Synthesis and antibacterial activity of chalcones bearing prenyl or geranyl groups from Angelica keiskei

Article abstract of DOI:10.1016/j.tet.2011.04.104

Chalcones bearing prenyl or geranyl groups from Angelica keiskei, such as 4-hydroxyderricin (1a), xanthoangelol (1e), xanthoangelol F (1f), xanthoangelol H (2), deoxyxanthoangelol H (3), and deoxydihydroxanthoangelol H (4) and their derivatives were synthesized. From the evaluation of antibacterial activity of the synthesized chalcones, 1a, isobavachalcone (1b), 1e, 1f, bavachalcone (5a), and broussochalcone B (5b) were found to inhibit Gram-positive bacteria.

Full text of DOI:10.1016/j.tet.2011.04.104

Tetrahedron 67 (2011) 5346e5359
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis and antibacterial activity of chalcones bearing prenyl or geranyl groups
from Angelica keiskei
*
Kazuhiro Sugamoto , Yoh-ichi Matsusita, Kana Matsui, Chiaki Kurogi, Takanao Matsui
Faculty of Engineering, University of Miyazaki, Gakuen-Kibanadai, Miyzaki 889-2192, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Chalcones bearing prenyl or geranyl groups from Angelica keiskei, such as 4-hydroxyderricin (1a), xan-
thoangelol (1e), xanthoangelol F (1f), xanthoangelol H (2), deoxyxanthoangelol H (3), and deoxydihy-
droxanthoangelol H (4) and their derivatives were synthesized. From the evaluation of antibacterial
activity of the synthesized chalcones, 1a, isobavachalcone (1b), 1e, 1f, bavachalcone (5a), and brousso-
chalcone B (5b) were found to inhibit Gram-positive bacteria.
Received 13 January 2011
Received in revised form 28 April 2011
Accepted 29 April 2011
Available online 6 May 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Prenylated chalcone
Geranylated chalcone
Angelica keiskei
[1,3]-Sigmatropic rearrangement
Antibacterial activity
1. Introduction
HO
O
O
OH O
R1
R2
Chalcones bearing prenyl or geranyl groups are an abundant
subclass of natural flavonoids and have exhibited a variety of bi-
ological activities. 4-Hydroxyderricin (1a),1 xanthoangelol (1e),1
xanthoangelol F (1f),2 xanthoangelol H (2),2 deoxyxanthoangelol
H (3),3 and deoxydihydroxanthoangelol H (4)3 were recently
reported to be isolated from Angelica keiskei as biologically active
chalcones (Fig. 1). For example, 1a showed hypotensive and lipid-
regulatory activity in hypertensive rats,4 as well as antimetastatic
activity;5 1a and 1e showed antibacterial activity against Gram-
positive pathogenic bacteria,6 and antitumor-promoting activity
in mouse skin carcinogenesis using DMBA plus TPA;7 1a, 1e, and 1f
showed phenylephrine-induced vasoconstriction in vivo;8 1a, 1e,
1f, and 2 showed cytotoxicity against neuroblastoma cells;9 1f
showed an inhibitory effect on the induction of EBV-EA by TPS in
Raji cells.10
R3 MeO
OH
2
1a: R1=prenyl, R2=OMe, R3=OH
1b: R1=prenyl, R2=OH, R3=OH
1c: R1=prenyl, R2=OMe, R3=OMe
1d: R1=prenyl, R2=OMe, R3=H
1e: R1=geranyl, R2=OH, R3=OH
1f: R1=geranyl, R2=OMe, R3=OH
O
O
MeO
R1
OH
R2
3
OH O
O
O
5a: R1=OMe, R2=OH
5b: R1=OH, R2=OH
5c: R1=OMe, R2=OMe
5d: R1=OMe, R2=H
MeO
OH
Recently, 1e was synthesized by Jung et al.11 However, no work
has been done on the synthesis of 1a, 1b, 1f, 2, 3, and 4. It seems to
be important to develop synthetic routes for these chalcones and
related derivatives for the elucidation of the relationship between
their structures and potential activities. We preliminarily reported
the first synthesis of prenylated chalcone 1a and its derivatives 2, 3,
and 4.12 In this paper, synthesis of these chalcones and their related
4
Fig. 1. Selected naturally occurring chalcones bearing prenyl or geranyl groups.
derivatives 1bed, 5aed, and additional synthesis of geranylated
chalcones 1e, 1f are reported in details. Furthermore, evaluation of
the antibacterial activity of these synthesized chalcones is also
reported.
* Corresponding author. Tel.: þ81 985 58 7390; fax: þ81 985 58 7323; e-mail
address: sugamoto@cc.miyazaki-u.ac.jp (K. Sugamoto).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.04.104

K. Sugamoto et al. / Tetrahedron 67 (2011) 5346e5359
5347
Table 1
2. Results and discussion
Rearrangement of 11a in the presence of solid acid catalyst
OH O
OH O
2.1. Synthesis of prenylated chalcones 1a, 2, 3, and 4
OH O
Scheme 1 shows our synthetic strategy for synthesis of prenylated
chalcones 1a, 2, 3, and 4. As illustrated, ClaiseneSchmidt condensa-
tionofthekey intermediate6with4-methoxymethoxybenzaldehyde
(7a) would give 1a. The key compound 6 could be obtained from
accessible 20-hydroxy-40-methoxyacetophenone (8a). Chroma-
nochalcones 2, 3, and 4 also would be prepared via 6.
MeO
MeO
+
+
MeO
O
O
6
13
14
MeO
OH O
O
O
11a
+
MeO
+
MeO
OH O
OH O
8a
10
OHC
+
1a
Entry
1
Conditions
Yield/%
OMOM MeO
MeO
6
13
14
10
8a
7a
6
8a
Montmorillonite K10
(1 wt equiv),
CH2Cl2, 0 ꢀC, 0.5 h
53
25
7
0
4
HO
O
O
2
Florisil (10 wt equiv),
toluene, reflux, 2 h
27
32
0
8
10
2
7a +
MeO
9
O
O
The ClaiseneSchmidt condensation of 6 with 7a was attempted
under several conditions as shown in Table 2, but the desired
chalcone 15a was obtained in unsatisfactory yields in all cases. The
low yield of 15a is presumably caused by secondary cyclization of
20-hydroxychalcone to flavanone as reported in the literature.16 In
contrast,11a was allowed to react directly with 7a prepared from 12
to afford 20-prenyloxychalcone 16a in very high yield (Scheme 3).
The [1,3]-sigmatropic rearrangement of 16a using montmorillonite
K10 at 0 ꢀC gave the desired 30-prenylchalcone 15a in 46% yield as
a main product, along with 50-prenylchalcone 17a (26%), 30,50-
diprenylchalcone 18a (0.9%), and chalcone with no prenyl group
19a (18%). Romano and Casillas were previously reported that
a 30-prenylchalcone was only obtained in low yield on a similar
[1,3]-sigmatropic rearrangement of 20-prenyloxychalcone with
montmorillonite KSF in toluene at 100 ꢀC.17 Since 30-prenylchalcone
15a was obtained in moderate yield in the present conditions,
montmorillonite K10 was ascertained to be more appropriate than
montmorillonite KSF on the rearrangement of 20-prenylox-
ychalcones. Deprotection of 15a using p-toluenesulfonic acid at
30 ꢀC in methanol gave 1a in high yield. Thus 1a could be prepared
from 8a in 41% yield over four steps.
3, 4
7a +
MeO
10
Scheme 1.
Synthesis of 1a via [1,3]-sigmatropic rearrangement of 20-pre-
nyloxyacetophenone or 20-prenyloxychalcone was first studied.
20-Prenyloxyacetophenone (11a) was prepared from 8a by treatment
with 1-chloro-3-methyl-2-butene in the presence of K2CO3 in 91%
yield and methoxymethyl (MOM)-protected 4-hydoxybenzaldehyde
(7a) was prepared from 4-hydroxybenzaldehyde (14) in 87% yield
(Scheme 2).
O
O
1-chloro-3-methyl-2-butene (2.0 equiv)
K CO (3.0 equiv)
OH O
2
3
acetone, reflux, 24 h
Y: 91%
MeO
MeO
OHC
8a
11a
ClCH OCH (2.0 equiv)
2
3
K CO (4.0 equiv)
OHC
2
3
acetone, rt, 2 h
Y: 87%
Table 2
OH
OMOM
ClaiseneSchmidt condensation of 11 with 10a
12
7a
OH O
Scheme 2.
11 +10a (1.2 equiv)
MeO
OMOM
15a
Dauben et al. reported a [1,3]-sigmatropic rearrangement cata-
lyzed by montmorillonite KSF clay of prenyl phenyl ethers to ortho-
and para-prenylated phenols.13 Montmorillonite K10 was reported
to be more effective than montmorillonite KSF as the catalyst on the
[1,3]-sigmatropic rearrangement by Dintzner et al.15 FlorisilÒ was
Entry
Conditions
Yield of 15a/%
1
2
3
3 M NaOH, EtOH, rt, 24 h
50% KOH, EtOH, rt, 35 h
Ba(OH)2$8H2O (2.5 equiv), EtOH, 50 ꢀC, rt, 1e72 h
38
33
23
also reported to promote the [1,3]-sigmatropic rearrangement
14
ꢀ
effectively by Talamas et al. Therefore, we first tried to compare
montmorillonite K10 with FlorisilÒ as the catalyst for the rear-
rangement reaction of 11a (Table 1). The reaction of 11a with
montmorillonite K10 in CH2Cl2 at 0 ꢀC gave desired compound 6 in
53% yield, along with 13 (25%), 14 (7%), and 8a (4%). In contrast, the
reaction of 11a using FlorisilÒ in toluene at 110 ꢀC provided 6 in 27%
yield, along with 13 (32%), 10 (8%), and chroman 8a (10%). Rear-
rangement with montmorillonite K10 provided a better yield of 6
than that with FlorisilÒ.
Scheme 4 shows the synthetic route for chromanochalcone 2
from 6. Oxidation of 6 with m-CPBA proceeded at room tempera-
ture to afford epoxide as an intermediate, which was immediately
converted in situ into chroman 9 by subsequent cyclization with
montmorillonite K10. The ClaiseneSchmidt condensation of 9 with
7a gave chalcone 20 in 76% yield. Deprotection of 20 using p-tol-
uenesulfonic acid in refluxing methanol afforded 2 in 94% yield
(28% total yield over six steps from 8a).

5348
K. Sugamoto et al. / Tetrahedron 67 (2011) 5346e5359
OH O
O
O
a
O
O
3M NaOH
Y: 96%
11a + 7a (1.2 equiv)
MeO
MeO
EtOH, rt, 24 h
Y: 98%
6
10
MeO
OMOM
O
O
O
b
16a
OH O
Y: 95%
montmorillonite K10 (1 wt equiv)
MeO
OMOM
CH2Cl2, 0 ºC, 1.5 h
OH O
21
O
c
+
MeO
OMOM
Y: 89%
MeO
MeO
OMOM
15a (Y: 46%)
OH O
17a (Y: 26%)
MeO
OH
3
Scheme 5. Reagents and conditions: (a) montmorillonite K10 (1 wt equiv), toluene,
50 ꢀC, under N2, 40 h; (b) 7a (1.2 equiv), 3 M NaOH, EtOH, rt, 20 h; (c) p-TsOH$H2O
(1 equiv), MeOH, reflux, 1 h.
OH O
+
+
OMOM
Scheme 6 shows synthesis of 4. Hydrogenation of 21 in the
presence of Pd/C catalyst gave 22, which was deprotected under the
same conditions as described above to yield 4 in 38% total yield over
six steps from 8a.
MeO
OMOM
18a (trace)
19a (Y: 18%)
OH O
p-TsOH·H2O (1 equiv)
15a
MeOH, 30 ºC, 24 h
Y: 99%
MeO
OH
O
O
1a
Scheme 3.
21
MeO
OMOM
OH O
OH O
O
O
O
a
a
O
Y: 94%
22
MeO
MeO
MeO
MeO
OMOM
OH
6
HO
O
O
O
b
b
Y: 93%
4
MeO
9
Scheme 6. Reagents and conditions: (a) Pd/C (0.1 wt equiv), under H2 (1 atm), EtOH, rt,
0.5 h; (b) p-TsOH$H2O (1 equiv), MeOH, reflux, 1 h.
(Y: 81% from 6)
HO
O
O
2.2. Synthesis of chalcones 1bed and 5aed and geranylated
chalcones 1e, f
c
Y: 76%
MeO
HO
OMOM
OH
20
Synthesis of prenylated chalcones 1bed and 5aed and gerany-
lated chalcones 1e, f was next performed. Synthetic route for these
chalcones is similar to that described in the synthesis of 4-hydroxy-
derricin (1a). 40-Methoxymethyloxy-20-prenyloxyacetophenone
(11b) was prepared from 23 by methoxymethylation followed by
prenylation (Scheme 7). Geranylation of 8a, b with geranyl bromide
O
O
d
Y: 94%
MeO
2
Scheme 4. Reagents and conditions: (a) m-CPBA (1.2 equiv), CH2Cl2, rt, 0.5 h; (b)
montmorillonite K10 (1 wt equiv), CH2Cl2, rt, 1 h; (c) 7a (1.2 equiv), 3 M NaOH, EtOH, rt,
20 h; (d) p-TsOH$H2O (1 equiv), MeOH, reflux, 2 h.
Synthetic route for chromanochalcone 3 from 6 is depicted in
Scheme 5 . Dauben et al. reported that short reaction times or low
temperatures permitted the isolation of ortho-prenyl phenols on
the [1,3]-sigmatropic rearrangement of prenyl phenyl ethers with
montmorillonite KSF clay, while longer reaction times or higher
temperatures provided the corresponding chromans in moderate
yields.13 Since the chromans probably produced from the in-
termediary o-prenylphenols under the reported conditions, cycli-
OH O
OH O
O
O
a
b
Y: 93%
Y: 83%
HO
MOMO
MOMO
23
8b
11b
Scheme 7. Reagents and conditions: (a) chloromethyl methyl ether (1.2 equiv), K2CO3
(3.0 equiv), acetone, 0 ꢀC, 3 h; (b) 1-chloro-3-methyl-2-butene (2.0 equiv), K2CO3
(3.0 equiv), acetone, reflux, 24 h.
zation of
6 into 10 was tried on similar conditions using
montmorillonite K10. Treatment of 6 with montmorillonite K10 at
50 ꢀC in toluene provided chroman 10 in 96% yield. The Clai-
seneSchmidt condensation of 10 with 7a gave chalcone 21 in 95%
yield. Deprotection of 21 under the same conditions as described
above afforded 3 in 89% yield (39% total yield over five steps
from 8a).
in the presence of K2CO3 afforded the corresponding 20-ger-
anyloxyacetophenone 11c, 11d in good yields (Scheme 8). Clai-
seneSchmidt condensation of 11aed with 7aec in the presence of
3 M NaOH afforded the corresponding chalcones 16bef in good
yields (Scheme 9). The rearrangement of 16bef using

