First synthesis of (±)-basidifferquinone C, an inducer for fruiting-body formation in polyporus arcularius

Article abstract of DOI:10.1271/bbb.90408

Basidifferquinones, isolated from Streptomyces sp., are potent inducers of fruiting-body formation in the basidiomycete, Polyporus arcularius. The first synthesis of (±)-basidifferquinone C was accomplished by starting from 3,5-dihydroxy-2-naphthoic acid.

Full text of DOI:10.1271/bbb.90408

Biosci. Biotechnol. Biochem., 73 (10), 2299–2302, 2009
First Synthesis of (Æ)-Basidifferquinone C, an Inducer
for Fruiting-Body Formation in Polyporus arcularius
Takashi HASHIMOTO,1 Takuya TASHIRO,2 Takeshi KITAHARA,3 Kenji MORI,2;4
y
1;
Mitsuru SASAKI,1 and Hirosato TAKIKAWA
1Department of Agrobioscience, Graduate School of Agricultural Science, Kobe University,
Rokkodai, Nada-ku, Kobe 657-8501, Japan
2Laboratory for Immune Regulation, RIKEN Research Center for Allergy and Immunology,
Hirosawa, Wako, Saitama 351-0198, Japan
3School of Pharmacy, Teikyo Heisei University, 2289 Uruido, Ichihara, Chiba 290-0193, Japan
4Photosensitive Materials Research Center, Toyo Gosei Co., Ltd.,
4-2-1 Wakahagi, Inba-mura, Inba-gun, Chiba 270-1609, Japan
Received June 10, 2009; Accepted June 17, 2009; Online Publication, October 7, 2009
[doi:10.1271/bbb.90408]
Basidifferquinones, isolated from Streptomyces sp.,
are potent inducers of fruiting-body formation in the
basidiomycete, Polyporus arcularius. The first synthesis
of (Æ)-basidifferquinone C was accomplished by start-
ing from 3,5-dihydroxy-2-naphthoic acid.
of B to A was feasible. To construct the lactone ring
of B, we envisaged adopting ortho-lithiation11) of
C and subsequent trapping with PhCHO. Amide C
could be prepared from commercially available starting
material D.
Scheme 2 illustrates our synthesis of (ꢀ)-3. The
starting material was 3,5-dihydroxy-2-naphthoic acid 4
(¼ D). This was converted to corresponding protected
amide 7 (¼ C) in three standard steps: methoxymethyl
(MOM) protection (82%), hydrolysis (92%), and ami-
dation (89%). The ortho-lithiation of 7 was successfully
performed by treating with n-BuLi in the presence
of N,N,N0,N0-tetramethylethylenediamine (TMEDA),12)
and generated 1-lithio-7 was trapped with benzaldehyde
to give an adduct which was then immediately heated in
refluxing toluene to afford desired lactone 8 (¼ B) in
59% yield (70% based on recovered SM). In this case,
n-BuLi was better than s-BuLi as a base, and TMEDA
was preferable as an additive. The oxidation of 8 was
successfully achieved by treating with ceric ammonium
nitrate (CAN) to give 9 (¼ A) in quantitative yield.
With naphthoquinone 9 in hand, we then attempted to
carry out the Diels-Alder reaction between 9 and
Danishefsky-Kitahara diene 1013,14) under Tietze’s con-
ditions.15) The Diels-Alder reaction occurred in CH2Cl2
at room temperature to give the adducts. These adducts
were then successively treated with SiO2 and K2CO3 to
afford the desired anthraquinone 11 and its regioisomer
110 (8-OH isomer) in 39% yield as an inseparable
mixture. The ratio of 11:110 was estimated to be 55:45
Key words: basidifferquinone; fruiting-body inducer;
anthraquinone; Diels-Alder reaction
Fruiting-body development in basidiomycetes is the
most striking expression of differentiation and morpho-
genesis among fungi; it is known to be induced not only
by environmental and physical stimuli, but also by
various chemicals.1–6) In 1990, basidifferquinone, an
inducer for fruiting-body formation in Polyporus
arcularius, was isolated from a culture medium of
Streptomyces sp. B-412 by Azuma et al.7,8) They then
also reported in 1993 the isolation of two basidifferqui-
none relatives.9) Thus, the originally isolated basidiffer-
quinone was renamed basidifferquinone A (BDQ A, 1),
and the others were named basidifferquinone B (BDQ B,
2) and basidifferquinone C (BDQ C, 3), respectively, as
shown in Scheme 1.9) Despite their interesting bio-
logical activity and structural uniqueness, no synthetic
studies on BDQs have so far been disclosed, apart from
a preliminary communication by the present authors.10)
We report here the first synthesis of (ꢀ)-3 with
experimental details.
