Total synthesis of angucyclines. Part 15: A short synthesis of (±)-6- deoxybrasiliquinone B

Article abstract of DOI:10.1016/S0040-4020(00)00398-7

The 6-deoxybrasiliquinones 2 and 14a were prepared by a boron triacetate mediated Diels-Alder reaction of juglone (9) with the crude mixture of ethoxy dienes 6 and 7. The primary non-aromatic Diels-Alder product 10 was isolated after reaction of the dienol 8 with 9. Dimethyldioxirane oxidation of 10 afforded the epoxide 11. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(00)00398-7

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 4753±4758
Total Synthesis of Angucyclines. Part 15:1 A Short Synthesis of
(^)-6-Deoxybrasiliquinone B
*
Karsten Krohn, Jorg Micheel and Mariola Zukowski
È
È
Fachbereich Chemie und Chemietechnik, Universitat Paderborn, Warburger Strasse 100, D-33098 Paderborn, Germany
Received 27 March 2000; accepted 15 May 2000
AbstractÐThe 6-deoxybrasiliquinones 2 and 14a were prepared by a boron triacetate mediated Diels±Alder reaction of juglone (9) with the
crude mixture of ethoxy dienes 6 and 7. The primary non-aromatic Diels±Alder product 10 was isolated after reaction of the dienol 8 with 9.
Dimethyldioxirane oxidation of 10 afforded the epoxide 11. q 2000 Published by Elsevier Science Ltd.
Introduction
to the vinyl bromide 5 was best achieved by treatment with
oxalyl bromide according to a protocol of Mewshaw11
(Scheme 1). Anderson and Hallberg have previously
investigated the palladium-catalyzed vinylation of alkyl
vinyl ethers with enol tri¯ates and vinyl bromides.12 In
most cases, the 2-alkoxy 1,3-dienes were the major
products. By contrast, with bromocyclohexanones similar
to 5, the b-addition products such as 7 predominated over
The brasiliquinones were isolated from the actinomycete
Nocardia brasiliensis.2 They represent the ®rst angucycli-
nones3,4 with an ethyl side chain instead of the usual methyl
group at C-3 on ring A of the benzo[a]anthraquinone
skeleton as shown in ochromycinone (3) (Fig. 1). Thus,
their polyketide biosynthesis probably involves a propionate
starter unit, similar as postulated for the majority of the
anthracycline antitumor antibiotics.5,6 The brasiliquinones
show activity against Gram-positive bacteria including
Mycobacterium sp. and are also active against multiple
drug-resistant P388/ADR tumor cells.
Recently, two syntheses of brasiliquinones B (1) were
published which were both based on disconnection `a' as
shown in Fig. 1. In the approach of Deshpande et al.7 a
Friedel±Crafts type reaction was used, whereas Mal and
Roy8 employed the anionic Michael type anellation
strategy. We now disclose a very short synthesis via dis-
connection `b', using the Diels±Alder reaction of juglone
(9) with the 1-ethoxy diene (8). In addition, we wanted to
study the possibility to arrive at non-aromatic derivatives of
1 for further functional group manipulations.
Figure 1. Structures of brasiliquinones 1 and 2 and ochromycinone (3).
Results and Discussion
For the construction of diene 7, a Heck reaction of a vinyl
halide and vinyl ethyl ether was envisaged. The required
5-ethyl-1,3-cyclohexanedione (4)9 was prepared by conden-
sation of acetoacetate with ethyl 2-pentenoate analogous to
a procedure of Szychowski and MacLean.10 Conversion of 4
Keywords: Diels±Alder reaction; boron triacetate; angucycline antibiotics;
brasiliquinones; dimethyldioxirane oxidation.
* Corresponding author. Tel.: 15251-602172; fax: 15251-603245;
e-mail: kk@chemie.uni-paderborn.de
Scheme 1. Synthesis of the cyclic dienes 6±8 for the Diels±Alder reaction
with juglone (9).
0040±4020/00/$ - see front matter q 2000 Published by Elsevier Science Ltd.