K. Sugamoto et al. / Tetrahedron 67 (2011) 5346e5359
16b-f
5349
montmorillonite K10 (1 wt equiv)
CH2Cl2, 0 ºC,
OH O
R1
R2
OH O
O
O
R3
geranyl bromide (1.5 equiv)
K2CO3 (3.0 equiv)
15b: R1=prenyl, R2=R3=OMOM (Y: 33%)
1c: R1=prenyl, R2=R3=OMe (Y: 37%)
acetone, reflux, 24 h
R
R
1d: R1=prenyl, R2=OMe, R3=H (Y: 43%)
15e: R1=geranyl, R1=R2=OMOM (Y: 44%)
15f: R1=geranyl, R1=OMe, R2=OMOM (Y: 36%)
8a: R=OMOM
8b: R=OMe
11c: R=OMOM (Y: 97%)
11d R=OMe (Y: 87%)
Scheme 8.
OH O
+
R3
R2
R1
R1
O
O
OHC
17b: R1=prenyl, R2=R3=OMOM (Y: 28%)
(1.2 equiv)
R3
5c: R1=prenyl, R2=R3=OMe (Y: 27%)
+
R2
5d: R1=prenyl, R2=OMe, R3=H (Y: 28%)
17e: R1=geranyl, R1=R2=OMOM (Y: 12%)
17f: R1=geranyl, R1=OMe, R2=OMOM (Y: 9%)
11a: R1=prenyl, R2=OMe
11b: R1=prenyl, R2=OMOM
11c: R1=geranyl, R2=OMOM
11d: R1=geranyl, R2=OMe
7a: R3=OMOM
7b: R3=OMe
7c: R3=H
OH O
R1
R1
O
O
+
R3
R2
3M NaOH
R1
EtOH, rt, 24 h
R3
R2
18b: R1=prenyl, R2=R3=OMOM (Y: 0.9%)
18c: R1=prenyl, R2=R3=OMe (Y: 0.7%)
18d: R1=prenyl, R2=OMe, R3=H (Y: 0.8%)
18e: R1=geranyl, R1=R2=OMOM (Y: 0%)
18f: R1=geranyl, R1=OMe, R2=OMOM (Y: 0.1%)
16b: R1=prenyl, R2=R3=OMOM (Y: 94%)
16c: R1=prenyl, R2=R3=OMe (Y: 81%)
16d: R1=prenyl, R2=OMe, R3=H (Y: 88%)
16e: R1=geranyl, R2=R3=OMOM (Y: 92%)
16f: R1=geranyl, R2=OMe, R3=OMOM (Y: 79%)
OH O
Scheme 9.
+
R3
R2
montmorillonite K10 at 0 ꢀC gave: 30-prenylated or 30-geranylaed
chalcone 15b, 1c, d, and 15e, 15f; 50-prenylated or 50-geranylated
chalcones 17b, 2c, d, and 17e, 17f; trace amounts of diprenylated or
digeranylated chalcones 18bef; and non-substituted chalcones
19aed, respectively (Scheme 10). Thus we achieved first geranyl
rearrangement of 16e and 16f using montmorillonite K10. Derricin
(1d) could be prepared over three steps from 8a in 27% yield: 1d
was reported to be isolated from Derris sericea,18 Lonchocarpus
neuroscapha,19 Lonchocarpus sericeus,20 and Erythroxylum barba-
tum;21 it exhibited inhibitory effects on platelet aggregation,22 and
had already been prepared by Khanna et al.22 Deprotection of 15b,
15e, 15f, and 17a, b gave naturally occurring chalcones (Scheme 11).
Isobavachalcone (1b) was first synthesized by deprotection of 15b
with 3 M HCl in MeOH under reflux in 72% yield. Compound 1b was
reported to be isolated from A. keiskei3 and the other plants;23e29 it
exhibited inhibitory effects on the induction of EBV-EA by TPS in
Raji cells,3 and exhibited antimycobacterial activity.28 50-Pre-
nylchalcone 17b was deprotected with 3 M HCl to give brousso-
chalcone B (5b) in 35% yield along with bavachin (42%) as
a by-product. On the other hand, the yield of 5b could be improved
by deprotection with a catalytic amount of carbon tetrabromide in
refluxing 2-propanol according to the procedure reported by Lee
et al.30 5b was reported to be isolated from Broussonetia papy-
rifera31 and had already been prepared by Noungoue-Tchamo
et al.32 Deprotection of 17a by the same conditions gave bava-
chalcone (5a) in 84% yield, which was reported to be isolated from
Psoralea corylifolia;33 it exhibited antibacterial activities24 as well as
inhibitory effects on osteoclast differentiation through suppression
of NFATc1 induction by RANKL.34 Although synthesis of 5a had al-
ready been prepared from 8a in only 1.5% yield by Jain et al.,35 the
19b: R2=R3=OMOM (Y: 28%)
19c: R2=R3=OMe (Y: 24%)
19d: R2=OMe, R3=H (Y: 26%)
19b: R2=R3=OMOM (Y: 42%)
19a: R2=OMe, R3=OMOM (Y: 54%)
Scheme 10.
yield of 5a from 8a could be increased up to 20% in the present
study. Xanthoangelol (1e) was synthesized in 77% yield from ger-
anylated chalcone 15e by the deprotection using carbon tetra-
bromide: 1e could be prepared from 23 in 28% yield over five steps.
Jung et al. previously reported that another method for synthesis of
1e was via direct geranylation of 23 in 17% yield from 23.11 The yield
of 1e on our synthesis is somewhat high. Deprotection of 15f with
p-toluenesulfonic acid in CH2Cl2/MeOH at room temperature
afforded Xanthoangelol F (1f) in 92% yield. Thus 1f could be first
synthesized from 8a in 23% yield over four steps. Moreover 40-
methylisoliquiritigenin (24a) and isoliquiritigenin (24b) were pre-
pared from 19a and 19b, respectively (Scheme 12).
2.3. Antibacterial activity
Antibacterial activity of synthesized chalcones 1aef, 2e4, 5aed,
24aeb, and 19ced was examined against both Gram-negative
(Escherichia coli, Proteus mirabilis, Pseudomonas fluorescens) and
Gram-positive bacteria (Bacillus subtilis, Staphylococcus epidermidis,
Micrococcus luteus). The MIC values are summarized in Table 3. All
chalcones had no effect against Gram-negative bacteria.

5350
K. Sugamoto et al. / Tetrahedron 67 (2011) 5346e5359
4-Hydroxyderricin (1a), isobavachalcone (1b), xanthoangelol (1e),
OH O
xanthoangelol F (1f), bavachalcone (5a), and broussochalcone B
(5b) were active compounds against Gram-positive bacteria. From
comparison of antibacterial activity against Gram-positive bacteria
between prenylated chalcones, such as 4-hydroxyl analogs 1a, 1b,
5a, and 5b, 4-methoxy analogs 1c and 5c, and non-substituted
analogs 1d and 5d, the hydroxyl group on the B-ring is found to
enhance antibacterial activity. The 30-prenylchalcones 1a and 5a
and 50-prenylchalcones 1b and 5c showed significant activity, but
chalcones with no prenyl group, such as 24a, 24b, 2, 3, and 4
showed very weak activity. The prenyl moiety on the A-ring is
revealed to contribute an increase in bacterial activity. The methoxy
group at 40-position on the A-ring slightly influence on the activity.
On the other hand, 30-geranylchalcone with 40-hydroxy group 1e
showed stronger activity than that with 40-hydroxy group 1f. Yin
3M HCl
15b
MeOH, reflux, 0.5 h
Y: 72%
HO
OH
1b
OH O
OH
HO
O
O
+
OH
HO
3M HCl
MeOH, reflux,
3 h
17b
5b (Y: 35%)
Bavachin (Y: 42%)
CBr (0.2 equiv)
4
5b
2-PrOH, reflux, 8 h
Y: 61%
OH O
et al.33 and Avila et al.36 previously reported antibacterial activities
ꢀ
CBr (0.1 equiv)
of 1b, 5a and 1aee, 24b, respectively. The present tendency for the
activity of the synthesized chalcones is in agreement with their
reports.
4
MeO
OH
17a
15e
2-PrOH, reflux, 2.5 h
Y: 84%
5a
3. Conclusion
OH O
Total synthesis of prenylated chalcones, such as
4-hydroxyderricin (1a), isobavachalcone (1b), derricin (1d), xan-
CBr (0.1 equiv)
4
2-PrOH, reflux, 5 h
Y: 77%
HO
OH
thoangelol
H (2), deoxyxanthoangelol H (3), deoxydihydrox-
1e
1f
anthoangelol H (4), bavachalcone (5a), and broussochalcone B (5b)
and geranylated chalcones, such as xanthoangelol (1e), xan-
thoangelol F (1f) has been accomplished via the [1,3]-sigmatropic
rearrangement of 20-prenyloxyacetophenone, 20-prenyloxychal-
cones or 20-geranyloxychalcones using montmorillonite K10 as
a catalyst. 30-Prenylchalcones 1a, 1b, 50-prenylchalcones 5a, 5b, and
30-geranylchalcone 1e strongly inhibited Gram-positive bacteria.
OH O
p-TsOH·H O (3 equiv)
2
15f
CH Cl -MeOH, rt, 48 h
MeO
OH
2
2
Y: 92%
Scheme 11.
4. Experimental
4.1. General
OH O
p-TsOH·H2O (1 equiv)
19a
19b
MeOH, reflux, 3 h
Y: 82%
MeO
OH
24a
1H and 13C NMR spectra were recorded with a Bruker AV400 M
spectrometer in CDCl3, MeOD-d4, acetone-d6, or DMSO-d6 solution
with TMS (d 0.00) as an internal standard. IR spectra were recorded
OH O
conc.HCl
with a Jasco FT/IR-4100 spectrometer in Nujol mull, CHCl3 or using
KBr pellets. Melting points were measured on a Buchi melting point
M565 (uncorrected). High resolution mass spectrometry (HRMS)
was performed on a Hitachi M-2000AM mass spectrometer in
electron impact mode at 70 eV. Silica gel 60 N purchased from Fuji
Silysia Co. Ltd. was used for column chromatography. TLC plates
silica gel 60 F254 (layer thickness 0.25 mm) and PLC plate silica gel
60 F254 (20ꢁ20 cm, layer thickness 1 mm) were purchased from
Kanto Chemical Co., Inc. All commercial chemicals were analytical
grade quality.
MeOH, rt, 5 h
Y: 60%
HO
OH
24b
Scheme 12.
Table 3
Antibacterial activity of chalcones
Chalcone
MIC (
mg/ml)
E. coli P. mirabilis P. fluorescens B. subtilis S. epidermidis M. luteus
1a
1b
1c
1d
1e
1f
2
3
4
5a
5b
5c
5d
24a
24b
19c
>256 >256
>256 >256
>256 >256
>256 >256
>256 >256
>256 >256
>256 >256
>256 >256
>256 >256
>256 >256
>256 >256
>256 >256
>256 >256
>256 >256
>256 >256
>256 >256
>256 >256
>256
>256
>256
>256
>256
>256
>256
>256
>256
>256
>256
>256
>256
>256
>256
>256
>256
<2
2
4
2
4
2
4
4.2. 20-Prenyloxy-40-methoxyacetophenone (11a)
>256
>256
4
>256
>256
4
>256
>256
4
A mixture of 20-hydroxy-40-methoxyacetophenone 8a (167 mg,
1 mmol), anhydrous K2CO3 (415 mg, 3 mmol), and 80% 1-chloro-3-
methyl-2-butene (261 mg, 2 mmol) was stirred in dry acetone
(5 cm3) under reflux for 24 h. The reaction mixture was monitored
by TLC. After completion of the reaction, the reaction mixture was
filtrated and evaporated under vacuum. The residue was purified
by silica gel column chromatography with hexane/ethyl acetate to
afford compound 11a (214 mg, 91%) as colorless oil; Rf (10% EtOAc/
hexane) 0.18; nmax (CHCl3)/cmꢂ1 3050, 3000, 2950, 1675, 1620,
1600, 1500, 1450, 1390, 1360, 1260, 1170, 1140, 1000; dH (CDCl3)
1.76 (3H, s, CH3), 1.81 (3H, s, CH3), 2.60 (3H, s, COCH3), 3.84 (3H, s,
OCH3), 4.58 (2H, d, J¼6.6 Hz, OCH2CH), 5.47e5.54 (1H, m, CH2CH]
64
64
64
>256
>256
>256
4
>256
>256
>256
4
>256
>256
>256
4
8
8
16
>256
>256
>256
128
>256
>256
2
>256
>256
>256
128
>256
>256
2
>256
>256
>256
128
>256
>256
2
19d
Streptomycin
<2
<2
0
C), 6.45 (1H, d, J¼2.3 Hz, C3 H), 6.50 (1H, dd, J¼2.3 and 8.8 Hz,

