Novel flavonoids in dragon's blood of Daemonorops draco

Article abstract of DOI:10.1002/hlca.200900086

The three novel methylene bis[flavonoids] 1 - 3, the novel 2-flavene 4, the new naturally occurring flavan 5, and the new retro-dihydrochalcone 6 were isolated from dragon's blood of Daemonorops draco, together with seven known compounds. The structures w

Full text of DOI:10.1002/hlca.200900086

Helvetica Chimica Acta – Vol. 92 (2009)
1999
Novel Flavonoids in Dragonꢀs Blood of Daemonorops draco
by Ken-ichi Nakashima, Naohito Abe, Fumiko Kamiya, Tetsuro Ito, Masayoshi Oyama, and
Munekazu Iinuma*
Laboratory of Pharmacognosy, Department of Bioactive Molecules, Gifu Pharmaceutical University,
5-6-1 Mitahora-higashi, Gifu 502-8585, Japan
(phone: þ 81-58-2373931; fax: þ 81-58-2375979; e-mail: iinuma@gifu-pu.ac.jp).
The three novel methylene bis[flavonoids] 1 – 3, the novel 2-flavene 4, the new naturally occurring
flavan 5, and the new retro-dihydrochalcone 6 were isolated from dragonꢀs blood of Daemonorops draco,
together with seven known compounds. The structures were elucidated by extensive 1D- and 2D-NMR
spectroscopic analysis.
Introduction. – ꢁDragonꢀs bloodꢀ is a common name of a red resin obtained from
different genera such as Daemonorops (Arecaceae), Dracaena (Agavaceae), Pter-
ocarpus (Leguminosae), and Croton (Euphorbiaceae). Each generous plant produces
red pigments of dracorhodin [1], dracoflavylium [2], santalin A [3], and procyanidin B1
[4], respectively, which unequivocally identify the original source of the resin.
Chemical constituents of the dragonꢀs blood derived from Daemonorops draco
have particularly been studied to disclose the presence of novel secobiflavonoids [5],
secotriflavonoids [6], and the precursors of the complex flavonoids, C-methylated
flavans and/or chalcones. Pharmacological studies on the resin obtained from D. draco
have so far revealed its antimicrobial [7], antiplatelet [8], and apoptotic activities [9].
In our successive research of the phytochemicals in secretes, we have isolated
secobiflavonoids in farinose exudate of Pentagramma triangularis [10] and kamala-
chalcones in glandular hair of Mallotus philippensis [11], and the chemical constituents
in the red resin originated from D. draco were investigated. Herein, the structures of
three novel secobiflavonoids, daemonorols A – C1) (1 – 3), a novel 2-flavene, daemo-
norol D1) (4), a new naturally occurring flavan, daemonorol E1) (5), a new retro-
dihydrochalcone, daemonorol F1) (6), and the seven known compounds 7 – 13 are
discussed (Fig. 1).
Results and Discussion. – All compounds 1 – 13 were isolated from the acetone
extract of Daemonorops draco resin by repeated column chromatography (CC),
vacuum liquid chromatography (VLC), and prep. TLC.
Daemonorol A (1) was obtained as a colorless, optically active solid. It exhibited a
UV absorption at 277 nm. The molecular formula was established as C33H32O6 by HR-
1
EI-MS showing Mþ at m/z 524.2207. The H-NMR spectrum (Table 1) showed typical
1
)
Trivial atom numbering; for systematic names, see Exper. Part.
