Synthesis of mukonine and seven further 1-oxygenated carbazole alkaloids

Article abstract of DOI:10.1055/s-1998-2184

As an intermediate in the synthesis of seven further 1-oxygenated 3- C₁-substituted carbazole alkaloids, mukonine (1) was synthesized in 46% overall yield, starting from indole-3-carbaldehyde (12) with a Horner-Emmons reaction as the crucial st

Full text of DOI:10.1055/s-1998-2184

SYNTHESIS
October 1998
1501
Synthesis of Mukonine and Seven Further 1-Oxygenated Carbazole Alkaloids
Gerhard Bringmann,*a Stefan Tasler,a Heike Endress,a Karl Peters,b Eva-Maria Petersb
a Institut für Organische Chemie, Universität Würzburg, Am Hubland, D-97074 Würzburg, Germany
Fax +49(931)8884755; E-mail: bringman@chemie.uni-wuerzburg.de
b Max-Planck-Institut für Festkörperforschung, Heisenbergstr. 1, D-70506 Stuttgart, Germany
Received 5 March 1998; revised 23 March 1998
Abstract: As an intermediate in the synthesis of seven further
ly moderate, only few of the reaction sequences lead to
overall yields of more than 30%.15, 17
1-oxygenated 3-C1-substituted carbazole alkaloids, mukonine (1)
was synthesized in 46% overall yield, starting from indole-3-car-
baldehyde (12) with a Horner–Emmons reaction as the crucial
step. From 1, the other desired alkaloids were obtained in high
yields. Among them, clausine E (6) and O-demethylmurrayanine
(7) were synthesized for the first time.
In the course of our studies we attempted to attach a C4
unit to indole-3-carbaldehyde (12) by Stobbe conden-
sation19 and Wittig reaction20 with reagent 9 and 10, re-
spectively (Scheme 2). Both methods could not compete
with the Horner–Emmons variant in which phosphonate
11 is used (Scheme 2). In the synthesis of 11 according to
a protocol by Owton et al.,21 we could increase the yield
to 87% by distilling the product in high vacuum.
Key words: carbazole alkaloids, mukonine, Horner–Emmons
reaction, natural product
Carbazole alkaloids, which have their richest source in
species of the genus Murraya, are of great interest because
of their numerous biological activities.1 Chakraborty ar-
ranged this group of natural products by the size of the
carbon skeleton.1 In the following we present an effective
synthetic access to 1-oxygenated 3-C1-substituted carb-
azoles of the ‘C13 group’ like mukonine (1),2 mukoeic
acid (2),3 murrayanine (3),4 koenoline (4),5 murrayafoline
A (5),6 clausine E (clauszoline I, 6),7, 8 O-demethylmur-
rayanine (7),9 and 1-hydroxy-3-methylcarbazole (8)10
(Scheme 1). Some of them show antibiotic,11 antifungal,12
and cytotoxic5 properties and neoplasm inhibitory effects
on mitosis13 as well as a good activity against the malaria
parasite Plasmodium falciparum, also exhibited by some
dimeric carbazoles.14, 15
Scheme 2
In order to avoid side reactions at the indole nitrogen and,
at the same time, to activate the aldehydic carbonyl func-
tion for nucleophilic attack, the nitrogen was protected
with the Boc unit.22 Further conversions to the carbazole
skeleton took place according to analogous syntheses of
naphthalenes.20a, 23 After N-protection of 12 and olefina-
tion with phosphonate 11 to compound 13, the Boc group
was removed and the tert-butyl ester cleaved in a single
step. Cyclization with sodium acetate in acetic anhydride
and subsequent methanolysis directly yielded clausine E
(6), though it was not easily separated from its impurities
at this point. After removal of residual acetic anhydride,
O-methylation with dimethyl sulfate in acetone led to
mukonine (1) in an overall yield of 46% after purification
by chromatography and recrystallization (Scheme 3). Fur-
ther structural evidence was obtained from a crystal struc-
ture analysis24 of 1 (Scheme 3).