K. Sugamoto et al. / Tetrahedron 67 (2011) 5346e5359
5351
0
0
C5 H), 7.83 (1H, d, J¼8.8 Hz, C6 H); dC (CDCl3) 18.21, 25.68, 31.98,
55.43, 65.35, 99.23, 105.02, 119.00, 121.44, 132.55, 138.29, 160.39,
164.32, 197.89; HRMS: Mþ, found 234.1291. C14H18O3 requires
234.1256.
4.5. 20-Hydroxyl-40-methoxy-4-methoxymethoxy-30-prenyl-
chalcone (15a)
To a stirred solution of 6 (118 mg, 0.5 mmol) and 7a (100 mg,
0.6 mmol) in ethanol (5 cm3) was slowly added 3 M NaOH (5 cm3)
at 0 ꢀC, after which the reaction mixture was stirred at room
temperature for 24 h. After completion of reaction (TLC), the so-
lution was extracted with ethyl acetate (3ꢁ20 cm3). The organic
layers were combined, washed with saturated sodium chloride
solution, dried over sodium sulfate, filtrated, and evaporated under
vacuum. The residue was purified by silica gel column chroma-
tography with hexane/ethyl acetate to afford compound 15a
(73 mg, 38%) as yellow needle crystal; mp (EtOAc/hexane)
109.1e110.0 ꢀC; Rf (20% EtOAc/hexane) 0.34; nmax (KBr)/cmꢂ1 3050,
3000, 2950, 2900, 1640, 1620, 1590, 1460, 1430, 1380, 1320, 1290,
1220, 1180, 1160, 1120, 1080, 1000; dH (CDCl3) 1.68 (3H, d, J¼1.7 Hz,
CH3), 1.80 (3H, s, CH3), 3.39 (2H, d, J¼7.1 Hz, PheCH2CH), 3.49 (3H, s,
OCH2OCH3), 3.90 (3H, s, OCH3), 5.21 (2H, S, OCH2OCH3), 5.21e5.26
4.3. 4-Methoxymethoxybenzaldehyde (7a)
To a stirred solution of 4-hydroxybenzaldehyde (12) (122 mg,
1 mmol) and anhydrous K2CO3 (553 mg, 4 mmol) in dry acetone
(5 cm3) was slowly added chloromethyl methyl ether (161 mg,
1.2 mmol) at room temperature and stirred for 2 h. The reaction
mixture was monitored by TLC. After completion of the reaction,
the reaction mixture was filtrated and evaporated under vacuum.
The residue was purified by silica gel column chromatography with
hexane/ethyl acetate to afford compound 7a (145 mg, 87%) as col-
orless oil; Rf (10% EtOAc/hexane) 0.24; nmax (CHCl3)/cmꢂ1 3050,
3000, 2980, 2950, 2850, 2780, 1700, 1620, 1600, 1520, 1440, 1400,
1320, 1260, 1160, 1120, 1100, 1000; dH (CDCl3) 3.50 (3H, s, OCH3),
5.26 (2H, s, OCH2O), 7.17 (2H, d, J¼8.8 Hz, C3H and C5H), 7.89 (2H, d,
J¼8.8 Hz, C2H and C4H), 9.90 (1H, s, OH); dC (CDCl3) 56.3, 94.09,
116.26, 130.74, 131.84, 162.19, 190.85.
0
(1H, m, C]CHCH2), 6.49 (1H, d, J¼9.0 Hz, C5 H), 7.07 (2H, d,
J¼8.8 Hz, C3H and C5H), 7.48 (1H, d, J¼15.4 Hz, CaH), 7.59 (2H,
0
d, J¼8.8 Hz, C2H and C6H), 7.79 (1H, d, J¼9.0 Hz, C6 H), 7.84 (1H, d,
J¼15.4 Hz, CbH), 13.44 (1H, s, OH); dC (CDCl3) 17.80, 21.72, 25.79,
55.75, 56.17, 94.20, 102.04, 114.67, 116.53, 117.58, 118.65, 122.05,
128.67, 129.09, 130.16, 131.85, 143.77, 159.24, 163.01, 163.21, 192.23;
HRMS: Mþ, found 382.1826. C23H26O5 requires 382.1780.
4.4. Rearrangement of compound 11a with montmorillonite
K10
To a stirred solution of 11a (2812 mg, 12 mmol) in dry CH2Cl2
(12 cm3) was added montmorillonite K10 (2810 mg) at 0 ꢀC and
stirred for 0.5 h. The reaction mixture was monitored by TLC. After
completion of the reaction, the reaction mixture was filtrated and
evaporated under vacuum. The residue was purified by silica gel
column chromatography with hexane/ethyl acetate to afford
compound 6(1482 mg, 53%), 13 (447 mg, 17%), 14 (236 mg, 7%), and,
8a (70 mg, 4%).
4.6. 40-Methoxy-4-methoxymethoxy-20-prenyloxychalcone
(16a)
To a stirred solution of 11a (118 mg, 0.5 mmol) and 7a (100 mg,
0.6 mmol) in ethanol (5 cm3) was slowly added 3 M NaOH (5 cm3)
at 0 ꢀC, after which the reaction mixture was stirred at room
temperature for 12 h. After completion of reaction (TLC), the so-
lution was extracted with ethyl acetate (3ꢁ20 cm3). The organic
layers were combined, washed with saturated sodium chloride
solution, dried over sodium sulfate, filtrated, and evaporated under
vacuum. The residue was purified by silica gel column chroma-
tography with hexane/ethyl acetate to afford compound 16a
(187 mg, 98%) as yellow needle crystal; mp (EtOAc/hexane)
78.6e79.6; Rf (20% EtOAc/hexane) 0.22; nmax (KBr)/cmꢂ1 3100,
3032, 3013, 2960, 2937, 2905, 2865, 2837, 2905, 2866, 2838, 2360,
1646, 1604, 1589, 1567, 1509, 1460, 1442, 1432, 1384, 1316, 1282,
1245, 12,004, 1171, 1151, 1120, 1078, 1024; dH (CDCl3) 1.74 (3H, s,
CH3), 1.79 (3H, s, CH3), 3.48 (3H, s, OCH2OCH3), 3.85 (3H, s, OCH3),
4.58 (2H, d, J¼6.8 Hz, PheCH2CH), 5.20 (2H, s, OCH2OCH3),
4.4.1. 20-Hydroxy-40-methoxy-30-prenylacetophenone (6). Compound
(6) as colorless oil; Rf (10% EtOAc/hexane) 0.20; nmax (CHCl3)/cmꢂ1
3300, 3050, 2980, 2930, 2850, 1630, 1500, 1420, 1370, 1340, 1270,
1090; dH (CDCl3) 1.67 (3H, d, J¼0.9 Hz, CH3), 1.78 (3H, s, CH3), 2.56
(3H, s, COCH3), 3.35 (2H, d, J¼7.1 Hz, PheCH2CH), 3.89 (3H, s, OCH3),
0
5.16e5.23 (1H, m, C]CHCH2), 7.45 (1H, d, J¼9.0 Hz, C5 H), 7.60 (1H,
0
d, J¼9.0 Hz, C6 H), 12.7 (1H, s, OH); dC (CDCl3) 17.75, 21.59, 25.76,
26.21, 55.72, 102.06, 114.36, 117.33, 121.93, 130.17, 131.85, 161.74,
163.21, 202.83; HRMS: Mþ, found 234.1246. C14H18O3 requires
234.1256.
0
5.52e5.56 (1H, m, C]CHCH2), 6.49 (1H, d, J¼2.0 Hz, C3 H), 6.55 (1H,
4. 4. 2. 20-H ydroxy-4 0-methoxy-50-prenylaceto phenone
(13). Compound (13) as colorless oil; Rf (10% EtOAc/hexane) 0.32;
nmax (CHCl3)/cmꢂ1 3050, 2980, 2930, 2850, 1630, 1500, 1440, 1380,
1340, 1270, 1080; dH (CDCl3) 1.71 (3H, s, CH3), 1.75 (3H, s, CH3), 2.54
(3H, s, COCH3), 3.22 (2H, d, J¼7.1 Hz, PheCH2CH), 3.86 (3H, s, OCH3),
dd, J¼2.0 and 8.8 Hz, C5 H), 7.03 (2H, d, J¼8.8 Hz, C3H and C5H), 7.52
0
(2H, d, J¼8.8 Hz, C2H and C6H), 7.59 (1H, d, J¼15.9 Hz, CaH), 7.65 (1H,
0
d, J¼15.9 Hz, CbH), 7.83 (1H, d, J¼8.8 Hz, C6 H); dC (CDCl3) 18.28,
25.26, 55.51, 56.11, 65.56, 94.24, 99.770, 105.44, 116.37, 119.16,
122.40, 125.94, 129.55, 129.76, 133.09, 138.77, 141.13, 158.61, 159.99,
164.11, 189.99; HRMS: Mþ, found 382.1789. C23H26O5 requires
382.1780.
0
0
5.22e5.29 (1H, m, C]CHCH2), 6.39 (1H, s, C3 H), 7.40 (1H, s, C6 H),
12.71 (1H, s, OH); dC (CDCl3) 17.74, 25.74, 26.15, 27.75, 55.95, 99.00,
113.13, 121.63, 121.99, 130.69, 133.01, 163.85, 164.03, 202.50; HRMS:
Mþ, found 234.1240. C14H18O3 requires 234.1256.
4.7. Rearrangement of compound 16a
4.4.3. 30,50-Diprenyl-20-hydroxy-40-methoxyacetophenone
(14). Compound (14) as colorless oil; Rf (10% EtOAc/hexane) 0.44;
dH (CDCl3) 1.68 (3H, d, J¼1.1 Hz, CH3), 1.73 (3H, s, CH3), 1.76 (3H, d,
J¼1.0 Hz, CH3), 1.79 (3H, s, CH3), 1.75 (3H, s, CH3), 2.57 (3H, s,
COCH3), 3.30 (2H, d, J¼7.1 Hz, PheCH2CH), 3.38 (2H, d, J¼6.7 Hz,
PheCH2CH), 376 (3H, s, OCH3), 5.20e5.29 (2H, m, C]CHCH2 ꢁ2),
To a stirred solution of 16a (3825 mg, 10 mmol) in dry CH2Cl2
(10 cm3) was added montmorillonite K10 (3830 mg) at 0 ꢀC and
stirred for 1.5 h. The reaction mixture was monitored by TLC. After
completion of the reaction, the reaction mixture was filtrated and
evaporated under vacuum. The residue was purified by silica gel
column chromatography with hexane/ethyl acetate to afford
compound 15a (1748 mg, 46%), 17a (1010 mg, 26%), 18a (22 mg,
0.9%), and 19a (575 mg, 18%).
0
7.40 (1H, s, C6 H), 12.60 (1H, s, OH); dC (CDCl3) 17.90, 22.84, 25.74,
26.55, 27.99, 61.19, 116.31, 122.40, 122.72, 123.51, 125.59, 129.34,
131.89, 133.02, 160.96, 162.91, 203.55.

5352
K. Sugamoto et al. / Tetrahedron 67 (2011) 5346e5359
4.7.1. 20-Hydroxyl-40-methoxy-4-methoxymethoxy-50-pre-
nylchalcone (17a). Compound (17a) as yellow needle crystal; mp
(EtOAc/hexane) 82.8e83.8 ꢀC; Rf (20% EtOAc/hexane) 0.38; nmax
(KBr)/cmꢂ1 3004, 2980, 2959, 2911, 2897, 2853, 2784, 2730, 2687,
2657, 1633, 1602, 1562, 1506, 1440, 1422, 1404, 1381, 1321, 1297,
1278, 1233, 1206, 1171, 1155, 1135, 1112, 1096, 1085; dH (CDCl3) 1.74
(3H, d, J¼0.5 Hz, CH3), 1.78 (3H, d, J¼1.0 Hz, CH3), 3.26 (2H, d,
J¼7.1 Hz, PheCH2CH), 3.49 (3H, s, OCH2OCH3), 3.87 (3H, s, OCH3),
5.23 (2H, S, OCH2OCH3), 5.26e5.31 (1H, m, C]CHCH2), 6.43 (1H, s,
4.9. 8-Acetyl-2,2-dimethyl-3-hydroxy-5-methoxychroman (9)
To a stirred solution of 6 (696 mg, 3.0 mmol) in dry CH2Cl2
(30 cm3) was added 77% 3-chloroperbenzoic acid (m-CPBA)
(807 mg, 3.6 mmol) at 0 ꢀC, after which the reaction mixture was
stirred for 0.5 h at room temperature. After consumption of com-
pound 6 (TLC), montmorillonite K10 (696 mg) was added and
stirred 1 h at room temperature. The reaction mixture was filtrated.
After addition of 10 cm3 of ethyl acetate, the organic layer was
washed with saturated Na2CO3, water, brine, dried over sodium
sulfate, filtrated, and evaporated under vacuum. The residue was
purified by silica gel column chromatography with hexane/ethyl
acetate to afford compound 9 (603 mg, 81%) as colorless crystal; mp
(EtOAc/hexane) 100.8e101.8 ꢀC; Rf (33% EtOAc/hexane) 0.12; nmax
(KBr)/cmꢂ1 3367, 2980, 2931, 2899, 2866, 2841, 1643, 1590, 1487,
1467, 1433, 1362, 1326, 1271, 1223, 1192, 1174, 1160, 1142, 1122, 1096,
1053, 1024, 1013; dH (CDCl3) 1.38 (3H, s, CH3), 1.41 (3H, s, CH3), 1.78
(1H, br d, J¼5.8 Hz, OH), 2.60 (3H, s, COCH3), 2.69 (1H, dd, J¼5.6 and
17.6 Hz, C4H), 2.93 (1H, dd, J¼5.2 and 17.6 Hz, C4H), 3.84e3.86 (1H,
m, C3H), 3.87 (3H, s, OCH3), 6.50 (1H, d, J¼8.8 Hz, C6H), 7.75 (1H, d,
J¼8.8 Hz, C7H); dC (CDCl3) 21.86, 24.86, 26.51, 32.18, 55.66, 68.71,
77.57, 102.29, 108.13, 121.26, 130.20, 153.95, 161.65, 198.24; HRMS:
Mþ, found 250.2988. C23H26O5 requires 250.2903.
0
C3 H), 7.09 (2H, d, J¼8.7 Hz, C3H and C5H), 7.45 (1H, d, J¼15.4 Hz,
0
CaH), 7.59 (1H, s, C6 H), 7.60 (2H, d, J¼8.7 Hz, C2H and C6H), 7.84 (1H,
d, J¼15.4 Hz, CbH), 13.47 (1H, s, OH); dC (CDCl3) 17.77, 21.68, 25.76,
55.70, 56.13, 94.14, 102.01, 114.61, 116.47, 117.49, 118.59, 122.02,
128.60, 129.07, 130.12, 131.79, 143.73, 159.20, 162.96, 163.16, 192.17;
HRMS: Mþ, found 382.1819. C23H26O5 requires 382.1780.
4 . 7 . 2 . 3 0, 5 0- D i p r e n y l - 2 0- h y d r o x y l - 4 0- m e t h o x y - 4 -
methoxymethoxychalcone (18a). Compound (18a) as yellow needle
crystal; Rf (20% EtOAc/hexane) 0.42; dH (CDCl3) 1.70 (3H, d, J¼1.0 Hz,
CH3), 1.76 (3H, s, CH3), 1.79 (3H, d, J¼1.0 Hz, CH3), 1.80 (3H, s, CH3),
3.34 (2H, d, J¼7.0 Hz, PheCH2CH), 3.41 (2H, d, J¼6.7 Hz,
PheCH2CH), 3.50 (3H, s, OCH2OCH3), 3.78 (3H, s, OCH3), 5.23 (2H, S,
OCH2OCH3), 5.25e5.32 (2H, m, C]CHCH2 ꢁ2), 7.09 (2H, d, J¼8.8 Hz,
0
C3H and C5H), 7.47 (1H, d, J¼15.4 Hz, CaH), 7.58 (1H, s, C6 H), 7.60
(2H, d, J¼8.8 Hz, C2H and C6H), 7.86 (1H, d, J¼15.4 Hz, CbH), 13.27
(1H, s, OH).
4.10. 4-Methoxymethylxanthoangelol H (20)
To a stirred solution of 9 (151 mg, 0.6 mmol) and 7a (120 mg,
0.72 mmol) in ethanol (10 cm3) was slowly added 3 M NaOH
(10 cm3) at 0 ꢀC, after which the reaction mixture was stirred at
room temperature for 20 h. After completion of reaction (TLC), the
solution was extracted with ethyl acetate (3ꢁ25 cm3). The organic
layers were combined, washed with saturated sodium chloride
solution, dried over sodium sulfate, filtrated, and evaporated under
vacuum. The residue was purified by silica gel column chroma-
tography with hexane/ethyl acetate to afford compound 20
(182 mg, 76%) as yellow needle crystal; mp (EtOAc/hexane)
134.8e135.8 ꢀC; Rf (33% EtOAc/hexane) 0.10; nmax (KBr)/cmꢂ1 3453,
3100, 3078, 3035, 3020, 2979, 2938, 2912, 2846, 2830, 1639, 1591,
1508, 1490, 1468, 1449, 1435, 1422, 1404, 1370, 1346, 1330, 1308,
1281, 1226, 1207, 1190, 1167, 1153, 1100, 1080, 1008; dH (CDCl3) 1.39
4.7.3. 20-Hydroxyl-40-methoxy-4-methoxymethoxychalcone
(19a). Compound (19a) as yellow needle crystal, mp (EtOAc/hex-
ane) 74.2e75.2 ꢀC; Rf (20% EtOAc/hexane) 0.26; nmax (KBr)/cmꢂ1
3005, 2956, 2937, 2920, 2901, 2849, 2833, 2788, 2750, 2688, 2665,
2560, 2373, 1631, 1604, 1577, 1509, 1468, 1444, 14,213, 1367, 1327,
1311, 1296, 1282, 1220, 1173, 1152, 1135, 1113, 1080, 1018; dH (CDCl3)
3.49 (3H, s, OCH2OCH3), 3.85 (3H, s, OCH3), 5.22 (2H, S, OCH2OCH3),
0
0
6.47 (1H, s, C3 H), 6.48 (1H, d, J¼9.2 Hz, C5 H), 7.08 (2H, d, J¼8.7 Hz,
C3H and C5H), 7.46 (1H, d, J¼15.5 Hz, CaH), 7.60 (2H, d, J¼8.7 Hz, C2H
0
and C6H), 7.82 (1H, d, J¼9.2 Hz, C6 H), 7.85 (1H, d, J¼15.5 Hz, CbH),
13.52 (1H, s, OH); dC (CDCl3) 55.58, 56.21, 94.21, 101.09, 107.65,
114.15, 116.57, 118.35, 128.57, 130.25, 131.15, 144.11, 159.36, 166.10,
166.66, 191.87; HRMS: Mþ, 314.1181. C18H18O5 requires 314.1154.
00
(3H, s, CH3), 1.41(3H, s, CH3), 2.72 (1H, dd, J¼5.5 and 17.6 Hz, C4 H),
00
4.8. 4-Hydroxyderricin (1a)
2.94 (1H, dd, J¼5.2 and 17.6 Hz, C4 H), 3.49 (3H, s, OCH2OCH3),
3.83e3.87 (1H, m, C3H), 3.87 (3H, s, OCH3), 5.21 (2H, s, OCH2OCH3),
0
To a stirred solution of 15a (192 mg, 0.5 mmol) in MeOH
(50 cm3) was added p-toluenesulfonic acid monohydrate (95 mg,
0.5 mmol) and stirred at 30 ꢀC for 24 h. The reaction mixture was
monitored by TLC. After completion of the reaction, the reaction
mixture was evaporated under vacuum. After addition of 30 cm3 of
water, the mixture was extracted with ethyl acetate (3ꢁ50 cm3).
The organic layers were combined, washed with brine, dried over
sodium sulfate, filtrated, and evaporated under vacuum. The resi-
due was purified by silica gel column chromatography with hex-
ane/ethyl acetate to afford compound 1a (167 mg, 99%) as yellow
needle crystal, mp (EtOAc/hexane) 136.0e137.0 ꢀC; Rf (33% EtOAc/
hexane) 0.18; nmax (CHCl3)/cmꢂ1 3640, 3050, 3000, 2950, 2890,
1650, 1620, 1590, 1520, 1507, 1450, 1430, 1390, 1322, 1250, 1230,
1180, 1122, 1082; dH (CDCl3) 1.68 (3H, d, J¼0.6 Hz, CH3), 1.80 (3H, d,
J¼0.2 Hz, CH3), 3.39 (2H, d, J¼7.0 Hz, PheCH2CH), 3.91 (3H, s, OCH3),
5.21e5.25 (1H, m, C]CHCH2), 5.50 (1H, br s, OH), 6.48 (1H, d,
6.52 (1H, d, J¼8.7 Hz, C5 H), 7.05 (2H, d, J¼8.8 Hz, C3H and C5H), 7.53
(2H, d, J¼8.8 Hz, C2H and C6H), 7.54 (1H, d, J¼15.8 Hz, CaH), 7.63 (1H,
0
d, J¼15.8 Hz, CbH), 7.71 (1H, d, J¼8.7 Hz, C6 H); dC (CDCl3) 22.02,
26.58, 55.67, 56.14, 68.83, 77.48, 94.24, 108.12, 116.48, 122.23,
125.83, 129.44, 129.67, 130.02, 141.01, 153.24, 158.67, 161.35, 190.63;
HRMS: Mþ, found 398.1729. C23H26O6 requires 398.1765.
4.11. Xanthoangelol H (2)
A mixture of 20 (198 mg, 0.5 mmol) and p-toluenesulfonic acid
monohydrate (96 mg, 0.5 mmol) in MeOH (12 cm3) was stirred
under reflux for 2 h. The reaction mixture was monitored by TLC.
After completion of the reaction, the reaction mixture was evapo-
rated under vacuum. After addition of 10 cm3 of water, the mixture
was extracted with ethyl acetate (3ꢁ10 cm3). The organic layers
were combined, washed with brine, dried over sodium sulfate,
filtrated, and evaporated under vacuum. The residue was purified
by silica gel column chromatography with hexane/ethyl acetate to
afford compound 2 (166 mg, 94%) as yellow needle crystal, mp
(EtOH) 219e220 ꢀC; Rf (50% EtOAc/hexane) 0.10; nmax (KBr)/cmꢂ1
3270, 3118, 3005, 2977, 2938, 2872, 2841, 1641, 1592, 1556, 1439,
1401, 1385, 1367, 1335, 1310, 1283, 1234, 1209, 1186, 1166, 1141, 1101,
1073, 1055, 1022; dH (DMSO-d6) 1.23 (3H, s, CH3), 1.30(3H, s, CH3),
0
J¼9.0 Hz, C5 H), 6.89 (2H, d, J¼8.6 Hz, C3H and C5H), 7.45 (1H,
d, J¼15.4 Hz, CaH), 7.53 (2H, d, J¼8.6 Hz, C2H and C6H), 7.79 (1H, d,
0
J¼9.0 Hz, C6 H), 7.83 (1H, d, J¼15.4 Hz, CbH), 13.48 (1H, s, OH); dC
(CDCl3) 17.82, 21.73, 25.81, 55.78, 102.10, 114.66, 116.00, 117.59,
118.18, 122.03, 128.00, 129.14, 130.52, 131.94, 143.97, 157.97, 162.99,
163.25, 192.36; HRMS: Mþ, found 338.150. C21H22O4 requires
338.1518.