Results and Discussion
1
based on H-NMR analysis. The mixture of 11 and 110
As already discussed in our preliminary communica-
tion, the construction of the C-ring portion of BDQs
proved to be much more problematic than expected.10)
We therefore designed a new and simple synthetic plan
as shown in Scheme 1. This plan allowed us to circum-
vent the difficulty of C-ring construction. The target
compound, BDQ C (3), should be prepared by a Diels-
Alder reaction between naphthoquinone derivative A
and a properly functionalized diene. For the synthesis of
A, an appropriate precursor was B, because oxidation
was then converted to a mixture of 12 and 120 (55:45) in
99% yield by cleavage of the MOM protecting group.
The structures of 12/120 were confirmed by HMBC
spectroscopy as depicted in Scheme 2. The overall yield
of the mixture of 12 and 120 was 19% in seven steps
based on starting material 4.
We next focused on the synthesis of (ꢀ)-BDQ C (3).
After the preparation of diene 13,15,16) a Diels-Alder
reaction between 9 and 13 was effected in a similar
manner. Although desired product 14 and its regioisomer
y
To whom correspondence should be addressed. Tel/Fax: +81-78-803-5958; E-mail: takikawa@kobe-u.ac.jp

2300
T. HASHIMOTO et al.
1
H
Ph
O
OMe O
O
O
O
D
10
11
HO
R2
O
Diels-Alder
3
O
9
A
B
C
BDQC (3)
8
OH
4
7
R1
6
O
OR
5
A
BDQ A (1): R1 = OH, R2 = Me
BDQ B (2): R1 = OH, R2 = H
BDQ C (3): R1 = H, R2 = H
oxid.
Ph
O
ortho-
lithiation
CO2H
OH
O
CONR2
OR
OR
PhCHO
OH
OR
OR
B
C
D
(R = H, alkyl or protecting group)
Scheme 1. Structures of BDQs and Synthetic Plan for BDQ C.
Ph
O
Ph
O
O
O
CO2R
OR
COR
O
O
e
b
d
OMOM
OMOM
OMOM
OR
OMOM
OMOM
4 (R =H)
5 (R = MOM)
6 (R = OH)
7 (R = NEt2)
9
8
a
c
Ph
Ph
O
1
O
O
O
O
10
11
HO
HO
O
O
3
g
9
8
TMSO
OH
OMOM
4
6
5
7
O
12
10
11
OMe
(+ its regioisomer 12')
(12:12' = 55:45)
(+ its regioisomer 11')
f
(
: HMBC correlation)
9
h
Ph
Ph
O
O
OMe O
OMe
OEt
OMe O
HO
O
TMSO
HO
O
g
13
OMOM
OH
O
O
14
(+ its regioisomer 14')
( )-BDQ C (3)
Scheme 2. Synthesis of (ꢀ)-3.
