Synthesis of benzophenone glucopyranosides from phaleria macrocarpa and related benzophenone glucopyranosides

Article abstract of DOI:10.1271/bbb.90242

The first total syntheses of benzophenone glucopyranosides reported from Phaleria macrocarpa and related benzophenone glucopyranosides were successfully carried out. The alkoxy groups present ortho to the carbonyl group in polyalkoxybenzophenones were sel

Full text of DOI:10.1271/bbb.90242

Biosci. Biotechnol. Biochem., 73 (10), 2172–2182, 2009
Synthesis of Benzophenone Glucopyranosides from Phaleria macrocarpa
and Related Benzophenone Glucopyranosides
Phebe HENDRA, Yukiharu FUKUSHI,y and Yasuyuki HASHIDOKO
Division of Applied Bioscience, Graduate School of Agriculture, Hokkaido University,
Sapporo, Hokkaido 060-8589, Japan
Received April 3, 2009; Accepted June 16, 2009; Online Publication, October 7, 2009
[doi:10.1271/bbb.90242]
The first total syntheses of benzophenone glucopyr-
anosides reported from Phaleria macrocarpa and related
benzophenone glucopyranosides were successfully car-
ried out. The alkoxy groups present ortho to the carbonyl
group in polyalkoxybenzophenones were selectively
deprotected by AlCl3–PhNMe2 in high yields, leaving
other alkoxy groups unaffected. It was concluded in the
current synthetic study that all the reported benzophe-
none glucopyranosides possessed the same structure
as 2,40,6-trihydroxy-4-methoxybenzophenone 2-O-ꢀ-D-
glucopyranoside.
as constituents of P. macrocarpa, and of related benzo-
phenone glucopyranosides (5 and 6) for further inves-
tigation into the structure-activity relationship.
Results and Discussion
We chose the following reactions to synthesize the
benzophenone glucopyranosides: i) Friedel-Crafts acy-
lation for synthesis of the benzophenone skeleton and ii)
regioselective dealkylation of alkyl aryl ethers by
AlCl3–PhNMe2. Compound 1 was synthesized as shown
in Scheme 1. 3,4,40,5-Tetramethoxybenzophenone (8)
was prepared by the Friedel-Crafts acylation of anisole
with 3,4,5-trimethoxybenzoyl chloride (7),10) and sub-
sequent demethylation with boron tribromide at 0 ꢀC
gave 3,4,5-trihydroxy-40-methoxybenzophenone (9).11,12)
Protection of the hydroxyl groups at C-4 and C-5 in 9
by using such protection reagents as p-anisaldehyde
dimethyl acetal13) and benzylidene dichloride14) failed to
give the desired compound, but eventually the reaction
was successful by using benzaldehyde dimethyl acetal
in refluxed toluene to yield 10. Glucosylation of 10
with 2,3,4,6-tetra-O-acetyl-ꢀ-D-glucopyranosyl bromide
under a phase transfer-catalyzed condition15) afforded 11
as a 1:1 mixture of diastereomers. Deacetylation of 11 in
a mixture of MeOH/Et3N (3:1) gave diastereomers of
deacetylated glucopyranoside (12). Hydrogenolysis of
12 with palladium on charcoal as a catalyst in ethanol16)
led to 3,4,5-trihydroxy-40-methoxybenzophenone 3-O-
ꢀ-D-glucopyranoside (1).
A comparison of the NMR data for synthesized 1 with
those for phalerin1) showed they were different. In a
current report,3) another benzophenone glucopyranoside
(2) was isolated from the same plant, and the structure of
phalerin had been revised to that of 2. Compound 2 had
first been isolated from Gnidia involucrata (Thymelaea-
ceae).17) The [ꢁ]D value (þ4ꢀ in MeOH) for 2 from
P. macrocarpa,3) however, was an opposite sign to that
of originally reported 2 from G. involucrata with a [ꢁ]D
value of ꢁ23ꢀ in MeOH.17) We therefore prepared 2
(Scheme 2). 2,4,6-Trimethoxy-40-benzyloxybenzophe-
none (15) was obtained from 1,3,5-trimethoxybenzene
and 4-benzyloxybenzoic acid (14) by triflouroacetic
anhydride (TFAA) condensation.18) A combination
system of AlCl3–PhNMe2 was used to cleave the
benzyl, allyl and methyl ethers.19) We demonstrated
that selective ortho monodemethylation of 15 occurred
Key words: benzophenone glucopyranoside; Phaleria
macrocarpa; selective dealkylation; AlCl3–
PhNMe2
Phaleria macrocarpa (Scheff.) Boerl. [mahkota dewa
in Indonesian], which belongs to the family Thymelaea-
ceae, has been used for traditional medicine in Java
Island, Indonesia. The phytochemical analysis of this
plant has shown the presence of benzophenone gluco-
sides (Fig. 1), 3,4,5-trihydroxy-40-methoxybenzophe-
none 3-O-ꢀ-D-glucopyranoside (phalerin, proposed as
1),1) 2,40,6-trihydroxy-4-methoxybenzophenone 2-O-ꢀ-
D-glucopyranoside (2),2,3) 2,40,6-trihydroxy-4-methoxy-
benzophenone 2-O-ꢁ-D-glucopyranoside (3) reported by
Tambunan et al.,4) 2,4,40-trihydroxy-6-methoxybenzo-
phenone 2-O-ꢀ-D-glucopyranoside (mahkoside A, pro-
posed as 4), mangiferin, kaempferol 3-O-ꢀ-D-glucopyr-
anoside, dodecanoic acid, palmitic acid, ethyl stearate
and sucrose,5) gallic acid,6) desacetylfevicordin A,
fevicordin A, fevicordin A glucoside and fevicordin D
glucoside,7) and the lignans, pinoresinol, lariciresinol
and matairesinol.8)
Benzophenone derivatives are a series of diphenyl
ketones used primarily as photoinitiators and fragrance
enhancers. They are also used in the manufacturing of
insecticides, agricultural chemicals, hypnotics, antihist-
amines and other pharmaceuticals, ultraviolet curing
agents in sunglasses and inks, as an additive in plastics,
coatings and adhesive formulations, and in flavor
ingredients.9) This class of compounds has recently
shown notable cytotoxicity against cancer cells and
antioxidative activity.1–3) It is necessary for in vivo
experiments to obtain these compounds in sufficient
quantity. We describe here total syntheses of the
benzophenone glucopyranosides (1, 2 and 4) reported
y
To whom correspondence should be addressed. Fax: +81-11-706-4182; Email: y-fuku@abs.agr.hokudai.ac.jp
Abbreviations: DMAP, 4-N,N-dimethylaminopyridine; TFAA, trifluoroacetic anhydride; NBA, 3-nitrobenzylalcohol; TEA, triethanolamine

Synthesis of Benzophenone Glucopyranosides from Phaleria macrocarpa
2173
with the system at 0 ꢀC to yield 16. The resulting
hydroxyl group was benzoylated, and subsequent prod-
uct 17 was ortho monodemethylated by the same
system. After debenzoylation of 18 in N,N-dimethyl-
1,3-propanediamine, the product (19) was then subjected
to glucosylation with 2,3,4,6-tetra-O-acetyl-ꢀ-D-gluco-
pyranosyl bromide in the presence of 18-crown-6 under
an alkaline condition20) to give 20. Finally, deacetylation
of 20 in MeOH/Et3N (3:1) and subsequent hydro-
genolysis yielded 2.
The 13C-NMR spectral data for phalerin (proposed as
structure 1)1) and those for synthesized 2 were identical.
The 1H-NMR spectra of phalerin1) and synthesized 2
closely resembled each other. However, the reported
proton chemical shifts of phalerin1) and those of
synthesized 2 are quite different (Table 1). By moving
all the proton signals of phalerin to the left around
0.17 ppm, we found that the signals of phalerin and those
of synthesized 2 overlapped. We therefore consider that
phalerin and synthesized 2 were same.
The [ꢁ]D value for phalerin (þ0:53ꢀ in EtOH)1) and
isolated 2 (þ4ꢀ in MeOH)3) from the same plant showed
an opposite sign and smaller values than those of
synthesized 2 (ꢁ26ꢀ in MeOH, ꢁ15ꢀ in EtOH) and
originally reported 2 (ꢁ23ꢀ in MeOH).17) We therefore
started to isolate compound 2 (phalerin) from the leaves
and fruits of P. macrocapra. We found one constituent
in the MeOH extract that had the same Rf value as
synthesized 2. This compound was obtained in a 0.98%
yield from dried fruits and in 2.0% yield from dried
leaves. The compound showed identical physiochemical
data to those of synthesized 2. The [ꢁ]D values of the
compound from the fruits and leaves were ꢁ18ꢀ in
MeOH and ꢁ2:7ꢀ in EtOH, and ꢁ14ꢀ in MeOH and
ꢁ2:8ꢀ in EtOH, respectively. These results indicate that
phalerin was compound 2.
We also confirmed that 2,40,6-trihydroxy-4-methox-
ybenzophenone 2-O-ꢁ-D-glucopyranoside (3) reported
from P. macrocarpa4) should be revised to 2-O-ꢀ-D-
glucopyranoside (2), because the coupling constant
(J ¼ 7:5 Hz) of the anomeric proton signal at ꢂ 5.64 in
pyridine-d5 of 3 was characteristic of a ꢀ-anomer. We
therefore measured synthesized 2 in pyridine-d5 and
found that compounds 3 and 2 were the same.
O
HO
5
HO
β-D-glc-O
OMe
3
1
Phalerin (proposed)
The synthetic route for mahkoside A (proposed as 4)5)
is shown in Scheme 3. A coupling reaction of 1,3,5-
tribenzyloxybenzene and 14 was established with TFAA
to obtain benzophenone (23). Selective ortho monode-
benzylation of 23 by AlCl3–PhNMe2 afforded 24 in a
high yield. Methylation of 24 with dimethyl sulfate21)
gave 25 which was again selectively ortho monodeben-
zylated by AlCl3–PhNMe2 to yield 26 in a high yield.
The dealkylation reaction of 25 was examined by
using AlCl3, BBr3 and AlCl3–PhNMe2 (Table 2).
Deprotection of the alkyl group of 25 by using AlCl3
at 0 ꢀC and then for 3 h at room temperature, failed to
give the desired benzophenone (26; entry 1). Deal-
kylation of 25 with BBr3 (1 eq.) at low temperature gave
a mixture of 26 and 24 (4.6:1) as determined by
1H-NMR (entry 2). Akiyama et al.19) have reported that
a combination system of AlCl3 (3 eq.) and PhNMe2
OR1
O
2'
1
3'
5
R2O
OR3
OR4
3
2 R1= H, R2=Me, R3= β-D-glc, R4= H
3 R1= H, R2=Me, R3= α-D-glc, R4= H
4 R1= Me, R2=H, R3= β-D-glc, R4= H
Mahkoside A (proposed)
5 R1= Me, R2= H, R3= H, R4= β-D-glc
6 R1= Me, R2= β-D-glc, R3= H, R4= H
Fig. 1. Proposed Structures for Benzophenone Derivatives from
Phaleria macrocarpa and Related Benzophenone Glucopyranosides.
O
7
O
8
O
MeO
MeO
MeO
MeO
HO
b
a
Cl
OMe
HO
OMe
OMe
78%
77%
MeO
MeO
OH
9
O
O
O
O
O
d
c
O
OMe
OMe
44%
69%
AcO
10
11
O
O O
OH
AcO
AcO
AcO
O
O
O
HO
e
f
HO
HO
67%
82%
OMe
HO
O O
HO
HO
O O
HO
HO
HO
12
1
HO
Scheme 1. Synthesis of 3,4,5-Trihydroxy-40-methoxybenzophenone 3-O-ꢀ-D-Glucopyranoside (1).
Reagents and conditions: (a) anisole, CHCl3, AlCl3, 0 ꢀC ! r.t., 2 h; (b) BBr3, CH2Cl2, 0 ꢀC, 1 h; (c) benzaldehyde dimethyl acetal, p-TsOH,
toluene, refl., 2 h; (d) 2,3,4,6-tetra-O-acetyl-ꢀ-D-glucopyranosyl bromide, BnBu3NCl, K2CO3, CHCl3, r.t., 72 h; (e) MeOH/Et3N (3:1), r.t., 72 h;
(f) H2, Pd–C, EtOH, r.t., 15 h.

2174
P. HENDRA et al.
OMe
13
OMe O
a
b
HOOC
+
OBn 72%
MeO
OBn
84%
OMe
OMe
MeO
14
15
OH
O
OMe
OMe
O
O
d
c
98%
72%
OBz
18
OBn
OH
16
OBn
OBz
17
OBn
MeO
O
MeO
MeO
OH
OH
O
f
61%
e
MeO
AcO
61%
O
OH
OBn
MeO
OBn
O
20
19
AcO
AcO
AcO
OH
O
OH
O
O
g
h
MeO
MeO
HO
91%
70%
O
O
OBn
OH
HO
HO
O
HO
HO
HO
2
21
HO
HO
Scheme 2. Synthesis of 2,40,6-Trihydroxy-4-methoxybenzophenone 2-O-ꢀ-D-Glucopyranoside (2).