K. Sugamoto et al. / Tetrahedron 67 (2011) 5346e5359
5353
00
00
00
2.45 (1H, dd, J¼7.0 and 17.3 Hz, C4 H), 2.82 (1H, dd, J¼5.4 and
(2H, t, J¼6.8 Hz, C3 H), 2.66 (2H, t, J¼6.8 Hz, C4 H), 3.89 (3H, s,
00
0
17.3 Hz, C4 H), 3.66e3.70 (1H, m, C3H), 3.83 (3H, s, OCH3), 5.23 (1H,
OCH3), 6.67 (1H, d, J¼8.8 Hz, C5 H), 6.88 (2H. d, J¼8.6 Hz, C3H and
0
0
br s, OH), 6.62 (1H, d, J¼8.8 Hz, C5 H), 6.82 (2H, d, J¼8.8 Hz, C3H and
C5H), 7.47 (1H, s, CaH), 7.47 (1H, s, CbH), 7.56 (1H, d, J¼8.6 Hz, C6 H),
0
C5H), 7.42 (1H, s, CaH), 7.42 (1H, s, CbH), 7.48 (1H, d, J¼8.7 Hz, C6 H),
7.57 (2H, d, J¼8.8 Hz, C2H and C6H), 10.10 (1H, br s, OH); dC (DMSO-
d6) 16.77, 26.39, 30.81, 55.65, 74.76, 102.15, 119.57, 115.92, 121.72,
124.13,125.95,129.30,129.94,140.97,153.69,159.55,160.40,189.78;
HRMS: Mþ, found 3382.1510. C21H22O4 requires 338.1518.
7.51 (2H, d, J¼8.8 Hz, C2H and C6H); dC (DMSO-d6) 20.71, 25.35,
26.20, 55.69, 66.89, 77.56, 102.47, 109.07, 115.92, 121.49, 124.07,
125.97, 129.38, 129.94, 141.05, 152.89, 159.57, 160.56, 189.60; HRMS:
Mþ, found 354.1446. C21H22O5 requires 354.1467.
4.15. 4-Methoxymethyl deoxydihydroxanthoangelol H (22)
4.12. 8-Acetyl-2,2-dimethyl-5-methoxychroman (10)
A mixture of 21 (495 mg, 1.3 mmol) and 10% palladium on car-
bon (50 mg) in EtOH (5 cm3) was stirred at room temperature
under H2 for 0.5 h. After completion of the reaction (TLC), the re-
action mixture was vacuum-filtered through a pad of Celite. The
mixture was evaporated under vacuum. The residue was purified
by silica gel column chromatography with hexane/ethyl acetate to
afford compound 22 (467 mg, 94%) as colorless oil; Rf (20% EtOAc/
hexane) 0.20; nmax (CHCl3)/cmꢂ1 3050, 3000, 2990, 2940, 2860,
1675, 1600, 1520, 1500, 1478, 1450, 1438, 1380, 1358, 1285, 1220,
1160, 1100, 1090, 1050; dH (CDCl3) 1.35 (6H, s, CH3 ꢁ2), 1.79 (2H, t,
A mixture of 6 (59 mg, 0.25 mmol) and montmorillonite K10
(60 mg) was heated at 50 ꢀC under N2 for 40 h. The reaction mixture
was monitored by TLC. After completion of the reaction, the re-
action mixture was filtrated and evaporated under vacuum. The
residue was purified by silica gel column chromatography with
hexane/ethyl acetate to afford compound 10 (56 mg, 96%) as col-
orless oil; Rf (10% EtOAc/hexane) 0.16; nmax (CHCl3)/cmꢂ1 3050,
3000, 2950, 1680, 1590, 1495, 1470, 1450, 1435, 1395, 1380, 1365,
1280, 1220, 1160, 1120, 1100; dH (CDCl3) 1.38 (6H, s, CH3 ꢁ2), 1.84
(2H, t, J¼6.9 Hz, C3H), 2.59 (3H, s, COCH3), 2.66 (2H, t, J¼6.9 Hz,
C4H), 3.86 (3H, s, OCH3), 6.45 (1H, d, J¼8.8 Hz, C6H), 7.72 (1H, d,
J¼8.8 Hz, C7H); dC (CDCl3) 17.07, 26.78, 31.60, 62.20, 55.55, 74.95,
101.50, 109.80, 121.31, 129.64, 155.19, 161.23, 198.58; HRMS: Mþ,
found 234.1268. C14H18O3 requires 234.1256.
00
00
J¼6.9 Hz, C3 H), 2.65 (2H, t, J¼6.9 Hz, C4 H), 2.96 (2H, t, J¼7.8 Hz,
CbH), 3.29 (2H, t, J¼7.8 Hz, CaH), 3.47 (3H, s, OCH2OCH3), 3.86 (3H, s,
0
OCH3), 5.15 (2H, s, OCH2OCH3), 6.45 (1H, d, J¼8.8 Hz, C5 H), 6.95 (2H,
d, J¼8.7 Hz, C3H and C5H), 7.14 (2H, d, J¼8.7 Hz, C2H and C6H), 7.67
0
(1H, d, J¼8.8 Hz, C6 H); dC (CDCl3) 17.14, 26.81, 29.79, 31.67, 45.22,
55.59, 55.90, 75.03, 94.64, 101.65, 109.84, 116.22, 121.36, 129.36,
129.80, 135.49, 154.77, 155.36, 161.09, 200.58; HRMS: Mþ, found
384.198. C23H28O6 requires 384.1937.
4.13. 4-Methoxymethyldeoxyxanthoangelol H (21)
To a stirred solution of 10 (77 mg, 0.25 mmol) and 7a (50 mg,
0.3 mmol) in ethanol (3 cm3) was slowly added 3 M NaOH (3 cm3)
at 0 ꢀC, after which the reaction mixture was stirred at room
temperature for 20 h. After completion of reaction (TLC), the so-
lution was extracted with ethyl acetate (3ꢁ15 cm3). The organic
layers were combined, washed with saturated sodium chloride
solution, dried over sodium sulfate, filtrated, and evaporated under
vacuum. The residue was purified by silica gel column chroma-
tography with hexane/ethyl acetate to afford compound 21 (90 mg,
95%) as yellow needle crystal; mp (EtOAc/hexane) 72.8e73.8 ꢀC; Rf
(10% hexane/EtOAc) 0.10; nmax (CHCl3)/cmꢂ1 3004, 3000, 2952,
2930, 1658, 1600, 1520, 1495, 1485, 1445, 1423, 1338, 1320, 1282,
1243, 1240,1180, 1160, 1122, 1100, 1080, 1000; dH (CDCl3) 1.38 (6H, s,
4.16. Deoxydihydroxanthoangelol H (4)
A mixture of 22 (385 mg, 1.0 mmol) and p-toluenesulfonic acid
monohydrate (190 mg, 1.0 mmol) in MeOH (10 cm3) was stirred
under reflux for 1 h. The reaction mixture was monitored by TLC.
After completion of the reaction, the reaction mixture was evapo-
rated under vacuum. After addition of 10 cm3 of water, the mixture
was extracted with ethyl acetate (3ꢁ30 cm3). The organic layers
were combined, washed with brine, dried over sodium sulfate,
filtrated, and evaporated under vacuum. The residue was purified
by silica gel column chromatography with hexane/ethyl acetate to
afford compound 4 (315 mg, 93%) as colorless crystal; mp (EtOH)
120.0e121.0 ꢀC; Rf (20% EtOAc/hexane) 0.10; nmax (KBr)/cmꢂ1 3390,
3002, 2905, 1650, 1628, 1595, 1525, 1460, 1455, 1435, 1390, 1375,
1300, 1280, 1235, 1220, 1165, 1100; dH (MeOD-d4) 1.34 (6H, s, CH3
00
00
CH3 ꢁ2), 1.83 (2H, t, J¼6.9 Hz, C3 H), 2.68 (2H, t, J¼6.9 Hz, C4 H),
3.49 (3H, s, OCH2OCH3), 3.90 (3H, s, OCH3), 5.20 (2H, s, OCH2OCH3),
0
6.49 (1H, d, J¼8.7 Hz, C5 H), 7.05 (2H. d, J¼8.8 Hz, C3H and C5H), 7.49
00
00
(1H, d, J¼15.4 Hz, CaH), 7.60 (2H, d, J¼8.8 Hz, C2H and C6H), 7.79 (1H,
ꢁ2), 1.82 (2H, t, J¼6.8 Hz, C3 H), 2.66 (2H, t, J¼6.8 Hz, C4 H), 2.66
0
d, J¼8.7 Hz, C6 H), 7.85 (1H, d, J¼15.4 Hz, CbH); dC (CDCl3) 17.15,
(2H, t, J¼8.0 Hz, CbH), 3.24 (2H, t, J¼8.0 Hz, CaH), 3.86 (3H, s, OCH3),
0
26.86, 31.72, 55.57, 56.09, 74.87, 94.21, 101.74,109.90,116.42, 122.28,
126.11, 129.57, 138.08, 140.44, 154.50, 158.53, 160.96, 190.91; HRMS:
Mþ, found 382.1768. C23H26O5 requires 382.1780.
6.55 (1H, d, J¼9.2 Hz, C5 H), 6.67 (2H, d, J¼8.4 Hz, C3H and C5H), 7.00
0
(2H, d, J¼8.4 Hz, C2H and C6H), 7.54 (1H, d, J¼8.8 Hz, C6 H); dC
(MeOD-d4) 18.11, 26.95, 31.10, 32.62, 46.68, 56.21, 76.42, 102.97,
111.27, 116.10, 122.29, 130.16, 130.08, 130.80, 133.72, 156.09, 156.50,
162.97, 203.56; HRMS: Mþ, found 340.1665. C21H24O4 requires
340.1675.
4.14. Deoxyxanthoangelol H (3)
A mixture of 21 (77 mg, 0.2 mmol) and p-toluenesulfonic acid
monohydrate (38 mg, 0.2 mmol) in MeOH (5 cm3) was stirred
under reflux for 1 h. The reaction mixture was monitored by TLC.
After completion of the reaction, the reaction mixture was evapo-
rated under vacuum. After addition of 7 cm3 of water, the mixture
was extracted with ethyl acetate (3ꢁ10 cm3). The organic layers
were combined, washed with brine, dried over sodium sulfate,
filtrated, and evaporated under vacuum. The residue was purified
by silica gel column chromatography with hexane/ethyl acetate to
afford compound 3 (60 mg, 89%) as yellow needle crystal; mp
(EtOH) 214.0e215.0 ꢀC; Rf (33% hexane/EtOAc) 0.10; nmax (KBr)/
cmꢂ1 3104, 3014, 2981, 2945, 2843, 2805, 1630, 1592, 1529, 1510,
1487, 1439, 1421, 1382, 1368, 1338, 1284, 1244, 1227, 1202, 1188,
1164, 1119, 1098, 1075, 1018; dH (DMSO-d6) 1.37 (6H, s, CH3 ꢁ2), 1.85
4.17. 20-Hydroxyl-40-methoxymethoxyacetophenone (8b)
To
a
stirred solution of 20,40-dihydroxyacetophenone (23)
(1.55 g, 10.2 mmol) and anhydrous K2CO3 (4.16 g, 30 mmol) in dry
acetone (60 cm3) was slowly added 80% chloromethyl methyl ether
(1.21 g, 12 mmol) at 0 ꢀC and stirred for 3 h. The reaction mixture
was monitored by TLC. After completion of the reaction, the re-
action mixture was filtrated and evaporated under vacuum. The
residue was purified by silica gel column chromatography with
hexane/ethyl acetate to afford compound 8b (1.86 g, 93%) as col-
orless oil; Rf (20% EtOAc/hexane) 0.4; nmax (neat)/cmꢂ1 3095, 3076,
3049, 3003, 2964, 2942, 2918, 2856, 2832, 1623, 1587, 1503, 1466,
1445, 1428, 1408, 1364, 1335, 1303, 1265, 1233, 1210, 1169, 1160,

