Total synthesis of (±)-brasiliquinone B

Article abstract of DOI:10.1016/S0040-4020(02)00740-8

The total synthesis of (±)-brasiliquinone B has been achieved via a Friedel-Crafts alkylation approach. In contrast, a Friedel-Crafts acylation approach for the synthesis of (±)-brasiliquinone B resulted in formation of A ring aromatized tetracyclic produ

Full text of DOI:10.1016/S0040-4020(02)00740-8

Tetrahedron 58 (2002) 6615–6620
Total synthesis of (6)-brasiliquinone B
*
Mahesh L. Patil, Hanumant B. Borate, Datta E. Ponde and Vishnu H. Deshpande
National Chemical Laboratory, Dr Homi Bhabha Road, Pune 411 008, India
Received 15 January 2002; revised 5 June 2002; accepted 27 June 2002
Abstract—The total synthesis of (^)-brasiliquinone B has been achieved via a Friedel–Crafts alkylation approach. In contrast, a Friedel–
Crafts acylation approach for the synthesis of (^)-brasiliquinone B resulted in formation of A ring aromatized tetracyclic products. q 2002
Published by Elsevier Science Ltd.
1. Introduction
(2) via Friedel–Crafts alkylation and Friedel–Crafts
acylation approaches.
Brasiliquinones A–C1,2 are cytotoxic benz[a ]anthra-
quinone antibiotics isolated from the pathogenic species of
Nocardia of the strain IFM 0089. Brasiliquinones belong to
a large group of antibiotics commonly called angucyclines.
As a special feature, brasiliquinones A–C possess an ethyl
group at C-3 whereas all other angucyclines reported
possess a methyl group at C-3.
2. Results and discussion
Our synthetic route for the synthesis of (^)-brasiliquinone
B (2) was based on the Friedel–Crafts acylation of
functionalised AB ring synthon 5 and its condensation
with D ring synthon 4 for the construction of ring C as
shown in Scheme 1. The most appropriate D ring synthon
was considered to be acid chloride 4,6 which has been
widely used in the syntheses of anthracyclines.
Although the key intermediate tetralin 5 looked structurally
simple it has not been reported in literature. We undertook
synthesis of this substituted tetralin 5 starting from
commercially available 7-methoxy-1-tetralone (Scheme 2).
7-Methoxy-1-tetralone (6) was acylated using acetic
anhydride and boron trifluoride etherate at room tempera-
ture followed by treatment with sodium acetate in refluxing
methanol to give 2-acetyl-7-methoxy-1-tetralone (7) in 65%
Brasiliquinones A–C showed a remarkable antitumour
activity along with very good antiviral and antimicrobial
activities. In vitro antitumor activity of brasiliquinones
against L1210 and P388 proved brasiliquinones B (2) and C
(3) more effective than brasiliquinone A (1). Previously we
have reported the first total synthesis of (^)-brasiliquinone
B (2)3 using a Friedel–Crafts alkylation as the key step.
Subsequently Mal et al.4 reported syntheses of (^)-
brasiliquinone B (2) and C (3) involving phthalide
annulation and photooxygenation as the key steps. Krohn
et al.5 used a boron triacetate mediated Diels–Alder
reaction for the synthesis of (^)-6-deoxybrasiliquinone
B. We describe herein our synthesis of (^)-brasiliquinone B
Keywords: antitumor; antibiotics; Friedel–Crafts reaction; regiospecificity.
*
Corresponding author. Tel.: þ91-20-5893300x2284; fax: þ91-20-
5893614; e-mail: vhdesh@dalton.ncl.res.in
Scheme 1. Retrosynthetic plan for brasiliquinone B (2).
0040–4020/02/$ - see front matter q 2002 Published by Elsevier Science Ltd.
PII: S0040-4020(02)00740-8

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M. L. Patil et al. / Tetrahedron 58 (2002) 6615–6620
aim was to cyclize the compound 9 and further oxidize it to
give the desired dimethyl ether of brasiliquinone B.
