Total synthesis of carbazole-1,4-quinone alkaloid koeniginequinones a and B based on a one-pot cyclocarbonylation procedure from 2-alkenyl-3-iodoindole

Article abstract of DOI:10.3987/COM-15-S(T)5

Total syntheses of koeniginequinones A and B, isolated from Murraya koenigii, were newly achieved by constructing of carbazole-1,4-quinone using a one-pot Pd-catalyzed cyclocarbonylation method with 2-(but-2-en-1-yl)-3-iodoindoles derived from known methyl 6-methoxyindole-2-carboxylate and methyl 5,6-dimethoxyindole-2-carboxylate, followed by desilylation, and an oxidation sequence.

Full text of DOI:10.3987/COM-15-S(T)5

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HETEROCYCLES, Vol. 93, No. 1, 2016
HETEROCYCLES, Vol. 93, No. 1, 2016, pp. 84 - 100. © 2016 The Japan Institute of Heterocyclic Chemistry
Received, 4th July, 2015, Accepted, 27th July, 2015, Published online, 24th August, 2015
DOI: 10.3987/COM-15-S(T)5
TOTAL SYNTHESIS OF CARBAZOLE-1,4-QUINONE ALKALOID
KOENIGINEQUINONES
A
AND
B
BASED ON
A
ONE-POT
FROM
CYCLOCARBONYLATION
PROCEDURE
2-ALKENYL-3-IODOINDOLE
a
a
a
a
Takashi Nishiyama, Nanase Satsuki, Satoshi Hibino, * Mami Fujii, Takumi
b
b
a
Abe, Minoru Ishikura, and Tominari Choshi *
aGraduate School of Pharmacy and Pharmaceutical Sciences, Faculty of Pharmacy
and Pharmaceutical Sciences, Fukuyama University, Fukuyama, Hiroshima
b
7
29-0292, Japan Faculty of Pharmaceutical Sciences, Health Sciences University
of
Hokkaido,
Ishikari-Tobetsu,
Hokkaido
061-0293,
Japan
e-mail: choshi@fupharm.fukuyama-u.ac.jp
We dedicate this paper to Professor Dr. Lutz F. Tietze, University of Göttingen, on
the celebration of his 75th birthday
Abstract – Total syntheses of koeniginequinones A and B, isolated from Murraya
koenigii, were newly achieved by constructing of carbazole-1,4-quinone using a
one-pot
Pd-catalyzed
cyclocarbonylation
derived from
method
known
with
2
6
-(but-2-en-1-yl)-3-iodoindoles
methyl
-methoxyindole-2-carboxylate and methyl 5,6-dimethoxyindole-2-carboxylate,
followed by desilylation, and an oxidation sequence.
INTRODUCTION
The quinone framework is an important core structure in many chemotherapeutic agents, such as
mitomycins and anthracyclines.1 Carbazole quinone alkaloids exhibit antitumor,2 neuronal
3
4
cell-protecting, and antimalarial activities (Figure 1), and are therefore attractive targets for synthetic
5
and medicinal chemists. Murrayaquinone A (1) was isolated by Furukawa et al. from Murraya
6
euchrestifolia in 1983, and exhibits cardiotonic and antitumor activities. Total synthesis of 1, including a
formal synthesis, was reported by 14 groups using original synthetic approaches.7-10 Fifteen years later,
8
koeniginequinones A (2a) and B (2b) were isolated by Chowdhury from Murraya koenigii, and their first
total synthesis was completed by a Japp-Klingemann reaction of aryldiazonium salts and

HETEROCYCLES, Vol. 93, No. 1, 2016
85
O
O
O
R1
R2
Me
N
X
N
N
N
H
O
H
O
H
O
1
2
murrayaquinone A (1) : R =R =H
ellipticine quinone (3)
calothrixin A (4a) : X=N®O
calothrixin B (4b): X=N
1
2
koeniginequinone A (2a) : R =H, R =OMe
1
2
koeniginequinone B (2b): R =R =OMe
Figure 1
cyclohexane-1,2-dione, followed by cyclization of the obtained arylhydrazone. Furthermore, the Knölker
group reported the total synthesis of 2a and 2b based on regioselective addition of arylamines to
2
-methyl-1,4-benzoquinone, followed by a palladium(II)-catalyzed oxidative cyclization.12b To date, the
total synthesis of koeniginequinones A (2a) and B (2b) has been achieved by four11,12 and two11,12b groups,
respectively.
We are interested in the unique structure and pharmacologic action of poly-substituted carbazole and
carbazolequinone alkaloids. To date, we have constructed the carbazole framework by an allene-mediated
electrocyclic reaction of the 6-electron system as a key step. Based on this method, the total synthesis of
8
13
14
15
16
murrayaquinone A (1), carbazomycin G, carquinostatin A, carbazoquinocins, carbazomadurins,
and calothrixins (4)17 has been established. We also recently reported the construction of
carbazole-1,4-quinone using a tandem ring-closing metathesis (RCM) and dehydrogenation reaction, and
developed the total synthesis of murrayaquinone A (1) from N-MOM-3-iodoindole-2-carbaldehyde in
9
four steps. In addition, we achieved a new, efficient one-pot synthesis of carbazole-1,4-quinone 7 by a
cyclocarbonylation reaction between 3-iodo-2-propenylindole 5 and CO (1 atm) in the presence of a
tributyl(vinyl)tin and Pd-catalyst, followed by desilylation and oxidation reactions through an
intermediate 6 (Scheme 1).10
1)
SnBu3
CO (1 atm)
O
O
Me
BHT, PdCl (dppf)
Me
Me
2
I
o
DMF, 70 C, 20 h
2) TBAF, O2
N
N
N
R
OTBS
OTBS
O
MOM
MOM
6
M HCl
7: R=MOM
1: R=H
5
6
MeOH
Scheme 1
Herein we describe a new total synthesis of koeniginequinones A (2a) and B (2b) based on the
construction of a carbazole-1,4-quinone framework using a one-pot cyclocarbonylation method with the
appropriate 3-iodo-2-propenylindoles.