Reagents and conditions: (a) (CF3CO)2O, CH2Cl2, 0 ꢀC ! r.t., overnight; (b) AlCl3, PhNMe2, CH2Cl2, 0 ꢀC, 20 min; (c) BzCl, Et3N, DMAP,
CH2Cl2, r.t., 20 min; (d) AlCl3, PhNMe2, CH2Cl2, 0 ꢀC, 15 min; (e) NH2(CH2)3NMe2, r.t., 1 h; (f) 2,3,4,6-tetra-O-acetyl-ꢀ-D-glucopyranosyl
bromide, 18-crown-6, K2CO3, CH3CN, r.t., 24 h; (g) MeOH/Et3N (3:1), r.t., 15 h; (h) H2, Pd–C, dioxane, r.t., 15 h.
OBn
OBn O
HOOC
a
b
+
OBn
81%
78%
OBn
OBn
OBn
23
BnO
BnO
22
14
OMe
O
OMe
OH
O
O
c
d
98%
OBn
93%
OBn
OH
26
OBn
25
OBn
24
BnO
OBn
BnO
BnO
OMe
O
OMe
O
OMe
O
e
f
g
29%
92%
75%
BnO
AcO
HO
BnO
HO
O
O
O
OBn
OH
OBn
O
O
O
HO
HO
27
4
28
AcO
AcO
HO
HO
HO
AcO
HO
HO
Scheme 3. Synthesis of 2,4,40-Trihydroxy-6-methoxybenzophenone 2-O-ꢀ-D-Glucopyranoside (4).
Reagents and conditions: (a) (CF3CO)2O, CH2Cl2, 0 ꢀC ! r.t., overnight; (b) AlCl3, PhNMe2, CH2Cl2, 0 ꢀC, 10 min; (c) (MeO)2SO2, K2CO3,
18-crown-6, CH3CN, refl., 1 h; (d) AlCl3, PhNMe2, CH2Cl2, 0 ꢀC, 10 min; (e) O-(2,3,4,6-tetra-O-acetyl-ꢀ-D-glucopyranosyl) trichloroaceti-
ꢀ
.
midate, BF3 OEt2, CH2Cl2, 0 C ! r.t., 6 h; (f) MeOH/Et3N (3:1), r.t., 15 h; (g) H2, Pd–C, dioxane, r.t., 15 h.
Table 1. Comparison of 1H-NMR Data for the Aglycon Moieties of Synthesized 1, 2, 4-6 and Proposed 1, 3 and 4
Synthesized Proposed
1(ref.1)
Proposed Proposed
3(ref.4) 4(ref.5)
Synthesized Synthesized
5
Synthesized 2
Synthesized 4
1
6
Position
CD3OD
500 MHz 500 MHz 500 MHz 500 MHz 500 MHz
CD3ODꢂ CD3OD DMSO-d6 Pyridine-d5 Pyridine-d5 DMSO-d6 CD3OD DMSO-d6
500 MHz 400 MHz 500 MHz 270 MHz
CD3OD
500 MHz
CD3OD
500 MHz
H-20 and
H-60
H-30 and
H-50
H-6
7.75 (8.6)
6.60 (8) 7.68 (8.7) 7.57 (8.7) 8.23 (8.6) 8.26 (8.5) 7.57 (8.6) 7.66 (8.7) 7.55 (8.0) 7.62 (8.8)
7.63 (8.8)
6.78 (8.8)
7.03 (8.6)
7.03 (2)
7.52 (8) 6.78 (8.7) 6.78 (8.7) 7.12 (8.6) 7.13 (8.5) 6.80 (8.7) 6.78 (8.7) 6.77 (8.0) 7.10 (8.8)
6.19
H-5
H-3
6.17 (1.7) 6.12 (2)
6.39 (1.7) 6.29 (2)
6.60
7.02
6.60
7.05
6.30 (1.9) 6.22 (1.9) 6.26
6.12 (1.9) 6.37 (1.9) 6.16
5.99
5.99
6.35 (2)
6.30 (2)
H-2 7.20 (2)
OCH3 3.88
6.00
3.55
3.79
3.72
3.73
3.76
3.73
3.62
3.55
3.54
3.63
ꢂCDCl3 was described as NMR solvent in ref. 1. CD3OD signals, however, were detected in 13C-NMR spectra.

Synthesis of Benzophenone Glucopyranosides from Phaleria macrocarpa
2175
Table 2. Results of the Cleavage of Benzophenone 25 in CH2Cl2 under Different Reaction Conditions
Product ratioꢂ
Yield of
Entry
Conditions
26 (%)
24 (%)
26 (%)
1
2
3
4
AlCl3 (3 eq.), 0 ꢀC ! r.t. 3 h
—
18
0
—
82
0
41
98
96
BBr3 (1 eq.), ꢁ78 ꢀC 2 h ! ꢁ60 ꢀC 30 min
AlCl3 (3 eq.)-PhNMe2 (6 eq.), 0 ꢀC 10 min
AlCl3 (3 eq.)-PhNMe2 (6 eq.), 0 ꢀC 10 min ! r.t. 2 h
>99
>99
0
ꢂdetermined by 1H NMR
OBn
OBn O
OH
O
HOOC
+
a
b
O
O
82%
80%
O
OBn
OBn
30
BnO
OBn
31
BnO
O
BnO
22
29
OMe
O
OMe
OMe
O
O
e
c
d
95%
98%
62%
OBn
AcO
AcO
OBn
32
OBn
BnO
BnO
OH
BnO
O
O
33
OMe
AcO
AcO
34
O
OMe
O
f
g
OH
98%
81%
OBn
HO
HO
O
BnO
O
HO
O
O
HO
HO
HO
HO
HO
HO
5
35
Scheme 4. Synthesis of 2,4,40-Trihydroxy-6-methoxybenzophenone 40-O-ꢀ-D-Glucopyranoside (5).
Reagents and conditions: (a) (CF3CO)2O, CH2Cl2, 0 ꢀC ! r.t., 48 h; (b) AlCl3, PhNMe2, CH2Cl2, 0 ꢀC, 5 min; (c) (MeO)2SO2, K2CO3, 18-
crown-6, acetone, refl., 2 h; (d) Pd(PPh3)4, K2CO3, dioxane, MeOH, r.t., 20 h; (e) 2,3,4,6-tetra-O-acetyl-ꢀ-D-glucopyranosyl bromide,
BnBu3NCl, K2CO3, CH2Cl2, r.t., 24 h; (f) MeOH/Et3N (3:1), r.t., 30 h; (g) H2, Pd–C, dioxane, r.t., 15 h.
(4 eq.) was available to cleave general aliphatic and
aromatic benzyl ethers mostly in less than 1 h at room
temperature. The cleavage reaction, however, didn’t
proceed at 0 ꢀC, except for the p-methoxybenzyl
ethers.19) Chemo- and regioselective monodebenzylation
of 25 occurred by using the combination system at 0 ꢀC
to give 26 (entry 3 in Scheme 3). Although the reaction
was continued for 2 h at room temperature, no other
product was obtained (entry 4).
Glucosylation of 26 with O-(2,3,4,6-tetra-O-acetyl-ꢀ-
D-glucopyranosyl) trichloroacetimidate22) afforded 27.
Deacetylation of 27 in MeOH/Et3N and subsequent
hydrogenolysis gave 4.
The spectral data did not match those of mahkoside A
and synthesized 4 (Table 1). The distinguishable dif-
ferences between them were the chemical shifts of the
methoxy and H-3 and H-5 aromatic proton signals. The
methoxy proton signal of mahkoside A resonated at
ꢂ 3.73 in DMSO-d6. Synthesized 4 however showed the
signal at ꢂ 3.55 in the same solvent. The ortho methoxy
protons in 4 may have been affected by the shielding
effect of another benzene ring of the benzophenone
skeleton. The downfield appearance of the methoxy
signal (ꢂ 3.73) of mahkoside A indicates that the
methoxyl group was located at the para position of
benzophenone. Therefore, we also compared the re-
ported 1H-NMR data of mahkoside A with those of
synthesized 2 in DMSO-d6 (Table 1), and found that
their data were indistinguishable. Consequently, the
correct structure of mahkoside A should be 2,40,6-
trihydroxy-4-methoxybenzophenone 2-O-ꢀ-D-glucopyr-
anoside (2).
Details for the synthesis of 5 are depicted in
Scheme 4. Benzophenone (30) was prepared from
1,3,5-tribenzyloxybenzene and 4-allyloxybenzoic acid,
using TFAA as a condensing agent. After ortho
monodebenzylation of 30 by AlCl3–PhNMe2, product
31 was methylated and then subjected to a cleaving
23)
reaction of the allyl group with Pd(PPh3)4
in the
presence of potassium carbonate to afford 33. Glucosy-
lation of 33 yielded 34. Deacetylation of 34 and
subsequent hydrogenolysis led to 5.
Compound 6 was synthesized as shown in Scheme 5.
Selective ortho debenzylation of 32 by AlCl3–PhNMe2
and subsequent deallylation yielded 37. The resulting
hydroxyl groups of 37 were acetylated, and 38 was
subsequently hydrogenated into 39. Glucosylation of 39
afforded 40. Deacetylation of 40 in MeOH/Et3N gave
product 6.
The structures of compounds 1, 2 and 4–6 were
determined by 2D-NMR analyses (Fig. 2). We made it
possible to provide five synthetically pure benzophenone
glucopyranosides. Enough of each glucoside was avail-
able for a bioassay by scaling up the reactions. In
addition, we found that selective ortho monodealkyla-
tion to polyalkoxybenzophenones could be achieved by
AlCl3–PhNMe2. AlCl3–PhNMe2 may selectively cleave
the alkoxy groups located at the ortho carbonyl group in
the substrate. Thus, we could synthesize some benzo-
phenone glucopyranosides related with the reported
benzophenone glucopyranosides from P. macrocarpa.
Comparing the NMR data of the four benzophenone
glucopyranosides (for proposed structures 1–4) from
P. macrocarpa with those of the synthesized material

2176
P. HENDRA et al.
OMe
O
OMe
OMe
O
O
a
b
82%
90%
OBn
32
O
O
OH
37
OH
36
BnO
BnO
OH
BnO
O
OMe
OMe
O
c
d
e
99%
83%
73%
OAc
38
OAc
39
BnO
OAc
HO
OAc
OMe
OMe
O
O
f
AcO
HO
O
O
O
O
OAc
40
79%
OH
6
OAc
OH
AcO
HO
HO
AcO
AcO
HO
Scheme 5. Synthesis of 2,4,40-Trihydroxy-6-methoxybenzophenone 4-O-ꢀ-D-Glucopyranoside (6).
Reagents and conditions: (a) AlCl3, PhNMe2, CH2Cl2, 0 ꢀC, 20 min; (b) Pd(PPh3)4, K2CO3, dioxane, MeOH, r.t., 20 h; (c) Ac2O, Et3N,
.
CH2Cl2, r.t., 1 h; (d) H2, Pd-C, dioxane, r.t., overnight; (e) O-(2,3,4,6-tetra-O-acetyl-ꢀ-D-glucopyranosyl) trichloroacetimidate, BF3 OEt2,
CH2Cl2, 0 ꢀC ! r.t., 6 h; (f) MeOH/Et3N (3:1), r.t., 15 h.
O
O
H
O
H
O
H
H
HO
HO
HO
HO
H
H
H
H H
O Me
O Me
HO
HO
O
HO
HO
HO
HO
O
1
HO
NOESY
1
HO
HMBC
H
H
OH
H
OH
H
O
O
H
H
H
H
H
O
Me
O
OH
OH
Me
O
H
O
O
HO
HO
O
HO
HO
HO
HO
HO
2
HMBC
2
NOESY
HO
H
H
Me
Me
O
O
H
O
H
H
O
H
H
H
H
HO
OH
O
HO
HO
OH
H
O
O
HO
HO
HO
HO
O
HO
4
4
HMBC
NOESY
HO
HO
H
H
OH
H
O
H
H
H
OH
O
H
H
H
H
HO
O
HO
O
O
5
O
Me
HO
H
Me
HO
HO
HO
HO
O
O
HO
HO
HO
H
H
HMBC
NOESY
5
OH
H
O
OH
H
O
H
H
H
H
O
H
HO
HO
HO
HO
O
O
O
OH
O
Me
OH
HO
HO
O
H
Me
HO
H
HO
H
6
NOESY
6
HMBC
Fig. 2. Selected NOESY and HMBC Correlations for 1, 2 and 4-6.
Dashed arrows are correlations with overlapping signals.

Synthesis of Benzophenone Glucopyranosides from Phaleria macrocarpa
2177
3,4-(Benzylidenedioxy)-5-hydroxy-40-methoxybenzophenone 5-(2,3,4,6-
tetra-O-acetyl)-ꢀ-D-glucopyranoside (11). A mixture of 10 (0.70 g,
2.0 mmol), 2,3,4,6-tetra-O-acetyl-ꢀ-D-glucopyranosyl bromide (1.66 g,
4.0 mmol), K2CO3 (1.38 g, 10 mmol) and benzyltributylammonium
chloride (0.12 g, 0.4 mmol) were added to CHCl3 (30 ml), and the
solution stirred for 72 h at room temperature. The reaction mixture was
acidified with aq. 2 M HCl and diluted with EtOAc. The organic layer
was separated, washed with aq. sat. NaHCO3 and dried over MgSO4;
the solvent was evaporated under reduced pressure. Purification by
flash column chromatography on silica gel (hexane/EtOAc 5:1) gave
11 (0.93 g, 69%) as a 1:1 mixture of diastereomers as determined by
1H-NMR.