Starting from 1, the alkaloids 2–8 were synthesized in a
few steps (Scheme 4). Treatment of 1 with boron tri-
bromide in dichloromethane23a afforded clausine E (6),
which was isolated very easily now. Reduction of the ester
function of 1 with lithium aluminum hydride did not yield
the expected alcohol koenoline (4),3 but ended in almost
total reduction to give the methyl group of murrayafoline
A (5). The yield of 5 was enhanced to 80% by running
the reaction in a solvent mixture of diethyl ether and
dichloromethane. Reduction of 1 with the milder reducing
agent diisobutylaluminum hydride25 gave 4 in 90% yield.
Oxidation of 4 with activated manganese dioxide led to
Scheme 1
Three general approaches to the synthesis of these com-
pounds have been described so far: the classical Fischer–
Borsche synthesis starts with appropriate cyclohexanone
arylhydrazones,2, 15, 16 Moody et al. build up the carbazole
ring system from indole-2-carboxylate derivatives and
γ-butyrolactones,17 and Knölker et al. construct the skele-
ton via iron tricarbonyl complexes.18 The yields are most-

SYNTHESIS
Papers
1502
The reaction sequences described constitute the as yet best
synthetic access to these carbazole alkaloids, all of them
were synthesized in overall yields of 31–46%, clausine E
(6) and O-demethylmurrayanine (7) were prepared for the
first time. These compounds are also important intermedi-
ates in the atropo-selective synthesis of dimeric carba-
zoles, which will be the subject of forthcoming investiga-
tions.
Mps are uncorrected (Reichert Thermovar microscope). IR spectra
1
were measured using a Perkin–Elmer 1420 spectrophotometer. H
and 13C NMR spectra were recorded at r.t. on a Bruker AM 250
(250.1 and 62.9 MHz, respectively). Chemical shifts δ are reported in
ppm and coupling constants J in Hz. The solvent signal was used as
the internal standard [1H: δ(CDCl3) = 7.26, δ(acetone-d6) = 2.05,
δ(CD3OD) = 3.31; 13C: δ(CDCl3) = 77.01, δ(acetone-d6) = 29.82,
δ(CD3OD) = 48.00]. EI-MS were measured on a Finnigan MAT 90
and MAT 8200 mass spectrometer, the relative intensities are given
in brackets. Microanalyses were performed by the microanalytical
laboratory of the Inorganic Institute of the University of Würzburg.
Column chromatography was performed on silica gel 63–200 µm
(Merck). All reactions, except those involving water, were performed
under N2 and with dried solvents and glassware. Starting compounds
and other reagents were commercially available. Phosphonate 11 was
synthesized as published by Owton et al.21
(a) Boc2O, DMAP, CH2Cl2, r.t., 1 h (96%); (b) 11, NaH, THF, 0°C
then 50°C, 18 h (69%); (c) TFA, CH2Cl2/H2O, r.t., 5 h; (d) NaOAc,
Ac2O, 140°C, 24 h (86% over 2 steps); (e) K2CO3, MeOH, 65°C,
4.5 h; (f) DMS, K2CO3, acetone, 56°C, 7 h (80% over 2 steps)
Scheme 3
1-tert-Butoxycarbonylindole-3-carbaldehyde:
Indole-3-carbaldehyde (12) (5.81 g, 40.0 mmol) was dissolved in
CH2Cl2 (80 mL) and treated at r.t. with DMAP (489 mg, 4.00 mmol)
and di-tert-butyl dicarbonate (10.48 g, 48.0 mmol). After stirring for
1 h, 1 N KHSO4 (70 mL) was added and the CH2Cl2 was evaporated.
The aqueous layer was extracted with several portions of Et2O and the
combined organic extracts were washed with 1 N KHSO4, water, 1 N
NaHCO3, and brine. The organic layer was dried (MgSO4) and the
solvent was removed. Recrystallization of the remaining solid (EtOH)
gave the aldehyde as colorless needles; yield: 9.40 g (96%); mp
129°C (Lit.26 125.5°C).
IR (KBr): ν = 3090, 3020, 3000, 2960, 2940, 2720, 2700, 1715,
1650 cm–1.
1H NMR (CDCl3): δ = 1.71 (s, 9 H, OtBu), 7.37 (td, 1 H, J = 7.3/1.2
Hz, H-5), 7.42 (ddd, 1 H, J = 7.6/7.3/1.5 Hz, H-6), 8.15 (d, 1 H, J =
7.6 Hz, H-7), 8.23 (s, 1 H, H-2), 8.29 (d, 1 H, J = 7.3 Hz, H-4), 10.10
(s, 1 H, CHO).