5354
K. Sugamoto et al. / Tetrahedron 67 (2011) 5346e5359
00
00
0
1142, 1080, 1066, and 1002; dH (CDCl3) 2.56 (3H, s, CH3), 3.48 (3H, s,
(1H, m, C6 H), 5.49e5.53 (1H, m, C2 H), 6.45 (1H, d, J¼2.2 Hz, C3 H),
0
0
0
OCH3), 5.21 (2H, s, OCH2O), 6.55 (1H, dd, J¼2.4 and 8.8 Hz, C5 H),
6.51 (1H, dd, J¼2.2 and 8.7 Hz, C5 H), 7.83 (1H, d, J¼8.7 Hz, C6 H); dC
(CDCl3) 16.60, 17.66, 25.61, 26.16, 32.02, 39.39, 55.43, 65.34, 99.22,
105.04, 118.88, 121.42, 123.55, 141.62, 160.43, 164.34, 197.89.
0
0
6.59 (1H, d, J¼2.4 Hz, C3 H), 7.65 (1H, d, J¼8.8 Hz, C6 H), 12.61 (1H, s,
OH); dC (CDCl3) 26.21, 56.31, 93.93, 103.69, 108.12, 114.60, 132.34,
163.52, 164.78, 202.72; HRMS: Mþ, found 196.0745. C10H12O4 re-
quires 196.1999.
4.21. 4,40-Bis(methoxymethoxy)-20-prenyloxychalcone (16b)
4.18. 20-Prenyloxy-40-methoxymethoxyacetophenone (11b)
To a stirred solution of 11b (3.97 g, 15 mmol) and 7a (2.70 g,
18 mmol) in ethanol (70 cm3) was slowly added 3 M NaOH
(80 cm3) at 0 ꢀC, after which the reaction mixture was stirred at
room temperature for 20 h. After completion of reaction (TLC), the
solution was extracted with ethyl acetate (3ꢁ250 cm3). The or-
ganic layers were combined, washed with saturated sodium
chloride solution, dried over sodium sulfate, filtrated, and evapo-
rated under vacuum. The residue was purified by silica gel column
chromatography with hexane/ethyl acetate to afford compound
16b (5.81 g, 94%) as yellow oil; Rf (20% EtOAc/hexane) 0.20; nmax
(neat)/cmꢂ1 2955, 2933, 2905, 2827, 1735, 1652, 1600, 1573, 1509,
1428, 1382, 1329, 1314, 1173, 1153, 1121, 1080; dH (CDCl3) 1.75 (3H,
d, J¼0.6 Hz, CH3), 1.79 (3H, d, J¼0.6 Hz, CH3), 3.49 (3H, s, OCH3),
3.50 (3H, s, OCH3), 4.60 (2H, d, J¼6.8 Hz, PheCH2CH), 5.21 (2H, s,
OCH2OCH3), 5.22 (2H, s, OCH2OCH3), 5.51e5.55 (1H, m, C]
A
mixture of 20-hydroxy-40-methoxymethoxyacetophenone
(8b) (196 mg, 1 mmol), anhydrous K2CO3 (415 mg, 3 mmol), and
80% 1-chloro-3-methyl-2-butene (261 mg, 2 mmol) was stirred in
dry acetone (5 cm3) under reflux for 24 h. The reaction mixture
was monitored by TLC. After completion of the reaction, the re-
action mixture was filtrated and evaporated under vacuum. The
residue was purified by silica gel column chromatography with
hexane/ethyl acetate to afford compound 11b (219 mg, 83%) as
colorless oil; Rf (5% EtOAc/hexane) 0.10; nmax (neat)/cmꢂ1 2978,
2931, 2911, 2827, 1666, 1598, 1573, 1496, 1431, 1384, 1358, 1314,
1255, 1213, 1170, 1155, 1135, 1083, 1062, 1016; dH (CDCl3) 1.76 (3H,
s, CH3), 1.80 (3H, d, J¼0.7 Hz, CH3), 2.58 (3H, s, COCH3), 3.49 (3H, s,
OCH3), 4.59 (2H, d, J¼6.6 Hz, OCH2CH), 5.48e5.52 (1H, m, CH2CH]
0
0
C), 6.60 (1H, d, J¼2.2 Hz, C3 H), 6.64 (1H, dd, J¼2.2 and 8.7 Hz,
CHCH2), 6.64 (1H, d, J¼2.0 Hz, C3 H), 6.70 (1H, dd, J¼2.2 and 8.6 Hz,
0
0
0
C5 H), 7.80 (1H, d, J¼8.7 Hz, C6 H); dC (CDCl3) 18.27, 25.75, 32.05,
56.25, 65.44, 94.19, 100.81, 107.61, 119.01, 122.29, 132.38, 138.44,
160.31, 161.94, 198.08; HRMS: Mþ, found 264.1383. C15H20O4 re-
quires 264.1362.
C5 H), 7.03 (2H, d, J¼6.8 Hz, C3H and C5H), 7.52 (2H, d, J¼6.8 Hz,
C2H and C6H), 7.56 (1H, d, J¼15.8 Hz, CaH), 7.64 (1H, d, J¼15.8 Hz,
0
CbH), 7.79 (1H, d, J¼8.6 Hz, C6 H); dC (CDCl3) 18.29, 25.77, 56.13,
56.26, 65.61, 94.25, 101.23, 108.00, 116.38, 119.14, 123.23, 125.87,
129.50, 129.80, 132.81, 138.80, 141.36, 158.66, 159.80, 161.65,
190.24; HRMS: Mþ, found 412.1916. C24H28O6 requires 412.1886.
4.19. 20-Gerenyloxy-40-methoxymethoxyacetophenone (11c)
A mixture of 20-hydroxy-40-methoxymethoxy acetophenone
(8b) (196 mg, 1 mmol), anhydrous K2CO3 (415 mg, 3 mmol), and
geranyl bromide (326 mg, 1.5 mmol) was stirred in dry acetone
(5 cm3) under reflux for 24 h. The reaction mixture was monitored
by TLC. After completion of the reaction, the reaction mixture was
filtrated and evaporated under vacuum. The residue was purified
by silica gel column chromatography with hexane/ethyl acetate to
afford compound 11c (321 mg, 97%) as colorless oil; Rf (5% EtOAc/
hexane) 0.15; nmax (neat)/cmꢂ1 2964, 2925, 2854, 2827, 1653, 1606,
1577, 1495, 1448, 1431, 1379, 1331, 1315, 1379, 1331, 1315, 1275,
1248, 1207, 1171, 1154, 1122, 1080, 1013; dH (CDCl3) 1.61 (3H, s,
CH3), 1.67 (3H, d, J¼0.9 Hz, CH3), 1.75 (3H, d, J¼0.4 Hz, CH3),
4.22. 4,40-Dimethoxy-20-prenyloxychalcone (16c)
To a stirred solution of 11a (1170 mg, 5 mmol) and 4-
methoxybenzaldehyde (7b) (820 mg,
6 mmol) in ethanol
(50 cm3) was slowly added 3 M NaOH (50 cm3) at 0 ꢀC, after which
the reaction mixture was stirred at room temperature for 72 h.
After completion of reaction (TLC), the solution was extracted with
ethyl acetate (3ꢁ200 cm3). The organic layers were combined,
washed with saturated sodium chloride solution, dried over so-
dium sulfate, filtrated, and evaporated under vacuum. The residue
was purified by silica gel column chromatography with hexane/
ethyl acetate to afford compound 16c (1430 mg, 81%) as yellow
needle crystal; mp (EtOAc/hexane) 93.4e94.4 ꢀC; Rf (20% EtOAc/
hexane) 0.26; nmax (KBr)/cmꢂ1 3111, 3029, 3018, 2994, 2982, 2969,
22,949, 2936, 2911, 2836, 1647, 1602, 1572, 1509, 1499, 1460, 1440,
1420, 1387, 1328, 1309, 1283, 1246, 1213, 1194, 1174, 1119, 1024,
1003; dH (CDCl3) 1.74 (3H, d, J¼0.4 Hz, CH3), 1.79 (3H, d, J¼0.6 Hz,
CH3), 3.84 (3H, s, OCH3), 3.86 (3H, s, OCH3), 4.59 (2H, d, J¼6.8 Hz,
PheCH2CH), 5.53e5.57 (1H, m, C]CHCH2), 6.49 (1H, d, J¼2.3 Hz,
00
00
2.08e2.15 (4H, m, C4 H and C5 H), 2.59 (3H, s, COCH3), 3.48 (3H, s,
00
00
OCH2OCH3), 4.62 (2H, d, J¼6.6 Hz, C1 H), 5.06e5.10 (1H, m, C6 H),
00
5.20 (2H, s, OCH2OCH3), 5.49e5.52 (1H, m, C2 H), 6.60 (1H, d,
0
0
J¼2.2 Hz, C3 H), 6.64 (1H, dd, J¼2.2 and 8.7 Hz, C5 H), 7.80 (1H, d,
0
J¼8.7 Hz, C6 H); dC (CDCl3) 16.64, 17.70, 25.66, 26.22, 32.05, 39.46,
56.25, 65.42, 94.19, 100.78, 107.63, 118.85, 122.27, 123.61, 131.91,
132.39, 141.78, 161.96, 198.09; HRMS: Mþ, found 332.1996.
C15H20O4 requires 332.1988.
0
0
C3 H), 6.56 (1H, dd, J¼2.3 and 8.7 Hz, C5 H), 6.90 (2H, d, J¼8.8 Hz,
C3H and C5H), 7.53 (2H, d, J¼8.8 Hz, C2H and C6H), 7.58 (1H, d,
J¼15.7 Hz, CaH), 7.65 (1H, d, J¼15.7 Hz, CbH), 7.83 (1H, d, J¼8.7 Hz,
4.20. 20-Gerenyloxy-40-methoxyacetophenone (11d)
0
C6 H); dC (CDCl3) 18.29, 25.78, 55.37, 55.52, 65.59, 99.73, 105.44,
A mixture of 20-hydroxy-40-methoxyacetophenone (8a) (1.63 g,
5 mmol), anhydrous K2CO3 (2.07 g, 15 mmol), and geranyl bromide
(1.63 g, 7.5 mmol) was stirred in dry acetone (50 cm3) under reflux
for 24 h. The reaction mixture was monitored by TLC. After com-
pletion of the reaction, the reaction mixture was filtrated and
evaporated under vacuum. The residue was purified by silica gel
column chromatography with hexane/ethyl acetate to afford
compound 11d (1.38 g, 87%) as colorless oil; Rf (5% EtOAc/hexane)
0.15; nmax (neat)/cmꢂ1 2968, 2925, 2856, 1664, 1598, 1574, 1498,
1443, 1378, 1358, 1308, 1293, 1265, 1201, 1170, 1137, 1120, 1071,
1036; dH (CDCl3) 1.60 (3H, s, CH3), 1.67 (3H, s, CH3), 1.75 (3H, d,
114.23, 119.19, 122.46, 125.48, 128.50, 129.88, 133.07, 138.75, 141.39,
159.95, 161.08, 164.08, 190.06; HRMS: Mþ, found 352.1647.
C23H26O5 requires 352.1675.
4.23. 40-Methoxy-20-prenyloxychalcone (16d)
To a stirred solution of 11a (4.69 g, 20 mmol) and benzaldehyde
(7c) (2.55 g, 24 mmol) in ethanol (120 cm3) was slowly added 3 M
NaOH (110 cm3) at 0 ꢀC, after which the reaction mixture was
stirred at room temperature for 72 h. After completion of reaction
(TLC), the solution was extracted with ethyl acetate (3ꢁ300 cm3).
The organic layers were combined, washed with saturated sodium
chloride solution, dried over sodium sulfate, filtrated, and
00
00
J¼0.3 Hz, CH3), 2.08e2.14 (4H, m, C4 H and C5 H), 2.58 (3H, s,
00
COCH3), 3.84 (3H, s, OCH3), 4.61 (2H, d, J¼6.5 Hz, C1 H), 5.07e5.10