(1, 2 and 4) showed that the proposed structures for the
natural products of the four benzophenone glucopyrano-
sides were all 2.
Experimental
General procedures. The solvent and reagents used were each a
pure grade of the commercial product. Unless otherwise stated, they
were used without purification. NMR spectra were recorded at
270 MHz/67.5 MHz (1H/13C) in CDCl3, using tetramethylsilane as
an internal standard, unless otherwise stated. Compounds 1, 2 and 4–6
were recorded at 500 MHz/126 MHz (1H/13C), and the chemical shifts
were calculated from the residual solvent signals of ꢂH 3.30 ppm and ꢂC
49.0 ppm in CD3OD, ꢂH 2.49 ppm and ꢂC 39.5 ppm in DMSO-d6,
ꢂH 2.04 ppm and ꢂC 29.0 ppm in acetone-d6, and ꢂH 8.71 ppm and
ꢂC 149 ppm in pyridine-d5. Complete attribution was performed
on the basis of 2D-NMR (COSY, NOESY, HMBC and HMQC)
experiments.
27
11: white solid; [ꢁ]D ꢁ15ꢀ (c 0.3, MeOH); NMR ꢂH (500 MHz,
CDCl3): 7.77 (4H, d, J ¼ 8:9 Hz), 7.54–7.56 (4H, m), 7.45–7.47 (6H,
m), 7.18 (1H, d, J ¼ 1:5 Hz), 7.16 (1H, d, J ¼ 1:5 Hz), 7.08 (2H, d,
J ¼ 2:3 Hz), 7.06 (2H, d, J ¼ 2:3 Hz), 6.94 (4H, d, J ¼ 8:9 Hz), 5.22–
5.25 (6H, m), 5.13 (2H, dd, J ¼ 9:8, 7.3 Hz), 4.23 (1H, dd, J ¼ 12:3,
4.9 Hz), 4.16 (1H, dd, J ¼ 12:3, 4.8 Hz), 4.08 (1H, dd, J ¼ 12:3,
2.4 Hz), 3.94 (1H, dd, J ¼ 12:3, 2.3 Hz), 3.87 (6H, s), 3.76 (1H, m),
3.70 (1H, m), 2.01 (3H, s), 2.00 (6H, s), 1.99 (6H, s), 1.98 (3H, s), 1.97
(3H, s), 1.92 (3H, s); NMR ꢂC (CDCl3): 193.2, 170.6, 170.2, 169.3,
169.24, 169.22, 169.18, 163.2, 149.3, 140.1, 139.8, 139.0, 138.9,
135.4, 135.2, 132.9, 132.8, 132.3, 130.75, 130.71, 130.1, 128.8, 126.4,
126.3, 116.8, 116.5, 113.6, 111.9, 111.87, 106.1, 106.0, 99.8, 96.1,
72.7, 72.6, 72.2, 71.1, 71.0, 68.2, 68.1, 61.8, 61.5, 55.5, 20.6, 20.57,
20.5; FABMS (positive, NBA matrix) m=z (rel. int. %): 701 ½M þ
Naꢃþ (6), 679 ½M þ Hꢃþ (14); HRFABMS m=z ½M þ Hꢃþ calcd. for
C35H35O14, 679.2027; found, 679.2018.
3,4,5,40-Tetramethoxybenzophenone (8). To a stirred solution of
3,4,5-trimethoxybenzoyl chloride (7; 4.6 g, 20 mmol) and anisole
(2.8 ml, 28 mmol) in CHCl3 (20 ml) was added powdered AlCl3 (2.9 g,
22 mmol) at 0 ꢀC. The solution was stirred for 2 h at room temperature.
The reaction mixture was then diluted with EtOAc, poured into ice-
cold aq. 2 M HCl and mixed. The organic layer was separated, washed
with aq. sat. NaHCO3 and dried over MgSO4; the solvent was
evaporated under reduced pressure. Purification by flash column
chromatography on silica gel (hexane/EtOAc 20:1) afforded
8
(4.6 g, 77%).
3,4-(Benzylidenedioxy)-5-hydroxy-40-methoxybenzophenone 5-O-ꢀ-
D-glucopyranoside (12). Compound 11 (204 mg, 0.301 mmol) was
dissolved in MeOH (6 ml) and triethylamine (2 ml), and the solution
stirred for 72 h at room temperature. To the reaction mixture was added
toluene, before evaporating to dryness. Purification by flash column
chromatography on silica gel (CHCl3/MeOH 5:1) afforded 12 (103 mg,
67%) as a 1:1 mixture of diastereomers as determined by 1H-NMR.
8: colorless prisms; mp 81.0–81.5 ꢀC (EtOH), lit. 72–73 ꢀC;10) NMR
ꢂH (CDCl3): 7.83 (2H, d, J ¼ 8:9 Hz), 7.02 (2H, s), 6.97 (2H, d,
J ¼ 8:9 Hz), 3.93 (3H, s), 3.90 (3H, s), 3.88 (6H, s); NMR ꢂC (CDCl3):
194.4, 162.9, 152.7, 141.5, 133.2, 132.3, 130.2, 113.4, 107.4, 61.0,
56.3, 55.5; EIMS m=z (rel. int. %): 303 (Mþ þ1, 18), 302 (Mþ, 100),
287 (16), 271 (11), 259 (25), 195 (17), 135 (52), 92 (10), 77 (15).
26
12: white solid; [ꢁ]D ꢁ23ꢀ (c 0.3, MeOH); NMR ꢂH (500 MHz,
3,4,5-Trihydroxy-40-methoxybenzophenone (9). To a stirred solution
CD3OD): 7.76 (2H, d, J ¼ 8:9 Hz), 7.75 (2H, d, J ¼ 8:9 Hz), 7.59–
7.62 (4H, m), 7.30–7.49 (6H, m), 7.21 (1H, d, J ¼ 1:8 Hz), 7.20 (1H, d,
J ¼ 2:0 Hz), 7.18 (1H, s), 7.16 (1H, s), 7.033 (1H, d, J ¼ 2:0 Hz),
7.030 (4H, d, J ¼ 8:9 Hz), 7.027 (1H, d, J ¼ 1:8 Hz), 5.12 (1H, d,
J ¼ 7:0 Hz), 5.10 (1H, d, J ¼ 7:4 Hz), 3.89 (3H, s), 3.88 (3H, s), 3.80
(1H, dd, J ¼ 12:2, 2.6 Hz), 3.77 (1H, dd, J ¼ 12:2, 2.5 Hz), 3.70 (2H,
dd, J ¼ 12:2, 4.5 Hz), 3.38–3.53 (6H, m), 3.32–3.34 (2H, m); NMR ꢂC
(CD3OD): 195.9, 195.8, 165.0, 164.7, 150.84, 150.81, 147.0, 146.6,
141.5, 141.1, 137.2, 137.1, 133.72, 133.70, 133.5, 133.4, 131.7, 131.3,
129.9, 129.83, 127.8, 127.5, 117.0, 114.8, 114.6, 113.2, 113.0, 105.5,
105.4, 104.6, 104.3, 102.44, 102.4, 78.2, 78.1, 77.9, 77.6, 74.85, 74.82,
71.0, 70.9, 62.3, 62.1, 56.5, 56.1; FABMS (positive, NBA matrix) m=z
(rel. int. %): 533 ½M þ Naꢃþ (12), 511 ½M þ Hꢃþ (32); HRFABMS
m=z ½M þ Hꢃþ calcd. for C27H27O10, 511.1604; found, 511.1597.
of
8 (1.51 g, 4.99 mmol) in CH2Cl2 (20 ml) was added boron
tribromide (15.0 ml of 1 M in hexane, 15 mmol) at 0 ꢀC. The solution
was stirred for 1 h at 0 ꢀC. The reaction mixture was decomposed by
ice-cold aq. 2 M HCl and diluted with EtOAc. The organic layer was
separated and dried over MgSO4; the solvent was evaporated under
reduced pressure. The crude product was purified by flash column
chromatography on silica gel (CHCl3/MeOH 10:0.5) to afford 9
(1.02 g, 78%).
9: colorless prisms; mp 182.0–184.0 ꢀC (acetone); NMR ꢂH
(acetone-d6): 7.73 (2H, d, J ¼ 8:9 Hz), 7.03 (2H, d, J ¼ 8:9 Hz),
6.88 (2H, s), 3.89 (3H, s); NMR ꢂC (acetone-d6): 183.7, 163.6, 148.2,
147.0, 145.9, 132.6, 131.9, 130.0, 114.2, 110.6, 55.8; EIMS m=z (rel.
int. %): 261 (Mþ þ1, 16), 260 (Mþ, 100), 243 (21), 229 (21), 153 (21),
135 (87); HREIMS m=z (Mþ) calcd. for C14H12O5, 260.0685; found,
260.0722.
3,4,5-Trihydroxy-40-methoxybenzophenone 3-O-ꢀ-D-glucopyrano-
side (1). To a solution of 12 (20 mg, 0.039 mmol) in EtOH (5 ml)
was added 10% Pd/C (20 mg), and the resulting suspension was stirred
vigorously under a hydrogen atmosphere for 15 h at room temperature.
The catalyst was filtered off through Celite, and the filtrate was
evaporated under reduced pressure. The crude product was suspended
in EtOH and filtered to afford 1 (13.6 mg, 82%).
3,4-(Benzylidenedioxy)-5-hydroxy-40-methoxybenzophenone (10). A
flask equipped with a Dean-Stark trap and water condenser was
charged with 9 (0.91 g, 3.5 mmol), benzaldehyde dimethyl acetal
(0.52 ml, 3.4 mmol) and p-toluene-sulfonic acid monohydrate (3 mg) in
toluene (50 ml). The reaction mixture was refluxed for 2 h. The solvent
collected from the side arm of the Dean-Stark trap was continuously
removed. The reaction mixture was then diluted with EtOAc and
washed with aq. sat. Na2CO3. The organic layer was separated and
dried over MgSO4; the solvent was evaporated under reduced pressure.
The crude product was purified by flash column chromatography on
silica gel (toluene/EtOAc 10:1) to afford 10 (0.54 g, 44%).
10: amorphous white solid; mp 162.5–164.5 ꢀC (EtOAc); NMR ꢂH
(CDCl3): 7.80 (2H, d, J ¼ 8:8 Hz), 7.46–7.62 (5H, m), 7.10 (1H, d,
J ¼ 1:5 Hz), 7.07 (1H, d, J ¼ 1:5 Hz), 6.96 (1H, s), 6.94 (2H, d,
J ¼ 8:8 Hz), 5.67 (OH, brs), 3.88 (3H, s); NMR ꢂC (CDCl3):
194.3, 163.1, 148.7, 138.9, 138.0, 135.3, 132.6, 132.4, 130.6, 130.2,
128.7, 126.4, 114.8, 113.5, 111.8, 103.8, 56.3, 55.5; EIMS m=z
(rel. int. %): 349 (Mþ þ1, 21), 348 (Mþ, 100), 347 (17), 241 (15), 135
(44); HREIMS m=z (Mþ) calcd. for C21H16O5, 348.0998; found,
348.0962.
27
1: colorless prisms; mp 117.5–119.5 ꢀC (EtOH); [ꢁ]D ꢁ38ꢀ (c 0.3,
MeOH); NMR ꢂH (500 MHz, CD3OD): 7.75 (2H, d, J ¼ 8:6 Hz, H-20
and 60), 7.20 (1H, d, J ¼ 2:0 Hz, H-2), 7.03 (1H, d, J ¼ 2:0 Hz, H-6),
7.03 (2H, d, J ¼ 8:6 Hz, H-30 and H-50), 4.81 (1H, d, J ¼ 7:5 Hz,
H-100), 3.88 (3H, s, OCH3), 3.77 (1H, dd, J ¼ 12:1, 2.2 Hz, H-600b),
3.70 (1H, dd, J ¼ 12:1, 4.6 Hz, H-600a), 3.52 (1H, m, H-200), 3.48 (1H,
m, H-400), 3.45 (1H, m, H-300), 3.34 (1H, m, H-500); NMR ꢂC (CD3OD):
196.7 (C=O), 164.7 (C-40), 147.0 (C-5), 146.6 (C-3), 141.6 (C-4),
133.4 (C-20 and C-60), 131.6 (C-10), 129.7 (C-1), 114.6 (C-30 and C-50),
113.9 (C-6), 112.9 (C-2), 104.2 (C-100), 78.2 (C-500), 77.5 (C-300), 74.8
(C-200), 70.9 (C-400), 62.0 (C-600), 56.0 (OCH3); FABMS (positive,
NBA matrix) m=z (rel. int. %): 445 ½M þ Naꢃþ (37), 423 ½M þ Hꢃþ
(22); HRFABMS m=z ½M þ Hꢃþ calcd. for C20H23O10, 423.1291;
found, 423.1299.