13C NMR (CDCl3): δ = 28.02 (OtBu), 85.61 (OtBu), 115.1 (C-7),
121.5 (Cq), 122.1 (C-4), 124.5 (C-5), 126.0 (C-6), 135.9 (Cq), 136.5
(C-2), 148.7 (Cq), 185.7 (CHO).
MS (70 eV): m/z (%) = 245 (M+, 18), 189 (35), 172 (7), 145 (69), 144
(60), 116 (19), 57 (100).
tert-Butyl 4-(1'-tert-butoxycarbonylindol-3'-yl)-3-ethoxycarbon-
ylbut-3-enoate (13):
To a solution of NaH (955 mg, 39.8 mmol) in THF (90 mL) was add-
ed phosphonate 11 (12.96 g, 38.3 mmol) at 0°C. After stirring for 2 h
at 0°C and 2 h at r.t., the mixture was added dropwise to 1-tert-but-
oxycarbonylindole-3-carbaldehyde (8.59 g, 35.0 mmol) in THF
(120 mL). The solution was stirred for 18 h at 50°C then treated with
water (80 mL) and the THF was removed. The aqueous residue was
extracted with Et2O and the combined organic layers were dried
(MgSO4). The oil obtained after evaporation of the solvent was puri-
fied by column chromatography (petroleum ether/Et2O 5:1) to give 13
as a yellow oil; yield: 10.34 g (69%).
(a) LiAlH4, Et2O/CH2Cl2, r.t., 2h (80%); (b) DIBAL, Et2O, –78°C,
3.5 h (90%); (c) MnO2, CCl4, r.t., 6 h (84%); (d) BBr3, CH2Cl2, 0°C,
3 h, to r.t., 15 h then MeOH (90–97%); (e) KOH, EtOH/H2O, 78°C,
4 h (99%)
Scheme 4
murrayanine (3),16b which was converted to 7 by treat-
ment with boron tribromide. Likewise by BBr3 mediated
O-demethylation, 5 was converted into 8. Mukoeic acid
(2) was obtained by quantitative saponification of 1 with
potassium hydroxide in ethanol.3, 19
IR (film): ν = 3120, 3040, 2980, 2920, 1720, 1695, 1620 cm–1.
1H NMR (CDCl3): δ = 1.36 (t, 3 H, J = 7.0 Hz, CO2Et), 1.47 (s, 9 H,
OtBu), 1.68 (s, 9 H, OtBu), 3.58 (s, 2 H, H-2), 4.31 (q, 2 H, J = 7.0
Hz, CO2Et), 7.29 (ddd, 1 H, J = 8.2/7.3/1.2 Hz, H-5'), 7.37 (td, 1 H, J
= 7.3/1.2 Hz, H-6'), 7.67 (dd, 1 H, J = 7.3/1.2 Hz, H-7'), 7.87 (s, 1 H,

SYNTHESIS
October 1998
1503
H-2'), 7.97 (d, 1 H, J = 1.2 Hz, H-4), 8.15 (d, 1 H, J = 8.2 Hz, H-4').
13C NMR (CDCl3): δ = 14.27 (CO2Et), 27.94 (OtBu), 28.07 (OtBu),
35.91 (C-2), 60.95 (CO2Et), 81.04 (OtBu), 84.36 (OtBu), 115.2 (C-
4'), 115.6 (Cq), 119.0 (C-7'), 123.1 (C-5'), 125.1 (C-6'), 125.7 (Cq),
125.9 (C-2'), 129.9 (Cq), 131.1 (C-4), 135.0 (Cq), 149.3 (C=O), 167.3
(C=O), 170.0 (C=O).
(607 µL, 6.40 mmol) were added and the mixture was refluxed for
7 h. Aq NH3 (7 mL) was used to scavenge excessive DMS by refluxing
the solution for further 60 min. Evaporation of the solvent and purifi-
cation by column chromatography (petroleum ether/Et2O 5:1) yielded
crude 1. The formation of the N,O-dimethylated compound as a minor
product could not be entirely avoided (6% yield). Recrystallization
from EtOH/pentane afforded colorless crystals; yield over two steps:
1.64 g (80%); mp 201°C (Lit.1a 195°C, Lit.2, 3 198–200°C).