i
Reagents and conditions: (a) MOMCl, Pr2NEt, DMF (82%); (b) KOH, aq. MeOH (92%); (c) EtOCOCl, Et3N, THF then Et2NH (89%);
(d) i) n-BuLi, TMEDA, THF ꢁ78 ꢂC, then PhCHO; ii) toluene reflux [59% (70% based on the recovered SM)]; (e) CAN, aq. CH3CN (quant.);
(f) i) CH2Cl2, r.t., 4.5 h; ii) SiO2, THF; iii) K2CO3, aq. THF (39%; 11:110 ¼ 55:45); (g) p-TsOH, MeOH, CHCl3 (99% for 12/120; 95% for 3);
(h) i) CH2Cl2, r.t., 2 h, then SiO2; ii) K2CO3, aq. THF (26%; 14:140 ¼ 1:1)
140 (7-OMe 8-OH isomer) were obtained, the reprodu-
cibility, yield and regioselectivity were all worse in
comparison to the case with 10. After a considerable
number of attempts to optimize the reaction conditions,
we found the following: i) removal of CH2Cl2 before the
SiO2 treatment was not necessary and should be avoided
to obtain a better yield; ii) a shorter reaction time was of
some benefit; iii) a lower temperature did not contribute
to a better yield; and iv) the Lewis acid-mediated Diels-
Alder reaction and MOM-deprotection of 9 gave no
substantive results.10) These effects may mainly be the
results of the intrinsic instability of the substrates,
intermediates, and/or products. Regarding the best
result, we succeeded in obtaining a mixture of 14 and
140 (1:1) in 26% yield. It should be noted that both the
isolated yield (17–26%) and the ratio of 14:140 (1:2–1:1)
fluctuated considerably depending on certain unknown
factors, even under the foregoing optimized conditions.
The regiochemistry of 14/140 was tentatively estimated
on the basis of the NMR spectral similarity between
14/140 and 12/120; this was later confirmed by the fact
that 14 could be converted to (ꢀ)-3. The obtained
mixture of 14 and 140 was carefully purified by
preparative TLC to give pure 17 which was then
deprotected by treating with p-TsOH to give (ꢀ)-3 in
95% yield. The various spectral data for synthetic (ꢀ)-3
were in good accordance with those of the natural
product. The overall yield was 6% in seven steps.
Finally, a bioassay employing synthetic samples, (ꢀ)-3,
and a mixture of 12 and 120, showed that both of these

First Synthesis of (ꢀ)-Basidifferquinone C
2301
4,6-Bis(methoxymethoxy)-1-phenylnaphtho[1,2-c]furan-3(1H)-one
(8). To a solution of TMEDA (6.1 ml, 41 mmol) and n-BuLi (2.77 M in
THF; 13 ml, 36 mmol) in THF (150 ml), 7 (9.41 g, 27.1 mmol) in THF
(30 ml) was added dropwise at ꢁ78 ꢂC under Ar. After stirring for 2 h,
PhCHO (5.5 ml, 54 mmol) was added dropwise to this mixture. After
stirring at ꢁ78 ꢂC for 30 min, the reaction mixture was quenched with
saturated aq. NH4Cl and extracted with EtOAc. The organic layer was
successively washed with water and brine, dried (MgSO4), and
concentrated under reduced pressure to give a residue which was then
heated under reflux in toluene (60 ml) for 3 h. After removing toluene
under reduced pressure, the residue was recrystallized from
hexane:ether ¼ 1:1 to give recovered 7 (1.51 g, 4.35 mmol) and 8
[6.07 g, 16.0 mmol, 59% (70% based on recovered 8)] as pale-yellow
crystalline powder. Mp 165–166 ꢂC. IR ꢁmax (nujol) cmꢁ1: 1760
(C=O). NMR ꢀH (CDCl3): 3.55 (3H, s), 3.63 (3H, s), 5.39 (2H, dd,
J ¼ 6:9, 7.8 Hz), 5.54 (2H, dd, J ¼ 6:9, 8.7 Hz), 6.58 (1H, s), 7.05 (1H,
m), 7.16–7.22 (2H, m), 7.24–7.28 (2H, m), 7.34–7.37 (3H, m), 7.98
(1H, s). NMR ꢀC (CDCl3): 56.2, 56.5, 81.7, 94.8, 94.9, 106.3, 111.2,
116.0, 117.4, 123.8, 125.6, 128.1, 128.9, 129.5, 130.3, 136.0, 150.6,
151.1, 152.7, 168.0. HRFABMS m=z ½M þ Hꢃþ: calcd. for C22H21O6,
381.1338; found, 381.1338.
were active as a fruiting-body inducer for Polyporus
arcularius, although the latter was less active than the
former.