2178
P. HENDRA et al.
40-Benzyloxy-2,4,6-trimethoxybenzophenone (15). To a suspension
d, J ¼ 2:5 Hz), 6.35 (1H, d, J ¼ 2:5 Hz), 4.79 (2H, s), 3.87 (3H, s);
NMR ꢂC (CDCl3): 196.9, 164.9, 164.5, 163.9, 161.8, 151.7, 136.2,
133.3, 133.2, 130.6, 129.8, 128.6, 128.5, 128.2, 127.9, 127.3, 114.1,
108.9, 102.5, 99.4, 96.2, 70.0, 55.7; EIMS m=z (rel. int. %): 455
(Mþ þ1, 11), 454 (Mþ, 37), 105 (100), 91 (53), 77 (21); HREIMS m=z
(Mþ) calcd. for C28H22O6, 454.1416; found, 454.1409.
of 4-benzyloxybenzoic acid (2.28 g, 10 mmol) in CH2Cl2 (15 ml)
cooled to 0 ꢀC was added trifluoroacetic anhydride (1.81 ml, 13 mmol),
and the mixture was stirred for 10 min to give a clear solution. To this
solution was added 1,3,5-trimethoxybenzene 13 (2.19 g, 13 mmol), and
the mixture stirred overnight at room temperature. The reaction
mixture was diluted with EtOAc, ice water and aq. sat. Na2CO3, and
stirred vigorously again to yield a suspension. Sodium 4-benzylox-
ybenzoate was filtered off through Celite, and the organic layer was
separated and successively washed with aq. sat. NaHCO3 and brine.
The organic layer was dried over MgSO4, filtered, and concentrated
under reduced pressure. The crude product was suspended in EtOH and
filtered to afford 15 (2.72 g, 72%).
15: colorless prisms; mp 120.5–122.0 ꢀC (EtOH); NMR ꢂH
(CDCl3): 7.81 (2H, d, J ¼ 8:9 Hz), 7.32–7.43 (5H, m), 6.96 (2H, d,
J ¼ 8:9 Hz), 6.15 (2H, brs), 5.10 (2H, s), 3.85 (3H, s), 3.68 (6H, s);
NMR ꢂC (CDCl3): 193.4, 162.7, 162.2, 158.5, 136.3, 131.8, 131.6,
128.6, 128.2, 127.5, 114.3, 111.2, 96.1, 90.7, 70.1, 55.8, 55.40, 55.36;
EIMS m=z (rel. int. %): 379 (Mþ þ1, 10), 378 (Mþ, 40), 361 (12), 258
(35), 195 (11), 91 (100); HREIMS m=z (Mþ) calcd. for C23H22O5,
378.1467; found, 378.1491.
40-Benzyloxy-2,6-dihydroxy-4-methoxybenzophenone (19). Com-
pound 18 (0.70 g, 1.5 mmol) was added to N,N-dimethyl-1,3-propane-
diamine (2.0 ml) at 0 ꢀC, and then the solution was stirred for 1 h at
room temperature. The reaction mixture was diluted with EtOAc and
aq. 2 M HCl, and then mixed. The organic layer was separated, washed
with brine and dried over MgSO4; the solvent was evaporated under
reduced pressure. Purification by flash column chromatography on
silica gel (hexane/EtOAc 3:1) afforded 19 (0.33 g, 61%).
19: amorphous white solid; mp 110.0–112.0 ꢀC (EtOH); NMR ꢂH
(CDCl3): 8.68 (OH, brs), 7.67 (2H, d, J ¼ 8:6 Hz), 7.34–7.42 (5H, m),
7.06 (2H, d, J ¼ 8:6 Hz), 6.03 (2H, s), 5.13 (2H, s), 3.82 (3H, s); NMR
ꢂC (CDCl3): 195.8, 166.5, 162.5, 161.9, 135.9, 131.7, 130.9, 128.7,
128.3, 127.5, 115.3, 104.6, 96.1, 94.9, 70.3, 55.1; EIMS m=z (rel. int.
%): 351 (Mþ þ1, 8), 350 (Mþ, 33), 259 (5), 230 (5), 166 (7), 121 (5),
91 (100), 65 (5); HREIMS m=z (Mþ) calcd. for C21H18O5, 350.1154;
found, 350.1109.
40-Benzyloxy-2-hydroxy-4,6-dimethoxybenzophenone (16). To
a
stirred solution of 15 (2.22 g, 5.87 mmol) and PhNMe2 (4.45 ml,
35.2 mmol) in CH2Cl2 (40 ml) was added powdered AlCl3 (5.48 g,
41.1 mmol) at 0 ꢀC. The solution was stirred for 20 min at 0 ꢀC. The
reaction mixture was then diluted with EtOAc, poured into ice-cold aq.
2 M HCl and mixed. The organic layer was separated, washed with
brine and dried over MgSO4; the solvent was evaporated under
reduced pressure. Purification by flash column chromatography on
silica gel (hexane/EtOAc 3:1) afforded 16 (1.79 g, 84%).
16: colorless prisms; mp 119.0–120.5 ꢀC (EtOH); NMR ꢂH
(CDCl3): 11.85 (OH, brs), 7.56 (2H, d, J ¼ 8:8 Hz), 7.32–7.45 (5H,
m), 6.94 (2H, d, J ¼ 8:8 Hz), 6.15 (1H, d, J ¼ 2:3 Hz), 5.93 (1H, d,
J ¼ 2:3 Hz), 5.11 (2H, s), 3.83 (3H, s), 3.49 (3H, s); NMR ꢂC (CDCl3):
197.4, 165.9, 165.2, 161.51, 161.47, 136.4, 134.0, 130.8, 128.6, 128.1,
127.5, 113.7, 105.8, 93.7, 91.3, 70.1, 55.6, 55.1; EIMS m=z (rel. int.
%): 365 (Mþ þ1, 6), 364 (Mþ, 27), 363 (17), 244 (14), 91 (100);
HREIMS m=z (Mþ) calcd. for C22H20O5, 364.1311; found, 364.1310.
40-Benzyloxy-2,6-dihydroxy-4-methoxybenzophenone 2-(2,3,4,6-tetra-
O-acetyl)-ꢀ-D-glucopyranoside (20). A mixture of 19 (55 mg, 0.16
mmol), 2,3,4,6-tetra-O-acetyl-ꢀ-D-glucopyranosyl bromide (110 mg,
0.268 mmol), 18-crown-6 (10 mg, 0.038 mmol), K2CO3 (108 mg,
0.781 mmol) and CH3CN (5 ml) was stirred at room temperature for
24 h. The reaction mixture was acidifed with aq. 2 M HCl and diluted
with EtOAc. The organic layer was separated, washed with aq. sat.
NaHCO3 and dried over MgSO4; the solvent was evaporated under
reduced pressure. Purification by flash column chromatography on
silica gel (CHCl3/acetone 15:1) gave 20 (107 mg, 61%).
28
20: colorless prisms; mp 65.0–67.0 ꢀC (EtOH); [ꢁ]D ꢁ19ꢀ (c 0.3,
CHCl3); NMR ꢂH (CDCl3): 11.3 (OH, brs), 7.60 (2H, d, J ¼ 8:7 Hz),
7.32–7.48 (5H, m), 6.94 (2H, d, J ¼ 8:7 Hz), 6.27 (1H, d, J ¼ 2:1 Hz),
6.15 (1H, d, J ¼ 2:1 Hz), 5.18 (2H, s), 5.05 (1H, dd, J ¼ 9:3, 8.8 Hz),
4.98 (1H, dd, J ¼ 9:3, 9.3 Hz), 4.88 (1H, d, J ¼ 7:5 Hz), 4.40 (1H, dd,
J ¼ 8:8, 7.5 Hz), 4.20 (1H, dd, J ¼ 12:4, 6.3 Hz), 4.11 (1H, dd,
J ¼ 12:4, 2.3 Hz), 3.74 (1H, m), 3.82 (3H, s), 2.09 (3H, s), 2.00 (3H, s),
1.91 (3H, s), 1.87 (3H, s); NMR ꢂC (CDCl3): 196.6, 170.5, 170.0,
169.3, 168.3, 165.0, 164.3, 162.3, 157.6, 136.5, 132.9, 131.3, 128.6,
128.1, 127.5, 114.0, 107.2, 98.5, 96.1, 95.9, 95.6, 91.7, 72.9, 72.2, 70.8,
70.1, 67.9, 62.0, 55.6, 20.6; FABMS (negative, TEA matrix) m=z
(rel. int. %) 679 ½M ꢁ Hꢃꢁ (8); HRFABMS m=z ½M ꢁ Hꢃꢁ calcd. for
2-Benzoyloxy-40-benzyloxy-4,6-dimethoxybenzophenone (17). To a
stirred solution of 16 (1.62 g, 4.45 mmol), triethylamine (0.92 ml,
6.6 mmol) and 4-N,N-dimethylaminopyridine (DMAP, 5 mg, 0.04
mmol) in CH2Cl2 (20 ml) was added benzoyl chloride (0.62 ml,
5.3 mmol) at room temperature. The solution was stirred for 20 min.
The reaction mixture was then diluted with CHCl3, successively
washed with aq. 2 M HCl, aq. sat. NaHCO3 and brine, and then dried
over MgSO4; the solvent was evaporated under reduced pressure.
Purification by flash column chromatography on silica gel (hexane/
EtOAc 3:1) afforded 17 (2.04 g, 98%).
C35H35O14, 679.2027; found, 679.2033.
40-Benzyloxy-2,6-dihydroxy-4-methoxybenzophenone 2-O-ꢀ-D-glu-
copyranoside (21). Compound 20 (41 mg, 0.060 mmol) was dissolved
in MeOH (3 ml) and triethylamine (1 ml) and stirred for 15 h at room
temperature. To the reaction mixture was added toluene, before being
evaporated to dryness. The crude product was suspended in hexane and
diethyl ether and then filtered to afford 21 (39 mg, 91%).
17: colorless oil; NMR ꢂH (CDCl3): 8.15 (2H, dd, J ¼ 7:3, 1.3 Hz),
7.83 (1H, t, J ¼ 7:3 Hz), 7.79 (2H, d, J ¼ 8:9 Hz), 7.67 (2H, dd,
J ¼ 7:6, 7.3 Hz), 7.46–7.55 (2H, m), 7.30–7.38 (3H, m), 6.90 (2H, d,
J ¼ 8:9 Hz), 6.52 (1H, d, J ¼ 2:0 Hz), 6.44 (1H, d, J ¼ 2:0 Hz), 5.05
(2H, s), 3.85 (3H, s), 3.72 (3H, s); NMR ꢂC (CDCl3): 191.5, 164.2,
162.8, 162.2, 161.7, 158.7, 149.8, 136.2, 134.5, 133.6, 133.4, 131.8,
131.3, 130.5, 130.2, 130.1, 128.8, 128.6, 128.4, 128.3, 128.2, 127.4,
115.4, 114.3, 99.8, 96.7, 96.1, 70.0, 55.9, 55.6; EIMS, m=z (rel. int. %):
469 (Mþ þ1, 12), 468 (Mþ, 38), 243 (28), 105 (100), 91 (66), 77 (24);
HREIMS m=z (Mþ) calcd. for C29H24O6, 468.1573; found, 468.1539.
27
21: colorless plates; mp 74.5–76.0 ꢀC (EtOH); [ꢁ]D ꢁ27ꢀ (c 0.3,
CHCl3); NMR ꢂH (CDCl3): 7.55 (2H, d, J ¼ 8:7 Hz), 7.25–7.33 (5H,
m), 6.90 (2H, d, J ¼ 8:7 Hz), 6.18 (1H, d, J ¼ 2:0 Hz), 6.06 (1H, d,
J ¼ 2:0 Hz), 5.05 (2H, s), 4.62 (1H, d, J ¼ 7:5 Hz), 3.74 (3H, s), 3.60–
3.80 (3H, m), 3.25–3.34 (3H, m), 2.56 (OH, brs); NMR ꢂC (CDCl3):
197.1, 165.4, 164.3, 161.8, 157.5, 136.1, 134.1, 130.8, 128.7, 128.2,
127.4, 114.1, 107.0, 100.1, 96.1, 95.9, 95.2, 75.7, 74.7, 73.2, 70.2,
69.8, 62.1, 55.7; FABMS (negative, TEA matrix) m=z (rel. int. %) 511
2-Benzoyloxy-40-benzyloxy-6-hydroxy-4-methoxybenzophenone (18).
To a stirred solution of 17 (2.0 g, 4.3 mmol) and PhNMe2 (3.1 ml,
25 mmol) in CH2Cl2 (30 ml) was added powdered AlCl3 (2.19 g,
16.4 mmol) at 0 ꢀC. The solution was stirred for 15 min at 0 ꢀC. The
reaction mixture was then diluted with EtOAc, poured into ice-cold aq.
2 M HCl and mixed. The organic layer was separated, washed with
brine and dried over MgSO4; the solvent was evaporated under
reduced pressure. Purification by flash column chromatography on
silica gel (hexane/EtOAc 3:1) afforded 18 (1.40 g, 72%).