Accordingly cyclization of the compound 9 was attempted
using boric acid and sulfuric acid7 but surprisingly it
resulted in formation of A ring aromatized tetracyclic
products, the members of tetrangulol group of angucycline
antibiotics8 (Scheme 4). Careful examination of the 1H
NMR spectrum of the reaction product suggested formation
of the mixture of regioisomers 10aþ10b possessing one
methoxy group and one hydroxyl group which could not be
separated while compound 11 had hydroxyl groups at C-6
and C-8 positions. Decreasing the temperature and time of
the reaction also resulted in the same products. Cyclization
was also attempted with sulfuric acid alone at 808C, which
resulted in the cyclized and aromatized product 12 having
both methoxy groups intact. The structure of compound 11
was established with the help of spectral data. Shifting of the
triplet of methyl protons from d 0.97–1.39 and appearance
of a quartet at d 2.82 indicated the presence of an aromatic
ethyl group as well as singlets at d 12.20 and 12.38
suggested the presence of chelated –OH groups.
Scheme 2. Synthesis of tetralin derivative 5.
Scheme 3. Acylation of tetralin derivative 5.
yield. Hydrogenation of the compound 7 using 10% Pd/C
and HCl in methanol followed by Clemmensen’s reduction
afforded desired tetralin derivative 5.
2.1. Friedel–Crafts acylation approach for the synthesis
of (6)-brasiliquinone B
In the literature, angucyclines possessing aromatic A rings
have been reported. Tetrangulol, an angucycline antibiotic
possessing an aromatic A ring was isolated by Kunstman8–9
and synthesized by Brown and Thomson10 using a Michael
reaction. The compounds obtained in the present work are
novel analogues of brasiliquinone B belonging to the
tetrangulol type of angucyclines. Although the attempted
Friedel–Crafts acylation approach to brasiliquinone B
resulted in the synthesis of new tetrangulol type of the
angucyclines, the synthesis of natural product remained as a
challenge.
After synthesis of the AB ring synthon, we explored the use
of a Friedel–Crafts acylation approach for the construction
of the C ring of the angularly fused tetracyclic skeleton. The
tetralin derivative 5 on Friedel–Crafts acylation with
benzoyl chloride 4 in the presence of aluminium chloride
yielded acylated product 9 in 70% yield as shown in
Scheme 3.
1
The H NMR spectrum of 9 revealed two singlets, each
integrating for one proton at d 6.58 and 7.68 indicating
regioselectivity in the acylation reaction. Our immediate
Scheme 4. Cyclization of the compound 9.

M. L. Patil et al. / Tetrahedron 58 (2002) 6615–6620
6617
4. Experimental
4.1. General
1H and 13C NMR spectra were recorded on Bruker AC-200
spectrometer in CDCl3 containing TMS as an internal
standard. Infrared spectra (nmax in cm21) were recorded as
either nujol mull or in CHCl3 on Perkin–Elmer Infra-red
683 B or 160S FT-IR spectrometer with sodium chloride
optics. All solvents and reagents were purified and dried by
standard procedures. TLC was carried out on silica gel
plates prepared by spreading the slurry (in CCl4) and drying
at room temperature. The plates were analyzed by keeping
in iodine chamber. Column chromatography was performed
on silica gel (60–120 mesh). Petroleum ether refers to the
fraction boiling in the range of 60–808C.
Scheme 5. Friedel–Crafts alkylation approach for (^)-brasiliquinone B.
4.1.1. 2-Acetyl-7-methoxy-1-tetralone (7). BF3-etherate
(7.5 mL) was added dropwise to a stirred mixture of
7-methoxy-1-tetralone (2.5 g, 0.014 mol) in acetic
anhydride (25 mL). The dark brown solution was then
stirred at room temperature for 2 h. It was then poured into
ice-water (250 mL), stirred for 1 h, filtered and the residue
was dissolved in methanol (150 mL). A saturated solution of
sodium acetate (100 mL) was added to it, followed by
refluxing for 4 h. The methanol was removed by distillation
and the solution was extracted with chloroform (3£50 mL).
The chloroform layer was washed successively with water
(50 mL) and brine (50 mL) and dried over sodium sulfate.
Evaporation of the solvent followed by purification by
column chromatography (20% EtOAc/petroleum ether)
afforded 7 as yellow solid (2 g, 65%); mp 60–628C. IR
(CHCl3): 3300, 1640 cm21. 1H NMR (CDCl3, 200 MHz): d
2.25 (s, 3H, COCH3), 2.55–2.65 (m, 2H), 2.75–2.90 (m,
2H), 3.85 (s, 3H, –OMe), 6.92–7.20 (m, 2H, aromatic),
7.45 (s, 1H, aromatic), 16.45 (s, 1H, enolic –OH). Mass
(m/z): 218 (Mþ). Anal. calcd for C13H14O3: C 71.55, H
6.42; Found C 71.35, H 6.60.