In conclusion, we accomplished the first synthesis of
(ꢀ)-BDQ C by employing a Diels-Alder strategy. It was
shown that synthesized (ꢀ)-BDQ C was biologically
active as a fruiting-body inducer. Our established
synthetic method was relatively simple and straightfor-
ward; it will be applicable for the synthesis of other
BDQs and their derivatives.
Experimental
IR spectra were measured with a Shimadzu IR-408 spectrometer.
1H-NMR spectra were recorded at 300 MHz with a Jeol JNM-AL300
spectrometer. TMS or the residual solvent peak in CDCl3 (at
ꢀH ¼ 7:26), DMSO-d6 (at ꢀH ¼ 2:49), or C5D5N (at ꢀH ¼ 7:21) was
used as the internal standard. 13C-NMR spectra were recorded at
75 MHz with the Jeol JNM-AL300 spectrometer, the peak for CDCl3
(at ꢀC ¼ 77:0), DMSO-d6 (at ꢀC ¼ 39:5), or C5D5N (at ꢀC ¼ 123:5)
being used as the internal standard. Mass spectra were measured with a
Jeol JMS-SX102A spectrometer.
4-Methoxymethoxy-1-phenylnaphtho[1,2-c]furan-3,6,9(1H)-trione
(9). To a solution of 8 (980 mg, 2.57 mmol) in CH3CN (80 ml), a
solution of CAN (4.25 g, 10.3 mmol in 30 ml H2O) was added. After
stirring at room temperature for 15 min, a further solution of CAN
(1.41 g, 2.57 mmol in 10 ml H2O) was added. After stirring for 15 min,
the reaction mixture was diluted with water and extracted with EtOAc.
The organic layer was successively washed with water and brine, dried
(MgSO4), and concentrated under reduced pressure. The residue was
recrystallized from hexane:ether ¼ 1:1 to give 9 (901 mg, 2.57 mmol,
quant.) as red-orange crystalline powder. Mp 167–168 ꢂC. IR ꢁmax
(nujol) cmꢁ1: 1760 (C=O), 1660 (C=O). NMR ꢀH (CDCl3): 3.52 (3H,
s), 5.49 (2H, q-like, J ¼ 6:6 Hz), 6.73 (1H, d, J ¼ 10:2 Hz), 6.76 (1H,
s), 6.87 (1H, d, J ¼ 10:2 Hz), 7.11–7.26 (5H, m), 7.86 (1H, s). NMR ꢀC
(CDCl3): 57.2, 83.2, 95.2, 112.9, 119.3, 120.4, 128.0, 128.5, 129.1,
135.2, 137.9, 138.4, 139.1, 152.8, 159.6, 165.9, 182.4, 183.7.
HRFABMS m=z ½M þ Hꢃþ: calcd. for C20H15O6, 351.0869; found,
351.0868.
Methoxymethyl 3,5-bis(methoxymethoxy)-2-naphthoate (5). To an
ice-cooled solution of 4 (5.11 g, 25.0 mmol) in DMF (120 ml),
(i-Pr)2NEt (18 ml, 0.10 mol) and MOMCl (7.6 ml, 0.10 mol) were
successively added. After stirring at room temperature overnight, the
reaction mixture was quenched with saturated aq. NH4Cl and extracted
with EtOAc. The organic layer was successively washed with water and
brine, dried (MgSO4), and concentrated under reduced pressure. The
residue was chromatographed on SiO2 to give 5 (6.92 g, 20.6 mmol,
82%) as a white solid. Mp 47–48 ꢂC. IR ꢁmax (nujol) cmꢁ1: 1740
(C=O). NMR ꢀH (CDCl3): 3.53 (3H, s), 3.57 (3H, s), 3.59 (3H, s), 5.36
(2H, s), 5.40 (2H, s), 5.52 (2H, s), 7.16 (1H, d, J ¼ 7:8 Hz), 7.28 (1H, t,
J ¼ 7:8 Hz), 7.46 (1H, d, J ¼ 7:8 Hz), 7.88 (1H, s), 8.32 (1H, s). NMR
ꢀC (CDCl3): 56.1, 56.2, 57.5, 90.8, 94.7, 94.9, 105.7, 110.2, 121.8,
122.2, 124.7, 128.3, 129.0, 132.3, 151.8, 152.7, 165.4. HRFABMS m=z
[M]þ: calcd. for C17H20O7, 336.1209; found, 336.1208.