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HETEROCYCLES, Vol. 93, No. 1, 2016
RESULTS AND DISCUSSION
As depicted in Scheme 2, indole-2-carbaldehydes 12a and 12b were prepared from the methyl
indole-2-carboxylates 8a and 8b according to Dierk’s procedure.18 Reduction of methyl
indole-2-carboxylates 8a and 8b with LiAlH
oxidized with active MnO to give the indole-2-carbaldehydes 10a (51%) and 10b (62%), respectively.
Subsequent treatment of 10a and 10b with I in the presence KOH afforded 3-iodoindole 11a (81%) and
1b (93%), respectively, which were treated with chloromethyl methyl ether to produce the
N-MOM-indoles 12a (83%) and 12b (94%), respectively.
4
gave the alcohols 9a (76%) and 9b (70%), which were
2
2
1
R1
R2
R1
R2
R1
R2
LiAlH4
act. MnO2
CH Cl
OH
CO Me
CHO
2
THF
rt, 5 h
N
N
2
2
N
H
H
rt, 12 h
H
1
2
1
2
1
2
8
a: R =H, R =OMe
9a: R =H, R =OMe (76%)
10a: R =H, R =OMe (51%)
1
2
1
2
1
2
8
b: R =R =OMe
9b: R =R =OMe (70%)
R1
R2
10b: R =R =OMe (62%)
R1
R2
I2, KOH
I
I
MOMCl, NaH
DMF
rt, 4 h
DMF
CHO
CHO
N
N
rt, 2 h
H
MOM
1
2
1
2
1
1a: R =H, R =OMe (81%)
12a: R =H, R =OMe (83%)
1
2
1
2
1
1b: R =R =OMe (93%)
12b: R =R =OMe (94%)
Scheme 2
R1
R2
R1
R2
Me
Me
I
I
TBSCl, imidazole
MgBr
CHO
THF
0 oC, 20 min
CH Cl2
N
2
N
o
OH
50 C, 12 h
MOM
MOM
1
2
1
2
1
2a: R =H, R =OMe
13a: R =H, R =OMe
1
2
1
2
1
2b: R =R =OMe
13b: R =R =OMe
1)
SnBu3
CO (1 atm)
O
R1
R2
Me
R1
R2
Me
I
BHT, PdCl (dppf)
2
o
DMF, 70 C, 20 h
N
N
2
) TBAF, O2
OTBS
O
MOM
MOM
1
2
1
2
1
4a: R =H, R =OMe (97%)
15a: R =H, R =OMe (30%)
1
2
1
2
1
4b: R =R =OMe (87%)
15b: R =R =OMe (41%)
Scheme 3
For the synthesis of carbazole-1,4-quinones 15a and 15b, we prepared important substrates 14a and 14b
Scheme 3). The Grignard reaction of 3-iodoindole-2-carbaldehydes 12a and 12b with
(

HETEROCYCLES, Vol. 93, No. 1, 2016
87
propenylmagnesium bromide gave unstable alcohols 13a and 13b, which were immediately treated with
TBSCl in the presence of imidazole to yield O-TBS ethers 14a (97%) and 14b (87%), respectively, in two
steps. The O-TBS ethers 14 were subjected to a one-pot cyclocarbonylation reaction under CO (1 atm)
atmosphere in the presence of a tributyl(vinyl)tin and Pd-catalyst, followed by desilylation and oxidation
reactions to provide the corresponding carbazole-1,4-quinones 15a (30%) and 15b (41%), respectively, as
expected. Finally, cleavage of the N-MOM group of 15a and 15b was examined under several acid
conditions, but koeniginequinones A (2a) and B (2b) were not obtained at all, contrary to our expectation.
This result indicated that the MOM group was not a suitable protecting group for carbazolequinones.
R1
R2
R1
R2
BOMCl, K CO
DMF, rt, 12 h
2
3
I
Me
I
MgBr
or
CHO
THF
CHO
N
R3
N
SEMCl, NaH
DMF, rt, 12 h
o
H
0 C, 20 min
1
2
1
2
3
11a: R =H, R =OMe
16a: R =H, R =OMe, R =BOM (92%)
1
2
1
2
3
11b: R =R =OMe
17a: R =H, R =OMe, R =SEM (94%)
1
2
3
1
1
6b: R =R =OMe, R =BOM (91%)
1
2
3
7b: R =R =OMe, R =SEM (98%)
R1
R2
R1
Me
Me
I
I
TBSCl, imidazole
R2
CH Cl
2
2
N
R3
N
R3
o
OH
50 C, 12 h
OTBS
1
2
3
1
2
3
1
8a: R =H, R =OMe, R =BOM
20a : R =H, R =OMe, R =BOM (80% from 16a)
1
2
3
1
2
3
1
9a: R =H, R =OMe, R =SEM
21a : R =H, R =OMe, R =SEM (85% from 17a)
1
2
3
1
2
3
1
1
8b : R =R =OMe, R =BOM
20b : R =R =OMe, R =BOM (92% from 16b)
1
2
3
1
2
3
9b : R =R =OMe, R =SEM
21b : R =R =OMe, R =SEM (61% from 17b)
1)
SnBu3
CO (1 atm)
O
BHT, PdCl (dppf)
R1
2
Me
o
DMF, 70 C, 20 h
R2
2) TBAF, O2
N
R3
or
air
O
1
2
3
2
2
2
2
2a : R =H, R =OMe, R =BOM (69%)
3a : R =H, R =OMe, R =SEM (59%)
2b : R =R =OMe, R =BOM (39%)
3b : R =R =OMe, R =SEM (37%)
1
2
3
1
2
3
1
2
3
Scheme 4
For the total synthesis of koeniginequinones A (2a) and B (2b), we selected benzyloxymethyl (BOM) and
trimethylsilylethoxymethyl (SEM) groups as protecting groups (Scheme 4). Treatment of 11a and 11b
with chloromethyl benzyl ether gave N-BOM-indoles 16a and 16b in excellent yields. Treatment of 11a
and 11b with trimethylsilylethoxymethyl chloride also afforded N-SEM-indoles 17a and 17b,

88
HETEROCYCLES, Vol. 93, No. 1, 2016
respectively. The Grignard reaction of indole-2-carbaldehydes 16a, 16b, 17a, and 17b with
propenylmagnesium bromide gave unstable alcohols 18a, 18b, 19a, and 19b, which were immediately
treated with TBSCl and imidazole to produce O-TBS ethers 20a (80%), 20b (92%), 21a (85%), and 21b
(61%), respectively, in two steps. Four O-TBS ethers 20a, 20b, 21a, and 21b were subjected to a similar
one-pot cyclocarbonylation reaction under CO (1 atm) atmosphere in the presence of a tributyl(vinyl)tin
and Pd-catalyst, followed by desilylation and oxidation to give N-protected carbazole-1,4-quinones 22a
(69%), 22b (39%), 23a (59%), and 23b (37%).
Finally, to complete the total synthesis of koeniginequinones A (2a) and B (2b), we attempted to
deprotect the BOM and SEM groups of 22 and 23 (Scheme 5). Treatment of N-BOM-carbazolequinones
2
2a and 22b with Na in liquid NH
3
gave the desired koeniginequinones A (2a) (78%) and B (2b) (72%),
in the presence of 10% Pd-C afforded
respectively, in good yields. Reduction of 22a with H
2
koeniginequinone A (2a) in a low yield. On the other hand, treatment of N-SEM-koeniginequinones 23a
and 23b with 6 M HCl in EtOH provided koeniginequinones A (2a) (48%) and B (2b) (52%) in moderate
yields. The BOM group was a better protecting group than the SEM and MOM groups in
carbazolequinone compounds. The physical and spectroscopic data of our synthetic koeniginequinones A
(2a) and B (2b) were consistent with natural and synthetic koeniginequinones A (2a) and B (2b) in all
respects.
O
O
R1
R2
R1
R2
Me
Me
Na
liq.NH3
N
o
N
H
-
78 C, 30 min
O
O
BOM
1
2
2
2
2a : R =H, R =OMe
koeniginequinone A (2a):
1
2
1
2
2b : R =R =OMe
R =H, R =OMe (78%)
koeniginequinone B (2b):
1
2
R =R =OMe (72%)
H , 10% Pd-C
2
22a
koeniginequinone A (2a)
rt, 12 h
0%
2
O
O
R1
R2
R1
R2
Me
Me
6
M HCl
EtOH
o
N
N
O
O
50 C, 1 h
SEM
H
2
1
2
1
2
2
3a : R =H, R =OMe
2a: R =H, R =OMe (48%)
2b: R =R =OMe (52%)
1
2
1
2
3b: R =R =OMe
Scheme 5