ꢂ 2009 Verlag Helvetica Chimica Acta AG, Zꢃrich

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Helvetica Chimica Acta – Vol. 92 (2009)
Fig. 1. Compounds1) isolated from the resin of Daemonorops draco
signals for five H-atoms at d(H) 5.12 (dd, J ¼ 10.4, 2.0 Hz, 1 H), 2.04 – 2.23 (m, 2 H),
2.73 (ddd, J ¼ 17.0, 5.8, 3.4 Hz, 1 H), and 2.62 (ddd, J ¼ 17.0, 10.8, 6.2 Hz, 1 H) which
were assignable to HꢀC(2), CH2(3), and CH2(4) of a flavan skeleton. Furthermore, a
Ph group (d(H) 7.47 (br. d, J ¼ 7.8 Hz, 2 H), 7.42 (br. t, J ¼ 7.8 Hz, 2 H), and 7.35 (dt, J ¼
7.8, 1.6 Hz, 1 H)) and an additional aromatic H-atom (d(H) 6.06 (s)) were observed, as
well as a MeO group (d(H) 3.70 (s)) and an OH group (d(H) 7.71 (s)). A fragment ion
at m/z 104, caused by retro-Diels – Alder fragmentation, was attributed to
C6H5ꢀCH¼CHþ2 and demonstrated that 1 had an unsubstituted ring B. Thus, the
MeO group and the OH group were supposed to be at ring A. The location of the MeO
group was determined to be C(5) by the HMBCs between CH2(4) at d(H) 2.62 and 2.73
and C(5) at d(C) 156.8, and between MeO at d(H) 3.70 and C(5). Then, the OH group
was estimated to be at C(7). In the HMQC spectrum, a remaining signal at d(H) 3.77 (s,
2 H) was correlated with a signal at d(C) 15.9 attributable to a CH2 group, which was
established by the DEPT spectrum. These findings suggested that the molecule consists
of two equivalent flavan moieties connected symmetrically through the CH2 group. The
CH2-bridge H-atoms at d(H) 3.77 were coupled with C(7) at d(C) 154.7 and C(9) at
151.6, in the HMBC spectrum, which demonstrated that the flavan moieties were
connected at C(8) and C(8’’). Consequently, the structure of daemonorol A (1) was
determined as 8,8’-methylenebis[3,4-dihydro-5-methoxy-2-phenyl-2H-1-benzopyran-
7-ol].
Daemonorol B (2), a colorless, optically active solid, exhibited an absorption at
281 nm in the UV spectrum. The molecular formula was determined to be C33H32O6 by

Helvetica Chimica Acta – Vol. 92 (2009)
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Table 1. 1H- and 13C-NMR Spectral Data of 11)a). d in ppm, J in Hz.
d(H)
d(C) HMBC
HꢀC(2,2’’)
CH2(3,3’’)
CH2(4,4’’)
5.12 (dd, J ¼ 10.4, 2.0)
2.04 – 2.23 (m)
79.3 C(4,4’’), C(1’,1’’’), C(2’,2’’’), C(6’,6’’’)
29.1 C(2,2’’), C(4,4’’), C(10,10’’), C(1’,1’’’)
2.62 (ddd, J ¼ 17.0, 10.8, 6.2), 19.2 C(2,2’’), C(3,3’’), C(5,5’’), C(9,9’’), C(10,10’’)
2.73 (ddd, J ¼ 17.0, 5.8, 3.4)
6.06 (s)
C(2,2’’), C(3,3’’), C(5,5’’), C(9,9’’), C(10,10’’)
C(5,5’’)
156.8
HꢀC(6,6’’)
93.0 C(7,7’’), C(8,8’’), C(10,10’’)
154.7
C(7,7’’)
C(8,8’’)
105.6
C(9,9’’)
151.6
C(10,10’’)
C(1’,1’’’)
102.6
140.3
HꢀC(2’,6’,2’’’,6’’’) 7.47 (br. d, J ¼ 7.8)
126.3 C(2,2’’), C(4’,4’’’)
128.7 C(3’,5’, 3’’’,5’’’), C(1’,1’’’)
128.4 C(2’,6’, 2’’’,6’’’)
15.9 C(7,7’’), C(8,8’’), C(9,9’’)
55.4 C(5,5’’)
HꢀC(3’,5’,3’’’,5’’’) 7.42 (br. t, J ¼ 7.8)
HꢀC(4’,4’’’)
ArꢀCH2ꢀAr
MeOꢀC(5,5’’)
OHꢀC(7,7’’)
7.35 (dt, J ¼ 7.8, 1.6)
3.77 (s)
3.70 (s)
7.71 (s)
C(6,6’’), C(7,7’’), C(8,8’’)
a) Measured in CDCl3 at 400 (1H) and 100 MHz (13C).