PII: S0040-4020(00)00398-7

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K. Krohn et al. / Tetrahedron 56 (2000) 4753±4758
epoxide 11 to 1508C. A ring opening to the aldehyde 13 was
observed to occur in 57% yield. At least three bonds are
broken in this reaction which was also observed by Larsen et
al. in a related case.14 Tricyclic rearrangement products
have also been found to occur with natural products such
as aquayamycin.22
In a second Diels±Alder reaction, the mixture of the keto
dienes 6 and 7 was treated with juglone (9). Both the diene
and the dienophile are electron-de®cient and such reactions
are known to proceed very sluggishly. High pressure con-
ditions are the normal solution to the problem due to the
negative activation volume of Diels±Alder reactions.
However, Guingant and Barreto found that boron triacetate
also effectively catalyzes this reaction in related cases.23
Under the boron triacetate catalyzed conditions, the primary
Diels±Alder adduct A cannot be isolated but undergoes
rapid elimination of ethanol followed by isomerization
and air oxidation to the 1-keto quinone 2 (6-deoxbrasiliqui-
none, 50% yield, Scheme 3). In addition, a polar minor
product 14a of very low solubility resulting from reaction
of juglone (9) with the 2-ethoxy diene 6 via intermediate B
was isolated in 7% yield. A non-chelated phenolic group
was easily established in 14a by analysis of the mass spec-
trum and selective mono-acetylation to 14b inducing the
Scheme 2. Diels±Alder reaction of juglone (9) with hydroxy diene (8) and
functional group transformations of adduct 10.
1
expected low®eld shift of the 6-H signal in the H NMR
spectrum.
the 2-ethoxy dienes 6 (ratio 7:6 ca. 6:1).12 The pure
E-isomer of 7 could be isolated after chromatographic
separation from 6 as deduced from the large coupling
The remaining question was the location of the chelated
phenolic hydroxyl group in 14a at C-8 or C-11. Experi-
mental evidence in uncatalized reactions of juglone with
2-alkoxysubstituted dienes24±27 and also theoretical frontier
orbital considerations28 suggested the formation of an
11-hydroxy angucyclinone. However, using the carbonyl
1
constant of 12.8 Hz in the H NMR spectrum. The allylic
alcohol 8, which was also required for Diels±Alder
reactions, could be prepared by LAH reduction of 7 to afford
stereoselectively the 1,5-cis alcohol 8.
The reaction of the electron-rich diene 8 with juglone 9 was
studied ®rst. Larsen et al.13,14 and also Sulikowski et al.15
previously used similar hydroxy dienes. In subsequent steps,
the hydroxyl group at C-1 in the products was then oxidized
to a carbonyl group present in most angucyclines. The boron
triacetate catalyzed reaction of 8 with juglone 9 proceeded
at 08C in a short time to afford the non-aromatic adduct 10 in
71% yield (Scheme 2). The ole®n 10 was selectively
converted to the all-cis epoxide 11 by treatment at 08C
with dimethyldioxirane. The quinoide double bond was
not attacked under these mild conditions. Both derivatives
10 and 11 are thus easily accessible starting materials for
non-aromatic angucyclines.16
In the present study, we also wanted to investigate the
thermal and chemical stability of the epoxide 11. Treatment
of 11 with the mild Lewis acid boron triacetate afforded the
aromatized acetate 12 in modest (23%) yield. Interestingly,
in addition to elimination, the acetylation of the benzylic
hydroxyl group in the presence of boron triacetate had
occurred. The intermediate alcohol obtained by saponi®ca-
tion of 12 was then converted to 6-deoxybrasiliquinone (2)
by photoxidation with diffuse sunlight. This remarkably
mild oxidation reaction was discovered in our laboratory
during the synthesis of a daunomycinone/rabelomycinone
hydride17 (compare18) and is now frequently used as a
reaction in the last step of angucycline syntheses.8,19±21
Scheme 3. Diels±Alder reaction of juglone (9) with the keto dienes 6 and 7
to yield the brasiliquinones 2 and 14a.