½M ꢁ Hꢃꢁ (2); HRFABMS m=z ½M ꢁ Hꢃꢁ calcd. for C27H27O10
,
511.1604; found, 511.1584.
2,40,6-Trihidroxy-4-methoxybenzophenone 2-O-ꢀ-D-glucopyrano-
side (2). To a solution of 21 (20 mg 0.039 mmol) in dioxane (3 ml)
was added 10% Pd/C (20 mg), and the resulting suspension was stirred
vigorously under a hydrogen atmosphere for 15 h at room temperature.
The catalyst was filtered off through Celite, and the filtrate was
evaporated under reduced pressure. The crude product was suspended
in CHCl3 and filtered to afford 2 (11.5 mg, 70%).
18: colorless needles; mp 117.5–119.0 ꢀC (EtOH); NMR ꢂH
(CDCl3): 11.48 (OH, brs), 7.43–7.54 (5H, m), 7.47 (2H, d,
J ¼ 8:9 Hz), 7.24–7.38 (5H, m), 6.71 (2H, d, J ¼ 8:9 Hz), 6.47 (1H,
2: colorless prisms; mp 103.5–104.5 ꢀC (EtOH), lit. 202–204 ꢀC,2)

Synthesis of Benzophenone Glucopyranosides from Phaleria macrocarpa
2179
27
133–135 ꢀC,17) 103–105 ꢀC;5) [ꢁ]D ꢁ26ꢀ (c 0.1, MeOH), ꢁ15ꢀ (c 0.5,
136.5, 135.9, 135.6, 134.4, 130.6, 128.7, 128.6, 128.3, 128.11, 128.06,
127.7, 127.5, 127.4, 126.5, 113.8, 106.2, 96.1, 94.8, 92.9, 70.3,
70.1, 70.0; EIMS m=z (rel. int. %): 516 (Mþ, 10), 425 (5), 211 (8),
91 (100); HREIMS m=z (Mþ) calcd. for C34H28O5, 516.1937; found,
516.1929.
EtOH), lit. ꢁ23ꢀ (c 0.1, MeOH),17) þ4ꢀ (c 0.9, MeOH),3) þ0; 53ꢀ
(c 0.15, EtOH);1) NMR ꢂH (500 MHz, CD3OD): 7.68 (2H, d,
J ¼ 8:7 Hz, H-20 and H-60), 6.78 (2H, d, J ¼ 8:7 Hz, H-30 and H-50),
6.39 (1H, d, J ¼ 1:7 Hz, H-3), 6.17 (1H, d, J ¼ 1:7 Hz, H-5), 4.86 (1H,
d, J ¼ 7:9 Hz, H-100), 3.84 (1H, brd, J ¼ 12:0 Hz, H-600b), 3.79 (3H, s,
OCH3), 3.63 (1H, dd, J ¼ 12:0, 6.0 Hz, H-600a), 3.37 (1H, m, H-500),
3.37 (1H, m, H-300), 3.24 (1H, dd, J ¼ 9:5, 9.2 Hz, H-400), 3.12 (1H, dd,
J ¼ 8:9, 7.9 Hz, H-200); NMR ꢂH (500 MHz, DMSO-d6): 10.26 (OH,
brs), 9.70 (OH, brs), 7.57 (2H, d, J ¼ 8:7 Hz, H-20 and H-60), 6.78 (2H,
d, J ¼ 8:7 Hz, H-30 and H-50), 6.29 (1H, d, J ¼ 2:0 Hz, H-3), 6.12 (1H,
d, J ¼ 2:0 Hz, H-5), 4.96 (OH, d, J ¼ 5:3 Hz, OH-C-400), 4.92 (OH, d,
J ¼ 5:2 Hz, OH-C-300), 4.78 (1H, d, J ¼ 8:0 Hz, H-100), 4.54 (OH, d,
J ¼ 5:7 Hz, OH-C-600), 4.52 (OH, d, J ¼ 5:0 Hz, OH-C-200), 3.72 (3H,
s, OCH3), 3.66 (1H, ddd, J ¼ 11:0, 5.7, 5.2 Hz, H-600a), 3.38 (1H, brdd,
J ¼ 11:0, 5.7 Hz, H-600b), 3.27 (1H, m, H-500), 3.17 (1H, ddd, J ¼ 9:2,
8.8, 5.2 Hz, H-300), 3.01 (1H, ddd, J ¼ 9:3, 9.2, 5.3 Hz, H-400), 2.91
(1H, ddd, J ¼ 8:8, 8.0, 5.0 Hz, H-200); NMR ꢂH (500 MHz, pyridine-
d5): 8.23 (2H, d, J ¼ 8:6 Hz, H-20 and H-60), 7.12 (2H, d, J ¼ 8:6 Hz,
H-30 and H-50), 7.02 (1H, s, H-3), 6.60 (1H, s, H-5), 5.60 (1H, d,
J ¼ 8:2 Hz, H-100), 4.54 (1H, brd, J ¼ 12:0 Hz, H-600b), 4.30 (1H, dd,
J ¼ 12:0, 6.0 Hz, H-600a), 4.25 (1H, dd, J ¼ 10:0, 8.7 Hz, H-300), 4.13
(1H, dd, J ¼ 9:6, 8.7 Hz, H-400), 4.06 (1H, m, H-500), 4.03 (1H, dd,
J ¼ 10:0, 8.2 Hz, H-200), 3.73 (3H, s); NMR ꢂC (CD3OD): 197.1
(C=O), 164.3 (C-4), 163.8 (C-40), 159.0 (C-6), 158.4 (C-2), 133.6
(C-20 and C-60), 131.9 (C-10), 115.9 (C-30 and C-50), 111.7 (C-1), 102.5
(C-100), 96.8 (C-5), 94.9 (C-3), 78.3 (C-500), 77.8 (C-300), 74.8 (C-200),
71.2 (C-400), 62.6 (C-600), 55.9 (OCH3); NMR ꢂC (DMSO-d6): 192.5,
161.9, 161.0, 156.3, 156.1, 131.7, 129.8, 114.9, 110.6, 100.6, 95.1,
92.9, 77.2, 76.7, 73.2, 69.8, 60.8, 55.1; NMR ꢂC (pyridine-d5): 194.1,
163.1, 162.2, 158.0, 157.8, 132.5, 115.4, 107.9, 102.5, 96.2, 93.6, 78.6,
77.9, 74.2, 70.7, 62.0, 54.8; FABMS (negative, TEA matrix) m=z (rel.
int. %) 421 ½M ꢁ Hꢃꢁ (8); HRFABMS m=z ½M ꢁ Hꢃꢁ calcd. for
C20H21O10, 421.1135; found, 421.1138.
2,4,40-Tribenzyloxy-6-methoxybenzophenone (25). A mixture of 24
(3.49 g, 6.76 mmol), dimethyl sulfate (1.11 g, 8.80 mmol), potassium
carbonate (1.39 g, 10.1 mmol) and 18-crown-6 (0.10 mg, 0.38 mmol) as
a catalyst in CH3CN (15 ml) was refluxed for 1 h. To the reaction
mixture was added conc. NH4OH (0.5 ml), and the solution stirred
for 10 min, EtOAc subsequently added and the whole washed with
brine. The organic layer was separated, dried over MgSO4, and the
solvent was evaporated under reduced pressure. Purification by flash
column chromatography on silica gel (hexane/EtOAc 6:1) gave 25
(3.20 g, 93%).
25: amorphous white solid; mp 104.0–105.0 ꢀC (EtOH); NMR ꢂH
(CDCl3): 7.82 (2H, d, J ¼ 8:9 Hz), 7.31–7.39 (10H, m), 7.04–7.18
(5H, m), 6.95 (2H, d, J ¼ 8:9 Hz), 6.24 (2H, s), 5.10 (2H, s), 5.03 (2H,
s), 4.94 (2H, s), 3.67 (3H, s); NMR ꢂC (CDCl3): 193.3, 162.6, 161.2,
158.6, 157.4, 136.6, 136.5, 136.4, 131.9, 131.8, 128.7, 128.3, 128.2,
127.5, 127.4, 126.7, 117.4, 114.3, 112.1, 96.2, 93.1, 92.2, 70.2, 70.1,
55.8; EIMS m=z (rel. int. %): 530 (Mþ, 17), 439 (7), 333 (5), 257 (4),
211 (5), 910 (100), 65 (5), 44 (5); HREIMS m=z (Mþ) calcd. for
C35H30O5, 530.2093; found, 530.2071.
4,40-Dibenzyloxy-2-hydroxy-6-methoxybenzophenone (26). To
a
stirred solution of 25 (1.80 g, 3.39 mmol) and PhNMe2 (2.57 ml,
20.3 mmol) in CH2Cl2 (15 ml) was added powdered AlCl3 (1.36 g,
10.2 mmol) at 0 ꢀC. The solution was stirred for 10 min at 0 ꢀC. The
reaction mixture was then diluted with EtOAc, poured into ice-cold aq.
2 M HCl and mixed. The organic layer was separated, and the aqueous
phase was extracted with CHCl3. The combined organic layer was
washed with brine, dried over MgSO4 and filtered through a silica-gel
pad; the solvent was evaporated under reduced pressure to give a white
solid. The crude product was suspended in EtOAc and filtered to afford
26 (1.48 g, 98%).
26: amorphous white solid; mp 111.0–113.0 ꢀC (EtOH); NMR ꢂH
(CDCl3): 11.82 (OH, brs), 7.56 (2H, d, J ¼ 8:9 Hz), 7.32–7.44 (10H,
m), 6.94 (2H, d, J ¼ 8:9 Hz), 6.23 (1H, d, J ¼ 2:1 Hz), 6.02 (1H, d,
J ¼ 2:1 Hz), 5.11 (2H, s), 5.08 (2H, s), 3.48 (3H, s); NMR ꢂC (CDCl3):
197.4, 165.2, 164.9, 161.5, 136.4, 136.0, 134.0, 130.8, 128.7, 128.6,
128.3, 128.1, 127.7, 127.5, 113.7, 106.0, 94.6, 91.9, 70.3, 70.1, 55.2;
EIMS m=z (rel. int. %): 440 (Mþ, 30), 349 (7), 320 (4), 91 (100),
65 (5); HREIMS m=z (Mþ) calcd. for C28H24O5, 440.0998; found,
440.1659.
2,4,6,40-Tetrabenzyloxybenzophenone (23). To a suspension of
4-benzyloxybenzoic acid (2.32 g, 10.2 mmol) in CH2Cl2 (20 ml)
cooled to 0 ꢀC was added trifluoroacetic anhydride (1.67 ml,
12.0 mmol), and the mixture was stirred for 10 min to gave a clear
solution. To this solution was added 1,3,5-tribenzyloxybenzene 22
(3.0 g, 7.6 mmol), and the mixture stirred overnight at room temper-
ature. The reaction mixture was diluted with EtOAc, ice water and aq.
sat. Na2CO3, and stirred vigorously to yield a suspension again.
Sodium 4-benzyloxybenzoate was filtered off through Celite, and the
organic layer was separated and successively washed with aq. sat.
NaHCO3 and brine. The organic layer was dried over MgSO4, filtered,
and concentrated under reduced pressure. The crude product was
suspended in diethyl ether and filtered to afford 23 (3.71 g, 81%).
23: amorphous white solid; mp 119.0–121.0 ꢀC (EtOH); NMR ꢂH
(CDCl3): 7.82 (2H, d, J ¼ 8:9 Hz), 7.32–7.43 (10H, m), 7.18–7.24
(5H, m), 7.07–7.10 (5H, m), 6.95 (2H, d, J ¼ 8:9 Hz), 6.24 (2H, s),
5.11 (2H, s), 4.97 (2H, s), 4.96 (4H, s); NMR ꢂC (CDCl3): 193.3, 162.6,
161.4, 161.1, 157.6, 137.0, 136.6, 136.5, 136.4, 132.1, 131.8, 128.9,
128.7, 128.3, 128.2, 127.9, 127.8, 127.6, 127.54, 127.45, 126.7, 114.3,
93.6, 70.3, 70.1; EIMS m=z (rel. int. %): 606 (Mþ, 3), 273 (9), 91
(100), 44 (15); HREIMS m=z (Mþ) calcd. for C41H34O5, 606.2406;
found, 606.2403.
Dealkylation reaction of 25 with Lewis acids (AlCl3 and BBr3).
(a) Reaction with AlCl3
To a stirred solution of 25 (200 mg, 0.38 mmol) in CH2Cl2 (5 ml)
was added powdered AlCl3 (151 mg, 1.13 mmol) at 0 ꢀC. The solution
was stirred for 3 h at room temperature. No reaction occurred.
(b) Reaction with BBr3
To a stirred solution of 25 (206 mg, 0.39 mmol) in CH2Cl2 (5 ml)
was added BBr3 (0.39 ml of 1 M in hexane, 0.39 mmol) at ꢁ78 ꢀC. The
solution was stirred for 2 h at ꢁ78 ꢀC and then for 30 min at ꢁ60 ꢀC.
The reaction mixture was decomposed by ice-cold aq. 2 M HCl and
diluted with EtOAc. The organic layer was separated and dried over
MgSO4; the solvent was evaporated under reduced pressure. A product
with the same Rf value as that of 26 was purified by flash column
chromatography on silica gel (hexane/EtOAc 2:1). This product
suspended in hexane gave a white solid (86 mg). 1H-NMR indicated
this to be a mixture of 26 (68 mg, 41%) and 24 (18 mg, 9%).