2.2. Friedel–Crafts alkylation approach for the
synthesis of (6)-brasiliquinone B
Johnson et al.11 introduced a phthalido-residue into the
aromatic nucleus by a Friedel–Crafts reaction of an
appropriate AB ring synthon with 3-bromo-4-methoxy-
phthalide (13)11 in the presence of stannic chloride. It was
thought to utilize this approach for the construction of the
benz[a ]anthraquinone structural framework. Friedel–
Crafts alkylation of tetralin 5 with 3-bromo-4-methoxy-
phthalide (13) in the presence of stannic chloride in
dichloromethane at 08C afforded regiospecifically the
lactone 14 in 84% yield as shown in Scheme 5. The lactone
14 underwent smooth reductive opening12 with zinc in 1 M
sodium hydroxide, pyridine, and cupric sulfate under reflux
for 10 h to give acid 15 in 85% yield. Cyclization of the acid
15 to the anthrone 16 was achieved effectively under mild
conditions using trifluoroacetic anhydride in dichloro-
methane. Our next target was to oxidize the anthrone 16
to the dimethyl ether of brasiliquinone B (17). The desired
oxidation was carried out under chromium trioxide–acetic
acid conditions to afford the compound 17 in 93% yield.
Finally the desired synthesis of (^)-brasiliquinone B (2)
was achieved by demethylating the dimethyl ether of
brasiliquinone B (17) using aluminum chloride in 80%
yield. This compound was characterized by IR, 1H
NMR and mass spectra. All spectral data for compound 2
were in good agreement with the values reported in
literature.1–2
4.1.2. 2-Acetyl-7-methoxytetralin (8). 2-Acetyl-7-meth-
oxy-1-tetralone (2.2 g, 10 mmol) was dissolved in methanol
(50 mL), followed by addition of conc. HCl (1 mL) and
water (1 mL). 10% Pd/C (0.5 g) was then added to it and the
mixture was subjected to hydrogenation at 50 psi pressure
for 8 h. The mixture was filtered through Celite and
methanol was removed from the filtrate under reduced
pressure. The oily residue obtained was extracted with
chloroform (3£25 mL). The combined organic layer was
washed with water (30 mL), brine (30 mL) and dried over
sodium sulfate. Evaporation of the solvent and purification
of the residue by column chromatography (15% EtOAc/
petroleum ether) yielded compound 8 as a colourless liquid
3. Conclusion
1
(1.2 g, 60%). IR (CHCl3): 1690 cm21. H NMR (CDCl3,
200 MHz): d 1.60–1.78 (m, 2H), 2.15–2.22 (m, 1H), 2.25
(s, 3H, COCH3), 2.70–2.80 (m, 2H), 2.90–2.98 (m, 2H),
3.79 (s, 3H, –OMe ), 6.61 (s, 1H, aromatic), 6.70 (d,
J¼8 Hz, 1H, aromatic), 7.00 (d, J¼8 Hz, 1H, aromatic).
Mass (m/z): 204 (Mþ). Anal. calcd for C13H16O2: C 76.47,
H 7.84; Found C 76.23, H 7.95.
Thus a short, simple and regioselective methodology has
been developed for the total synthesis of (^)-brasiliquinone
B using a Friedel–Crafts alkylation approach. Although the
Friedel–Crafts acylation approach failed to give brasili-
quinone B, it can be utilized for the synthesis of tetrangulol
analogues. This method of synthesis of the angucyclines is
regioselective and would prove to be a convenient route
towards the synthesis of other angucycline antibiotics,
especially angucyclines possessing a hydroxy group at C-6
position.