Another interesting reaction was discovered by heating the

K. Krohn et al. / Tetrahedron 56 (2000) 4753±4758
4755
Figure 2. Crystal structure of 14b.
substituted 2-ethoxy diene 6 in a boron triactetate-catalyzed
reaction, the 5,8-dihydroxybenzonaphthacene 14a was
formed, as proven by X-ray analysis29 of the acetate 14b
shown in Fig. 2. The phenol 14a represents the ®rst
synthetic angucyclinone hydroxylated at C-5 and has
analogy to the naturally occurring 5,6-dihydroxylated
fridamycinone C.30
(25 ml) was treated at 08C within 5 min with oxalyl bromide
(1.00 ml, 2.33 g, 10.80 mmol). The solution was allowed to
warm to 208C and stirring was continued for 40 min. The
mixture was then dissolved in diethyl ether (100 ml) and
washed with water (40 ml). The organic phase was sepa-
rated, dried (MgSO4), and concentrated at reduced pressure.
The residue was puri®ed by ¯ash chromatography on silica
gel (CH2Cl2) to yield the vinyl bromide 5 (1.63 g, 89%) as a
colorless oil which cystallized on standing in the refrigera-
tor, mp: 1168C (pentane/diethyl ether). 1H NMR (200 MHz,
CDCl3): dˆ0.98 (t, Jˆ7.3 Hz; 3H, CHCH2CH3), 1.47
(quint, Jˆ7.3 Hz; 2H, CHCH2CH3), 2.08±2.23 (m; 2H),
2.48±2.65 (m; 2H), 2.91 (m; 1H), 6.48 (s; 1H, 2-H). 13C
NMR (50 MHz, CDCl3): dˆ11.42 (q, CH2CH3), 28.47 (t,
CH2CH3), 37.54 (d, C-5), 42.83 (t), 43.03 (t), 132.73 (d,
C-2), 150.10 (s, C-3), 197.07 (s, C-1).
The biological activities of the 6-deoxybrasiliquinones 2
and 14a as well as the non-aromatic products 10 and 11
are presently under investigation.
In summary, the 6-deoxybrasiliquinones 2 and 14a are
prepared in only four steps starting from cyclohexadione 4
and juglone (9). Aromatization of ring B can be prevented
by reaction of the dienol 8 with 9. Dimethyldioxirane is an
excellent reagent for selective epoxidation of allylic ethers
such as 10.
(E)-3-(2-Ethoxyvinyl)-5-ethylcyclohex-2-enone (7).
A
solution of the vinyl bromide 5 (1.20 g, 5.91 mmol), Et3N
(1.2 ml, 0.87 g, 8.61 mmol), vinyl diethyl ether (2.9 ml,
2.18 g, 30.21 mmol), and Pd(OAc)2 (0.13 g, 0.58 mmol) in
dry toluene (6 ml) was kept under argon for 5 h at 908C
(TLC monitoring).12 The dark reaction mixture was then
dissolved in diethyl ether (100 ml), washed with water
(2£30 ml), dried (MgSO4), and concentrated at reduced
pressure. The residue was puri®ed by column chromato-
graphy on silica gel (CH2Cl2) to afford the dienone 7
(0.88 g, 77%) as a colorless oil. For one experiment, the
crude mixture of 6 and 7 was used in a Diels±Alder reaction
(see below). 1H NMR (200 MHz, CDCl3): dˆ0.99 (t,
Jˆ7.3 Hz; 3H, CHCH2CH3), 1.37 (t, Jˆ7.0 Hz; 3H,
OCH2CH3), 1.43±1.51 (quin, Jˆ7.0 Hz; 2H, CHCH2CH3),
Experimental
For general methods and instrumentation see Ref. 31. NMR
assignments are veri®ed by two dimensional spectra.