9-Hydroxy-4-methoxymethoxy-1-phenylanthra[1,2-c]furan-3,6,11(1H)-
trione (11) and 8-hydroxy-4-methoxymethoxy-1-phenylanthra[1,2-
c]furan-3,6,11(1H)-trione (110). To a solution of 9 (66 mg, 0.19 mmol)
in CH2Cl2 (5 ml), 10 (70 ml, 0.36 mmol) was added at room temper-
ature under Ar. After stirring for 4.5 h, the reaction mixture was
concentrated under reduced pressure. To this residue, THF (5 ml) and
SiO2 (3 g) were added, and stirring was continued for 30 min. The
reaction mixture was filtered, and the filtrate was concentrated under
reduced pressure. To this residue, K2CO3 (24 mg, 0.19 mmol) in aq.
THF (50 vol%; 6 ml) was added. After stirring at room temperature for
30 min, the reaction mixture was diluted with water and extracted with
EtOAc. The organic layer was successively washed with water and
brine, dried (MgSO4), and concentrated under reduced pressure. The
residue was chromatographed on SiO2 to give an inseparable mixture
of 11 and 110 (55:45; 28 mg, 0.068 mmol, 39%) as yellow crystalline
powder. Mp 202–204 ꢂC. IR ꢁmax (nujol) cmꢁ1: 3300 (O–H), 1730
(C=O), 1670 (C=O). NMR ꢀH (DMSO): 3.51 (3H, s), 5.63 (2H, dd,
J ¼ 12:3, 6.9 Hz), 6.99 and 7.00 [total 1H, 2 ꢄ s (55:45)], 7.10–7.43
(7H, m), 7.81 and 8.02 [total 1H, 2 ꢄ d (45:55), J ¼ 8:7 Hz], 7.94 and
7.95 [total 1H, 2 ꢄ s (45:55)], 11.0–11.1 (1H, m). NMR ꢀC (DMSO):
56.68, 56.70, 83.0, 83.1, 89.5, 95.0, 112.0, 112.4, 112.8, 118.5, 118.9,
121.55, 121.60, 121.7, 121.9, 124.7, 124.9, 127.98, 128.02, 128.5,
128.7, 128.8, 129.7, 130.3, 134.7, 135.0, 136.3, 136.6, 139.9, 140.3,
152.5, 152.7, 158.7, 159.2, 163.0, 163.6, 165.46, 165.50, 179.1,
180.22, 180.24, 181.9. HRFABMS m=z ½M þ Hꢃþ: calcd. for
C24H17O7, 417.0974; found, 417.0975.
3,5-Bis(methoxymethoxy)-2-naphthoic acid (6). To a solution of 5
(11.0 g, 32.7 mmol) in MeOH (100 ml), 1.5 M aq. KOH (100 ml) was
added and the stirring was continued for 1 h. After evaporating MeOH,
the residue was diluted with 1 M HCl and extracted with CHCl3. The
organic layer was successively washed with water and brine, dried
(MgSO4), and concentrated under reduced pressure. The residue was
recrystallized from hexane:ether ¼ 5:1 to give 6 (8.76 g, 30.0 mmol,
92%) as pale-yellow needles. Mp: 107–108 ꢂC. IR ꢁmax (nujol) cmꢁ1
:
1700 (C=O). NMR ꢀH (CDCl3): 3.56 (3H, s), 3.62 (3H, s), 5.40 (2H,
s), 5.56 (2H, s), 7.23 (1H, d, J ¼ 7:8 Hz), 7.36 (1H, t, J ¼ 7:8 Hz), 7.55
(1H, d, J ¼ 7:8 Hz), 7.95 (1H, s), 8.73 (1H, s). NMR ꢀC (CDCl3): 56.3,
57.2, 94.9, 96.0, 105.5, 111.1, 118.7, 122.5, 125.7, 128.9, 129.8, 135.5,
151.8, 152.0, 165.8. HRFABMS m=z [M]þ: calcd. for C15H16O6,
292.0947; found, 292.0944.