HETEROCYCLES, Vol. 93, No. 1, 2016
89
CONCLUSION
Total synthesis of the carbazole-1,4-quinone alkaloid koeniginequinones A (2a) and B (2b) was newly
achieved by applying of our one-pot cyclocarbonylation procedure to indole-2-carboxylates 8a and 8b in
eight steps. Novel carbazole-1,4-quinone synthesis was realized. The BOM group was a better protecting
group than the SEM and the MOM groups for the synthesis of carbazole-1,4-quinone natural products.
The biologic activity of koeniginequinones A (2a) and B (2b) and their derivatives is under evaluation.
EXPERIMENTAL
General Methods: All non-aqueous reactions were carried out under an atmosphere of nitrogen in dried
glassware unless otherwise noted. Solvents were dried and distilled according to standard protocols.
Analytical thin-layer chromatography was performed with Silica gel 60PF254 (Merck). Silica gel column
chromatography was performed with Silica gel 60 (70-230 mesh, Canto Co. Lit.). All melting points were
determined on Yanagimoto micro melting point apparatus and are uncorrected. Proton nuclear magnetic
1
resonance ( H NMR) spectra were recorded on a JEOL AL-300 at 300 MHz. Chemical shifts are reported
relative to Me
4
Si ( 0.00). NMR spectra were measured with CDCl unless otherwise noted. Multiplicity
3
is indicated by one or more of the following: s (singlet); d (doublet); t (triplet); q (quartet); m (multiplet);
1
3
br (broad). Carbon nuclear magnetic resonance ( C NMR) spectra were recorded on a JEOL AL-300 at
5 MHz. Chemical shifts are reported relative to CDCl ( 77.0) and DMSO-d ( 39.7). Infrared spectra
7
3
6
were recorded with ATR method using a Shimadzu FTIR-8000 spectrophotometer and Technologies
DuraScop. Low and High-resolution mass spectra were recorded on JEOL JMS-700 spectrometers by
direct inlet system.
6
-Methoxyindol-2-ylmethanol 9a
A solution of methyl indole-2-carboxylate 8a (500 mg, 2.44 mmol) in THF (10 mL) was added dropwise
to a solution of LiAlH (139 mg, 3.66 mmol) in THF (10 mL) under cooling with ice-water. After stirring
at rt for 5 h, the reaction mixture was quenched with water, and filtered through Celite pad. The filtrate
was extracted with EtOAc. The organic layer was washed with brine, dried over Na SO , and evaporated
in vacuo. The residue was purified by column chromatography using EtOAc-hexane (3:7, v/v) as an
4
2
4
o
1
eluent to give the alcohol 9a (330 mg, 76%). mp 104-105 C (EtOAc); H-NMR (CDCl
3
) : 8.21 (1H, br
s), 7.44 (1H, d, J=8.6 Hz), 6.81 (1H, d, J=2.1 Hz), 6.77 (1H, dd, J=8.6, 2.1 Hz), 6.33 (1H, s), 4.77 (2H, s),
1
3
3
5
.83 (3H, s), 1.85 (1H, br s); C-NMR (CDCl ) : 156.5, 137.2, 136.4, 122.2, 121.2, 109.9, 100.6, 94.5,
3
+
8.7, 55.6. MS m/z: 177 (M ); HR-MS (EI) Calcd for C10
H
11NO : 177.0790. Found: 177.0810.
2
5
,6-Dimethoxyindol-2-ylmethanol 9b

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HETEROCYCLES, Vol. 93, No. 1, 2016
The same procedure as above was carried out using methyl indole-2-carboxylate 8b (600 mg, 2.55 mmol)
o
1
to give the alcohol 9b (370 mg, 70%). mp 134-135 C (EtOAc); H-NMR (CDCl
3
) : 8.22 (1H, br s), 7.02
(1H, s), 6.81 (1H, s), 6.30 (1H, s), 4.76 (2H, d, J=4.2 Hz), 3.90 (3H, s), 3.89 (3H, s), 2.00 (1H, br s);
13C-NMR (CDCl
) : 147.1, 145.1, 136.1, 130.8, 120.6, 102.3, 100.6, 94.4, 58.6, 56.3, 56.1. MS m/z: 207
: 207.0895. Found: 207. 0879.
3
+
(
M ); HR-MS (EI) Calcd for C11
H13NO
3
6
-Methoxyindole-2-carbaldehyde 10a
A solution of alcohol 9a (500 mg, 2.82 mmol) in CH
2
Cl
2
(10 mL) was added dropwise to a solution of
o
activated MnO (486 mg, 28.2 mmol) in CH Cl
2
2
2
(20 mL). After stirring at 50 C for 12 h, the reaction
mixture was filtered through Celite pad. The organic layer was evaporated in vacuo. The residue was
purified by column chromatography using EtOAc-hexane (3:7, v/v) as an eluent to give the aldehyde 10a
o
-1 1
(
252 mg, 51%). mp 123-124 C (EtOAc); IR (ATR) : 1612 cm . H-NMR (CDCl
3
) : 9.72 (1H, s), 9.06
(1H, br s), 7.60 (1H, dd, J=8.6, 2.1 Hz), 7.21 (1H, d, J=2.1 Hz), 6.84 (1H, dd, J=8.6, 2.2 Hz), 6.83 (1H, s),
1
3
3
.88 (3H, s); C-NMR (CDCl
3
) : 181.0, 160.4, 139.5, 135.5, 124.3, 121.8, 115.6, 113.3, 93.6, 55.5. MS
NO : 175.0633. Found: 175.0617.
+
m/z: 175 (M ); HR-MS (EI) Calcd for C10
H
9
2
5
,6-Dimethoxyindole-2-carbaldehyde 10b
The same procedure as above was carried out using the alcohol 9b (500 mg, 2.42 mmol) to give the
o
-1 1
aldehyde 10b (307 mg, 62%). mp 162-164 C (EtOAc); IR (ATR) : 1619 cm . H-NMR (CDCl ) :
3
1
3
9
.69 (1H, s), 9.43 (1H, br s), 7.17 (1H, m), 7.07 (1H, s), 6.87 (1H, s), 3.96 (3H, s), 3.93 (3H, s); C-NMR
+
(CDCl
3
) : 180.7, 151.7, 146.5, 135.0, 134.6, 120.4, 115.6, 102.5, 93.9, 56.0, 55.9. MS m/z: 205 (M );
HR-MS (EI) Calcd for C11
H
11NO : 205.0739. Found: 205.0769.
3
3
-Iodo-6-methoxyindole-2-carbaldehyde 11a
A solution of I (1.67 g, 6.6 mmol) in DMF (30 mL) was added to a solution of the aldehyde 10a (0.96 g,
.6 mmol) and powdered KOH (1.3 g, 23.8 mmol) under cooling with ice-water. After stirring at rt for 4 h,
the mixture was poured into a solution of NH (50 mL) and NaHSO (500 mg, 4.8 mmol) in water (500
mL). The precipitates were separated by filtration to give the 3-iodoindole 11a (1.45 g, 81%) mp 166-168
2
6
3
3
o
-1 1
C (EtOAc); IR (ATR) : 1620 cm . H-NMR (CDCl ) : 9.70 (1H, s), 9.27 (1H, br s), 7.46 (1H, d, J=8.8
3
1
3
Hz), 6.90 (1H, dd, J=8.8, 2.1 Hz), 6.79 (1H, d, J=2.1 Hz), 3.88 (3H, s); C-NMR (CDCl
3
) : 181.9, 161.3,
INO
+
1
3
38.6, 133.1, 125.3, 124.4, 114.3, 93.6, 73.6, 55.7. MS m/z: 300 (M ); HR-MS (EI) Calcd for C10
H
8
2
:
00.9600. Found: 300.9575.
3
-Iodo-5,6-dimethoxyindole-2-carbaldehyde 11b