IR (KBr): ν = 3320, 3070, 3020, 2970, 2915, 2810, 1675, 1610, 1590,
1565 cm–1.
MS (70 eV): m/z (%) = 429 (M+, 15), 373 (14), 356 (5), 329 (15), 317
(40), 273 (30), 200 (12), 155 (21), 130 (6), 57 (100).
C24H31NO6 calcd
(429.5) found
C
67.12
66.85
H
7.28
7.50
N
3.26
3.18
1H NMR (acetone-d6): δ = 3.92 (s, 3 H, CO2Me), 4.07 (s, 3 H, OMe),
7.26 (t, 1 H, J = 7.6 Hz, H-6), 7.46 (t, 1 H, J = 7.6 Hz, H-7), 7.59 (s,
1 H, H-2), 7.64 (d, 1 H, J = 7.6 Hz, H-8), 8.21 (d, 1 H, J = 7.6 Hz, H-
5), 8.48 (s, 1 H, H-4), 10.78 (br s, 1 H, NH).
1-Acetoxy-9-acetyl-3-ethoxycarbonylcarbazole:
Compound 13 (5.18 g, 12.1 mmol) was dissolved in CH2Cl2 (18 mL)
and treated with TFA/H2O (69 mL/1 mL) at r.t. for 5 h. The solvents
were removed and without further purification the residue was re-
fluxed in Ac2O (44 mL) with NaOAc (2.17 g, 26.5 mmol) for 24 h.
The Ac2O was removed and purification of the remaining solid by
column chromatography (petroleum ether/CH2Cl2/MeOH 20:2:1) af-
forded a brownish mixture of differently acetylated carbazoles; yield
over two steps (determined by 1H NMR): 3.32 g (86%, ratio 1-acet-
oxy-9-acetyl-3-ethoxycarbonylcarbazole/1-acetoxy-3-ethoxycarbon-
ylcarbazole 1:0.9).
13C NMR (acetone-d6): δ = 52.04 (CO2Me), 56.05 (OMe), 107.1 (C-
2), 112.6 (C-8), 116.6 (C-4), 120.7 (C-6), 121.3 (C-5), 122.5 (Cq),
124.4 (Cq), 127.1 (C-7), 134.0 (Cq), 141.3 (Cq), 146.3 (C-1), 167.9
(CO2Me).
MS (70 eV): m/z (%) = 255 (M+, 100), 240 (51), 224 (40), 196 (14),
181 (15), 153 (17).
+
+
Murrayafoline A (5):
MS (70 eV): m/z (%) = 325 (M1 , 12), 283 (M2 , 22), 241 (100), 210
Reduction of 1 (100 mg, 392 µmol) with LiAlH4 (44.7 mg,
1.18 mmol) in CH2Cl2/Et2O (12 mL, 1:1) was carried out at r.t. for
2 h. The solution was neutralized with 2 N HCl at r.t. and the solvent
was removed. Purification by column chromatography (petroleum
ether/CH2Cl2/MeOH 20:2:1) yielded 5 as a colorless oil; yield: 66.6
mg (80%).
(23), 43 (100).
1-Acetoxy-9-acetyl-3-ethoxycarbonylcarbazole:
1H NMR (acetone-d6): δ = 1.42 (t, 3 H, J = 7.0 Hz, CO2Et), 2.40 (s, 3
H, OAc), 2.82 (s, 3 H, NAc), 4.42 (q, 2 H, J = 7.0 Hz, CO2Et), 7.53
(ddd, 1 H, J = 8.2/7.3/1.2 Hz, H-6), 7.59 (ddd, 1 H, J = 8.5/7.3/1.2 Hz,
H-7), 7.90 (d, 1 H, J = 1.5 Hz, H-2), 8.04 (dd, 1 H, J = 8.5/1.2 Hz, H-
8), 8.26 (dd, 1 H, J = 8.2/1.2 Hz, H-5), 8.67 (d, 1 H, J = 1.5 Hz, H-4).