HR-EI-MS (Mþ at m/z 524.2205). The 1H-NMR spectrum (Table 2) showed two series
of H-atoms assignable to HꢀC(2,2’’), CH2(3,3’’), and CH2(4,4’’) of the flavan moieties
at d(H) 5.14 (dd, J ¼ 10.2, 2.2 Hz, 1 H), 4.97 (dd, J ¼ 10.6, 2.2 Hz, 1 H), 2.71 – 2.80 (m,
3 H), 2.62 (ddd, J ¼ 17.1, 10.7, 6.1 Hz, 1 H), 2.03 – 2.27 (m, 3 H), and 1.85 – 2.02 (m,
1 H). The spectrum also revealed two unsubstituted B rings (d(H) 7.34 – 7.36 (m, 2 H),
7.33 – 7.34 (m, 2 H), 7.27 – 7.29 (m, 1 H), 7.45 (br. d, J ¼ 7.6 Hz, 2 H), 7.39 – 7.42 (m,
3 H)), two additional aromatic H-atoms of the A rings (d(H) 6.24 and 6.11 (2s)), two
MeO groups (d(H) 3.90 and 3.73 (2s)) and two OH groups (d(H) 8.26 and 7.56 (2s)). In
the case of 2, the CH2-bridge H-atoms were observed individually at d(H) 3.80 and 3.67
(d, J ¼ 15.6 Hz, each 1 H). By considering the above segments, 2 was predicted to be an
isomer of 1. The 5-methoxylated flavan moieties were deduced by the HMBCs between
the MeO group at d(H) 3.90 and C(5) at d(C) 154.7, and between the other MeO group
at d(H) 3.73 and C(5’’) at d(C) 157.0 (Fig. 2). The interlinkage between C(6) and C(8’’)
through the CH2 bridge was established by the essential correlations from the CH2 H-
atoms at d(H) 3.67 and 3.80 to C(5) and/or C(7’’) at d(C) 154.7, C(7) at d(C) 154.9, and
C(9’’) at d(C) 151.3. As a MeO group resonates at a lower field when both ortho-
positions are substituted, the downfield shift of MeOꢀC(5) (d(C) 61.5) corroborated
the idea that the CH2 group was connected to C(6). Thus, the structure of daemonorol
B (2) was determined as 6,8’-methylenebis[3,4-dihydro-5-methoxy-2-phenyl-2H-1-
benzopyran-7-ol], the constitutional isomer of 1.
Daemonorol C (3), a colorless, optically active solid, showed a UV absorption at
273 nm. The HR-EI-MS allowed to assign the molecular formula C34H34O6 (Mþ at m/z
1
538.2362). The H-NMR spectrum (Table 2) suggested the presence of two flavan
moieties with unsubstituted B rings, two MeO groups (d(H) 3.64 and 3.70 (2s)), two
OH groups (d(H) 7.70 and 7.79 (2s)), a Me group attached to an aromatic ring (d(H)

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Helvetica Chimica Acta – Vol. 92 (2009)
Table 2. 1H- and 13C-NMR Spectral Data of 2 and 3a). d in ppm, J in Hz.
21)
31)
d(H)
d(C)
d(H)
d(C)
HꢀC(2)
CH2(3)
CH2(4)
C(5)
C(6)
C(7)
4.97 (dd, J ¼ 10.6, 2.2)
1.85 – 2.02 (m), 2.03 – 2.27 (m)
2.71 – 2.80 (m)
77.6
29.6
19.9
5.19 (dd, J ¼ 9.7, 2.2)
2.09 – 2.24 (m)
2.72 – 2.88 (m)
79.2
29.1
18.9
154.7
111.3
154.9
101.5
154.4
106.7
141.6
125.9
128.5
128.4
79.3
155.6
111.5
153.0
109.0
149.2
106.8
140.3
126.3b)
128.7c)
128.4
79.3
HꢀC(8) or C(8)
6.24 (s)
C(9)
C(10)
C(1’)
HꢀC(2’,6’)
HꢀC(3’,5’)
HꢀC(4’)
HꢀC(2’’)
CH2(3’’)
CH2(4’’)
7.33 – 7.34 (m)
7.34 – 7.36 (m)
7.27 – 7.29 (m)
7.44 – 7.46 (m)
7.40 – 7.44 (m)
7.34 – 7.38 (m)
5.14 (dd, J ¼ 10.2, 2.2)
2.09 – 2.24 (m)