HETEROCYCLES, Vol. 93, No. 1, 2016
91
The same procedure as above was carried out using the aldehyde 10b (800 mg, 3.90 mmol) to give the
o
-1 1
3
9
1
-iodoindole 11b (1.20 g, 93%). mp 187-188 C (EtOAc); IR (ATR) : 1628 cm . H-NMR (CDCl
3
) :
) :
13
.67 (1H, s), 9.65 (1H, br s), 6.87 (1H, s), 6.83 (1H, s), 3.98 (3H, s), 3.97 (3H, s); C-NMR (CDCl
3
+
81.6, 152.7, 147.5, 133.1, 132.7, 124.2, 102.4, 93.8, 72.9, 56.3, 56.2. MS m/z: 330 (M ); HR-MS (EI)
Calcd for C11
H
10INO : 330.9705. Found: 330.9705.
3
3
-Iodo-6-methoxy-N-(methoxymethyl)indole-2-carbaldehyde 12a
A solution of 3-iodoindole 11a (500 mg, 1.84 mmol) in DMF (15 mL) was added to a suspension of 60%
NaH (89 mg, 2.21 mmol) in DMF (5 mL) under cooling with ice-water. After stirring at the same
temperature for 30 min, chloromethyl methyl ether (0.28 mL, 2.21 mmol) was added to the above mixture.
The reaction mixture was stirred at the rt for 2 h, which was treated with water (30 mL). The mixture was
extracted with EtOAc. The organic layer was washed with water and brine and dried over Na
2
SO . The
4
solvent was removed, and the residue was purified by column chromatography (silica gel, 30 g) using
o
EtOAc-hexane (3:7, v/v) as an eluent to give the N-MOM-indole 12a (632 mg, 83%). mp 96-97 C
-1 1
(
EtOAc); IR (ATR) : 1651 cm . H-NMR (CDCl ) : 9.87 (1H, s), 7.47 (1H, d, J=9.0 Hz), 6.94 (1H, dd,
3
1
3
J=9.0, 2.2 Hz), 6.88 (1H, d, J=2.2 Hz), 5.95 (2H, s), 3.91 (3H, s), 3.31 (3H, s); C-NMR (CDCl ) :
3
+
1
83.5, 161.5, 141.8, 131.0, 124.8, 124.6, 114.7, 92.8, 79.8, 74.5, 56.0, 55.7. MS m/z: 344 (M ); HR-MS
(EI) Calcd for C12
H
12INO : 344.9862. Found: 344.9879.
3
3
-Iodo-5,6-dimethoxy-N-(methoxymethyl)indole-2-carbaldehyde 12b
The same procedure as above was carried out using 3-iodoindole 11b (900 mg, 2.72 mmol) to give the
o
-1 1
N-MOM-indole 12b (966 mg, 94%). mp 156-157 C (EtOAc); IR (ATR) : 1651 cm . H-NMR (CDCl )
3
13

: 9.84 (1H, s), 6.90 (1H, s), 6.89 (1H, s), 5.97 (2H, s), 4.00 (3H, s), 3.99 (3H, s), 3.31 (3H, s); C-NMR
CDCl ) : 183.0, 152.8, 147.9, 135.8, 130.5, 123.7, 102.8, 92.9, 78.8, 74.6, 56.4, 56.3, 55.9. MS m/z: 374
M ); HR-MS (EI) Calcd for C13 : 374.9968. Found: 374.9983.
(
(
3
+
H14INO
4
2
-[1-(tert-Butyldimethylsilyloxy)but-2-en-1-yl]-3-iodo-6-methoxy-N-methoxymethylindole 14a
A solution of propenylmagnesium bromide (0.5 M in THF, 0.92 mL, 0.46 mmol) was added dropwise to
a solution of N-MOM-indole 12a (105 mg, 0.3 mmol) in THF (5 mL) under cooling with ice-water. After
stirring at rt for 1 h, the reaction mixture was quenched with aqueous NH
was extracted with EtOAc. The organic layer was washed with brine, dried over Na
in vacuo. The alcohol 13a was used then without purification, because it was unstable. A solution of
4
Cl solution (saturated), and then
2
SO , and evaporated
4
tert-butyldimethylsilyl chloride (137 mg, 0.91 mmol) in CH
2
Cl
2
(5 mL) was added to a solution of the
o
alcohol 13a and imidazole (228 mg, 1.52 mmol) under cooling with ice-water. After stirring at 50 C for

