Pharm. Bull. 1994,
42, 1399-1409.
R h oip t elea n in
J
(3): tan amorphous powder, [R]15
D
-29.0° (c 0.2, MeOH); negative FABMS m/z 1823 [M - H]-;
NP980361G