(c) Reaction with AlCl3 and PhNMe2 at room temperature
To a stirred solution of 25 (200 mg, 0.39 mmol) and PhNMe2
(0.29 ml, 2.26 mmol) in CH2Cl2 (5 ml) was added powdered AlCl3
(150 mg, 1.1 mmol) at 0 ꢀC. The solution was stirred for 10 min at 0 ꢀC
and then for 2 h at room temperature. The reaction mixture diluted with
EtOAc was poured into ice-cold aq. 2 M HCl and mixed. The organic
layer was separated, and the aqueous phase was extracted twice with
CHCl3. The combined organic layer was washed with brine, dried over
2,4,40-Tribenzyloxy-6-hydroxybenzophenone (24). To a stirred solu-
tion of 23 (4.35 g, 7.17 mmol) and PhNMe2 (5.43 ml, 43.0 mmol) in
CH2Cl2 (30 ml) was added powdered AlCl3 (2.87 g, 21.5 mmol) at
0 ꢀC. The solution was stirred for 10 min at 0 ꢀC. The reaction mixture
was then diluted with EtOAc, poured to ice-cold aq. 2 M HCl and
mixed. The organic layer was separated, and the aqueous phase was
extracted with CHCl3. The combined organic layer was washed with
brine, dried over MgSO4 and filtered through a silica-gel pad; the
filtrate was evaporated under reduced pressure. The crude product was
suspended in EtOAc and filtered to afford 24 (2.90 g, 78%).
24: amorphous white solid; mp 146.0–148.0 ꢀC (EtOH); NMR ꢂH
(CDCl3): 11.79 (OH, brs), 7.57 (2H, d, J ¼ 8:7 Hz), 7.31–7.42
(10H, m), 7.08–7.20 (5H, m), 6.84 (2H, d, J ¼ 8:7 Hz), 6.26 (1H,
d, J ¼ 2:1 Hz), 6.12 (1H, d, J ¼ 2:1 Hz), 5.08 (2H, s), 4.99 (2H, s),
4.80 (2H, s); NMR ꢂC (CDCl3): 197.9, 165.2, 164.9, 161.6, 160.5,
MgSO4 and filtered through
evaporated under reduced pressure to give
a
silica-gel pad; the solvent was
white solid. The
a

2180
P. HENDRA et al.
crude product was suspended in EtOAc and filtered to afford 26
(160 mg, 96%).
40-Allyloxy-2,4,6-tribenzyloxybenzophenone (30). To a suspension
of 4-allyloxybenzoic acid (2.14 g, 12.0 mmol) in CH2Cl2 (20 ml)
cooled to 0 ꢀC was added trifluoroacetic anhydride (1.81 ml,
13.0 mmol), and the mixture was stirred for 10 min. To the solution
was added 1,3,5-tribenzyloxybenzene (22; 3.96 g, 10.0 mmol) and the
mixture stirred at room temperature for 48 h. The reaction mixture was
diluted with EtOAc, ice-cooled water and aq. sat. Na2CO3, and then
stirred vigorously. The organic layer was separated, successively
washed with aq. sat. NaHCO3 and brine, dried over MgSO4 and filtered
through a silica-gel pad. The solvent was evaporated under reduced
pressure. The crude product was suspended in EtOH and filtered to
afford 30 (4.57 g, 82%).
30: colorless prisms; mp 121.5–123.5 ꢀC (EtOH); NMR ꢂH
(CDCl3): 7.83 (2H, d, J ¼ 8:7 Hz), 7.35–7.38 (5H, m), 7.20–7.22
(5H, m), 7.08–7.11 (5H, m), 6.90 (2H, d, J ¼ 8:7 Hz), 6.25 (2H, s),
6.04 (1H, ddt, J ¼ 18:8, 11.8, 5.3 Hz), 5.43 (1H, ddt, J ¼ 18:8, 2.5,
2.0 Hz), 5.31 (1H, ddt, J ¼ 11:8, 2.5, 1.0 Hz), 4.98 (4H, s), 4.97 (2H,
s), 4.58 (2H, ddt, J ¼ 5:3, 2.0, 1.0 Hz); NMR ꢂC (CDCl3): 193.1,
162.4, 161.1, 157.6, 155.6, 136.6, 132.7, 132.0, 131.7, 128.7, 128.4,
128.2, 127.6, 127.5, 126.7, 118.0, 114.2, 112.8, 96.1, 93.6, 70.3, 68.8,
25.0; EIMS m=z (rel. int. %): 557 (Mþ þ1, 6), 556 (Mþ, 16), 223 (29),
161 (15), 91 (100); HREIMS m=z (Mþ) calcd. for C37H32O5, 556.2250;
found, 556.2209.
4,40-Dibenzyloxy-2-hydroxy-6-methoxybenzophenone 2-(2,3,4,6-tetra-
O-acetyl)-ꢀ-D-glucopyranoside (27). To a stirred solution of 26 (200
mg, 0.454 mmol) and O-(2,3,4,6-tetra-O-acetyl-ꢀ-D-glucopyranosyl)
trichloroacetimidate (447 mg, 0.91 mmol) in dry CH2Cl2 (5 ml) was
added BF3 OEt2 (1 drop) at 0 ꢀC. The solution was stirred for 6 h at
.
room temperature. The reaction mixture was diluted with EtOAc and
successively washed with aq. sat. NH4Cl and brine. The organic layer
was separated and dried over MgSO4; the solvent was evaporated
under reduced pressure. Purification by flash column chromatography
on silica gel (CHCl3/acetone 15:1) afforded 27 (100.5 mg, 29%) and
26 (122.5 mg, 61%).
27
27: colorless prisms; mp 77.5–78.5 ꢀC (EtOH); [ꢁ]D ꢁ16ꢀ (c 0.3,
CHCl3); NMR ꢂH (CDCl3): 7.75 (2H, d, J ¼ 8:6 Hz), 7.26–7.40 (10H,
m), 6.95 (2H, d, J ¼ 8:6 Hz), 6.45 (1H, d, J ¼ 1:9 Hz), 6.34 (1H, d,
J ¼ 1:9 Hz), 5.16 (1H, dd, J ¼ 9:9, 9.2 Hz), 5.11 (2H, s), 5.09 (2H, s),
5.02 (1H, dd, J ¼ 9:9, 9.6 Hz), 4.93 (1H, dd, J ¼ 9:6, 7.6 Hz), 4.88
(1H, d, J ¼ 7:6 Hz) , 4.19 (1H, dd, J ¼ 12:4, 5.2 Hz), 4.10 (1H, dd,
J ¼ 12:4, 2.9 Hz), 3.73 (1H, m), 3.67 (3H, s), 2.04 (3H, s), 2.00 (3H, s),
1.95 (3H, s), 1.90 (3H, s); NMR ꢂC (CDCl3): 193.7, 171.9, 171.5,
170.7, 170.5, 164.3, 162.4, 159.6, 156.7, 137.7, 133.3, 132.6, 130.12,
130.07, 129.7, 129.6, 129.0, 128.9, 115.8, 101.4, 98.0, 97.5, 95.6, 74.0,
73.4, 71.8, 71.7, 71.5, 69.4, 57.3, 22.00, 21.97, 21.7; FABMS
(negative, TEA matrix) m=z (rel. int. %) 769 ½M ꢁ Hꢃꢁ (1);
HRFABMS m=z ½M ꢁ Hꢃꢁ calcd. for C42H41O14, 769.2496; found,
769.2519.
40-Allyloxy-2,4-dibenzyloxy-6-hydroxybenzophenone (31). To
a
stirred solution of 30 (1.04 g, 1.87 mmol) and PhNMe2 (1.42 ml,
11.2 mmol) in CH2Cl2 (10 ml) was added powdered AlCl3 (0.75 g,
5.6 mmol) at 0 ꢀC. The solution was stirred for 5 min at 0 ꢀC. The
reaction mixture was then diluted with EtOAc, poured into ice-cold aq.
2 M HCl and mixed. The organic layer was separated and washed with
brine, dried over MgSO4 and filtered through a silica-gel pad. The
solvent was evaporated under reduced pressure to give a white solid.
The crude product was suspended in EtOH and filtered to afford 31
(0.70 g, 80%).
31: colorless needles; mp 114.0–115.5 ꢀC (EtOH); NMR ꢂH
(CDCl3): 11.76 (OH, brs), 7.56 (2H, d, J ¼ 8:9 Hz), 7.35–7.45 (5H,
m), 7.10–7.18 (3H, m), 6.79 (2H, d, J ¼ 8:9 Hz), 6.73–6.80 (2H, m),
6.27 (1H, d, J ¼ 2:3 Hz), 6.13 (1H, d, J ¼ 2:3 Hz), 6.01 (1H, ddt,
J ¼ 18:8, 11.8, 5.3 Hz), 5.39 (1H, ddt, J ¼ 18:8, 2.5, 2.0 Hz), 5.29 (1H,
ddt, J ¼ 11:8, 2.5, 1.0 Hz), 5.09 (2H, s), 4.81 (2H, s), 4.48 (2H, ddt,
J ¼ 5:3, 2.0, 1.0 Hz); NMR ꢂC (CDCl3): 197.9, 165.1, 164.9, 161.4,
160.5, 135.9, 135.6, 134.2, 132.8, 130.6, 128.7, 128.3, 128.1, 127.7,
127.5, 126.5, 117.9, 113.7, 106.3, 96.1, 94.8, 92.9, 70.3, 70.1, 68.8;
EIMS m=z (rel. int. %): 467 (Mþ þ1, 7), 466 (Mþ, 24), 375 (6), 243
(6), 224 (5), 161 (18), 91 (100); HREIMS m=z (Mþ) calcd. for
C30H26O5, 466.1780; found, 466.1775.
4,40-Dibenzyloxy-2-hydroxy-6-methoxybenzophenone 2-O-ꢀ-D-glu-
copyranoside (28). Compound 27 (70 mg, 0.091 mmol) was dissolved
in MeOH (6 ml) and triethylamine (2 ml), and then stirred at room
temperature for 15 h. To the reaction mixture was added toluene, and
the solution evaporated to dryness. The crude product was suspended
in hexane and diethyl ether, and filtered to afford 28 (50 mg, 92%).
27
28: colorless prisms; mp 79.5–81.5 ꢀC (EtOH); [ꢁ]D ꢁ6ꢀ (c 0.1,
MeOH); NMR ꢂH (CDCl3): 7.78 (2H, d, J ¼ 8:4 Hz), 7.39–7.42 (10H,
m), 6.94 (2H, d, J ¼ 8:4 Hz), 6.45 (1H, d, J ¼ 1:9 Hz), 6.32 (1H, d,
J ¼ 1:9 Hz), 5.09 (4H, brs), 4.73 (1H, d, J ¼ 7:5 Hz), 3.75–3.86 (2H,
m), 3.71 (3H, s), 3.51–3.57 (3H, m), 3.41 (1H, m), 2.34 (OH, brs);
NMR ꢂC (CDCl3): 194.1, 163.1, 161.7, 158.7, 157.1, 136.2, 132.1,
131.5, 128.8, 128.7, 128.3, 128.2, 127.5, 114.4, 103.9, 96.3, 96.1, 94.5,
75.9, 73.7, 70.4, 70.2, 70.2, 69.9, 62.4, 55.8; FABMS (negative, TEA
matrix) m=z (rel. int. %) 601 ½M ꢁ Hꢃꢁ (1); HRFABMS m=z ½M ꢁ Hꢃꢁ
calcd. for C34H33O10, 601.2074; found, 601.2075.
2,4,40-Trihydroxy-6-methoxybenzophenone 2-O-ꢀ-D-glucopyranoside
(4). To a solution of 28 (53 mg, 0.088 mmol) in dioxane (4 ml) was
added 10% Pd/C (50 mg), and the resulting suspension was stirred
vigorously under a hydrogen atmosphere for 15 h at room temperature.
The catalyst was filtered off through Celite, and the filtrate was
evaporated under reduced pressure. The crude product was suspended
in CHCl3 and filtered to afford 4 (28 mg, 75%).
40-Allyloxy-2,4-dibenzyloxy-6-methoxybenzophenone (32). A sus-
pension of 31 (3.45 g, 7.40 mmol), potassium carbonate (1.42 g,
10.3 mmol), 18-crown-6 (0.10 g, 0.38 mmol), and dimethyl sulfate
(1.08 g, 8.56 mmol) in acetone (30 ml) was refluxed for 2 h. To the
reaction mixture was added conc. NH4OH (2 ml), EtOAc and water.
The organic layer was separated, washed with brine and dried over
MgSO4; the solvent was evaporated under reduced pressure. The crude
product was suspended in hexane and filtered to afford 32 (3.36 g, 95%).