IR and MS data were identical with those reported in the literature.6
1H NMR (acetone-d6): δ = 2.49 (s, 3 H, Me), 3.97 (s, 3 H, OMe), 6.81
(s, 1 H, H-2), 7.14 (ddd, 1 H, J = 7.9/7.0/0.9 Hz, H-6), 7.36 (ddd, 1 H,
J = 8.2/7.0/0.9 Hz, H-7), 7.49 (s, 1 H, H-4), 7.55 (dt, 1 H, J = 8.2/0.9
Hz, H-8), 8.03 (dd, 1 H, J = 7.9/0.9 Hz, H-5), 10.21 (br s, 1 H, NH).
13C NMR (acetone-d6): δ = 21.93 (Me), 55.73 (OMe), 108.4 (C-2),
112.1 (C-8), 113.1 (C-4), 119.4 (C-6), 120.9 (C-5), 124.1 (Cq), 125.0
(Cq), 126.0 (C-7), 129.2 (Cq), 129.6 (Cq), 141.0 (Cq), 146.6 (C-1).
1-Acetoxy-3-ethoxycarbonylcarbazole:
1H NMR (acetone-d6): δ = 1.41 (t, 3 H, J = 7.0 Hz, CO2Et), 2.41 (s, 3
H, OAc), 4.40 (q, 2 H, J = 7.0 Hz, CO2Et), 7.29 (ddd, 1 H, J = 7.6/7.0/
1.2 Hz, H-6), 7.46 (dd, 1 H, J = 7.9/1.2 Hz, H-8), 7.46 (ddd, 1 H, J =
7.9/7.0/1.2 Hz, H-7), 7.86 (d, 1 H, J = 1.5 Hz, H-2), 8.29 (dd, 1 H, J
= 7.6/1.2 Hz, H-5), 8.73 (d, 1 H, J = 1.5 Hz, H-4), 10.91 (br s, 1 H,
NH).
Koenoline (4):
1 M DIBAH in hexane (3.52 mL) was added to a solution of 1
(600 mg, 2.35 mmol) in Et2O (50 mL) at –78°C. After 1.5 h stirring
at –78°C, the mixture was treated with another portion of DIBAH
(2.64 mL) and stirring was continued for further 2 h. The solution was
poured into iced water (70 mL) and extracted with several portions of
Et2O. The combined organic layers were dried (MgSO4), the solvent
was evaporated and the product was purified by column chromatog-
raphy (petroleum ether/Et2O 2:1). Recrystallization from EtOH/pen-
tane yielded 4 as colorless crystals; yield: 478 mg (90%); mp 142°C
(Lit.5 130°C, Lit.16b 127°C).
3-Ethoxycarbonyl-4-(indol-3'-yl)but-3-enoic Acid:
Purification of a small product sample of the TFA mediated hydroly-
sis by filtration through a short silica gel column (petroleum ether/
CH2Cl2/MeOH 20:2:1) and recrystallization of the obtained solid
from MeOH provided light beige crystals; mp 194°C.
IR (KBr): ν = 3220, 3090, 3030, 2960, 2910, 2690, 1695, 1670,
1590 cm–1.
1H NMR (CD3OD): δ = 1.35 (t, 3 H, J = 7.0 Hz, CO2Et), 3.66 (s, 2 H,
H-2), 4.28 (q, 2 H, J = 7.0 Hz, CO2Et), 7.14 (td, 1 H, J = 7.3/1.2 Hz,
H-5'), 7.20 (td, 1 H, J = 7.3/1.2 Hz, H-6'), 7.42 (d, 1 H, J = 7.3 Hz, H-
7'), 7.61 (d, 1 H, J = 0.6 Hz, H-2'), 7.69 (d, 1 H, J = 7.3 Hz, H-4'), 8.17
(s, 1 H, H-4).
1
IR, H and 13C NMR data were identical with those reported in the
literature.5
MS (70 eV): m/z (%) = 227 (M+, 6), 212 (5), 210 (100), 195 (10), 180
13C NMR (CD3OD): δ = 14.67 (CO2Et), 35.32 (C-2), 61.96 (CO2Et),
112.2 (Cq), 112.8 (C-4'), 119.1 (C-7'), 120.7 (Cq), 121.6 (C-5'), 123.8
(C-6'), 127.7 (C-2'), 129.1 (Cq), 134.8 (C-4), 137.6 (Cq), 170.0
(CO2Et), 175.2 (CO2H).