4.1.3. 2-Ethyl-7-methoxy-1,2,3,4-tetrahydronaphthalene
(5). Zinc wool (7 g), mercuric chloride (0.7 g), conc. HCl
(2 mL) and water (10 mL) were mixed together with stirring

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M. L. Patil et al. / Tetrahedron 58 (2002) 6615–6620
for 10 min. The aqueous layer was decanted and the residue
was washed with water (2£50 mL). 2-Acetyl-7-methoxy
tetralin (2.3 g, 14.70 mmol) in toluene (20 mL) was added
to above prepared zinc amalgam, followed by concentrated
HCl (5 mL). After cooling, water (5 mL) was added and the
mixture was refluxed for 12 h. Then the mixture was filtered
through Celite, the toluene layer was separated and washed
with water (25 mL), brine (25 mL) and dried over sodium
sulfate. Removal of the toluene under reduced pressure and
purification of the residue by column chromatography (10%
EtOAc/petroleum ether) afforded compound 5 as colourless
7.38 (t, J¼7.8 Hz, 1H, aromatic), 7.47 (d, J¼7.8 Hz, 1H,
aromatic), 7.61 (s, 1H, aromatic), 7.68 (d, J¼7.8 Hz, 1H,
aromatic), 7.85 (d, J¼7.8 Hz, 1H, aromatic), 9.50 (d,
J¼7.8 Hz, 1H, aromatic), 12.20 (s, 1H, –OH), 12.38 (s,
1H, –OH). Mass (m/z): 318 (Mþ).
4.2.2. Compound 10a110b. Yield: 97 mg (30%). 1H NMR
showed inseparable mixture of regioisomers 10a and 10b.
1H NMR (CDCl3, 200 MHz): d 1.30–1.45 (m, 6H, –CH3),
2.70–2.90 (m, 4H, –CH2CH3), 4.08 (s, 3H, –OMe), 4.10 (s,
3H, –OMe), 7.20–7.80 (m, 11H, aromatic), 7.95 (d,
J¼7.8 Hz, 1H, aromatic), 9.00 (d, J¼7.8 Hz, 1H, aromatic),
9.45 (d, J¼7.8 Hz, 1H, aromatic), 12.20 (s, 1H, –OH),
12.70 (s, 1H, –OH). Mass (m/z): 332 (Mþ).
liquid (2.1 g, 77%). IR (CHCl3): 1608 cm21 1H NMR
.
(CDCl3, 200 MHz): d 1.00 (t, J¼7.3 Hz, 3H), 1.35–1.50 (m,
3H), 1.52–1.75 (m, 1H), 1.80–2.05 (m, 1H), 2.15–2.55 (m,
2H), 2.65–2.95 (m, 2H), 3.90 (s, 3H, –OMe), 6.55–6.80
(m, 2H, aromatic), 7.00 (d, J¼7.8 Hz, 1H, aromatic). Mass
(m/z): 190 (Mþ). Anal. calcd for C13H18O: C 82.10, H 9.47;
Found C 82.00, H 9.52.
4.2.3. Compound 12. A mixture of ester 9 (382 mg,
1 mmol) and conc. H2SO4 (2 mL) was heated at 808C for
30 min with stirring. The reaction mixture was cooled and
poured over crushed ice (5 g). The dark brown aqueous part
was extracted with chloroform (3£20 mL) and chloroform
layer was washed successively with saturated solution of
sodium bicarbonate (10 mL), water (10 mL), brine (10 mL)
and dried over sodium sulfate followed by column
chromatographic purification (10% EtOAc/petroleum
ether) to afford 12 (155 mg, 45%) as reddish foam. 1H
NMR (CDCl3, 200 MHz): d 1.38 (t, J¼7.5 Hz, 3H, –CH3),
2.75–2.95 (m, 2H, –CH2CH3), 4.05 (s, 3H, –OMe), 4.08 (s,
3H, –OMe), 7.25 (d, J¼7.6 Hz, 1H, aromatic), 7.48 (s, 1H,
aromatic), 7.52 (d, J¼7.6 Hz, 1H, aromatic), 7.58 (s, 1H,
aromatic), 7.65 (t, J¼7.6 Hz, 1H, aromatic), 7.78 (d,
J¼7.6 Hz, 1H, aromatic), 8.95 (d, J¼7.6 Hz, 1H, aromatic).
Mass (m/z): 346 (Mþ).
4.1.4. 3-Ethyl-6-methoxy-7-(20-carbomethoxy-60-meth-
oxybenzoyl)-1,2,3,4-tetrahydronaphthalene (9). The
compound 5 (380 mg, 2 mmol) in dry dichloromethane
(5 mL) under a nitrogen atmosphere, was cooled to 08C.