N,N-Diethyl-3,5-bis(methoxymethoxy)-2-naphthamide (7). To an
ice-cooled solution of 6 (3.30 g, 11.3 mmol) in THF (100 ml), Et3N
(6.3 ml, 45 mmol) and ClCO2Et (1.3 ml, 14 mmol) were added. After
stirring at 0 ꢂC for 15 min, Et2NH (1.5 ml, 14 mmol) was added, and
the stirring was continued at 0 ꢂC for 15 min. The reaction mixture was
quenched with saturated aq. NH4Cl and extracted with EtOAc. The
organic layer was successively washed with water and brine, dried
(MgSO4), and concentrated under reduced pressure. The residue was
chromatographed on SiO2 to give 7 (3.48 g, 10.0 mmol, 89%) as
colorless crystals. Mp 62–63 ꢂC. IR ꢁmax (nujol) cmꢁ1: 1730 (C=O).
NMR ꢀH (CDCl3): 1.05 (3H, t, J ¼ 7:2 Hz), 1.29 (3H, t, J ¼ 7:2 Hz),
3.20 (2H, q, J ¼ 7:2 Hz), 3.21–3.78 (2H, m), 3.52 (3H, s), 3.55 (3H, s),
5.30–5.41 (4H, m), 7.12 (1H, d, J ¼ 7:8 Hz), 7.28 (1H, t, J ¼ 7:8 Hz),
7.42 (1H, d, J ¼ 7:8 Hz), 7.67 (1H, s), 7.83 (1H, s). NMR ꢀC (CDCl3):
12.8, 14.0, 38.8, 42.7, 56.2, 56.3, 94.6, 94.8, 104.1, 108.8, 121.2, 124.5,
126.49, 126.51, 129.2, 129.9, 150.7, 152.0, 168.2. HRFABMS m=z
½M þ Hꢃþ: calcd. for C19H26O5N, 348.1811; found, 348.1810.
4,9-Dihydroxy-1-phenylanthra-[1,2-c]furan-3,6,11(1H)-trione (12)
and
4,8-dihydroxy-1-phenylanthra-[1,2-c]furan-3,6,11(1H)-trione
(120). A solution of a mixture of 11 and 110 (36 mg, 0.087 mmol),
and p-TsOH (ca. 1 mg) in MeOH (10 ml) was heated under reflux for
2 h. After removing MeOH under reduced pressure, the residue was
chromatographed on SiO2 to give an inseparable mixture of 12 and 120

2302
T. HASHIMOTO et al.
(55:45; 32 mg, 0.086 mmol, 99%) as orange-yellow crystalline powder.
Mp > 250 ꢂC (decomp.). IR ꢁmax (nujol) cmꢁ1: 3300 (O–H), 1730
(C=O), 1660 (C=O). NMR ꢀH (DMSO): 6.92 and 6.94 [total 1H, 2 ꢄ s
(55:45), 7.11–7.41 (7H, m), 7.69 (1H, s), 7.79 and 7.99 [total 1H, 2 ꢄ s
(45:55), J ¼ 8:7 Hz]. NMR ꢀC (DMSO): 82.9, 83.0, 111.9, 112.2,
115.0, 115.2, 116.3, 116.7, 118.9, 119.1, 121.2, 121.8, 124.7, 125.0,
127.9, 128.4, 128.6, 129.4, 130.0, 134.7, 135.2, 136.7, 136.9, 139.6,
139.9, 152.9, 153.4, 161.4, 162.2, 162.7, 163.4, 166.2, 178.8, 179.7,
180.5, 182.2. HRFABMS m=z ½M þ Hꢃþ: calcd. for C22H13O6,
373.0712; found, 373.0712.