2.58 – 2.73 (m)
5.14 (dd, J ¼ 10.2, 2.2)
2.03 – 2.27 (m)
29.1
19.1
28.9
19.8
2.62 (ddd, J ¼ 17.1, 10.7, 6.1),
2.71 – 2.80 (m)
C(5’’)
157.0
93.3
156.8
92.9
HꢀC(6’’)
6.11 (s)
6.07 (s)
C(7’’)
154.7
105.3
151.3
102.8
140.3
126.2
128.7
127.8
16.9
154.8
105.2
151.6
102.6
140.4
126.3b)
128.7c)
128.3
16.3
C(8’’)
C(9’’)
C(10’’)
C(1’’’)
HꢀC(2’’’,6’’’)
HꢀC(3’’’,5’’’)
HꢀC(4’’’)
ArꢀCH2ꢀAr
MeOꢀC(5)
MeꢀC(6)
OHꢀC(7)
MeOꢀC(5’’)
OHꢀC(7’’)
7.45 (br. d, J ¼ 7.6)
7.39 – 7.42 (m)
7.39 – 7.42 (m)
7.41 – 7.42 (m)
7.40 – 7.44 (m)
7.34 – 7.38 (m)
3.80 (s)
3.64 (s)
2.03 (s)
7.70 (s)
3.70 (s)
7.79 (s)
3.67 (d, J ¼ 15.6), 3.80 (d, J ¼ 15.6)
3.90 (s)
61.5
59.9
8.9
7.56 (s)
3.73 (s)
8.26 (s)
55.4
55.3
a) Measured in CDCl3 at 400 (1H) and 100 MHz (13C). b)c) Overlapped signals.
2.03 (s)), an aromatic H-atom (d(H) 6.07 (s)), and a CH2 bridge (d(H) 3.80 (s)). The
MeOꢀC(5) substitution was confirmed by the HMBCs between CH2(4) at d(H) 2.72 –
2.88 and C(5) at d(C) 155.6, and between MeO at d(H) 3.64 and C(5) (Fig. 3). The
MeOꢀC(5’’) substitution was determined by the HMBCs between CH2(4’’) at d(H)
2.58 – 2.73 and C(5’’) at d(C) 156.8, and between MeO at d(H) 3.70 and C(5’’). The
C(5) atom was also coupled with the aromatic Me group, which substantiated that the
Me group was at C(6). Therefore, the CH2 bridge was supposed to be at C(8). The
cross-link between C(8) and C(8’’) through the CH2 bridge was established by the
HMBCs from the CH2 group at d(H) 3.80 to C(7) at d(C) 153.0, C(9) at d(C) 149.2,
C(7’’) at d(C) 154.8, and C(9’’) at d(C) 151.6. The structure of 3 was accordingly

Helvetica Chimica Acta – Vol. 92 (2009)
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Fig. 2. HMBCs (H ! C) observed in 21)
Fig. 3. HMBCs (H ! C) observed in 31)
established to be 8-[(3,4-dihydro-7-hydroxy-5-methoxy-2-phenyl-2H-1-benzopyran-8-
yl)methyl]-3,4-dihydro-5-methoxy-6-methyl-2-phenyl-2H-1-benzopyran-7-ol.
Arnone et al. [6] have determined the configuration at C(2) of the monomeric
flavans based on the CD spectrum. The CD spectra of 1 – 3, however, showed no
obvious Cotton effects. This result may be attributed to the chirality of the whole
molecules. The absolute configurations at C(2) and C(2’’) were tentatively assigned to
be (S), judging from the fact that only (2S)-flavans have been reported from the resin
of D. draco as well as from the (2S) configuration of 8 and 9 (see below).
Daemonorol D (4), a red solid, had the molecular formula C17H16O3 (Mþ at m/z
1
268.1107). The H-NMR spectrum (Table 3) suggested the presence of a Ph group
(d(H) 7.64 (br. d, J ¼ 8.0 Hz, 2 H), 7.37 (br. t, J ¼ 8.0 Hz, 2 H), and 7.32 (br. t, J ¼ 8.0 Hz,
1 H)), an aromatic H-atom at d(H) 6.33 (s), a MeO group at d(H) 3.72 (s), an OH

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Table 3. 1H- and 13C-NMR Spectral Data of 4a) and 5b). d in ppm, J in Hz.