92
HETEROCYCLES, Vol. 93, No. 1, 2016
1
2 h, the reaction mixture was quenched with water, and then the mixture was extracted with EtOAc. The
organic layer was washed with brine, dried over Na
2
SO , and evaporated in vacuo. The residue was
4
purified by column chromatography using EtOAc-hexane (1:9, v/v) as an eluent to give the silyl ether 14a
1
(
148 mg, 97%). H-NMR (CDCl
3
) : 7.12 (1H, d, J=8.7 Hz), 6.82 (1H, d, J=2.4 Hz), 6.71 (1H, dd, J=8.7,
2
1
.4 Hz), 5.32-5.79 (5H, m), 3.72 (3H, s), 3.19 (9H/5, s), 3.13 (6H/5, s), 1.61 (9H/5, dd, J=6.7, 0.7 Hz),
.55 (6H/5, dd, J=5.3, 1.4 Hz), 0.75 (27H/5, s), 0.73 (18H/5, s), 0.02 (9H/5, s), 0.01 (6H/5, s), -0.18 (9H/5,
+
s), -0.22 (6H/5, s). MS m/z: 501 (M ); HR-MS (EI) Calcd for C21
H
32INO Si: 501.1196. Found: 501.1187.
3
2
-[1-(tert-Butyldimethylsilyloxy)but-2-en-1-yl]-3-iodo-5,6-dimethoxy-N-methoxymethylindole 14b
The same procedure as above was carried out using N-MOM-indole 12b (100 mg, 0.27 mmol) to give the
1
silyl ether 14b (125 mg, 87%). H-NMR (CDCl
3
) : 7.00 (2H/5, s), 6.99 (3H/5, s), 6.82 (1H, s), 5.48-5.92
(
(
-
5H, m), 3.96 (3H, s), 3.94 (3H, s), 3.32 (9H/5, s), 3.27 (6H/5, s), 1.75 (9H/5, dd, J=6.8, 1.2 Hz), 1.70
6H/5, dd, J=5.0, 1.0 Hz), 0.90 (27H/5, s), 0.88 (18H/5, s), 0.17 (9H/5, s), 0.15 (6H/5, s), -0.03 (9H/5, s),
+
0.07(6H/5, s). MS m/z: 531 (M ); HR-MS (EI) Calcd for C22
H
34INO Si: 531.1302. Found: 531.1277.
4
6
-Methoxy-3-methyl-N-(methoxymethyl)carbazole-1,4-quinone 15a
Carbon monoxide was bubbled for 5 min to a mixture of the silyl ether 14a (100 mg, 0.20 mmol),
tributyl(vinyl)tin (190 mg, 0.60 mmol), BHT (54 mg, 0.24 mmol), and PdCl (dppf) (33 mg, 0.040 mmol)
2
o
in DMF (20 mL) at rt. The resulting mixture was stirred at 70 C for 20 h under a CO atmosphere. After
cooling to an ambient temperature, TBAF (1 M in THF, 0.3 mL, 0.30 mmol) was added to the mixture
and then the mixture was stirred at the same temperature for 1 h under O
quenched with water and then the mixture was extracted with EtOAc. The organic layer was washed with
brine, dried over Na SO , and evaporated in vacuo. The residue was purified by column chromatography
using EtOAc-hexane (1:9, v/v) as an eluent to give the carbazole-1,4-quinone 15a (17 mg, 30%). mp
2
atmosphere. The mixture was
2
4
o
-1 1
1
45-146 C (EtOAc); IR (ATR) : 1647, 1654 cm . H-NMR (CDCl
3
) : 8.15 (1H, d, J=8.8 Hz), 7.02
(
(
1H, dd, J=8.8, 2.2 Hz), 6.96 (1H, d, J=2.2 Hz), 6.43 (1H, q, J=1.6 Hz), 5.98 (2H, s), 3.90 (3H, s), 3.44
1
3
3H, s), 2.13 (3H, d, J=1.6 Hz); C-NMR (CDCl
3
) : 184.3, 180.6, 160.1, 146.4, 140.5, 133.1, 133.1,
+
1
23.9, 118.5, 118.0, 116.1, 93.8, 75.0, 56.3, 55.6, 15.5 MS m/z: 285 (M ); HR-MS (EI) Calcd for
C
16
H
15NO : 285.1001. Found: 285.1002.
4
5
,6-Dimethoxy-3-methyl-N-(methoxymethyl)carbazole-1,4-quinone 15b
The same procedure as above was carried out using the silyl ether 14b (100 mg, 0.17 mmol) to give the
o
-1
carbazole-1,4-quinone 15b (22 mg, 41%). mp 228-230 C (EtOAc); IR (ATR) : 1635, 1624 cm .
1H-NMR (CDCl
) : 7.65 (1H, s), 6.96 (1H, s), 6.42 (1H, q, J=1.6 Hz), 5.99 (2H, s), 3.99 (3H, s), 3.98
3

HETEROCYCLES, Vol. 93, No. 1, 2016
93
1
3
(
3H, s), 3.33 (3H, s), 2.13 (3H, d, J=1.6 Hz); C-NMR (CDCl
3
) : 184.5, 180.1, 151.2, 149.4, 146.2,
+
1
34.5, 133.4, 132.3, 118.1, 117.5, 102.3, 93.5, 75.2, 56.3, 56.2, 56.2, 15.5. MS m/z: 315 (M ); HR-MS
(EI) Calcd for C17
H
17NO : 315.1107. Found: 315.1123.
5
N-(Benzyloxymethyl)-3-iodo-6-methoxyindole-2-carbaldehyde 16a
A solution of 3-iodoindole 11a (350 mg, 1.15 mmol) in DMF (10 mL) was added to a suspension of
K
2
CO (794 mg, 5.75 mmol) in DMF (5 mL) under cooling with ice-water. After stirring at the same
3
temperature for 30 min, benzyl chloromethyl ether (0.79 mL, 5.75 mmol) was added to the above mixture.
The reaction mixture was stirred at rt for 12 h, which was treated with water (30 mL). The mixture was
extracted with EtOAc. The organic layer was washed with water and brine and dried over Na
2
SO . The
4
solvent was removed, and the residue was purified by column chromatography (silica gel, 30 g) using
o
EtOAc-hexane (1:9, v/v) as an eluent to give the N-BOM-indole 16a (445 mg, 92%). mp 88-89 C
-1 1
(
EtOAc); IR (ATR) : 1662 cm . H-NMR (CDCl
3
) : 9.85 (1H, s), 7.45 (1H, d, J=8.8 Hz), 7.21-7.38
(5H, m), 6.93 (1H, dd, J=8.8, 2.2 Hz), 6.86 (1H, d, J=2.2 Hz), 6.08 (2H, s), 4.54 (2H, s), 3.87 (3H, s);
13C-NMR (CDCl
) : 183.5, 161.5, 141.8, 128.4, 128.3, 127.9, 127.8, 127.7 124.8, 124.7, 114.8, 92.9,
3
+
7
3.1, 70.4, 69.5, 55.8. MS m/z: 421 (M ); HR-MS (EI) Calcd for C18
H
16NO : 421.0175. Found: 421.0171.
3
N-(Benzyloxymethyl)-3-iodo-5,6-dimethoxyindole-2-carbaldehyde 16b
The same procedure as above was carried out using 3-iodoindole 11b (200 mg, 0.60 mmol) to give the
o
-1 1
N-BOM-indole 16b (246 mg, 91%). mp 109-111 C (EtOAc); IR (ATR) : 1651 cm . H-NMR (CDCl )
3
: 9.82 (1H, s), 7.19-7.38 (5H, m), 6.87 (2H, s), 6.08 (2H, s), 4.52 (2H, s), 3.99 (3H, s), 3.95 (3H, s);
13C-NMR (CDCl
) : 183.0, 152.7, 147.8, 137.3, 135.8, 130.3, 128.3, 127.8, 127.7, 123.6, 102.7, 93.1,
3
+
7
4
8.9, 73.1, 70.3, 56.4, 56.2. MS m/z: 451 (M ); HR-MS (EI) Calcd for C19
H
18NO : 451.0281. Found:
4
51.0281.
3
-Iodo-6-methoxy-N-(trimethylsilylethoxymethyl)indole-2-carbaldehyde 17a
A solution of 3-iodoindole 11a (200 mg, 0.66 mmol) in DMF (5 mL) was added to a suspension of 60%
NaH (32 mg, 0.80 mmol) in DMF (5 mL) under cooling with ice-water. After stirring at the same
temperature for 30 min, trimethylsilylethoxymethyl chloride (0.14 mL, 0.80 mmol) was added to the
above mixture. The reaction mixture was stirred at rt for 2 h, which was treated with water (15 mL). The
mixture was extracted with EtOAc. The organic layer was washed with water and brine and dried over
Na
2
SO
4
. The solvent was removed, and the residue was purified by column chromatography (silica gel,
3
5
0 g) using EtOAc-hexane (3:7, v/v) as an eluent to give the N-SEM-indole 17a (269 mg, 94%). mp
o
-1 1
2-54 C (EtOAc); IR (ATR) : 1616 cm . H-NMR (CDCl ) : 9.86 (1H, s), 7.45 (1H, d, J=8.6 Hz), 6.93
3