Anhydrous aluminum chloride (400 mg, 3 mmol) was
added to it slowly and allowed to stir for 15 min. The acid
chloride 4 (456 mg, 2 mmol) in dry dichloromethane (5 mL)
was added dropwise to the above reaction mixture at 08C.
The resulting mixture was allowed to stir at 08C for 30 min
and at room temperature overnight. After completion of
reaction (TLC), the reaction mixture was poured on the
mixture of crushed ice (5 g) and conc. HCl (2 mL), allowed
to stir for 10 min and extracted with dichloromethane
(3£20 mL). The combined organic layer was washed with
water (20 mL), brine (20 mL) and dried over sodium sulfate.
Evaporation of the solvent followed by column chromato-
graphic purification (20% EtOAc/petroleum ether) yielded
compound 9 as a colourless semisolid (535 mg, 70%). IR
(CHCl3): 1700, 1750 cm21. 1H NMR (CDCl3, 200 MHz): d
0.99 (t, J¼7.0 Hz, 3H), 1.30–1.50 (m, 3H), 1.51–1.80 (m,
2H), 1.89–2.00 (m, 1H), 2.30–2.55 (m, 1H), 2.65–2.97 (m,
2H), 3.50 (s, 3H, –OMe), 3.72 (s, 3H, –OMe), 3.75 (s, 3H,
–CO2Me), 6.58 (s, 1H, aromatic), 7.10 (d, J¼8.1 Hz, 1H,
aromatic), 7.40 (t, J¼8.1 Hz, 1H, aromatic), 7.62 (d,
J¼8.1 Hz, 1H, aromatic), 7.68 (s, 1H, aromatic). Mass
(m/z): 382 (Mþ). Anal. calcd for C23H26O5: C 72.23, H
6.85; Found C 72.27, H 6.92.
4.2.4. 3-(6-Ethyl-3-methoxy-5,6,7,8-tetrahydro-2-
napthalenyl)-4-methoxy-1 (3H)-isobenzofuranone (14).
The tetralin derivative 5 (570 mg, 3 mmol) was added to a
stirred solution of 3-bromo-4-methoxyphthalide (1.1 g,
45 mmol) in dichloromethane (10 mL) at 08C. Stannic
chloride (6.5 g, 0.252 mol) was then introduced and the
resulting mixture was stirred at 08C for 1 h. It was then
poured on the mixture of crushed ice (10 g) and conc. HCl
(3 mL), stirred for 30 min and extracted with dichloro-
methane (25 mL). The combined dichloromethane layer
was washed with water (20 mL), brine (20 mL) and dried
over sodium sulfate. Evaporation of the solvent and
purification by column chromatography (30% EtOAc/
petroleum ether) afforded compound 14 (887 mg, 84%) as
a white solid; mp 132–1338C. IR (Nujol): 1745 (lactone),
4.2. Cyclization of compound 9
1596 cm21 1H NMR (CDCl3, 200 MHz): d 0.99 (t,
.
A mixture of ester 9 (382 mg, 1 mmol), conc. H2SO4 (2 mL)
and boric acid (100 mg) was heated at 1208C for 1.5 h with
stirring. The reaction mixture was cooled and poured over
crushed ice (5 g). The dark brown aqueous part was
extracted with chloroform (3£20 mL) and the chloroform
layer was washed successively with saturated solution of
sodium bicarbonate (20 mL), water (20 mL), brine (20 mL)
and dried over sodium sulfate followed by column chromato-
graphic purification (5–10% EtOAc/petroleum ether) to
afford compounds (10aþ10b) and 11 as reddish foam.
J¼7.3 Hz, 3H), 1.22–1.49 (m, 3H), 1.50–1.65 (m, 1H),
1.80–1.99 (m, 1H), 2.30–2.51 (m, 1H), 2.55–2.65 (m, 2H),
2.75–2.92 (m, 1H), 3.75 (s, 3H, –OMe), 3.80 (s, 3H,
–OMe), 6.50 (s, 1H, aromatic), 6.62 (s, 1H, phthalide), 6.75
(s, 1H, aromatic), 7.00–7.15 (m, 1H, aromatic), 7.45–7.58
(m, 2H, aromatic). 13C NMR (CDCl3, 50 MHz): d 11.94,
28.81, 29.69 (2C), 36.31 (2C), 36.79, 56.27, 56.42, 112.32,
115.93, 117.47, 121.59, 128.94, 129.45, 131.44, 137.80,
139.86 (2C), 155.11, 156.43, 171.36. Mass (m/z): 352 (Mþ).