K. Sugamoto et al. / Tetrahedron 67 (2011) 5346e5359
5355
00
00
evaporated under vacuum. The residue was purified by silica gel
column chromatography with hexane/ethyl acetate to afford
compound 16d (5.68 g, 88%) as yellow needle crystal; mp (EtOAc/
hexane) 65.7e66.7 ꢀC; Rf (20% EtOAc/hexane) 0.32; nmax (KBr)/cmꢂ1
3102, 3086, 3058, 3049, 3031, 3010, 2979, 2962, 2935, 2913, 2962,
2935, 2913, 2889, 2840, 2913, 2889, 2839, 1676, 1648, 1612, 1587,
1496, 1477, 1461, 1445, 1385, 1330, 1296, 1279, 1248, 1213, 1120,
1173, 1119, 1073, 1056, 1031, 1024; dH (CDCl3) 1.74 (3H, d, J¼0.5 Hz,
CH3), 1.78 (3H, d, J¼0.7 Hz, CH3), 3.87 (3H, s, OCH3), 4.60 (2H, d,
J¼6.8 Hz, PheCH2CH), 5.53e5.57 (1H, m, C]CHCH2), 6.50 (1H, d,
C6 H) 5.18 (2H, s, OCH2OCH3), 5.51e5.55 (1H, m, C2 H), 6.49 (1H,
0
0
d, J¼2.1 Hz, C3 H), 6.55 (1H, dd, J¼2.2 and 8.7 Hz, C5 H), 7.02 (2H,
d, J¼8.7 Hz, C3H and C5H), 7.52 (2H, d, J¼8.7 Hz, C2H and C6H),
7.58 (1H, d, J¼15.8 Hz, CaH), 7.65 (1H, d, J¼15.8 Hz, CbH), 7.83 (1H,
0
d, J¼8.7 Hz, C6 H); dC (CDCl3) 16.68, 17.54, 25.50, 26.113, 39.33,
55.36, 55.95, 65.52, 94.08, 99.55, 105.36, 116.25, 118.72, 122.28,
123.52, 125.73, 129.34, 129.64, 131.73, 132.92, 141.04, 141.73,
158.55, 159.81, 163.99, 189.91.
0
0
J¼2.3 Hz, C3 H), 6.60 (1H, dd, J¼2.3 and 8.7 Hz, C5 H), 7.36e7.38 (3H,
m, C3H, C4H, and C5H), 7.57e7.59 (2H, m, C2H and C6H), 7.66 (1H, d,
J¼15.8 Hz, CaH), 7.72 (1H, d, J¼15.8 Hz, CbH), 7.86 (1H, d, J¼8.7 Hz,
4.26. Rearrangement of compound 16b
To a stirred solution of 16b (2053 mg, 5 mmol) in dry CH2Cl2
(100 cm3) was added montmorillonite K10 (2053 mg) at 0 ꢀC and
stirred for 0.5 h. The reaction mixture was monitored by TLC. After
completion of the reaction, the reaction mixture was filtrated and
evaporated under vacuum. The residue was purified by silica gel
column chromatography with hexane/ethyl acetate to afford
compound 15b (668 mg, 33%), 17b (557 mg, 28%), 18b (23 mg, 1%),
19b (473 mg, 28%).
0
C6 H); dC (CDCl3) 17.84, 21.75, 25.83, 55.79, 102.18, 114.65, 117.62,
120.63, 122.05, 128.50, 128.98, 129.27, 130.56, 131.90, 134.92, 144.11,
163.08, 163.39, 192.23; HRMS: Mþ, 322.1561. C21H22O3 requires
322.1569.
4.24. 4,40-Bis(methoxymethoxy)-20-gerenyloxychalcone (16e)
To a stirred solution of 11c (1.33 g, 4.0 mmol) and 7a (0.79 g,
4.8 mmol) in ethanol (30 cm3) was slowly added 3 M NaOH
(30 cm3) at 0 ꢀC, after which the reaction mixture was stirred at
room temperature for 72 h. After completion of reaction (TLC), the
solution was extracted with ethyl acetate (3ꢁ150 cm3). The organic
layers were combined, washed with saturated sodium chloride
solution, dried over sodium sulfate, filtrated, and evaporated under
vacuum. The residue was purified by silica gel column chroma-
tography with hexane/ethyl acetate to afford compound 16e (1.76 g,
92%) as yellow oil; mp (EtOAc/hexane) 65.7e66.7 ꢀC; Rf (20% EtOAc/
hexane) 0.32; nmax (neat)/cmꢂ1 2959, 2927, 2852, 2827, 1652, 1601,
1575, 1509, 1428, 1378, 1328, 1314, 1276, 1241, 1207, 1172, 1153, 1122,
1080; dH (CDCl3) 1.56 (3H, s, CH3), 1.65 (3H, s, CH3), 1.74 (3H, d,
4.26.1. 4,40-Bis(methoxymethoxy)-20-hydroxyl-30-prenylchalcone
(15b). Compound (15b) as yellow needle crystal; mp (EtOAc/
hexane) 81.0e82.0 ꢀC; Rf (20% EtOAc/hexane) 0.36; nmax (KBr)/
cmꢂ1 2989, 2975, 2954, 2921, 2912, 2853, 2824, 1633, 1611, 1585,
1561, 1507, 1491, 1419, 1372, 1306, 1293, 1274, 1239, 1199, 1169,
1152, 1115, 1083, 1049, 1011; dH (CDCl3) 1.68 (3H, d, J¼0.8 Hz, CH3),
1.81 (3H, s, CH3), 3.42 (2H, d, J¼7.1 Hz, PheCH2CH), 3.48 (3H, s,
OCH2OCH3), 3.49 (3H, s, OCH2OCH3), 5.22 (2H, S, OCH2OCH3),
5.22e5.28 (1H, m, C]CHCH2), 5.28 (2H, S, OCH2OCH3), 6.68 (1H, d,
0
J¼9.0 Hz, C5 H), 7.08 (2H, d, J¼8.7 Hz, C3H and C5H), 7.48 (1H, d,
J¼15.4 Hz, CaH), 7.60 (2H, d, J¼8.7 Hz, C2H and C6H), 7.75 (1H, d,
0
J¼9.0 Hz, C6 H), 7.85 (1H, d, J¼15.4 Hz, CbH), 13.48 (1H, s, OH); dC
00
00
J¼0.8 Hz, CH3), 2.07 (4H, br s, C4 H and C5 H), 3.48 (3H, s,
(CDCl3) 17.85, 21.97, 25.80, 56.20, 56.25, 93.84, 94.21, 104.80,
115.11, 116.56, 118.49, 118.58, 122.06, 128.62, 128.77, 130.23, 131.79,
144.02, 159.31, 160.71, 163.28, 192.40; HRMS: Mþ, 412.1861.
C24H28O6 requires 412.1886.
00
OCH2OCH3), 3.50 (3H, s, OCH2OCH3), 4.63 (2H, d, J¼6.6 Hz, C1 H),
00
5.05e5.09 (1H, m, C6 H) 5.20 (2H, s, OCH2OCH3), 5.22 (2H, s,
00
0
OCH2OCH3), 5.50e5.54 (1H, m, C2 H), 6.65 (1H, d, J¼2.2 Hz, C3 H),
0
6.70 (1H, dd, J¼2.2 and 8.6 Hz, C5 H), 7.02 (2H, d, J¼8.7 Hz, C3H and
C5H), 7.54 (2H, d, J¼8.7 Hz, C2H and C6H), 7.55 (1H, d, J¼15.8 Hz,
4.26.2. 4,40-Bis(methoxymethoxy)-20-hydroxyl-50-prenylchalcone
(17b). Compound (17b) as yellow needle crystal; mp (EtOAc/
hexane) 62.0e63.0 ꢀC; Rf (20% EtOAc/hexane) 0.38; nmax (KBr)/
cmꢂ1 3087, 2993, 2957, 2917, 2853, 2825, 2797, 2686, 1634, 1604,
1572, 1512, 1496, 1460, 1443, 1421, 1412, 1366, 1322, 1302, 1278,
1241, 1221, 1180, 1162, 1122, 1103, 1074; dH (CDCl3) 1.75 (3H, s, CH3),
1.77 (3H, d, J¼0.9 Hz, CH3), 3.29 (2H, d, J¼7.2 Hz, PheCH2CH), 3.48
(3H, s, OCH2OCH3), 3.50 (3H, s, OCH2OCH3), 5.23 (2H, S,
OCH2OCH3), 5.25 (2H, S, OCH2OCH3), 5.27e5.31 (1H, m, C]
0
CaH), 7.64 (1H, d, J¼15.8 Hz, CbH), 7.78 (1H, d, J¼8.6 Hz, C6 H); dC
(CDCl3) 16.69, 16.79, 17.65, 22.29, 25.43, 25.62, 26.25, 37.26, 38.98,
39.46, 56.07, 56.22, 65.67, 94.20, 94.22, 101.21, 107.99, 110.08, 116.37,
118.80, 118.89, 123.24, 123.65, 125.77, 129.40, 129.78, 131.83, 132.76,
141.38, 141.90, 158.70, 159.76, 161.64, 190.28; HRMS: Mþ, 480.2502.
C29H36O6 requires 480.2512.
4.25. 20-Geranyloxy-40-methoxy-4-methoxymethoxychalcone
(16f)
0
CHCH2), 6.65 (1H, s, C3 H), 7.09 (2H, d, J¼8.8 Hz, C3H and C5H), 7.46
(1H, d, J¼15.4 Hz, CaH), 7.60 (2H, d, J¼8.8 Hz, C2H and C6H), 7.62
0
To a stirred solution of 11d (150 mg, 0.5 mmol) and 7a (90 mg,
0.6 mmol) in ethanol (6 cm3) was slowly added 3 M NaOH
(5 cm3) at 0 ꢀC, after which the reaction mixture was stirred at
room temperature for 72 h. After completion of reaction (TLC),
the solution was extracted with ethyl acetate (3ꢁ50 cm3). The
organic layers were combined, washed with saturated sodium
chloride solution, dried over sodium sulfate, filtrated, and evap-
orated under vacuum. The residue was purified by silica gel
column chromatography with hexane/ethyl acetate to afford
compound 16f (177 mg, 79%) as yellow oil; Rf (10% EtOAc/hexane)
0.15; nmax (KBr)/cmꢂ1 3102, 3086, 3058, 3049, 3031, 3010, 2979,
2962, 2935, 2913, 2962, 2935, 2913, 2889, 2840, 2913, 2889,
2839, 1676, 1648, 1612, 1587, 1496, 1477, 1461, 1445, 1385, 1330,
1296, 1279, 1248, 1213, 1120, 1173, 1119, 1073, 1056, 1031, 1024; dH
(CDCl3) 1.56 (3H, s, CH3), 1.65 (3H, s, CH3), 1.74 (3H, d, J¼0.8 Hz,
(1H, s, C6 H), 7.84 (1H, d, J¼15.4 Hz, CbH), 13.30 (1H, s, OH); dC
(CDCl3) 17.89, 25.79, 28.37, 56.21, 56.34, 93.99, 94.22, 102.18,
114.28, 116.58, 118.54, 121.92, 122.41, 128.66, 130.05, 130.21, 132.82,
143.92, 159.31, 161.37, 164.81, 191.96; HRMS: Mþ, found 412.1890.
C24H28O6 requires 412.1886.
4.26.3. 4,40-Bis(methoxymethoxy)-30,50-diprenyl-20-hydroxyl-
chalcone (18b). Compound (18b) as yellow needle crystal; Rf (20%
EtOAc/hexane) 0.44; dH (CDCl3) 1.70 (3H, s, CH3), 1.75 (3H, s, CH3),
1.79 (3H, s, CH3), 1.80 (3H, s, CH3), 3.38 (2H, d, J¼6.9 Hz,
PheCH2CH), 3.42 (2H, d, J¼6.4 Hz, PheCH2CH), 3.50 (3H, s,
OCH2OCH3), 3.61 (3H, s, OCH2OCH3), 5.02 (2H, S, OCH2OCH3),
5.23 (2H, S, OCH2OCH3), 5.20e5.23 (1H, m, C]CHCH2), 5.30e5.33
(1H, m, C]CHCH2), 7.09 (2H, d, J¼8.7 Hz, C3H and C5H), 7.46 (1H,
0
d, J¼15.4 Hz, CaH), 7.58 (1H, s, C6 H), 7.60 (2H, d, J¼8.7 Hz, C2H
00
00
CH3), 2.06e2.08 (4H, m, C4 H and C5 H), 3.47 (3H, s, OCH2OCH3),
and C6H), 7.85 (1H, d, J¼15.4 Hz, CbH), 13.30 (1H, s, OH); dC
00
3.84 (3H, s, OCH3), 4.62 (2H, d, J¼6.5 Hz, C1 H), 5.05e5.08 (1H, m,
(CDCl3) 56.21, 56.40, 94.04, 94.21, 103.98, 108.14, 115.01, 116.57,

5356
K. Sugamoto et al. / Tetrahedron 67 (2011) 5346e5359
0
118.27, 128.52, 130.29, 131.24, 144.33, 159.41, 163.53, 166.18,
192.06.
C6 H), 7.61 (2H, d, J¼8.8 Hz, C2H and C6H), 7.86 (1H, d, J¼15.4 Hz,
CbH), 13.30 (1H, s, OH); dC (CDCl3) 17.96, 17.99, 22.98, 25.73, 25.76,
28.24, 55.45, 61.26, 114.50, 116.64, 118.20, 122.55, 123.07, 123.66,
125.43, 127.59, 128.31, 130.37, 131.86, 132.86, 144.42, 161.84, 162.26,
162.88, 192.85.
4.26.4. 4,40-Bis(methoxymethoxy)-20-hydroxylchalcone
(19b). Compound (19b) as yellow needle crystal; mp (EtOAc
hexane) 75.2e76.2 ꢀC: Rf (20% EtOAc/hexane) 0.32; nmax (KBr3)/
cmꢂ1 3079, 3049, 2956, 2939, 2907, 2830, 2791, 2681, 2592, 1633,
1603, 1568, 1508, 1420, 1360, 1312, 1299, 1277, 1216, 1198, 1160,
1126, 1084; dH (CDCl3) 3.49 (6H, s, OCH2OCH3 ꢁ2), 5.22 (4H, S,
4.27.4. 4,40-Dimethoxy-20-hydroxylchalcone (19c). Compound (19c)
as yellow needle crystal; mp (EtOAc/hexane) 114.4e115.3 ꢀC; Rf
(20% EtOAc/hexane) 0.36; nmax (KBr)/cmꢂ1 3080, 3009, 2973, 2940,
2916, 2844, 2750, 2721, 2687, 2667, 2596, 1627, 1604, 1582, 1512,
1462, 1442, 1365, 1312, 1282, 1259, 1217, 1178, 1128, 1019; dH (CDCl3)
0
OCH2OCH3 ꢁ2), 6.59 (1H, dd, J¼2.4 and 8.9 Hz, C5 H), 6.64 (1H, d,
0
J¼2.4 Hz, C3 H), 7.08 (2H, d, J¼8.8 Hz, C3H and C5H), 7.47 (1H,
0
d, J¼15.4 Hz, CaH), 7.60 (2H, d, J¼8.8 Hz, C2H and C6H), 7.84 (1H, d,
3.85 (3H, s, OCH3), 3.85 (3H, s, OCH3), 6.46 (1H, d, J¼1.3 Hz, C3 H),
0
0
J¼8.9 Hz, C6 H), 7.86 (1H, d, J¼15.4 Hz, CbH), 13.36 (1H, s, OH); dC
6.48 (1H, dd, J¼1.3 and 9.2 Hz, C5 H), 6.94 (2H, d, J¼8.8 Hz, C3H and
(CDCl3) 56.16, 56.35, 94.00, 94.17, 103.93, 108.10, 114.97, 116.52,
118.24, 128.48, 130.24, 131.20, 144.28, 159.37, 163.48, 166.13,
192.01; HRMS: Mþ, found 344.1310. C19H20O6 requires 334.1260.
C5H), 7.44 (1H, d, J¼15.4 Hz, CaH), 7.60 (2H, d, J¼8.8 Hz, C2H and
0
C6H), 7.82 (1H, d, J¼9.2 Hz, C6 H), 7.85 (1H, d, J¼15.4 Hz, CbH), 13.56
(1H, s, OH); dC (CDCl3) 55.44, 55.58, 101.09, 107.61, 114.17, 114.48,
117.84, 127.55, 130.37, 131.13, 144.28, 161.82, 166.05, 166.64, 191.90;
HRMS: Mþ, found 284.1045. C17H16O4 requires 284.1049.
4.27. Rearrangement of compound 16c
To a stirred solution of 16c (1019 mg, 2.9 mmol) in dry CH2Cl2
(50 cm3) was added montmorillonite K10 (1020 mg) at 0 ꢀC and
stirred for 1.0 h. The reaction mixture was monitored by TLC. After
completion of the reaction, the reaction mixture was filtrated and
evaporated under vacuum. The residue was purified by silica gel
column chromatography with hexane/ethyl acetate to afford
compound 1c (378 mg, 37%), 5c (276 mg, 27%), 18c (8 mg, 0.7%), 19c
(197 mg, 24%).
4.28. Rearrangement of compound 16d
To a stirred solution of 16d (644 mg, 2 mmol) in dry CH2Cl2
(20 cm3) was added montmorillonite K10 (644 mg) at 0 ꢀC and
stirred for 0.5 h. The reaction mixture was monitored by TLC. After
completion of the reaction, the reaction mixture was filtrated and
evaporated under vacuum. The residue was purified by silica gel
column chromatography with hexane/ethyl acetate to afford
compound 1d (276 mg, 43%), 5d (166 mg, 26%), 18d (6 mg, 0.8%),
19d (134 mg, 26%).
4.27.1. 4,40-Dimethoxy-20-hydroxyl-30-prenylchalcone (1c). Compound
(1c) as yellow needle crystal, mp (EtOAc/hexane) 97.6e98.2 ꢀC; Rf
(20% EtOAc/hexane) 0.40; nmax (KBr)/cmꢂ1 3006, 2985, 2979, 2917,
2847, 1633, 1607,1576,1515,1496, 1466,1444,1415,1371, 1323, 1310,
1295, 1283, 1261, 1239, 1283, 1261, 1239, 1194, 1175, 1153, 1117, 1098,
1070, 1024; dH (CDCl3) 1.68 (3H, d, J¼1.0 Hz, CH3), 1.80 (3H, s, CH3),
3.39 (2H, d, J¼7.1 Hz, PheCH2CH), 3.85 (3H, s, OCH3), 3.90 (3H, s,
4.28.1. Derricin (1d). Compound (1d) as yellow needle crystal; mp
(EtOAc/hexane) 85.5e86.5 ꢀC; Rf (20% EtOAc/hexane) 0.44; nmax
(KBr)/cmꢂ1 3059, 3033, 3013, 2992, 2957, 2912, 2849, 2745, 2719,
2641, 1635, 1605, 1573, 1496, 1446, 1418, 1361, 1325, 1311, 1280,
1232, 1205, 1188, 1167, 1120, 1098, 1078; dH (CDCl3) 1.68 (3H, d,
J¼1.0 Hz, CH3), 1.78 (3H, s, CH3), 3.38 (2H, d, J¼7.1 Hz, PheCH2CH),
3.89 (3H, s, OCH3), 5.21e5.26 (1H, m, C]CHCH2), 6.48 (1H, d,
0
OCH3), 5.22e5.26 (1H, m, C]CHCH2), 6.48 (1H, d, J¼9.0 Hz, C5 H),
6.93 (2H, d, J¼8.8 Hz, C3H and C5H), 7.47 (1H, d, J¼15.4 Hz, CaH), 7.59
0
(2H, d, J¼8.8 Hz, C2H and C6H), 7.63 (1H, d, J¼9.0 Hz, C6 H), 7.84 (1H,
0
d, J¼15.4 Hz, CbH), 13.47 (1H, s, OH); dC (CDCl3) 17.83, 21.74, 25.83,
55.43, 55.77, 102.04, 114.45, 114.70, 117.55, 118.14, 122.08, 127.65,
129.09, 130.60, 131.88, 143.88, 143.97, 161.72, 163.02, 163.19, 192.28;
HRMS: Mþ, found 352.1685. C22H24O4 requires 352.1675.
J¼9.0 Hz, C5 H), 7.39e7.42 (3H, m, C3H, C4H, and C5H), 7.58 (1H, d,
J¼15.5 Hz, CaH), 7.63 (2H, m, C2H and C6H), 7.78 (1H, d, J¼9.0 Hz,
0
C6 H), 7.85 (1H, d, J¼15.5 Hz, CbH), 13.37 (1H, s, OH); dC (CDCl3)
17.84, 21.75, 25.83, 55.79, 102.18, 114.65, 117.62, 120.63, 122.05,
128.50, 128.98, 129.27, 130.56, 131.90, 134.92, 144.11, 163.08,
163.39, 192.23; HRMS: Mþ, found 322.1561. C21H22O3 requires
322.1569.
4.27.2. 4,40-Dimethoxy-20-hydroxyl-50-prenylchalcone (5c). Compound
(5c) as yellow needle crystal; mp (EtOAc/hexane) 95.5e96.1 ꢀC; Rf
(20% EtOAc/hexane) 0.48; nmax (CHCl3)/cmꢂ1 3021, 3006, 2983,
2964, 2945, 2923, 2852, 2836, 1635, 1607, 1565, 1513, 1494, 1460,
1443, 1423, 1387, 1364, 1301, 1281, 1254, 1234, 1219, 1174, 1127, 1103,
1027; dH (CDCl3) 1.74 (3H, s, CH3), 1.78 (3H, d, J¼0.8 Hz, CH3), 3.26
(2H, d, J¼7.2 Hz, PheCH2CH), 3.86 (3H, s, OCH3), 3.87 (3H, s, OCH3),
4.28.2. 20-Hydroxyl-40-methoxy-50-prenylchalcone (5d). Compound
(5d) as yellow needle crystal; mp (EtOAc/hexane) 100.7e101.2 ꢀC;
Rf (20% EtOAc/hexane) 0.56; nmax (KBr)/cmꢂ1 3081, 3008, 2978,
2963, 2942, 2917, 2895, 2854, 2697, 1640, 1577, 1497, 1459, 1443,
1390, 1365, 1322, 1305, 1278, 1238, 1212, 1176, 1131, 1028; dH (CDCl3)
1.73 (3H, s, CH3), 1.78 (3H, d, J¼1.0 Hz, CH3), 3.26 (2H, d, J¼7.2 Hz,
PheCH2CH), 3.86 (3H, s, OCH3), 5.26e5.31 (1H, m, C]CHCH2), 6.43
0
5.26e5.30 (1H, m, C]CHCH2), 6.43 (1H, s, C3 H), 6.95 (2H, d,
J¼8.8 Hz, C3H and C5H), 7.44 (1H, d, J¼15.4 Hz, CaH), 7.60 (1H, s,
0
C6 H), 7.60 (2H, d, J¼8.8 Hz, C2H and C6H), 7.84 (1H, d, J¼15.4 Hz,
0
CbH), 13.50 (1H, s, OH); dC (CDCl3) 17.87, 25.80, 28.03, 55.43, 55.70,
99.36, 113.40, 114.47, 118.10, 121.56, 122.31, 127.67, 129.67, 130.29,
132.93, 143.86, 161.73, 164.08, 165.33, 191.81; HRMS: Mþ, found
352.1697. C22H24O4
(1H, s, C3 H), 7.41e7.43 (3H, m, C3H, C4H and C5H), 7.55 (1H, d,
0
J¼15.5 Hz, CaH), 7.59 (1H, s, C6 H), 7.64 (2H, m, C2H and C6H), 7.86
(1H, d, J¼15.5 Hz, CbH), 13.40 (1H, s, OH); dC (CDCl3) 17.81, 25.79,
28.02, 55.73, 99.38, 113.38, 120.62, 121.72, 122.24, 128.48, 129.00,
130.55, 133.02, 134.96, 143.98, 164.30, 165.46, 191.76; HRMS: Mþ,
found 322.1577. C21H22O3 requires 322.1569.
requires 352.1675.
4.27.3. 4,40-Dimethoxy-30,50-diprenyl-20-hydroxylchalcone
(18c). Compound (18c) as yellow needle crystal; Rf (20% EtOAc/
hexane) 0.56; dH (CDCl3) 1.70 (3H, d, J¼1.0 Hz, CH3),1.77 (3H, s, CH3),
1.79 (3H, d, J¼1.0 Hz, CH3), 1.80 (3H, s, CH3), 3.34 (2H, d, J¼7.0 Hz,
PheCH2CH), 3.42 (2H, d, J¼6.9 Hz, PheCH2CH), 3.78 (3H, s, OCH3),
3.87 (3H, s, OCH3), 5.24e5.32 (2H, m, C]CHCH2 ꢁ2), 6.96 (2H, d,
J¼8.8 Hz, C3H and C5H), 7.46 (1H, d, J¼15.4 Hz, CaH), 7.58 (1H, s,
4.28. 3. 30,50-Diprenyl-20-hydroxyl-40-methoxychalcone
(18d). Compound (18d) as yellow needle crystal; Rf (20% EtOAc/
hexane, 4:1) 0.64; dH (CDCl3) 1.70 (3H, s, CH3), 1.76 (3H, s, CH3), 1.78
(3H, s, CH3), 1.81 (3H, s, CH3), 3.34 (2H, d, J¼7.0 Hz, PheCH2CH), 3.42
(2H, d, J¼6.6 Hz, PheCH2CH), 3.77 (3H, s, OCH3), 5.24e5.32 (2H, m,
C]CHCH2 ꢁ2), 7.43e7.44 (3H, m, C3H, C4H, and C5H), 7.58 (1H, d,