94
HETEROCYCLES, Vol. 93, No. 1, 2016
(1H, dd, J=8.6, 2.2 Hz), 6.89 (1H, d, J=2.2 Hz), 5.97 (2H, s), 3.90 (3H, s), 3.57 (2H, t, J=8.1 Hz), 0.89
1
3
(
2H, t, J=8.1 Hz), -0.07 (9H, s); C-NMR (CDCl
3
) : 183.4, 161.3, 141.8, 130.9, 124.7, 124.6, 114.6,
+
9
3.0, 79.5, 72.9, 65.8, 55.7, 17.8, -1.4. MS m/z: 431 (M ); HR-MS (EI) Calcd for C16
H
22INO Si: 431.0414.
3
Found: 431.0444.
3
-Iodo-5,6-dimethoxy-N-(trimethylsilylethoxymethyl)indole-2-carbaldehyde 17b
The same procedure as above was carried out using 3-iodoindole 11b (200 mg, 0.60 mmol) to give the
o
-1 1
N-SEM-indole 17b (246 mg, 98%). mp 63-65 C (EtOAc); IR (ATR) : 1651 cm . H-NMR (CDCl
3
) :
9
.83 (1H, s), 6.92 (1H, s), 6.88 (1H, s), 5.98 (2H, s), 3.99 (6H, s), 3.56 (2H, t, J=7.9 Hz), 0.88 (2H, t,
1
3
J=7.9 Hz), -0.07 (9H, s); C-NMR (CDCl
3
) : 183.0, 152.6, 147.8, 135.9, 130.3, 123.7, 102.7, 93.2, 78.9,
+
7
3.0, 65.8, 56.4, 56.2, 17.8, -1.4. MS m/z: 461 (M ); HR-MS (EI) Calcd for C17
H
24INO Si: 461.0519.
4
Found: 461.0523.
N-Benzyloxymethyl-2-[1-(tert-butyldimethylsilyloxy)but-2-en-1-yl]-3-iodo-6-methoxyindole 20a
A solution of propenylmagnesium bromide (0.5 M in THF, 1.71 mL, 0.86 mmol) was added dropwise to
a solution of N-BOM-indole 16a (238 mg, 0.57 mmol) in THF (5 mL) under cooling with ice-water. After
stirring at rt for 1 h, the reaction mixture was quenched with aqueous NH
was extracted with EtOAc. The organic layer was washed with brine, dried over Na
in vacuo. The alcohol 18a was then used without purification, because it was unstable. A solution of
4
Cl solution (saturated), which
2
SO , and evaporated
4
tert-butyldimethylsilyl chloride (258 mg, 1.71 mmol) in CH
2
Cl
2
(10 mL) was added to a solution of the
o
alcohol 18a and imidazole (194 mg, 2.85 mmol) under cooling with ice-water. After stirring at 50 C for
1
2 h, the reaction mixture was quenched with water, and then the mixture was extracted with EtOAc. The
organic layer was washed with brine, dried over Na SO , and evaporated in vacuo. The residue was
2
4
purified by column chromatography using EtOAc-hexane (1:9, v/v) as an eluent to give the silyl ether 20a
1
(
264 mg, 80%). H-NMR (CDCl
3
) : 7.25-7.34 (6H, m), 6.83-6.95 (2H, m), 5.49-5.99 (5H, m), 4.57
(3H/5, d, J=11.7 Hz), 4.51 (3H/5, d, J=11.7 Hz), 4.49 (2H/5, d, J=11.7 Hz), 4.44 (2H/5, d, J=11.7 Hz),
3
.81 (3H, s), 1.77 (9H/5, dd, J=7.1, 1.5 Hz), 1.69 (6H/5, dd, J=4.8, 1.8 Hz), 0.89 (27H/5, s), 0.87 (18H/5,
+
s), 0.16 (9H/5, s), 0.15 (6H/5, s), -0.03 (9H/5, s), -0.06 (6H/5, s). MS m/z: 577 (M ); HR-MS (EI) Calcd
for C27
H
36INO Si: 577.1509. Found: 577.1495.
3
N-Benzyloxymethyl-2-[1-(tert-butyldimethylsilyloxy)but-2-en-1-yl]-3-iodo-5,6-dimethoxyindole 20b
The same procedure as above was carried out using N-BOM-indole 16b (248 mg, 0.55 mmol) to give the
1
silyl ether 20b (307 mg, 92%). H-NMR (CDCl
3
) : 7.26-7.34 (5H, m), 6.97 (3H/5, s), 6.92 (2H/5, s),
6
.83 (1H, s), 5.47-5.96 (5H, m), 4.54 (3H/5, d, J=11.7 Hz), 4.48 (3H/5, d, J=11.7 Hz), 4.46 (2H/5, d,