41)
51)
d(H)
d(C)
d(H)
d(C)
C(2) or HꢀC(2)
HꢀC(3) or CH2(3)
CH2(4)
148.6
96.4
19.9
4.87 (dd, J ¼ 2.4, 10.0)
78.0
30.2
20.0
159.5
96.7
157.7d)
92.2
157.4
102.7
133.9
128.2
115.9
157.8d)
55.6
5.51 (t, J ¼ 4.0)
3.48 (d, J ¼ 4.0)
1.86 – 1.98 (m), 2.04 – 2.15 (m)
2.53 – 2.61 (m), 2.61 – 2.69 (m)
C(5)
156.9
112.0
153.5
99.4
150.7
106.0
134.5
124.4
128.3c)
128.3c)
60.2
C(6) or HꢀC(6)
6.05 (d, J ¼ 2.2)
5.97 (d, J ¼ 2.2)
C(7)
HꢀC(8)
6.33 (s)
C(9)
C(10)
C(1’)
HꢀC(2’,6’)
HꢀC(3’,5’)
HꢀC(4’) or C(4’)
MeOꢀC(5)
MeꢀC(6)
OHꢀC(7)
OHꢀC(4’)
7.64 (br. d, J ¼ 8.0)
7.37 (br. t, J ¼ 8.0)
7.32 (br. t, J ¼ 8.0)
3.72 (s)
2.14 (s)
4.88 (br. s)
7.26 (d, J ¼ 8.4)
6.84 (d, J ¼ 8.4)
3.75 (s)
8.5
8.13 (br. s)
8.34 (br. s)
b
a) Measured in CDCl3 at 400 (1H) and 100 MHz (13C). ) Measured in (D6)acetone at 400 (1H) and
100 MHz (13C). c) Overlapping signals. d) Interchangeable signals.
group at d(H) 4.88 (br. s), an aromatic Me group at d(H) 2.14 (s), a CH2 group at d(H)
3.48 (d, J ¼ 4.0 Hz), and a vicinal olefin H-atom at d(H) 5.51 (t, J ¼ 4.0 Hz). The
olefinic HꢀC(3) showed essential HMBCs (Fig. 4) with C(1’) at d(C) 134.5 and C(10)
at d(C) 106.0, which suggested that 4 was a 2-flavene derivative. The 7-hydroxy-5-
methoxy-6-methyl substitution at the A ring was established by the following HMBCs:
CH2(4)/C(5), MeOꢀC(5)/C(5), MeꢀC(6)/C(5), and MeꢀC(6)/C(7). Therefore, the
structure of 4 was determined as 5-methoxy-6-methyl-2-flaven-7-ol. The reduction with
Pd/C and H2 gas produced a known compound, (2S)-5-methoxy-6-methylflavan-7-ol
(9), which certified the unusual flavonoid framework of 4.
Fig. 4. HMBCs (H ! C) observed in 41)
Daemonorol E (5), a colorless, weakly optically active solid, had a molecular
1
formula C17H18O4 as deduced by HR-EI-MS (Mþ at m/z 272.1044). In the H-NMR
spectrum (Table 3), a dd at d(H) 4.87 (dd, J ¼ 10.0, 2.4 Hz, 1 H) and four m (each 1 H)
ranging from d(H) 1.86 to 2.69 were preferably assigned to HꢀC(2), CH2(3), and

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CH2(4) of a flavan skeleton. A 4-oxygenated Ph group, appearing characteristically, at
d(H) 7.26 and 6.84 (d, J ¼ 8.4 Hz, each 2 H), existed in the molecule. Besides the m-
coupled H-atoms at d(H) 6.05 and 5.97 (d, J ¼ 2.2 Hz), a MeO group at d(H) 3.75 (s),
and two OH groups at d(H) 8.34 and 8.13 (2 br. s) were observed. Two significant
fragments at m/z 153 and 120 caused by a retro-Diels – Alder cleavage in the EI-MS
indicated that one of the OH groups and a MeO group had to be positioned at the A
ring, and the other OH group at the B ring. Therefore, the B ring moiety was a 4’-
hydroxyphenyl substituent. The location of the MeO group was confirmed to be at C(5)
by the essential HMBCs CH2(4)/C(5) and MeO/C(5) (Fig. 5). The structure of 5 was
consequently determined to be 4’-hydroxy-5-methoxyflavan-7-ol. The absolute config-
uration at C(2) of 5 was determined to be (S) since a negative Cotton effect (De ꢀ 0.93)
was observed at 281 nm in the CD spectrum [12].