(6), 167 (39).
Murrayanine (3):
MS (70 eV): m/z (%) = 273 (M+, 89), 229 (79), 200 (48), 156 (29),
155 (100), 154 (88), 130 (35).
Oxidation of crude 4 (450 mg, 1.98 mmol) was performed according
to literature procedures.16b After stirring for 6 h, the mixture was con-
centrated by evaporating parts of the solvent and filtered through a
short silica gel column (CH2Cl2). The crude product was recrystal-
lized from EtOH/pentane to give 3 as reddish crystals; yield: 374 mg
(84%); mp 170°C (Lit.4, 6, 16b 168°C).
C15H15NO4 calcd
(273.3) found
C
65.92
65.68
H
5.53
5.55
N
5.13
5.09
Mukonine (1):
1
The mixture of 1-acetoxy-9-acetyl-3-ethoxycarbonylcarbazole and
1-acetyl-3-ethoxycarbonylcarbazole obtained above (together 8.00
mmol) and K2CO3 (3.32 g, 24.0 mmol) was refluxed in MeOH
(30 mL) for 4.5 h. After evaporation of the MeOH, the residue was
dissolved in acetone (30 mL), K2CO3 (1.11 g, 8.00 mmol) and DMS
IR, MS and H data were identical with those reported in the litera-
ture.6
13C NMR (acetone-d6): δ = 56.09 (OMe), 104.2 (C-2), 112.8 (C-8),
120.4 (C-4), 121.0 (C-6), 121.4 (C-5), 124.3 (Cq), 124.5 (Cq), 127.2
(C-7), 131.1 (Cq), 135.0 (Cq), 141.3 (Cq), 147.3 (C-1), 191.8 (CHO).

SYNTHESIS
Papers
1504
Demethylation with BBr3; General Procedure:
‘Molekulare Wechselwirkungen zwischen Targets und Naturstoffen’,
FKZ: 0310722). Furthermore, we want to thank Dr. R. Götz for help-
ful advice.
1 M BBr3 in CH2Cl2 (4 equiv) was added to a solution of methyl ether
1, 3 or 5 (1 equiv) in CH2Cl2 (1 mL per 100 µmol) at 0°C. After
stirring for 3 h at 0°C and over night at r.t., the solution was treated
with MeOH (2 mL per 100 µmol). The solvent was evaporated and
the residue was purified by passing through a short silica gel column
to yield crude products 6, 7 and 8, respectively.27
(1) (a) Chakraborty, D. P. In Prog. Chem. Org. Nat. Prod., Vol. 34;
Herz, W.; Grisebach, H.; Kirby, G. W.; Springer: Wien, 1977;
p 299.
(b) Bhattacharyya, P.; Chakraborty, D. P. In Prog. Chem. Org.
Nat. Prod., Vol. 52; Merz, W.; Grisebach, H.; Kirby, G. W.;
Tamm, C., Ed.; Springer: Wien, 1987; p 159.
(c) Chakraborty, D. P.; Roy, S. In Prog. Chem. Org. Nat. Prod.
Vol. 57; Merz, W.; Kirby, G. W.; Steglich, W.; Tamm, C., Ed.;
Springer: Wien, 1991; p 71.
Clausine E (6):
1 (100.0 mg, 392 µmol) was converted into 6 as described above (col-
umn chromatography, petroleum ether/CH2Cl2/MeOH 10:4:1); yield:
91.5 mg (97%). Recrystallization from acetone/pentane afforded 6 as
colorless crystals; mp 203°C (Lit.7 218–220°C).
Spectral data (IR, MS, H and 13C NMR) in accordance with those
1
(d) Kapil, R. S. In The Alkaloids, Vol. 13; Manske, R. H. F., Ed.;
Academic: New York, 1971; p 273.
were reported in the literature.7
(2) Chakraborty, D. P.; Bhattacharyya, P.; Roy, S.; Bhattacharyya,
S. P.; Biswas, A. K. Phytochemistry 1978, 17, 834.
(3) (a) Chowdhury, B. K.; Chakraborty, D. P. Chem. Ind. (London)
1969, 549.