IR ꢁmax (nujol) cmꢁ1: 3300 (O=H), 1730 (C=O), 1660 (C=O). NMR
ꢀH (C5D5N): 3.53 (3H, s), 7.22–7.33 (4H, m), 7.43 (1H, d, J ¼ 8:4 Hz),
7.53–7.56 (2H, m), 8.13 (1H, s), 8.21 (1H, d, J ¼ 8:4 Hz). NMR ꢀC
(C5D5N): 61.0, 84.1, 116.2, 117.9, 120.9, 121.7, 125.9, 126.6, 127.3,
128.8, 128.9 (two coincident peaks), 137.7, 140.4, 148.6, 154.4, 159.5,
164.1, 168.5, 181.3, 181.9. HRFABMS m=z ½M þ Hꢃþ: calcd. for
C23H15O7, 403.0818; found, 403.0811.
Acknowledgments
We thank Professor Teruhiko Beppu and Associate
Professor Kenji Ueda of Nihon University for the
bioassay. This work was financially supported, in part,
by Otsuka Chemical Co., Ltd.
9-Hydroxy-10-methoxy-4-methoxymethoxy-1-phenylanthra[1,2-c]
furan-3,6,11(1H)-trione (14) and 8-hydroxy-7-methoxy-4-methoxyme-
thoxy-1-phenylanthra[1,2-c]furan-3,6,11(1H)-trione (140). To a solu-
tion of 9 (45 mg, 0.13 mmol) in CH2Cl2 (5 ml), 13 (10 ml, ca. 0.43
mmol) was added at room temperature under Ar. After stirring for 2 h,
SiO2 (2 g) was added to the reaction mixture, and stirring was
continued for 30 min. After filtration, the filtrate was concentrated
under reduced pressure. To this residue, K2CO3 (20 mg, 0.13 mmol) in
aq. THF (50 vol%; 4 ml) was added. After stirring at room temperature
for 30 min, the reaction mixture was diluted with water and extracted
with EtOAc. The organic layer was successively washed with water
and brine, dried (MgSO4), and concentrated under reduced pressure.
The residue was chromatographed on SiO2 to give a mixture of
14 and 140 (15 mg, 0.034 mmol, 26%). This mixture was further
purified by careful preparative TLC to give pure 14 (Rf ¼ 0:33,
toluene/EtOAc ¼ 1 : 1) and 140 (Rf ¼ 0:30, toluene/EtOAc ¼ 1:1), as
orange-yellow crystalline powder. 14: Mp >210 ꢂC (decomp.). IR ꢁmax
(nujol) cmꢁ1: 3300 (O–H), 1730 (C=O), 1660 (C=O). NMR ꢀH
(C5D5N): 3.52 (3H, s), 3.55 (3H, s), 5.68 (2H, dd, J ¼ 9:9, 6.9 Hz),
7.22–7.34 (3H, m), 7.46 (1H, d, J ¼ 8:4 Hz), 7.50–7.57 (2H, m), 8.21
(1H, d, J ¼ 8:4 Hz), 8.38 (1H, s). NMR ꢀC (C5D5N): 57.0, 61.0, 83.9,
95.7, 112.9, 113.5, 119.8, 122.2, 126.14, 126.18, 126.9, 128.86,
128.92, 129.1, 137.2, 140.5, 148.7, 153.6, 159.5, 159.8, 166.5, 181.1,
181.4. HRFABMS m=z ½M þ Hꢃþ: calcd. for C25H19O8, 447.1080;
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:
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4,9-Dihydroxy-10-methoxy-1-phenylanthra[1,2-c]furan-3,6,11(1H)-
C
trione: (ꢀ)-basidifferquinone
(3).
A
solution of 14 (1.8 mg,
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¨
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