Fig. 5. HMBCs (H ! C) observed in 51)
Daemonorol F (6), a colorless solid, showed the Mþ at m/z 286.1211 in the HR-EI-
MS and was assigned the molecular formula C17H18O4. The 1H-NMR spectrum (Table 4)
exhibited a pair of mutually coupled H-atoms at d(H) 3.39 (br. t, J ¼ 6.0 Hz, 2 H) and
Table 4. 1H- and 13C-NMR Spectral Data of 61)a). d in ppm, J in Hz.
d(H)
d(C)
HMBC
C(1)
C(2)
C(3)
C(4)
109.3
155.0
105.0
154.2
92.1
157.3
137.0
129.4
129.3
134.6
40.1
HꢀC(5)
6.02 (s)
C(1), C(3), C(4), C(6)
C(6)
C(1’)
HꢀC(2’,6’)
HꢀC(3’,5’)
HꢀC(4’)
CH2(a)
CH2(b)
C¼O
7.97 (br. d, J ¼ 8.0)
7.43 (br. t, J ¼ 8.0)
7.55 (br. t, J ¼ 8.0)
3.39 (br. t, J ¼ 6.0)
2.95 (br. t, J ¼ 6.0)
C(2’,6’), C(4’), C¼O
C(3’,5’), C(1’)
C(2’,6’)
C(1), C¼O, C(b)
17.7
204.5
C(1), C(2), C(6), C¼O, C(a)
OHꢀC(2)
MeꢀC(3)
OHꢀC(4)
MeOꢀC(6)
8.70 (s)
2.12 (s)
4.85 (s)
3.75 (s)
C(1), C(2), C(3)
C(2), C(3), C(4)
C(3), C(4), C(5)
C(6)
8.9
56.3
a) Measured in CDCl3 at 400 (1H) and 100 MHz (13C).

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2.95 (br. t, J ¼ 6.0 Hz, 2 H), assignable to the CH2(a) and CH2(b) groups of a
dihydrochalcone skeleton. A Ph group (d(H) 7.97 (br. d, J ¼ 8.0 Hz, 2 H), 7.43 (br. t,
J ¼ 8.0 Hz, 2 H), and 7.55 (br. t, J ¼ 8.0 Hz, 1 H)), an aromatic H-atom (d(H) 6.02 (s)),
a MeO group (d(H) 3.75 (s)), two OH groups (d(H) 8.70 and 4.85 (2s), and an
aromatic Me group (d(H) 2.12 (s)) were also present. In the HMBC spectrum, the
aromatic H-atoms at d(H) 7.97 were correlated with a C¼O group at d(C) 204.5, which
indicated that 3 is a retro-dihydrochalcone derivative. The CH2(b) H-atoms were
correlated with C(2) at d(C) 155.0 and C(6) at 157.3. The latter C-atom had a
correlation with the MeO H-atoms. Thus, a 2,4-dihydroxy-6-methoxy substitution in the
second ring derived from the malonate pathway was demonstrated. The location of the
aromatic Me group at C(3) was confirmed by the HMBCs Me/C(4) and C(2). Finally,
the structure of 6 was determined to be a,b-dihydro-2,4-dihydroxy-6-methoxy-3-
methylchalcone.
The other, known compounds were characterized as a,b-dihydro-4,6-dihydroxy-2-
methoxy-3-methylchalcone (7) [13], (2S)-5-methoxyflavan-7-ol (8) [14], (2S)-5-
methoxy-6-methylflavan-7-ol (9) [14], and dracoflavans B1 (10), B2 (11), C1 (12),
and C2 (13) [15] by comparison of the spectral data with the literature values.
Compounds 10/11 and 12/13 were obtained as racemates of the two corresponding
isomers.