32: colorless needles; mp 83.0–84.0 ꢀC (EtOH); NMR ꢂH (CDCl3):
7.82 (2H, d, J ¼ 8:4 Hz), 7.33–7.41 (5H, m), 7.18–7.24 (3H, m), 7.04–
7.07 (2H, m), 6.89 (2H, d, J ¼ 8:4 Hz), 6.25 (2H, s), 6.03 (1H, ddt,
J ¼ 17:5, 10.6, 5.3 Hz), 5.40 (1H, ddt, J ¼ 17:5, 2.1, 1.9 Hz), 5.29 (1H,
ddt, J ¼ 10:6, 2.1, 1.1 Hz), 5.04 (2H, s), 4.95 (2H, s), 4.57 (2H, ddt,
J ¼ 5:3, 1.9, 1.1 Hz), 3.67 (3H, s); NMR ꢂC (CDCl3): 193.3, 162.5,
161.2, 158.6, 157.4, 136.6, 136.5, 132.6, 131.7, 128.6, 128.3, 128.1,
127.5, 126.7, 118.0, 114.2, 112.1, 96.1, 93.0, 92.2, 70.3, 70.2, 68.8,
55.8; EIMS m=z (rel. int. %): 481 (Mþ þ1, 16), 480 (Mþ, 51), 463 (8),
439 (10), 257 (9), 161 (14), 91 (100), 43 (11); HREIMS m=z (Mþ)
calcd. for C31H28O5, 480.1937; found, 480.1958.
28
4: colorless plates; mp 136.0–138.0 ꢀC (EtOH); [ꢁ]D ꢁ10ꢀ (c 0.1,
MeOH); NMR ꢂH (DMSO-d6): 10.26 (OH, brs), 9.81 (OH, brs), 7.55
(2H, d, J ¼ 8:0 Hz), 6.77 (2H, d, J ¼ 8:0 Hz), 6.26 (1H, brs), 6.16 (1H,
brs), 4.94 (OH, d, J ¼ 4:9 Hz), 4.90 (OH, d, J ¼ 5:3 Hz), 4.73 (1H, d,
J ¼ 7:0 Hz), 4.52 (OH, d, J ¼ 4:6 Hz), 4.46 (OH, d, J ¼ 5:0 Hz), 3.63
(1H, m), 3.55 (3H, s), 3.48 (1H, m), 3.20 (1H, m), 3.17 (1H, m), 3.06
(1H, m), 2.89 (1H, m); NMR ꢂH (500 MHz, CD3OD): 7.66 (2H, d,
J ¼ 8:7 Hz, H-20 and H-60), 6.78 (2H, d, J ¼ 8:7 Hz, H-30 and H-50),
6.37 (1H, d, J ¼ 1:9 Hz, H-3), 6.22 (1H, d, J ¼ 1:9 Hz, H-5), 4.83 (1H,
d, J ¼ 7:9 Hz, H-100), 3.84 (1H, dd, J ¼ 12:0, 2.1 Hz, H-600b), 3.66 (1H,
dd, J ¼ 12:0, 5.5 Hz, H-600a), 3.62 (3H, s, OCH3), 3.37 (1H, dd,
J ¼ 9:3, 9.0 Hz, H-300), 3.36 (1H, m, H-500), 3.28 (1H, dd, J ¼ 9:3,
9.3 Hz, H-400), 3.19 (1H, dd, J ¼ 9:0, 7.9 Hz, H-200); NMR ꢂC (CD3OD):
196.4 (C=O), 164.1 (C-40), 161.9 (C-4), 160.2 (C-6), 157.9 (C-2),
133.5 (C-20 and C-60), 131.6 (C-10), 116.0 (C-30 and C-50), 112.1 (C-1),
102.8 (C-100), 96.9 (C-3), 94.6 (C-5), 78.2 (C-500), 77.8 (C-300), 74.7
(C-200), 71.1 (C-400), 62.5 (C-600), 56.1 (OCH3); FABMS (negative, TEA
matrix) m=z (rel. int. %) 421 ½M ꢁ Hꢃꢁ (7); HRFABMS m=z ½M ꢁ Hꢃꢁ
calcd. for C20H21O10, 421.1135; found, 421.1138.
2,4-Dibenzyloxy-40-hydroxy-6-methoxybenzophenone (33). To
a
solution of 32 (0.53 g, 1.0 mmol) in dioxane (3 ml) and MeOH (3 ml)
was added Pd(PPh3)4 (34 mg, 0.029 mmol) under an N2 atmosphere.
The solution was stirred for 10 min, K2CO3 (0.41 g, 3.0 mmol) was
added, and stirring was continued for 20 h. The reaction mixture was
then diluted with EtOAc, poured into ice-cold aq. 2 M HCl and mixed.

Synthesis of Benzophenone Glucopyranosides from Phaleria macrocarpa
2181
The organic layer was separated and washed with brine, dried over
MgSO4 and filtered through a silica-gel pad. The solvent was
evaporated under reduced pressure. The crude product was suspended
in hexane and filtered to afford 33 (0.43 g, 98%).
superscript may be interchangeable]; FABMS (negative, TEA matrix)
m=z (rel. int. %) 421 ½M ꢁ Hꢃꢁ (8); HRFABMS m=z ½M ꢁ Hꢃꢁ calcd.
for C20H21O10, 421.1135; found, 421.1130.
33: amorphous white solid; mp 195.0–197.0 ꢀC (EtOH); NMR
ꢂH (acetone-d6): 9.12 (OH, brs), 7.70 (2H, d, J ¼ 8:7 Hz), 7.35–7.51
(5H, m), 7.15–7.24 (5H, m), 6.90 (2H, d, J ¼ 8:7 Hz), 6.51 (1H, d,
J ¼ 2:0 Hz), 6.44 (1H, d, J ¼ 2:0 Hz), 5.17 (2H, s), 5.06 (2H, s), 3.69
(3H, s); NMR ꢂC (acetone-d6): 192.6, 162.6, 162.1, 159.4, 158.2,
138.0, 132.4, 131.9, 129.6, 129.3, 129.0, 128.8, 128.6, 128.3, 127.8,
115.9, 113.1, 94.0, 92.9, 70.8, 70.7, 56.1; EIMS m=z (rel. int. %): 441
(Mþ þ1, 8), 440 (Mþ, 30), 349 (7), 320 (4), 91 (100), 65 (5); HREIMS
m=z (Mþ) calcd. for C28H24O5, 440.0998; found, 440.1659.
40Allyloxy-4-benzyloxy-2-hydroxy-6-methoxybenzophenone (36). To
a stirred solution of 32 (1.06 g, 2.21 mmol) and PhNMe2 (1.51 ml,
12.0 mmol) in CH2Cl2 (10 ml) was added powdered AlCl3 (0.80 g,
6.0 mmol) at 0 ꢀC. The solution was stirred for 20 min at 0 ꢀC. The
reaction mixture was then diluted with EtOAc, poured into ice-cold aq.
2 M HCl and mixed. The organic layer was separated and washed with
brine, dried over MgSO4 and filtered through a silica-gel pad. The
solvent was evaporated under reduced pressure. The crude product was
suspended in EtOH and filtered to afford 36 (0.71 g, 82%).
36: colorless needles; mp 118.5–119.5 ꢀC (EtOH); NMR ꢂH
(CDCl3): 11.81 (OH, brs), 7.57 (2H, d, J ¼ 8:9 Hz), 7.33–7.45 (5H,
m), 6.88 (2H, d, J ¼ 8:9 Hz), 6.23 (1H, d, J ¼ 2:1 Hz), 6.05 (1H, ddt,
J ¼ 18:8, 11.9, 5.3 Hz), 6.02 (1H, d, J ¼ 2:1 Hz), 5.43 (1H, ddt,
J ¼ 18:8, 2.0, 1.5 Hz), 5.31 (1H, ddt, J ¼ 11:9, 2.0, 1.3 Hz), 5.09 (2H,
s), 4.59 (2H, ddt, J ¼ 5:3, 1.5, 1.3 Hz), 3.51 (3H, s); NMR ꢂC (CDCl3):
197.3, 165.2, 164.9, 161.5, 161.4, 136.0, 133.9, 132.8, 130.8, 128.7,
128.3, 127.7, 118.0, 114.5, 113.5, 96.2, 94.6, 91.9, 70.3, 68.8, 55.1;
EIMS m=z (rel. int. %): 391 (Mþ þ1, 11), 390 (Mþ, 46), 389 (21), 299
(8), 91 (100); HREIMS m=z (Mþ) calcd. for C24H22O5, 390.1467;
found, 390.1462.
2,4-Dibenzyloxy-40-hydroxy-6-methoxybenzophenone 40-(2,3,4,6-
tetra-O-acetyl)-ꢀ-D-glucopyranoside (34). A mixture of 33 (350 mg,
0.795 mmol), 2,3,4,6-tetra-O-acetyl-ꢀ-D-glucopyranosyl bromide
(653 mg, 1.59 mmol), BnBu3NCl (10.2 mg), K2CO3 (529 mg, 3.97
mmol) and CH2Cl2 (8 ml) was stirred at room temperature for 24 h.
The reaction mixture was acidifed with aq. 2 M HCl and diluted with
EtOAc. The organic layer was separated, washed with aq. sat.
NaHCO3, dried over MgSO4, and evaporated under reduced pressure.
Purification by flash column chromatography on silica gel (CHCl3/
acetone 15:1) afforded 34 (380 mg, 62%).
27
34: amorphous white solid; mp 152.5–154.5 ꢀC (EtOH); [ꢁ]D
ꢁ11ꢀ (c 0.3, CHCl3); NMR ꢂH (CDCl3): 7.82 (2H, d, J ¼ 8:9 Hz),
7.33–7.41 (5H, m), 7.20–7.22 (3H, m), 7.04–7.07 (2H, m), 6.97 (2H, d,
J ¼ 8:9 Hz), 6.25 (2H, brs), 5.29 (1H, d, J ¼ 7:7 Hz), 5.22 (2H, m)
5.16 (1H, dd, J ¼ 9:6, 9.0 Hz), 5.05 (2H, s), 4.95 (2H, s), 4.28 (1H, dd,
J ¼ 12:2, 5.6 Hz), 4.15 (1H, dd, J ¼ 12:2, 2.3 Hz), 3.89 (1H, m), 3.68
(3H, s), 2.10 (3H, s), 2.04 (9H, s); NMR ꢂC (CDCl3): 193.4, 170.5,
170.2, 169.3, 169.2, 161.4, 160.2, 158.7, 157.5, 136.4, 133.8, 131.6,
128.7, 128.3, 128.2, 127.7, 127.6, 126.7, 116.0, 106.1, 98.2, 96.1,
93.0, 92.1, 72.6, 72.2, 71.0, 70.3, 68.2, 63.9, 61.8, 55.8, 20.7, 20.6;
FABMS (negative, TEA matrix) m=z (rel. int. %) 679 ½M ꢁ Hꢃꢁ (8);
HRFABMS m=z ½M ꢁ Hꢃꢁ calcd. for C35H35O14, 679.2027; found,
679.2033.
4-Benzyloxy-2,40-dihydroxy-6-methoxybenzophenone (37). To
a
solution of 36 (0.55 g, 1.4 mmol) in dioxane (5 ml) and MeOH (5 ml)
was added Pd(PPh3)4 (35 mg, 0.030 mmol) under an N2 atmosphere.
The solution was stirred for 10 min, K2CO3 (0.97 g, 7.0 mmol) was
added, and stirring was continued for 20 h. The reaction mixture was
then diluted with EtOAc, poured into ice-cold aq. 2 M HCl and mixed.
The organic layer was separated and washed with brine, dried over
MgSO4 and filtered through a silica-gel pad. The solvent was
evaporated under reduced pressure. The crude product was purified
by flash column chromatography on silica gel (hexane/EtOAc 2:1)
afforded 37 (0.44 g, 90%).
37: colorless prisms; mp 59.0–61.0 ꢀC (EtOH); NMR ꢂH (CDCl3):
11.83 (OH, brs), 7.53 (2H, d, J ¼ 8:7 Hz), 7.33–7.43 (5H, m), 6.80
(2H, d, J ¼ 8:7 Hz), 6.24 (1H, d, J ¼ 2:3 Hz), 6.03 (1H, d, J ¼ 2:3 Hz),
5.43 (OH, brs), 5.09 (2H, s), 3.51 (3H, s); NMR ꢂC (CDCl3): 197.4,
165.2, 165.0, 161.5, 158.7, 135.9, 134.0, 131.1, 128.7, 128.4, 127.7,
114.4, 96.1, 94.6, 92.0, 70.3, 55.1; EIMS m=z (rel. int. %): 351 (Mþ
þ1, 11), 350 (Mþ, 50), 349 (16), 259 (14), 91 (100); HREIMS m=z
(Mþ) calcd. for C21H18O5, 350.1154; found, 350.1152.
2,4-Dibenzyloxy-40-hydroxy-6-methoxybenzophenone 40-O-ꢀ-D-glu-
copyranoside (35). Compound 34 (100 mg, 0.130 mmol) was dissolved
in MeOH (6 ml) and triethylamine (2 ml), and the solution stirred at
room temperature for 30 h. To the reaction mixture was added toluene,
and the solution evaporated to dryness. The crude product was
suspended in CHCl3 and filtered to afford 35 (78 mg, 98%).