(b) Chowdhury, B. K.; Chakraborty, D. P. Phytochemistry
1971, 10, 1967.
(4) Chakraborty, D. P.; Barman, B. K.; Bose, P. K. Tetrahedron
1965, 21, 681.
(5) Fiebig, M.; Pezzuto, J. M.; Soejarto, D. D.; Kinghorn, A. D.
Phytochemistry 1985, 24, 3041.
(6) Furukawa, H.; Wu, T.-S.; Ohta, T.; Kuoh, C.-S. Chem. Pharm.
Bull. 1985, 33, 4132.
(7) Wu, T.-S.; Huang, S.-C.; Wu, P.-L.; Teng, C.-M. Phytochemis-
try 1996, 43, 133.
O-Demethylmurrayanine (7):
3 (100 mg, 444 µmol) was converted into 7 as described above (col-
umn chromatography, petroleum ether/Et2O 1:1); yield: 84 mg
(90%). Recrystallization from acetone/pentane gave 7 as beige crys-
tals; mp 235°C (Lit.9 237–239°C).
1
Spectral data (IR, MS, H NMR) were in accordance with those re-
ported in the literature,9 except for the 13C NMR data, which were
attributed incorrectly in that publication.
13C NMR (acetone-d6): δ = 108.6 (C-2), 112.7 (C-8), 119.1 (C-4),
120.8 (C-6), 121.3 (C-5), 124.5 (Cq), 125.2 (Cq), 127.2 (C-7), 131.3
(Cq), 134.9 (Cq), 141.4 (Cq), 144.5 (C-1), 191.9 (CHO).
(8) Ito, C.; Katsuno, S.; Ohta, H.; Omura, M.; Kajiura, I.; Furuka-
wa, H. Chem. Pharm. Bull. 1997, 45, 48.
1-Hydroxy-3-methylcarbazole (8):
(9) Ngadjui, B. T.; Ayafor, J. F.; Sondengam, B. L.; Connolly, J. D.
Phytochemistry 1989, 28, 1517.
(10) Bhattacharyya, P.; Maiti, A. K.; Basu, K.; Chowdhury, B. K.
Phytochemistry 1994, 35, 1085.
5 (50.0 mg, 237 µmol) was converted into 8 as described above (col-
umn chromatography, petroleum ether/CH2Cl2/MeOH 10:2:1); yield:
44.8 mg (96%). Recrystallization from acetone/pentane gave 8 as col-
orless needles; mp 162°C (Lit.10 157–158°C).
(11) Chakraborty, D. P.; Das, K.; Das, B. P.; Chowdhury, B. K.
Trans. Bose Res. Inst., Calcutta 1975, 38, 1; Chem. Abstr. 1977,
86, 51029z.
(12) Das, K. C.; Chakraborty, D. P.; Bose, P. K. Experentia 1965, 21,
340.
IR (KBr): ν = 3360, 3020, 3000, 2940, 2900, 2835, 1615, 1595,
1570 cm–1.
1H NMR (acetone-d6): δ = 2.43 (s, 3 H, Me), 6.76 (d, 1 H, J = 0.8 Hz,
H-2), 7.13 (ddd, 1 H, J = 7.8/7.1/0.9 Hz, H-6), 7.35 (ddd, 1 H, J = 8.1/
7.1/1.2 Hz, H-7), 7.42 (s, 1 H, H-4), 7.54 (d, 1 H, J = 8.1 Hz, H-8),
8.02 (d, 1 H, J = 7.8 Hz, H-5), 8.59 (br s, 1 H, OH), 10.05 (br s, 1 H,
NH).
(13) (a) Sarma, M. Sci. Cult. 1976, 42, 285; Chem. Abstr. 1976, 85,
72096p.
13C NMR (acetone-d6): δ = 21.36 (Me), 112.0 (C-2), 112.3 (C-8),
112.7 (C-4), 119.3 (C-6), 120.9 (C-5), 124.3 (Cq), 126.0 (C-7), 129.6
(Cq), 134.0 (Cq), 141.2 (Cq), 143.5 (C-1).
(b) Sarma, M. Indian J. Exp. Biol. 1980, 18, 787; Chem. Abstr.