The present study revealed the following new findings. The occurrence of
secobiflavonoids is very limited in nature being present only in Pentagramma
triangularis [10], Bosistoa brassii [16], and Blutaparon portulacoides [17]. To the best
of our knowledge, daemonorols A – C (1 – 3) are the first compounds composed of two
flavan units and cross-linked through a CH2 group. The framework of a 2-flavene (¼2-
phenyl-4H-1-benzopyran) in daemonorol D (4) is the first observation as a natural
product, although the synthesis of 4 has been reported in [18]. Daemonorol E (5) has
been previously synthesized [19]; however, this is the first report of its isolation from a
natural source and of its detailed spectral data. Daemonorol F (6) is an isomer of 7,
suggesting that 8-methylated flavans were plausible precursors of 1 – 3.
Experimental Part
General. Column chromatography (CC): silica gel 60 (SiO2; 70 – 230 mesh; Merck), Chromatorex
DMS (100 – 200 mesh; Fuji Silysia Chemicals), or Sephadex LH-20 (GE Healthcare Bio-sciences).
Vacuum liquid chromatography (VLC): SiO2 60 H (Merck). TLC: SiO2 60 F254 and SiO2 RP-18 F254S
(both Merck). Optical rotation: Jasco-P-1020 polarimeter. CD Spectra: Jasco-J-820P spectropolarim-
eter; lext (De) in nm; at 258. UV Spectra: Shimadzu-UV-3100 spectrophotometer; lmax (log e) in nm.
NMR Spectra: Jeol-JNM-AL-400 spectrometer equipped with field-gradient system; d in ppm rel. to
Me4Si; J in Hz. MS: Jeol-JMS-DX-300 spectrometer; in m/z (rel. %).
Plant Material. The resin of Daemonorops draco (270 g) was purchased from Matsuura Yakugyo
(Nagoya; Japan) in 2006. A voucher specimen was deposited with the Gifu Pharmaceutical University,
Gifu, Japan.
Extraction and Isolation. The resin was thoroughly dissolved in acetone. The filtered soln. was
concentrated to yield an extract (252 g), part of which (250 g) was subjected to CC (SiO2, hexane/
AcOEt, finally acetone): Fractions A – F. Frs. A (with hexane/AcOEt 10 :1), D (with hexane/AcOEt
3 :1), and F (with acetone) were not further separated. Fr. B (with hexane/AcOEt 8 :1) was separated by
CC (Chromatorex DMS, MeOH/H2O 2 :3 ! 1:0). The resulting fractions abundant in flavonoids were
further purified by CC (Sephadex LH-20, MeOH) and VLC (SiO2, benzene): 1 (3.4 mg), 3 (2.3 mg), and

Helvetica Chimica Acta – Vol. 92 (2009)
2007
5 (49.0 mg). Fr. C (with hexane/AcOEt 5 :1) was separated by CC (Chromatorex DMS, MeOH/H2O
2 :3 ! 1:0). The resulting fractions were further purified by CC (Sephadex LH-20, MeOH) and VLC
(SiO2, hexane/benzene 5 :1 ! 1:1): 1 (230.6 mg), 2 (4.3 mg), 5 (18.7 mg), 8 (153.2 mg), and 9
(100.6 mg). Fr. E (with hexane/AcOEt 1:1) was separated by CC (Chromatorex DMS, MeOH/H2O
2 :3 ! 1:0). The fractions containing flavonoids were purified by CC (Sephadex LH-20, MeOH) and
VLC (SiO2, benzene/EtOH 40 :1 ! 1:1) and subsequently by prep. TLC (benzene/EtOH 20 :1): 4
(40.0 mg), 6 (32.2 mg), and 7 (48.0 mg) in pure forms, and 10/11 (21.7 mg) and 12/13 (23.7 mg) as
mixtures of the corresponding isomers. TLC: detection by 10% H2SO4 soln. made 1 – 4 orange, and, on
the contrary, 5 and 6 yellow.
Daemonorol A (¼ 8,8’-Methylenebis[3,4-dihydro]-5-methoxy-2-phenyl-2H-1-benzopyran-7-ol; 1):
Colorless solid. [a]2D5 ¼ ꢀ118 (c ¼ 0.1, CHCl3). UV (CHCl3): 277 (3.52). 1H- and 13C-NMR: Table 1.