HETEROCYCLES, Vol. 93, No. 1, 2016
95
J=11.3 Hz), 4.41 (2H/5, d, J=11.3 Hz), 3.97 (3H, s), 3.86 (3H, s), 1.77 (9H/5, dd, J=7.1, 1.5 Hz), 1.70
(6H/5, dd, J=5.3, 1.7 Hz), 0.90 (27H/5, s), 0.88 (18H/5, s), 0.17 (9H/5, s), 0.16 (6H/5, s), -0.02 (9H/5, s),
+
-
0.06 (6H/5, s). MS m/z: 607 (M ); HR-MS (EI) Calcd for C28
H
38INO Si: 607.1615. Found: 607.1590.
4
2
-[1-(tert-Butyldimethylsilyloxy)but-2-en-1-yl]-3-iodo-6-methoxy-N-(trimethylsilylethoxymethyl)-
indole 21a
The same procedure as above was carried out using N-SEM-indole 17a (190 mg, 0.44 mmol) to give the
1
silyl ether 21a (85 mg, 85%). H-NMR (CDCl
3
) : 7.26 (1H, d, J=8.8 Hz), 7.01 (3H/5, d, J=2.2 Hz), 6.99
(2H/5, J=2.2 Hz), 6.84 (1H, dd, J=8.8, 2.3 Hz), 5.46-5.92 (5H, m), 3.86 (3H, s), 3.48-3.67 (2H, m), 1.76
(9H/5, dd, J=7.1, 1.5 Hz), 1.70 (6H/5, J=4.8, 1.5 Hz), 0.88-0.98 (11H, m), 0.15 (9H/5, s), 0.14 (6H/5, s),
+
0
.08 (27H/5, s), -0.03 (18H/5, s), -0.05 (9H/5, s), -0.08 (6H/5, s). MS m/z: 587 (M ); HR-MS (EI) Calcd
for C25
H42INO
3
Si : 587.1748. Found: 587.1755.
2
2
-[1-(tert-Butyldimethylsilyloxy)but-2-en-1-yl]-3-iodo-5,6-methoxy-N-(trimethylsilylethoxymethyl)-
indole 21b
The same procedure as above was carried out using N-SEM-indole 17b (169 mg, 0.37 mmol) to give the
1
silyl ether 21b (60 mg, 61%). H-NMR (CDCl
3
) : 7.04 (3H/5, s), 7.03 (2H/5, s), 6.83 (1H, s), 5.47-5.90
(5H, m), 3.96 (3H, s), 3.93 (3H, s), 3.47-3.67 (2H, m), 1.75 (9H/5, dd, J=7.2, 1.0 Hz), 1.70 (6H/5, dd,
J=5.1, 1.2 Hz), 0.88-0.98 (11H, m), 0.16 (9H/5, s), 0.14 (6H/5, s), 0.02 (27H/5, s), 0.00 (18H/5, s), -0.05
+
(
9H/5, s), -0.09 (6H/5, s). MS m/z: 617 (M ); HR-MS (EI) Calcd for C26
H44INO
4
Si : 617.1854. Found:
2
6
17.1853.
N-(Benzyloxymethyl)-6-methoxy-3-methylcarbazole-1,4-quinone 22a
Carbon monoxide was bubbled for 5 min to a mixture of the silyl ether 20a (100 mg, 0.17 mmol),
tributyl(vinyl)tin (169 mg, 0.51 mmol), BHT (57 mg, 0.26 mmol), and PdCl (dppf) (28 mg, 0.034 mmol)
2
o
in DMF (20 mL) at rt. The resulting mixture was stirred at 70 C for 20 h under a CO atmosphere. After
cooling to an ambient temperature, TBAF (1 M in THF, 0.17 mL, 0.17 mmol) was added to the mixture
and then the mixture was stirred at the same temperature for 1 h under O
quenched with water and then the mixture was extracted with EtOAc. The organic layer was washed with
brine, dried over Na SO , and evaporated in vacuo. The residue was purified by column chromatography
2
atmosphere. The mixture was
2
4
using EtOAc-hexane (1:9, v/v) as an eluent to give the carbazole-1,4-quinone 22a (43 mg, 69%).
The same procedure as above was carried out using the silyl ether 20a (100 mg, 0.17 mmol) to give the
o
-1
carbazole-1,4-quinone 22a (43 mg, 69%). mp 117-118 C (EtOAc); IR (ATR) : 1639, 1624 cm .
1H-NMR (CDCl
) : 8.13 (1H, d, J=8.8 Hz), 7.20-7.28 (5H, m), 7.02 (1H, dd, J=8.8, 2.2 Hz), 6.96 (1H, d,
3

96
HETEROCYCLES, Vol. 93, No. 1, 2016
J=2.2 Hz), 6.42 (1H, q, J=1.6 Hz), 6.11 (2H, s), 4.57 (2H, s), 3.87 (3H, s), 2.13 (3H, d, J=1.6 Hz);
13C-NMR (CDCl
) : 184.3, 180.6, 160.1, 146.4, 140.6, 137.1, 133.0, 132.9, 128.4, 127.9, 127.7, 123.9,
3
+
1
3
18.6, 118.0, 116.1, 93.8, 73.6, 70.8, 55.7, 15.5. MS m/z: 361 (M ); HR-MS (EI) Calcd for C22
H
19NO :
4
61.1314. Found: 361.1299.
N-(Benzyloxymethyl)-5,6-dimethoxy-3-methylcarbazole-1,4-quinone 22b
The same procedure as above was carried out using the silyl ether 20b (100 mg, 0.17 mmol) to give the
o
-1
carbazole-1,4-quinone 22b (26 mg, 39%). mp 143-145 C (EtOAc); IR (ATR) : 1635, 1612 cm .
1H-NMR (CDCl
) : 7.64 (1H, s), 7.30-7.20 (5H, m), 6.95 (1H, s), 6.42 (1H, q, J=1.6 Hz), 6.12 (2H, s),
3
1
3
4
1
5
.55 (2H, s), 4.00 (3H, s), 3.94 (3H, s), 2.13 (3H, d, J=1.6 Hz); C-NMR (CDCl ) : 184.5, 180.1, 151.1,
3
49.4, 146.2, 137.0, 134.5, 133.4, 132.1, 128.4, 128.0, 127.9, 127.8, 118.2, 117.5, 102.3, 93.7, 73.8, 70.8,
+
6.3, 15.5. MS m/z: 391 (M ); HR-MS (EI) Calcd for C23
H
21NO : 391.1420. Found: 371.1546.
5
6
-Methoxy-3-methyl-N-(trimethylsilylethoxymethyl)carbazole-1,4-quinone 23a
Carbon monoxide was bubbled for 5 min to a mixture of the silyl ether 21a (50 mg, 0.09 mmol),
tributyl(vinyl)tin (86 mg, 0.27 mmol), BHT (30 mg, 0.135 mmol), and PdCl (dppf) (15 mg, 0.02 mmol)
2
o
in DMF (10 mL) at rt. The resulting mixture was stirred at 70 C for 20 h under a CO atmosphere. After
cooling to an ambient temperature, the mixture was stirred at the same temperature for 1 h under O
atmosphere. The mixture was quenched with water and then the mixture was extracted with EtOAc. The
organic layer was washed with brine, dried over Na SO , and evaporated in vacuo. The residue was
purified by column chromatography using EtOAc-hexane (1:9, v/v) as an eluent to give the
2
2
4
o
-1 1
carbazole-1,4-quinone 23a (20 mg, 59%). mp 95-96 C (EtOAc); IR (ATR) : 1635, 1612 cm . H-NMR
CDCl ) : 8.15 (1H, d, J=8.8 Hz), 7.01 (1H, dd, J=8.8, 2.2 Hz), 6.97 (1H, d, J=2.2 Hz), 6.41 (1H, q,
J=1.6 Hz), 6.00 (2H, s), 3.90 (3H, s) 3.58 (2H, t, J=8.0 Hz), 2.12 (3H, d, J=1.6 Hz), 0.91 (2H, t, J=8.0
(
3
1
3
Hz), -0.06 (9H, s); C-NMR (CDCl
3
) :184.3, 180.6, 160.0, 146.4, 140.6, 133.0, 133.0, 123.8, 118.4,
+
1
18.0, 116.1, 93.9, 73.3, 66.2, 55.6, 17.8, 15.6, -1.4. MS m/z: 371 (M ); HR-MS (EI) Calcd for
C
20
H
25NO Si: 371.1553. Found: 371.1546.
4
5
,6-Dimethoxy-3-methyl-N-(trimethylsilylethoxymethyl)carbazole-1,4-quinone 23b
The same procedure as above was carried out using the silyl ether 24b (50 mg, 0.08 mmol) to give the
o
-1
carbazole-1,4-quinone 23b (12 mg, 37%). mp 139-141 C (EtOAc); IR (ATR) : 1639, 1616 cm .
1H-NMR (CDCl
) : 7.65 (1H, s), 6.98 (1H, s), 6.41 (1H, q, J=1.6 Hz), 6.01 (2H, s), 3.99 (3H, s), 3.98
3H, s), 3.58 (2H, t, J=8.1 Hz), 2.13 (3H, d, J=1.6 Hz), 0.90 (2H, t, J=8.1 Hz), -0.07 (9H, s); C-NMR
3
1
3
(