K. Sugamoto et al. / Tetrahedron 67 (2011) 5346e5359
5357
0
J¼15.5 Hz, CaH), 7.59 (1H, s, C6 H), 7.63e7.66 (2H, m, C2H and C6H),
evaporated under vacuum. The residue was purified by silica gel
column chromatography with hexane/ethyl acetate to afford
compound 15f (81 mg, 36%), 17f (20 mg, 9%), 18f (2 mg, 0.1%), 19a
(85 mg, 54%).
7.88 (1H, d, J¼15.5 Hz, CbH), 13.19 (1H, s, OH).
4.28.4. 20-Hydroxyl-40-methoxychalcone (19d). Compound (19d) as
yellow needle crystal; mp (EtOAc/hexane) 106.7e107.7 ꢀC Rf (20%
EtOAc/hexane) 0.44; nmax (KBr)/cmꢂ1 3087, 3064, 3034, 3008, 2975,
2937, 2915, 2845, 2747, 2692, 2666, 2594, 2537, 1634, 1573, 1510,
1496, 1466, 1445, 1412, 1382, 1363, 1323, 1303, 1277, 1223, 1132,
1073, 1018; dH (CDCl3) 3.84 (6H, s, OCH2OCH3 ꢁ2), 6.46(1H, d,
4.30.1. 30-Geranyl-20-hydroxy-40-methoxy-4-methoxymethoxychalcone
(15f). Compound (15f) as yellow oil; Rf (10% EtOAc/hexane) 0.18;
nmax (KBr)/cmꢂ1 2963, 2916, 2846, 1633, 1611, 1577, 1568, 1509,
1496, 1442, 1421, 1373,1312, 1281, 1230, 1201, 1173, 1152, 1114,1080;
dH (CDCl3) 1.57 (3H, s, CH3), 1.64 (3H, d, J¼0.9 Hz, CH3), 1.79 (3H, d,
0
0
J¼2.6 Hz, C3 H), 6.48 (1H, dd, J¼2.6 and 8.7 Hz, C5 H), 7.40e7.42 (3H,
00
00
m, C3H, C4H, and C5H), 7.56 (1H, d, J¼15.5 Hz, CaH), 7.62e7.65 (2H,
J¼0.8 Hz, CH3), 1.95e1.99 (2H, m, C4 H), 2.03e2.09 (2H, m, C5 H),
0
00
m, C2H and C6H), 7.81 (1H, d, J¼8.7 Hz, C6 H), 7.87 (1H, d, J¼15.5 Hz,
3.39 (2H, d, J¼7.0 Hz, C1 H), 3.49 (3H, s, OCH2OCH3), 3.90 (3H, s,
00
CbH), 13.44 (1H, s, OH); dC (CDCl3) 55.59, 101.12, 107.74, 114.12,
120.32, 128.55, 129.00, 130.67, 131.27, 134.81, 144.39, 166.25, 166.73,
191.84; HRMS: Mþ, found 254.0891. C16H14O3 requires 254.0943.
OCH3), 5.05e5.09 (1H, m, C6 H), 5.21 (2H, s, OCH2OCH3), 5.22e5.25
00
0
(1H, m, C2 H), 6.49 (1H, d, J¼9.2 Hz, C5 H), 7.08 (2H, d, J¼8.8 Hz, C3H
and C5H), 7.49 (1H, d, J¼15.4 Hz, CaH), 7.60 (2H, d, J¼8.8 Hz, C2H and
0
C6H), 7.79 (1H, d, J¼9.2 Hz, C6 H), 7.84 (1H, d, J¼15.4 Hz, CbH), 13.43
4.29. Rearrangement of compound 16e
(1H, s, OH); dC (CDCl3) 16.14, 17.66, 21.67, 25.66, 26.74, 39.81, 55.75,
56.19, 94.22, 102.06, 114.68, 116.55, 117.08, 118.69, 121.91, 124.48,
128.70, 129.08, 130.18, 131.15, 135.32, 143.78, 159.26, 163.07, 163.29,
192.25; HRMS: Mþ, found 450.2414. C28H34O5 requires 450.2406.
To a stirred solution of 16e (240 mg, 0.5 mmol) in dry CH2Cl2
(5 cm3) was added montmorillonite K10 (240 mg) at 0 ꢀC and
stirred for 2 h. The reaction mixture was monitored by TLC. After
completion of the reaction, the reaction mixture was filtrated and
evaporated under vacuum. The residue was purified by silica gel
column chromatography with hexane/ethyl acetate to afford
compound 15e (105 mg, 44%), 5d (30 mg, 12%), 19b (73 mg, 42%).
4.30.2. 50-Geranyl-20-hydroxy-40-methoxy-4-methoxymethoxychal-
cone (17f). Compound (17f) as yellow oil; Rf (10% EtOAc/hexane)
0.22; nmax (KBr)/cmꢂ1 3006, 2972, 2926, 2851, 1632, 1583, 1566,
1504, 1444, 1383, 1320, 1304, 1279, 1227, 1207, 1155, 1124, 1079; dH
(CDCl3) 1.59 (3H, s, CH3),1.67 (3H, d, J¼0.9 Hz, CH3),1.72 (3H, s, CH3),
4.29.1. 4,40-Bis(methoxymethoxy)-30-geranyl-20-hydroxychalcone
(15e). Compound (15e) as yellow oil; Rf (20% EtOAc/hexane) 0.20
nmax (KBr)/cmꢂ1 2991, 2963, 2925, 2855, 2824, 1634, 1613, 1587,
1562, 1507, 1489, 1421, 1372, 1307, 1296, 1273, 1240, 1197, 1172, 1153,
1113, 1083, 1049, 1020; dH (CDCl3) 1.56 (3H, s, CH3), 1.64 (3H, d,
2.06e2.10 (2H, m, C4 H), 2.14e2.20 (2H, m, C5 H), 3.27 (2H, d,
00
00
00
J¼7.2 Hz, C1 H), 3.49 (3H, s, OCH2OCH3), 3.86 (3H, s, OCH3),
00
5.13e5.17 (1H, m, C6 H), 5.22 (2H, s, OCH2OCH3), 5.30e5.34 (1H, m,
00
0
C2 H), 6.44 (1H, s, C3 H), 7.07 (2H, d, J¼8.8 Hz, C3H and C5H), 7.45
(1H, d, J¼15.4 Hz, CaH), 7.58 (2H, d, J¼8.8 Hz, C2H and C6H), 7.60 (1H,
00
0
J¼1.4 Hz, CH3), 1.81 (3H, d, J¼0.6 Hz, CH3), 1.95e1.99 (2H, m, C4 H),
s, C6 H), 7.84 (1H, d, J¼15.4 Hz, CbH), 13.49 (1H, s, OH); dC (CDCl3)
00
00
2.03e2.09 (2H, m, C5 H), 3.43 (2H, d, J¼7.1 Hz, C1 H), 3.48 (3H, s,
16.20, 17.70, 25.69, 27.26, 27.62, 39.86, 55.69, 56.18, 94.22, 99.32,
113.37, 116.56, 118.55, 121.47, 121.94, 124.11, 128.69, 129.49, 130.18,
131.60, 137.09, 143.74, 159.27, 164.17, 165.37, 191.79; HRMS: Mþ,
found 450.2411. C28H34O5 requires 450.2406.
00
OCH2OCH3), 3.49 (3H, s, OCH2OCH3), 5.04e5.09 (1H, m, C6 H), 5.22
00
(2H, s, OCH2OCH3), 5.22e5.28 (1H, m, C2 H), 5.28 (2H, s,
0
OCH2OCH3), 6.68 (1H, d, J¼9.0 Hz, C5 H), 7.07 (2H, d, J¼8.7 Hz, C3H
and C5H), 7.48 (1H, d, J¼15.4 Hz, CaH), 7.60 (2H, d, J¼8.7 Hz, C2H and
C6H), 7.75 (1H, d, J¼9.0 Hz, C6 H), 7.85 (1H, d, J¼15.4 Hz, CbH), 13.48
4.30.3. 30,50-Digeranyl-20-hydroxyl-40-methoxy-4-methoxymethoxy-
chalcone (18f). Compound (18f) as yellow oil; Rf (10% EtOAc/hex-
ane) 0.33; dH (CDCl3) 1.57 (3H, s, CH3), 1.58 (3H, s, CH3), 1.63 (3H, s,
CH3), 1.66 (3H, s, CH3), 1.76 (3H, s, CH3), 1.80 (3H, s, CH3), 1.99e2.18
0
(1H, s, OH); dC (CDCl3) 16.15, 17.62, 21.87, 25.63, 26.72, 39.79, 56.18,
56.22, 93.83, 94.22, 104.79, 115.11, 116.56, 118.59, 118.63, 121.87,
124.40, 128.64, 128.73, 130.20, 131.21, 135.30, 143.99, 159.30, 160.75,
163.30, 192.41; HRMS: Mþ, found 480.2502. C29H36O6 requires
480.2512.
00
000
00
000
00
(8H, m, C4 H, C4 H, C5 H, and C5 H), 3.35 (2H, d, J¼7.0 Hz, C1 H),
000
3.42 (2H, d, J¼6.6 Hz, C1 H), 3.50 (3H, s, OCH2OCH3), 3.78 (3H, s,
00
000
OCH3), 5.04e5.06 (1H, m, C6 H), 5.13e5.16 (1H, m, C6 H), 5.23 (2H,
4.29.2. 4,40-Bis(methoxymethoxy)-50-geranyl-20-hydroxychalcone
(17e). Compound (17e) as yellow oil; Rf (20% EtOAc/hexane) 0.33;
nmax (neat)/cmꢂ1 2965, 2917, 2849, 2827, 1634, 1604, 1567, 1509,
1490, 1443, 1423, 1362, 1304, 1274, 1239, 1304, 1274, 1239, 1215,
1171, 1153, 1126, 1076; dH (CDCl3) 1.59 (3H, s, CH3), 1.67 (3H, s, CH3),
s, OCH2OCH3), 5.25e5.28 (1H, m, C2 H), 5.31e5.35 (1H, m, C2 H),
7.07 (2H, d, J¼8.7 Hz, C3H and C5H), 7.48 (1H, d, J¼15.4 Hz, CaH), 7.59
00
000
0
(2H, d, J¼8.7 Hz, C2H and C6H), 7.60 (1H, s, C6 H), 7.86 (1H, d,
J¼15.4 Hz, CbH), 13.29 (1H, s, OH).
00
00
1.75 (3H, s, CH3), 2.05e2.08 (2H, m, C4 H), 2.13e2.17 (2H, m, C5 H),
4.31. Isobavachalcone (1b)
00
3.31 (2H, d, J¼7.3 Hz, C1 H), 3.48 (3H, s, OCH2OCH3), 3.50 (3H, s,
00
OCH2OCH3), 5.13e5.17 (1H, m, C6 H), 5.25 (2H, s, OCH2OCH3), 5.33
To a stirred solution of 15b (81 mg, 0.19 mmol) in MeOH
(10 cm3) was added 3 M aqueous HCl (2 cm3) at room tempera-
ture, after which the reaction mixture was stirred under reflux for
0.5 h. The reaction mixture was monitored by TLC. After comple-
tion of the reaction, the reaction mixture was evaporated under
vacuum. After addition of 10 cm3 of water, the mixture was
extracted with ethyl acetate (3ꢁ30 cm3). The organic layers were
combined, washed with brine, dried over sodium sulfate, filtrated,
and evaporated under vacuum. The residue was purified by silica
gel column chromatography with hexane/ethyl acetate to afford
compound 1b (46 mg, 72%) as yellow needle crystal; mp (EtOAc/
hexane) 156.8e157.8 ꢀC; Rf (20% EtOAc/hexane) 0.04; nmax (KBr)/
cmꢂ1 3240, 3033, 2995, 2968, 2916, 2856, 2724, 1605, 1554, 1514,
1486, 1446, 1373, 1322, 1294, 1241, 1169, 1111, 1098, 1042, 1003; dH
(DMSO-d6) 1.61 (3H, s, CH3), 1.71 (3H, s, CH3), 3.22 (2H, d, J¼7.1 Hz,
00
0
(2H, s, OCH2OCH3), 5.32e5.35 (1H, m, C2 H), 6.66 (1H, s, C3 H), 7.07
(2H, d, J¼8.7 Hz, C3H and C5H), 7.46 (1H, d, J¼15.4 Hz, CaH), 7.59 (2H,
0
d, J¼8.7 Hz, C2H and C6H), 7.64 (1H, s, C6 H), 7.85 (1H, d, J¼15.4 Hz,
CbH), 13.31 (1H, s, OH); dC (CDCl3) 16.22, 17.66, 26.66, 27.17, 27.97,
39.83, 56.17, 56.33, 94.02, 94.22, 102.16, 114.26, 116.56, 118.48,
121.81, 122.05, 124.06, 129.87, 130.20, 143.95, 159.31, 164.81, 191.96;
HRMS: Mþ, found 480.2511. C29H36O6 requires 480.2512.
4.30. Rearrangement of compound 16f
To a stirred solution of 16f (226 mg, 0.5 mmol) in dry CH2Cl2
(10 cm3) was added montmorillonite K10 (225 mg) at 0 ꢀC and
stirred for 1 h. The reaction mixture was monitored by TLC. After
completion of the reaction, the reaction mixture was filtrated and