EI-MS: 524 (56, Mþ), 505 (16), 420 (28), 401 (8), 316 (8), 269 (100), 256 (43), 165 (44), 104 (50). HR-EI-
MS: 524.2207 (Mþ, C33H32O6þ; calc. 524.2199).
Daemonorol B (¼6,8’-Methylenebis[3,4-dihydro]-5-methoxy-2-phenyl-2H-1-benzopyran-7-ol ¼ 6-
[(3,4-Dihydro-7-hydroxy-5-methoxy-2-phenyl-2H-1-benzopyran-8-yl)methyl]-3,4-dihydro-5-methoxy-2-
phenyl-2H-1-benzopyran-7-ol; 2): Colorless solid. [a]2D5 ¼ ꢀ116 (c ¼ 0.1, CHCl3). UV (CHCl3): 281
(3.63). 1H- and 13C-NMR: Table 2. EI-MS: 524 (37, Mþ), 420 (8), 401 (8), 269 (100), 256 (54), 165 (34),
104 (42). HR-EI-MS: 524.2205 (Mþ, C33H32O6þ ; calc. 524.2199).
Daemonorol C (¼ 8-[(3,4-Dihydro-7-hydroxy-5-methoxy-2-phenyl-2H-1-benzopyran-8-yl)methyl]-
3,4-dihydro-5-methoxy-2-phenyl-2H-1-benzopyran-7-ol; 3): Colorless solid. [a]2D5 ¼ ꢀ85 (c ¼ 0.1, CHCl3).
UV (CHCl3): 273 (3.82). 1H- and 13C-NMR: Table 2. EI-MS: 538 (80, Mþ), 434 (8), 282 (88), 269 (100),
256 (40), 179 (28), 165 (60), 152 (24), 104 (82). HR-EI-MS: 538.2362 (Mþ, C34H34O6þ ; calc. 538.2355).
Daemonorol D (¼ 5-Methoxy-6-methyl-2-phenyl-4H-1-benzopyran-7-ol; 4): Red solid. UV
(MeOH): 316 (3.07), 283 (3.65), 228 (4.26). 1H- and 13C-NMR: Table 3. EI-MS: 268 (100, Mþ), 252
(16), 237 (12), 191 (20). HR-EI-MS: 268.1107 (Mþ, C17H16O3þ ; calc. 268.1100).
Daemonorol E (¼(2S)-3,4-Dihydro-2-(4-hydroxyphenyl)-5-methoxy-2H-benzopyrane-7-ol; 5): Col-
orless solid. [a]2D5 ¼ ꢀ85 (c ¼ 0.1, MeOH). UV (MeOH): 281 (3.83), 230 (4.69). CD (c ¼ 0.01, MeOH):
281 (ꢀ0.93). 1H- and 13C-NMR: Table 3. EI-MS: 272 (100, Mþ), 153 (93), 120 (60). HR-EI-MS: 272.1044
(Mþ, C17H18Oþ4 ; calc. 272.1049).
Daemonorol F (¼ 3-(2,4-Dihydroxy-6-methoxy-3-methylphenyl)-1-phenylpropan-1-one; 6): Color-
1
less solid. UV (MeOH): 279 (3.16), 238 (3.98). H- and 13C-NMR: Table 4. EI-MS: 286 (60, Mþ), 267
(8), 256 (7), 167 (100), 154 (71), 137 (11), 105 (33), 77 (22). HR-EI-MS: 286.1211 (Mþ, C17H18O4þ ; calc.
286.1205).
Catalytic Hydrogenation of 4. A mixture of 4 (3.5 mg) and 5% Pd/C (7 mg) in EtOH (6 ml) was
stirred under H2 at r.t. overnight. The mixture was filtered, the filtrate concentrated, and the residue
purified by prep. TLC (benzene/AcOEt 10 :1): 1.0 mg of reduced product. The product was identified as
(2S)-5-methoxy-6-methylflavan-7-ol ( ¼ (2S)-3,4-dihydro-5-methoxy-6-methyl-2-phenyl-2H-1-benzopyr-
an-7-ol) by comparison with the 1H-NMR data and Rf value on TLC (benzene/AcOEt 10 :1) of 9.
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Received March 12, 2009