27
35: colorless plates; mp 83.0–85.0 ꢀC (EtOH); [ꢁ]D ꢁ35ꢀ (c 0.3,
40,6-Diacetoxy-4-benzyloxy-6-methoxybenzophenone (38). A mix-
ture of 37 (0.40 g, 1.14 mmol), triethylamine (0.80 ml, 5.7 mmol),
DMAP (5 mg, 0.04 mmol) and acetic anhydride (0.30 ml, 3.4 mmol) in
CH2Cl2 (10 ml) was stirred at room temperature for 1 h. The reaction
mixture was added with toluene and evaporated to dryness. The crude
product purified by flash column chromatography on silica gel
(hexane/EtOAc 2:1) afforded 38 (0.50 g, 99%).
38: colorless prisms; mp 115.0–117.0 ꢀC (hexane); NMR ꢂH
(CDCl3): 7.65 (2H, d, J ¼ 8:0 Hz), 7.20–7.27 (5H, m), 6.97 (2H, d,
J ¼ 8:0 Hz), 6.29 (2H, brs), 4.89 (2H, s), 3.47 (3H, s), 1.86 (3H, s),
1.79 (3H, s); NMR ꢂC (CDCl3): 191.2, 168.2, 161.0, 158.7, 154.1,
149.7, 135.9, 135.5, 130.5, 128.4, 128.0, 127.3, 121.2, 114.7, 100.9,
97.0, 95.9, 70.1, 57.5, 55.5, 20.1, 18.1; EIMS m=z (rel. int. %): 434
(Mþ, 20), 392 (36), 259 (16), 91 (100); HREIMS m=z (Mþ) calcd. for
C25H22O7, 434.1366; found, 434.1392.
CHCl3); NMR ꢂH (CDCl3): 7.73 (2H, d, J ¼ 8:0 Hz), 7.30–7.35 (5H,
m), 7.08–7.11 (3H, m), 6.97 (2H, d, J ¼ 8:0 Hz), 6.94–6.98 (2H, m),
6.20 (1H, brs), 6.18 (1H, brs), 4.98 (3H, s), 4.84 (2H, s), 3.75–3.82
(2H, m), 3.60–3.74 (3H, m), 3.52 (3H, s), 3.36–3.40 (1H, m); NMR ꢂC
(CDCl3): 193.6, 161.4, 160.8, 158.6, 157.5, 136.5, 136.4, 133.2, 131.7,
128.6, 128.4, 128.1, 127.6, 126.7, 116.0, 105.4, 99.8, 96.1, 93.2, 92.2,
75.9, 75.1, 73.2, 70.2, 69.3, 65.5, 60.9, 55.7; FABMS (negative, TEA
matrix) m=z (rel. int. %) 601 ½M ꢁ Hꢃꢁ (1); HRFABMS m=z ½M ꢁ Hꢃꢁ
calcd. for C34H33O10, 601.2074; found, 601.2092.
2,4,40-Trihydroxy-6-methoxybenzophenone 40-O-ꢀ-D-glucopyrano-
side (5). To a solution of 35 (57 mg, 0.095 mmol) in dioxane (3 ml)
was added 10% Pd/C (20 mg), and the resulting suspension was stirred
vigorously under a hydrogen atmosphere for 15 h at room temperature.
The catalyst was filtered off through Celite, and the filtrate was
evaporated under reduced pressure. The crude product was suspended
in CHCl3 and filtered to afford 5 (32.2 mg, 81%).
2,40-Diacetoxy-4-hydroxy-6-methoxybenzophenone (39). To a solu-
tion of 38 (0.47 g, 1.1 mmol) in dioxane (20 ml) was added 10% Pd/C
(57 mg), and the resulting suspension was stirred vigorously overnight
under a hydrogen atmosphere at room temperature. The catalyst was
filtered off through Celite, and the filtrate was evaporated under
reduced pressure. The crude product was suspended in hexane and
filtered to afford 39 (0.31 g, 83%).
39: amorphous white solid; mp 132.0–134.0 ꢀC (EtOH); NMR ꢂH
(CDCl3): 7.82 (2H, d, J ¼ 8:6 Hz), 7.15 (2H, d, J ¼ 8:6 Hz), 6.28 (1H,
brs), 6.24 (1H, brs), 3.56 (3H, s), 2.32 (3H, s), 1.98 (3H, s); NMR ꢂC
(CDCl3): 192.9, 169.6, 168.9, 159.5, 159.2, 154.4, 149.7, 135.7, 131.1,
121.6, 113.6, 102.8, 97.3, 96.1, 55.8, 21.2, 20.6; EIMS m=z (rel. int.
27
5: colorless prisms; mp 245.5–247.5 ꢀC (EtOH); [ꢁ]D ꢁ55ꢀ (c 0.3,
MeOH); NMR ꢂH (500 MHz, CD3OD): 7.62 (2H, d, J ¼ 8:8 Hz, H-20
and H-60), 7.10 (2H, d, J ¼ 8:8 Hz, H-30 and H-50), 5.99 (2H, s, H-3
and H-5), 5.01 (1H, d, J ¼ 7:4 Hz, H-100), 3.89 (1H, dd, J ¼ 12:1,
2.0 Hz, H-600b), 3.69 (1H, dd, J ¼ 12:1, 5.6 Hz, H-600a), 3.54 (3H, s,
OCH3), 3.47–3.48 (3H, m, H-200, H-300 and H-500), 3.39 (1H, dd,
J ¼ 9:4, 9.1 Hz, H-400); NMR ꢂC (CD3OD): 198.1 (C=O), 164.2
(C-4a0 ), 162.28 and 162.25 (C-2a and C-6b), 162.21 (C-40b), 135.7
(C-100), 132.0 (C-20 and C-60), 116.7 (C-30 and C-50), 107.7 (C-1), 101.6
(C-1 ), 96.7 (C-5c), 92.2 (C-3c), 78.2 (C-500), 77.9 (C-300d), 74.8
(C-200d), 71.3 (C-400), 62.4 (C-600), 55.8 (OCH3) [signals with the same

2182
P. HENDRA et al.
%): 344 (Mþ, 29), 259 (100), 167 (20), 43 (27); HREIMS m=z (Mþ)
calcd. for C18H16O7, 344.0896; found, 344.0888.
The dried leaves of P. macrocarpa (1.49 g) were extracted
with MeOH (10 ml) for 2 weeks at room temperature and filtered.
The filtrate was concentrated to give a residue (0.389 g). Under
essentially the same conditions, the same compound (30.3 mg) was
obtained:
2,40-Diacetoxy-4-hydroxy-6-methoxybenzophenone 4-(2,3,4,6-tetra-
O-acetyl-ꢀ-D-glucopyranoside) (40). To a stirred solution of 39
(200 mg, 0.581 mmol) and O-(2,3,4,6-tetra-O-acetyl-ꢀ-D-glucopyrano-
syl) trichloroacetimidate (458 mg, 0.930 mmol) in dry CH2Cl2 (5 ml)
colorless prisms; mp 101.5–103.2 ꢀC (EtOH); [ꢁ]D ꢁ14ꢀ (c 0.3,
27
MeOH), ꢁ2:8ꢀ (c 0.3, EtOH); FABMS (negative, TEA matrix) m=z
(rel. int. %) 421 ½M ꢁ Hꢃꢁ (13); HRFABMS m=z ½M ꢁ Hꢃꢁ calcd. for
C20H21O10, 421.1135; found, 421.1138. The 1H- and 13C-NMR data
for the constituent were identical with those of synthesized 2.
was added BF3 OEt2 (1 drop) at 0 ꢀC. The solution was stirred for 6 h
.
at room temperature. The reaction mixture was diluted with EtOAc and
successively washed with NH4Cl and brine. The organic layer was
separated, dried over MgSO4, and evaporated under reduced pressure.
Purification by flash column chromatography on silica gel (CHCl3/
acetone 15:1) afforded 40 (284 mg, 73%).
Acknowledgments
27
40: colorless plates; mp 66.5–68.0 ꢀC (EtOH); [ꢁ]D ꢁ19ꢀ (c 0.3,
We are grateful to Mr. Yusuke Takata of our
laboratory, Mr. Kenji Watanabe and Dr. Eri Fukushi
of the GC-MS and NMR Laboratory, Faculty of
Agriculture, Hokkaido University for their skill and
assistance in analysing the NMR and MS data.
MeOH); NMR ꢂH (CDCl3): 7.82 (2H, d, J ¼ 8:6 Hz), 7.15 (2H, d,
J ¼ 8:6 Hz), 6.50 (1H, d, J ¼ 1:6 Hz), 6.45 (1H, d, J ¼ 1:6 Hz), 5.25–
5.35 (2H, m), 5.17 (1H, d, J ¼ 7:6 Hz), 5.12–5.21 (1H, m), 4.27 (1H,
dd, J ¼ 12:3, 5.4 Hz), 4.18 (1H, dd, J ¼ 12:3, 2.0 Hz), 3.91 (1H, m),
3.68 (3H, s), 2.31 (3H, s), 2.09 (3H, s), 2.07 (3H, s), 2.06 (3H, s), 2.04
(3H, s), 1.98 (3H, s); NMR ꢂC (CDCl3): 191.4, 170.4, 170.1, 169.34,
169.3, 168.7, 168.5, 158.8, 158.7, 154.5, 149.6, 135.2, 130.9, 121.6,
117.1, 103.2, 99.1, 96.1, 72.6, 72.3, 71.0, 68.2, 62.0, 56.1, 21.5,
21.2, 20.7, 20.6; FABMS (negative, TEA matrix) m=z (rel. int. %) 674
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25
6: colorless plates; mp 110.0–112.0 ꢀC (EtOH); [ꢁ]D ꢁ35ꢀ (c 0.3,
MeOH); NMR ꢂH (500 MHz, CD3OD): 7.63 (2H, d, J ¼ 8:8 Hz, H-20
and H-60), 6.78 (2H, d, J ¼ 8:8 Hz, H-30 and H-50), 6.35 (1H, d,
J ¼ 2:0 Hz, H-5), 6.30 (1H, d, J ¼ 2:0 Hz, H-3), 4.92 (1H, d,
J ¼ 7:4 Hz, H-100), 3.92 (1H, dd, J ¼ 12:0, 2.2 Hz, H-600b), 3.69 (1H,
dd, J ¼ 12:0, 6.1 Hz, H-600a), 3.63 (3H, s, OCH3), 3.44–3.49 (3H, m,
H-200, H-300 and H-500), 3.37 (1H, dd, J ¼ 9:4, 9.1 Hz, H-400); NMR ꢂC
(CD3OD): 197.1 (C=O), 164.0 (C-40), 162.1 (C-4), 160.6 (C-6), 158.8
(C-2), 133.2 (C-20 and C-60), 131.6 (C-10), 116.0 (C-30 and C-50), 111.6
(C-1), 102.1 (C-100), 97.8 (C-3), 93.3 (C-5), 78.4 (C-500), 78.0 (C-300),
74.8 (C-200), 71.4 (C-400), 62.6 (C-600), 56.1 (OCH3); FABMS (negative,
TEA matrix) m=z (rel. int. %) 421 ½M ꢁ Hꢃꢁ (4); HRFABMS m=z
½M ꢁ Hꢃꢁ calcd. for C20H21O10, 421.1135; found, 421.1138.
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Extraction and isolation of phalerin from the fruits and leaves of
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(a) Plant material
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4149–4156 (2005).
Sliced dry fruits of P. macrocarpa were purchased from a local
market in Yogyakarta, Indonesia, in 2006. The leaves of P. macrocarpa
were collected in Yogyakarta, Indonesia, in 2009 and air dried. A
voucher specimen was deposited at the Laboratory of Pharmacognosy-
Phytochemistry, Faculty of Pharmacy, Sanata Dharma University,
Yogyakarta.
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(b) Extraction and isolation of phalerin
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The sliced dry fruits of P. macrocarpa (2.94 g) were extracted with
MeOH (10 ml) for 2 weeks at room temperature and filtered. The
filtrate was concentrated to give a residue (0.444 g). The MeOH extract
and synthesized 1, 2 and 4–6 were developed on a silica gel TLC plate
(CHCl3/MeOH 3:1) by the technique of double spotting. One spot with
the same Rf value of synthesized 2 was observed in the MeOH extract.
There was, however, no corresponding spot to compounds 1 and 4–6 in
the MeOH extract. By using synthesized 2 as a reference compound,
the residue (0.444 g) was subjected to flash column chromatography on
silica gel (CHCl3/MeOH 3:1), and then applied to preparative TLC
(1 mm thickness) on silica gel (CHCl3/MeOH 3:1) to afford a white
solid (28.8 mg):
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colorless prisms; mp 101.8–103.5 ꢀC (EtOH); [ꢁ]D ꢁ18ꢀ (c 0.9,
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147–152 (1997).
27
MeOH), ꢁ2:7ꢀ (c 0.15, EtOH); FABMS (negative, TEA matrix) m=z
(rel. int. %) 421 ½M ꢁ Hꢃꢁ (8); HRFABMS m=z ½M ꢁ Hꢃꢁ calcd. for
C20H21O10, 421.1135; found, 421.1123. The 1H- and 13C-NMR data
for the constituent were identical with those of synthesized 2.
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Thayumanawan S, J. Org. Chem., 68, 1146–1149 (2003).