5358
K. Sugamoto et al. / Tetrahedron 67 (2011) 5346e5359
PheCH2CH), 5.14e5.18 (1H, m, C]CHCH2), 6.46 (1H, d, J¼8.9 Hz,
4.34. Xanthoangelol (1e)
0
C3 H), 6.83 (2H, d, J¼8.7 Hz, C3H and C5H), 7.74 (2H, s, CaH and
CbH), 7.74 (2H, d, J¼8.7 Hz, C2H and C6H), 8.02 (1H, d, J¼8.7 Hz,
To a stirred solution of 15e (50 mg, 0.10 mmol) in 2-PrOH
(10 cm3) was added CBr4 (6.9 mg, 0.02 mmol) at room tempera-
ture, after which the reaction mixture was stirred under reflux for
5 h. The reaction mixture was monitored by TLC. After completion of
the reaction, the reaction mixture was evaporated under vacuum.
The residue was purified by PLC with hexane/ethyl acetate to afford
compound 5a (31 mg, 77%) as yellow needle crystal; mp (EtOAc/
hexane) 122.7e123.7 ꢀC; Rf (33% EtOAc/hexane) 0.12; nmax (KBr)/
cmꢂ1 3376, 3183, 3164, 2972, 2923, 2878, 2855, 1628, 1604, 1544,
1513, 1485, 1442, 1372, 1320, 1284, 1244, 1210, 1166, 1110, 1030; dH
(CDCl3) 1.59 (3H, s, CH3),1.68 (3H, s, CH3),1.83 (3H, s, CH3), 2.08e2.13
0
C6 H), 10.11 (1H, br s, OH), 10.54 (1H, br s, OH), 13.98 (1H, s, OH); dC
(DMSO-d6) 17.67, 21.23, 25.44, 107.28, 112.68, 114.43, 115.81, 117.36,
122.34, 125.76, 129.76, 130.42, 131.14, 144.08, 160.19, 162.23,
163.50, 191.74; HRMS: Mþ, found 324.1330. C20H20O4 requires
324.1362.
4.32. Buroussochalcone B (5b)
To a stirred solution of 17a (50 mg, 0.12 mmol) in MeOH (5 cm3)
was added CBr4 (8 mg, 0.024 mmol) at room temperature, after
which the reaction mixture was stirred under reflux for 8 h. The
reaction mixture was monitored by TLC. After completion of the
reaction, the reaction mixture was evaporated under vacuum.
The residue was purified by PLC with hexane/ethyl acetate to afford
compound 5b (24 mg, 61%) and bavachin (10 mg, 25%).
00
00
00
(4H, m, C4 H and C5 H), 3.49 (2H, d, J¼7.1 Hz, C1 H), 5.04e5.07 (1H,
00
00
m, C6 H), 5.29e5.32 (1H, m, C2 H), 5.69 (1H, br s, OH), 6.25 (1H, br s,
0
OH), 6.43 (1H, d, J¼8.9 Hz, C5 H), 6.88 (2H, d, J¼8.6 Hz, C3H and C5H),
7.46 (1H, d, J¼15.4 Hz, CaH), 7.55 (2H, d, J¼8.6 Hz, C2H and C6H), 7.73
0
(1H, d, J¼8.9 Hz, C6 H), 7.84 (1H, d, J¼15.4 Hz, CbH),13.88 (1H, s, OH);
dC (CDCl3) 16.29, 17.72, 21.72, 25.68, 26.33, 39.72, 107.90, 113.95,
114.02, 115.60, 118.19, 121.00, 123.68, 127.92, 129.23, 130.54, 132.15,
139.92, 143.93, 157.83, 161.84, 163.85, 192.14. HRMS: Mþ, found
392.1966. C25H28O4 requires 392.1988.
Buroussochalcone B (5b) as yellow needle crystal; mp (EtOAc/
hexane) 161.7e162.2 ꢀC; Rf (33% EtOAc/hexane) 0.22; nmax (KBr)/
cmꢂ1 3309, 3031, 2966, 2917, 2854, 2729, 1636, 1606, 1582, 1571,
1543, 1512, 1438, 1420, 1368, 1318, 1292, 1254, 1217, 1167, 1126, 1106,
1021; dH (DMSO-d6) 1.68 (3H, d, J¼0.8 Hz, CH3), 1.72 (3H, s, CH3),
3.22 (2H, d, J¼7.0 Hz, PheCH2CH), 5.26e5.30 (1H, m, C]CHCH2),
4.35. Xanthoangelol F (1f)
0
6.33 (1H, s, C3 H), 6.86 (2H, d, J¼8.5 Hz, C3H and C5H), 7.73 (2H, s,
To a stirred solution of 15f (52 mg, 0.12 mmol) in MeOH (2 cm3)
and CH2Cl2 (2 cm3) was added p-toluenesulfonic acid monohydrate
(66 mg, 0.36 mmol) and stirred at room temperature for 48 h. The
reaction mixture was monitored by TLC. After completion of the
reaction, the reaction mixture was evaporated under vacuum. After
addition of 10 cm3 of water, the mixture was extracted with ethyl
acetate (3ꢁ15 cm3). The organic layers were combined, washed with
brine, dried over sodium sulfate, filtrated, and evaporated under
vacuum. The residue was purified by silica gel column chromatog-
raphy with hexane/ethyl acetate to afford compound 1f (43 mg, 92%)
as yellow needle crystal, mp (EtOAc/hexane) 124.0e125.0 ꢀC; Rf (33%
EtOAc/hexane) 0.15; nmax (KBr)/cmꢂ1 3278, 2968, 2925, 2844, 1626,
1605,1579,1543,1511,1490,1455,1442,1411,1373,1322,1279,1248,
1223, 1201, 1169, 1120, 1072; dH (CDCl3) 1.56 (3H, s, CH3), 1.63 (3H, d,
0
CaH and CbH), 7.75 (2H, d, J¼8.5 Hz, C2H and C6H), 7.97 (1H, s, C6 H),
10.12 (1H, s, OH), 10.66 (1H, s, OH), 13.46 (1H, s, OH); dC (DMSO-d6)
17.74, 25.43, 27.91, 102.26, 112.69, 115.81, 117.54, 120.42, 123.36,
125.77, 130.75, 131.12, 131.62, 143.97, 160.19, 162.90, 164.00, 191.32;
HRMS: Mþ, found 324.1376. C20H20O4 requires 324.1362.
Bavachin as yellow needle crystal; mp (EtOAc/hexane)
186.8e187.8 ꢀC; Rf (50% EtOAc/hexane) 0.32; nmax (KBr)/cmꢂ1 3328,
3207, 3134, 3089, 2981, 2964, 2909, 2857, 2798, 2740, 2643, 1655,
1585, 1520, 1504, 1468, 1453, 1372, 1349, 1335, 1306, 1279, 1259,
1167; dH (acetone-d6) 1.61 (3H, s, CH3), 1.63 (3H, d, J¼0.8 Hz, CH3),
2.54 (1H, dd, J¼2.9 and 16.7 Hz, C3H), 2.92 (1H, dd, J¼13.0 and
16.7 Hz, C3H), 3.17 (2H, d, J¼7.3 Hz, PheCH2CH), 5.21e5.26 (1H, m,
0
0
C]CHCH2), 6.35 (1H, s, C8H), 6.79 (2H, d, J¼8.6 Hz, C3 H and C5 H),
0
0
7.28 (2H, d, J¼8.6 Hz, C2 H and C6 H), 7.49 (1H, s, C5H), 8.43 (1H, br s,
OH), 9.46 (1H, br s, OH); dC (CDCl3) 17.83, 25.94, 28.23, 44.75, 80.53,
103.24, 114.89, 116.12, 123.22, 123.82, 128.25, 128.96, 131.41, 132.97,
158.55, 162.79, 162.96, 190.76; HRMS: Mþ, found 324.1383.
C20H20O4 requires 324.1362.
00
J¼0.9 Hz, CH3), 1.79 (3H, d, J¼0.9 Hz, CH3), 1.95e1.99 (2H, m, C4 H),
00
00
2.03e2.09 (2H, m, C5 H), 3.39 (2H, d, J¼7.0 Hz, C1 H), 3.90 (3H, s,
00
00
OCH3), 5.07e5.09 (1H, m, C6 H), 5.21e5.25 (1H, m, C2 H), 5.82 (1H, br
0
s, OH), 6.49 (1H, d, J¼9.2 Hz, C5 H), 6.87 (2H, d, J¼8.6 Hz, C3H and
C5H), 7.46 (1H, d, J¼15.4 Hz, CaH), 7.54 (2H, d, J¼8.6 Hz, C2H and C6H),
0
7.78 (1H, d, J¼9.2 Hz, C6 H), 7.82 (1H, d, J¼15.4 Hz, CbH), 13.44 (1H, s,
4.33. Bavachalcone (5a)
OH); dC (CDCl3) 16.15, 17.66, 21.68, 25.66, 26.74, 39.80, 55.77, 102.16,
114.66, 116.04, 117.70, 118.14, 121.89, 124.47, 127.70, 129.17, 130.17,
131.19, 135.39, 144.09, 158.14, 163.03, 163.36, 192.47; HRMS: Mþ,
found 406.2144. C26H30O4 requires 406.2144.
To a stirred solution of 17a (51 mg, 0.13 mmol) in MeOH (5 cm3)
was added CBr4 (4.5 mg, 0.013 mmol) at room temperature, after
which the reaction mixture was stirred under reflux for 2.5 h. The
reaction mixture was monitored by TLC. After completion of the
reaction, the reaction mixture was evaporated under vacuum.
The residue was purified by PLC with hexane/ethyl acetate to afford
compound 5a (35 mg, 84%) as yellow needle crystal; mp (EtOAc/
hexane) 169.9e170.1 ꢀC; Rf (33% EtOAc/hexane) 0.34; nmax (KBr)/
cmꢂ1 3436, 3319, 3069, 2973, 2943, 2911, 2854, 2821, 2751, 2697,
2604, 1628, 1604, 1544, 1508, 1443, 1363, 1306, 1284, 1205, 1170,
1130, 1105; dH (acetone-d6) 1.58 (3H, d, J¼1.0 Hz, CH3), 1.59 (3H, s,
CH3), 3.13 (2H, d, J¼7.2 Hz, PheCH2CH), 3.78 (3H, s, OCH3),
4.36. 40-Methylisoliquiritigenin (24a)
To a stirred solution of 19a (628 mg, 2 mmol) in MeOH (30 cm3)
was added p-toluenesulfonic acid monohydrate (380 mg,
2.0 mmol) and stirred under reflux for 3 h. The reaction mixture
was monitored by TLC. After completion of the reaction, the re-
action mixture was evaporated under vacuum. After addition of
10 cm3 of water, the mixture was extracted with ethyl acetate
(3ꢁ20 cm3). The organic layers were combined, washed with brine,
dried over sodium sulfate, filtrated, and evaporated under vacuum.
The residue was purified by silica gel column chromatography with
hexane/ethyl acetate to afford compound 24a (442 mg, 82%) as
yellow powder crystal; mp (EtOAc/hexane) 163.3e164.3 ꢀC; Rf (20%
EtOAc/hexane) 0.15; nmax (KBr)/cmꢂ1 3249, 3082, 3045, 3030, 3008,
2976, 2952, 1633, 1609, 1589, 1576, 1547, 1508, 1457, 1442, 1416,
1376, 1326, 1287, 1227, 1169, 1137, 1107, 1023; dH (MeOD-d4) 3.84
0
5.12e5.17 (1H, m, C]CHCH2), 6.34 (1H, s, C2 H), 6.80 (2H, d,
J¼8.6 Hz, C3H and C5H), 7.56 (2H, d, J¼8.6 Hz, C2H and C6H), 7.59
(1H, d, J¼15.4 Hz, CaH), 7.70 (1H, d, J¼15.4 Hz, CbH), 7.80 (1H, s,
0
C6 H), 8.93 (1H, s, OH), 13.51 (1H, s, OH); dC (acetone-d6) 17.89,
25.88, 29.28, 56.28, 100.00, 114.16, 118.35, 122.38, 123.78, 127.56,
131.21, 131.74, 132.50, 145.15, 161.08, 165.09, 166.44, 192.89; HRMS:
Mþ, found 338.1530. C21H22O4 requires 338.1518.

K. Sugamoto et al. / Tetrahedron 67 (2011) 5346e5359
5359
0
(3H, s, OCH3), 6.43 (1H, d, J¼2.5 Hz, C3 H), 6.52 (1H, dd, J¼2.5 and
References and notes
0
9.0 Hz, C5 H), 6.84 (2H, d, J¼8.7 Hz, C3H and C5H), 7.59 (1H, d,
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J¼15.4 Hz, CaH), 7.59 (2H, d, J¼8.7 Hz, C2H and C6H), 7.79 (1H, d,
0
J¼15.4 Hz, CbH), 8.00 (1H, d, J¼9.0 Hz, C6 H); dC (MeOD-d4) 56.11,
102.01, 108.33, 115.40, 116.95, 118.24, 127.81, 131.92, 132.91, 146.04,
161.67, 167.44, 167.64,193.76; HRMS: Mþ, found 270.0884. C16H14O4
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7. Okuyama, T.; Takata, M.; Takayasu, J.; Hasegawa, T.; Tokuda, H.; Nishino, A.;
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(10 cm3) was added 5 drops of concd HCl and stirred at room
temperature for 5 h. The reaction mixture was monitored by TLC.
After completion of the reaction, the reaction mixture was evapo-
rated under vacuum. After addition of 10 cm3 of water, the mixture
was extracted with ethyl acetate (3ꢁ30 cm3). The organic layers
were combined, washed with brine, dried over sodium sulfate,
filtrated, and evaporated under vacuum. The residue was purified
by silica gel column chromatography with hexane/ethyl acetate to
afford compound 24b (46 mg, 60%) as yellow powder crystal; mp
(MeOH) 197.3e198.3 ꢀC; Rf (50% EtOAc/hexane) 0.2; nmax (KBr)/
cmꢂ1 3518, 3435, 3291, 3034, 2916, 2831, 2713, 1633, 1589, 1555,
1513,1449,1373,1322,1298,1278, 1221,1198, 1173,1164,1127,1028;
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ꢁ
ꢁ
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8.8 Hz, C5 H), 6.85 (2H, d, J¼8.7 Hz, C3H and C5H), 7.76 (2H, s, CaH
and CbH), 7.60 (2H, d, J¼8.7 Hz, C2H and C6H), 8.17 (1H, d, J¼8.8 Hz,
0
C6 H), 10.14 (1H, br s, OH), 10.68 (1H, br s, OH), 13.62 (1H, s, OH); dC
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256 mg/ml. Streptomycin was used as a positive control.