HETEROCYCLES, Vol. 93, No. 1, 2016
97
(CDCl
3
) :184.5, 180.1, 151.0, 149.3, 146.2, 134.5, 133.3, 132.1, 117.9, 117.5, 102.2, 93.8, 73.5, 66.2,
+
5
4
6.2, 56.1, 17.7, 15.5, -1.4. MS m/z: 401 (M ); HR-MS (EI) Calcd for C21
H
27NO Si: 401.1658. Found:
5
01.1632.
Koeniginequinone A 2a from 22a by the Birch conditions
A solution of N-BOM-carbazole-1,4-quinone 22a (10 mg, 0.028 mmol) in THF (3 mL) was added to a liq.
o
NH
3
under -78 C. After stirring at the same temperature for 10 min, Na (6.4 mg, 0.28 mmol) was added
to the above mixture. The mixture was stirred for 30 min, which was quenched with NH
mixture was extracted with EtOAc. The organic layer was washed with brine, dried over Na
evaporated in vacuo. The residue was purified by column chromatography using EtOAc-hexane (1:9, v/v)
4
Cl, and then the
2
SO , and
4
o
o
11
as an eluent to give koeniginequinone A 2a (5 mg, 78%). mp 241-242 C (EtOAc) (mp 241 C, Lit. ); IR
-1 1
(
ATR) : 3221, 1651, 1631 cm . H-NMR (DMSO-d
6
) : 12.63 (1H, br s), 7.90 (1H, d, J=8.9 Hz), 6.96
(1H, dd, J=8.9, 2.2 Hz), 6.92 (1H, d, J=2.2 Hz), 6.56 (1H, q, J=1.6 Hz), 3.82 (3H, s), 2.04 (3H, d, J=1.6
1
3
Hz); C-NMR (DMSO-d
6
) : 183.3, 179.4, 158.7, 147.1, 138.8, 135.0, 131.6, 122.4, 117.7, 115.9, 115.1,
+
9
5.0, 55.3, 15.5. MS m/z: 241 (M ); HR-MS (EI) Calcd for C14
H
11NO : 241.0739. Found: 241.0721.
3
Koeniginequinone B 2b from 22b by the Birch conditions
The same procedure as above was carried out using N-BOM-carbazole-1,4-quinone 22b (50 mg, 0.13
o
o
11
mmol) to give koeniginequinone B 2b (25mg, 72%). mp 245-246 C (EtOAc) (mp 246-247 C, Lit. ); IR
-1 1
(
ATR) : 3286, 1631, 1619 cm . H-NMR (DMSO-d ) : 12.60 (1H, br s), 7.40 (1H, s), 6.92 (1H, s),
6
1
3
6
1
.54 (1H, q, J=1.6 Hz), 3.83 (6H, s), 2.04 (3H, d, J=1.6 Hz); C-NMR (DMSO-d
6
) :183.3, 178.8, 150.2,
+
48.5, 147.0, 134.0, 132.8, 131.9, 117.1, 115.8, 101.3, 95.2, 79.1, 55.6, 15.4. MS m/z: 241 (M ); HR-MS
(EI) Calcd for C15
H
13NO : 271.0845. Found: 271.0873.
4
Koeniginequinone A 2a from 22a by Pd-C catalyzed hydrogenation
A solution of N-BOM-carbazole-1,4-quinone 22a (15 mg, 0.042 mmol) was added dropwise to a solution
of 10% Pd-C (10 mg, 0.042 mmol) in MeOH (20 mL) under H atmosphere. After stirring at rt for 12 h,
2
the reaction mixture was filtered through Celite pad. The organic layer was evaporated in vacuo. The
residue was purified by column chromatography using EtOAc-hexane (3:7, v/v) as an eluent to give
koeniginequinone A 2a (2 mg, 20%). Physical and spectral data were consistent with the synthetic or
natural 2a in all respects
Koeniginequinone A 2a from 23a
A mixture of N-SEM-carbazole-1,4-quinone 23a (60 mg, 0.16 mmol) and 6 M HCl (5 mL) in EtOH (5

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HETEROCYCLES, Vol. 93, No. 1, 2016
o
mL) was heated at 50 C for 1 h. After cooling to an ambient temperature, the mixture was basified with
an aqueous Na CO (saturated) solution, and then the resulting mixture was extracted with EtOAc. The
organic layer was washed with brine, dried over Na SO and concentrated in vacuo. The residue was
2
3
2
4
purified by column chromatography (silica gel, 30 g) using EtOAc-hexane (3:7, v/v) as an eluent to give
the koeniginequinone A 2a (22 mg, 48%). Physical and spectral data were consistent with the synthetic or
natural 2a in all respects.
Koeniginequinone B 2b from 23b
The same procedure as above was carried out using N-SEM-carbazole-1,4-quinone 23b (20 mg, 0.05
mmol) to give koeniginequinone B 2b (7 mg, 52%). Physical and spectral data were consistent with the
synthetic or natural 2b in all respects.
ACKNOWLEDGEMENTS
This work was partly supported by Fukuyama University Grant for Academic Research Projects (Grant
Number: GARP2013-205 (T.N.)).
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