Analysis calculated for C22H24O4: C 75.00, H 6.81; Found C
74.52, H 6.36.
4.2.1. Compound 11. Yield: 111 mg (35%). 1H NMR
(CDCl3, 200 MHz): d 1.39 (t, J¼7.8 Hz, 3H, –CH2CH3),
2.82 (q, J¼7.8 Hz, 2H, –CH2CH3), 7.30 (s, 1H, aromatic),
4.2.5. 2-{(6-Ethyl-3-methoxy-5,6,7,8-tetrahydro-2-
naphthalenyl)methyl}-3-methoxybenzoic acid (15). The

M. L. Patil et al. / Tetrahedron 58 (2002) 6615–6620
6619
lactone 14 (704 mg, 2 mmol) was reductively opened by
heating with 1 M solution of NaOH (40 mL), activated zinc
(3.7 g, 58 mmol), CuSO4·5H2O (50 mg, 0.2 mmol) and
pyridine (10 mL) at 1258C for 10 h under a nitrogen
atmosphere. The mixture was then allowed to cool and
filtered through a pad of Celite. Acidification of the filtrate
with concentrated HCl (15 mL) afforded the corresponding
acid 15 (600 mg, 85%) as a white solid; mp 198–2008C. IR
brine (10 mL) and dried over sodium sulfate. Evaporation of
the solvent under reduced pressure followed by column
chromatographic purification (20% EtOAc/petroleum ether)
afforded compound 17 (37 mg, 93%) as a yellow coloured
semisolid. IR (nujol): 1705 (ketone), 1675 (quinone),
1595 cm21 1H NMR (CDCl3, 200 MHz): d 1.00 (t,
.
J¼7.3 Hz, 3H), 1.40–1.65 (m, 3H), 2.35- 2.75 (m, 2H),
2.85–3.05 (m, 2H), 3.97 (s, 3H, –OMe), 4.00 (s, 3H,
–OMe), 6.90 (s, 1H, aromatic), 7.20–7.32 (m, 1H,
aromatic), 7.60–7.75 (m, 2H, aromatic). 13C NMR
(CDCl3, 50 MHz): d 11.64, 29.18, 37.26, 37.52, 45.98,
56.97, 57.19, 115.15, 117.69, 118.90, 124.45, 127.87,
134.86, 137.47, 139.97, 151.32, 159.26, 161.51, 117.64,
182.35, 186.83, 198.63. Mass (m/z): 364 (Mþ, 12), 350 (20),
335 (55), 321 (22), 306 (25). Anal. calcd for C22H20O5: C
72.52, H 5.49; Found C 72.70, H 5.20.
(Nujol): 3450, 1609 cm21
.
1H NMR (acetone-d6,
200 MHz): d 0.86 (t, J¼7.3 Hz, 3H), 1.11–1.36 (m, 3H),
1.37–1.56 (m, 1H), 1.62–1.86 (m, 1H), 2.16–2.38 (m, 1H),
2.44–2.56 (m, 2H), 2.58–2.64 (br s, 1 H), 2.66–2.68 (m,
1H), 3.71 (s, 6H, 2£OMe), 4.26 (s, 2H benzylic), 6.38 (s, 1H
aromatic), 6.44 (s, 1H aromatic), 6.96 (d, J¼8.1 Hz, 1H
aromatic), 7.21 (t, J¼8.1 Hz, 1H aromatic), 7.42 (d,
J¼8.1 Hz, 1H aromatic). 13C NMR (acetone-d6, 50 MHz):
d 11.87, 25.96, 28.53, 29.19, 36.06, 40.95, 41.36, 55.65,
56.35, 110.83, 114.32, 122.00, 126.78, 127.70, 128.58,
134.65 (2C), 155.45, 158.57, 164.19, 170.92, 175.96. Mass
(m/z): 354 (Mþ). Anal. calcd for C22H26O4: C 74.57, H
7.34; Found C 74.20, H 7.17.