1980, 93, 198373k.
(14) Bringmann, G.; Ledermann, A.; Holenz, J.; Kao, M.-T.; Busse,
U.; Wu, H. G.; François, G. Planta Med. 1998, 64, 54.
(15) Bringmann, G.; Ledermann, A.; François, G. Heterocycles
1995, 40, 293.
MS (70 eV): m/z (%) = 197 (M+, 100), 196 (65), 168 (37), 167 (34).
(16) (a) Crum, J. D.; Sprague, P. W. J. Chem. Soc., Chem. Commun.
1966, 13, 417.
Mukoeic acid (2):
Saponification of 1 (70.0 mg, 274 µmol) was performed according to
literature procedures.3b, 19 Recrystallization from acetone/CH2Cl2/
pentane gave 2 as colorless crystals; yield: 65.2 mg (99%); mp 238–
239°C (Lit.3b 242°C).
(b) Chakraborty, D. P.; Chowdhury, B. K. J. Org. Chem. 1968,
33, 1265.
(17) Moody, C. J. Synlett 1994, 681; and references cited therein.
(18) (a) Knölker, H.-J.; Wolpert, M. Tetrahedron Lett. 1997, 38,
533; and references cited therein.
(b) Knölker, H.-J.; Bauermeister, M. Tetrahedron 1993, 49,
11221.
(19) El-Rayyes, N. R. J. Prakt. Chem. 1974, 316, 386.
(20) (a) Rizzacasa, M. A.; Sargent, M. V. Aust. J. Chem. 1987, 40,
1737.
IR and MS were in accordance with those reported in the literature.18b
1H NMR (acetone-d6): δ = 4.04 (s, 3 H, OMe), 7.23 (t, 1 H, J = 7.6 Hz,
H-6), 7.44 (t, 1 H, J = 7.6 Hz, H-7), 7.62 (d, 1 H, J = 7.6 Hz, H-8),
7.66 (s, 1 H, H-2), 8.18 (d, 1 H, J = 7.6 Hz, H-5), 8.55 (s, 1 H, H-4),
10.73 (br s, 1 H, NH).
13C NMR (acetone-d6): δ = 56.03 (OMe), 107.4 (C-2), 112.6 (C-8),
116.9 (C-4), 120.6 (C-6), 121.3 (C-5), 122.7 (Cq), 124.3 (Cq), 127.0
(C-7), 134.0 (Cq), 141.3 (Cq), 146.3 (C-1), 168.6 (CO2H).
(b) Tilve, S. G.; Tilve, A. S.; Desai, V. G. Synth. Commun.
1996, 26, 1921.
(21) Owton, W. M.; Gallagher, P. T.; Juan-Montesinos, A. Synth.
Commun. 1993, 23, 2119.
(22) Grehn, L.; Ragnarsson, U. Angew. Chem. 1984, 96, 291; Angew.
Chem., Int. Ed. Engl. 1984, 23, 296.
This work was supported by the Deutsche Forschungsgemeinschaft
(SFB 347 ‘Selektive Reaktionen Metall-aktivierter Moleküle’) and
the Bundesministerium für Bildung und Forschung (BMBF, project

SYNTHESIS
October 1998
1505
(23) (a) Bringmann, G.; Götz, R.; Harmsen, S.; Holenz, J.; Walter,
R. Liebigs Ann. Chem. 1996, 2045.
(25) Andreoli, P.; Cainelli, G.; Panunzio, M.; Bandini, E.; Martelli,
G.; Spunta, G. J. Org. Chem. 1991, 56, 5984.
(b) Boger, D. L.; McKie, J. A.; Cai, H.; Cacciari, B.; Baraldi, P.
G. J. Org. Chem. 1996, 61, 1710.
(26) Shin, C.-gi; Takahashi, N.; Yonezawa, Y. Chem. Pharm. Bull.
1990, 38, 2020.
(24) Further details of the structure investigation are available on re-
quest from the Cambridge Crystallographic Data Centre, on
quoting the depository number CCDC-101168, the names of the
authors and the journal citation.
(27) All 1-hydroxycarbazoles were just recrystallized in an analyti-
cal scale because all crude products were pure by 1H NMR and
recrystallization could only be achieved in low yields.