4.2.8. (6)-Brasiliquinone B (2). To the solution of
brasiliquinone dimethyl ether (17) (36 mg, 0.098 mmol) in
dichloromethane (5 mL) was added anhydrous aluminum
chloride (50 mg, 0.38 mmol) at 08C. The mixture was
stirred for 2 h and allowed to warm up to room temperature.
The reaction mixture was stirred at room temperature for
12 h. It was then poured into a mixture of crushed ice (3 g)
and conc. HCl (2 mL) and digested on water bath for
20 min. After cooling to room temperature, it was extracted
with dichloromethane (3£20 mL). The combined dichloro-
methane part was dried over sodium sulfate and concen-
trated to afford a residue which on column chromatographic
purification (25% EtOAc/petroleum ether) yielded (^)-
brasiliquinone B (2) (26 mg, 80%) as a yellow solid; mp
187–1918C. IR (CHCl3): 3435, 1980, 1690, 1640 cm21. 1H
NMR (CDCl3, 200 MHz): d 1.00 (t, J¼7.3 Hz, 3H), 1.40–
1.80 (m, 2H), 2.00–2.20 (m, 1H), 2.35–2.70 (m, 2H), 2.90–
3.08 (m, 2H), 7.02 (s, 1H, aromatic), 7.22–7.32 (m, 1H,
aromatic), 7.60–7.7.75 (m, 2H, aromatic), 11.70 (s, 1H,
chelated –OH), 12.30 (s, 1H, chelated –OH). Mass (m/z ):
337 (Mþ1, 26), 336 (Mþ, 38), 308 (55), 280 (100). Anal.
calcd for C20H16O5: C 71.42, H 4.76; Found C 71.50, H
5.00.
4.2.6. 6,8-Dimethoxy-3-ethyl-1,2,3,4,7-pentahydro-
benz[a]-anthracene-12(1H )-one (16). The acid 15
(495 mg, 14 mmol) in dry dichloromethane (15 mL) was
cooled to 08C, and freshly distilled trifluoroacetic anhydride
(5 mL) was added to it under a nitrogen atmosphere. The
mixture was allowed to stir at 08C for 30 min and the stirring
was continued overnight at room temperature. The trifluoro-
acetic anhydride and dichloromethane were removed under
reduced pressure and saturated solution of potassium
carbonate (20 mL) was added to it. This mixture was
extracted with chloroform (3£30 mL). The combined
chloroform layer was washed with water (20 mL) and
brine (20 mL), followed by drying over sodium sulfate and
evaporation of the chloroform to yield yellow coloured
crude anthrone 16. Its purification by column chromato-
graphy (18% EtOAc/petroleum ether) yielded anthrone 16
(300 g, 64%) as a pale yellow solid; mp 220–2228C. IR
(Nujol): 1660 (ketone), 1597 cm21 1H NMR (CDCl3,
.
200 MHz): d 1.02 (t, J¼7.3 Hz, 3H), 1.21–1.50 (m, 2H),
1.51–1.78 (m, 1H), 1.99–2.12 (m, 1H), 2.40–2.60 (m, 1H),
2.95–3.00 (m, 2H), 3.12–3.35 (m, 1H), 3.43–3.62 (m, 1H),
3.78–4.18 (m, 2H, benzylic), 3.90 (s, 3H, OMe), 3.95 (s,
3H, –OMe), 6.80 (s, 1H, aromatic), 7.05 (d, J¼8.1 Hz, 1H,
aromatic), 7.40 (t, J¼8.1 Hz, 1H, aromatic), 7.85 (d,
J¼8.1 Hz, 1H, aromatic). 13C NMR (CDCl3, 50 MHz): d
11.80, 22.50, 28.80, 30.00 (2C), 34.90, 36.95, 55.50 (2C),
111.80, 114.00, 118.50, 126.80, 128.80, 129.00, 130.90,
132.80, 135.00, 136.90, 153.50, 156.50, 186.90. Mass
(m/z): 336 (Mþ, 100), 332 (15), 321 (30), 307 (40). Anal.
calcd for C22H24O3: C 78.52, H 7.19; Found C 78.60, H
7.17.
Acknowledgments
M. L. P. thanks CSIR, New Delhi for the award of senior
research fellowship.
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