5-Ethylcyclohexane-1,3-dione (4). Methyl 2-pentenoate
(11.2 g, 87.5 mmol) and ethyl acetoacetate (11.4 g,
87.5 mmol) were added to a solution of sodium ethoxide
(2.0 g of sodium, 87.0 mmol) in dry ethanol (40 ml). The
solution was re¯uxed under nitrogen for 4 h, the solvent
removed under reduced pressure, and the residue dissolved
in water (120 ml). The solution was treated with KOH
(10.0 g, 178.6 mmol) and re¯uxed for 20 min. The mixture
was acidi®ed to pH 2 by careful addition of 4N H2SO4 and
again re¯uxed until the evolution of gas ceased (ca. 1 h).
Most of the ethanol was also distilled off this way. The
residue was stored for 18 h in the refrigerator and the
crystals were ®ltered off and recrystallized from acetone/
water, 1:1, to afford the dione 4 (12.2 g, 48%) as colorless
crystals; mp: 608C.
2.04±2.17 (m; 3H), 2.51±2.60 (m; 2H), 3.96 (q, Jˆ7.0 Hz;
0
0
0
2H, OCH2CH3), 5.70 (d, J1 ,2 ˆ12.8 Hz; 1H, 1 -H), 5.85 (s;
1H, 2-H), 7.03 (d, J2 ,1 ˆ12.8 Hz; 1H, 2 -H). 13C NMR
(50 MHz, CDCl3): dˆ11.56 (q, CH2CH3), 15.11 (q,
OCH2CH3), 29.03 (t, CH2CH3), 31.89 (t), 36.76 (d, C-5),
43.94 (t), 66.86 (t, OCH2CH3), 108.16 (d, C-10), 124.09
(d, C-20), 153.90 (d, C-2), 157.09 (s, C-3), 200.22 (s, C-1).
0
0
0
(E,1Rp,5Rp)-3-(2-Ethoxyvinyl)-5-ethyl-2-cyclohexenol (8).
A solution of the dienone 7 (0.80 g, 4.12 mmol) in dry
THF (1 ml) was added dropwise at 2788C to a suspension
3-Bromo-5-ethyl-2-cyclohexenone (5). A solution of dione
4 (1.26 g, 9.00 mmol) and DMF (1 ml) in dry CH2Cl2

4756
K. Krohn et al. / Tetrahedron 56 (2000) 4753±4758
of LAH (0.30 g, 7.92 mmol) in dry THF (10 ml). The
mixture was stirred for 0.5 h at 2788C and was then allowed
to warm to 208C overnight. Aqueous NaOH (6 N, ca.
0.5 ml) was then added dropwise. After stirring for
30 min, MgSO4 was added and the mixture was ®ltered
over a batch of Celite (diethyl ether). The ®ltrate was
concentrated at reduced pressure to yield the alcohol 8
(0.61 g, 76%) as a yellow oil that was used for the next
reduced pressure. The residue was crystallized from
CH2Cl2/diethyl ether to afford the epoxide 11 (215 mg,
83%) as a yellow solid, mp: 1458C. H NMR (200 MHz,
1
CDCl3): dˆ0.97 (t, Jˆ7.2 Hz; 3H, CH2CH3), 1.24 (t,
Jˆ6.9 Hz; 3H, OCH2CH3), 1.34±1.75 (m; 6H, 2-H2, 3-H,
4-Ha, CH2CH3), 2.19±2.29 (m; 2H, 4-He, 1-OH), 3.32 (m;
1H, 5-H), 3.39±3.44 (m; 1H, 12b-H), 3.67±3.87 (m; 3H,
1-H, OCH2CH3), 5.18 (s; 1H, 6-H), 7.28 (d, J9,10ˆ7.2 Hz;
1H, 9-H), 7.57±7.67 (m; 2H, 10-H, 11-H), 12.06 (s; 1H,
8-OH). 13C NMR (50 MHz, CDCl3): dˆ11.71 (q,
CH2CH3), 16.21 (q, OCH2CH3), 29.41 (t, CH2CH3), 35.03
(d, C-3), 38.74 (t), 42.92 (t), 45.03 (d, C-12b), 58.11 (d,
C-5), 58.89 (s, C-4a), 67.59 (t, OCH2CH3), 68.66 (d, C-1),
76.00 (d, C-6), 115.12 (s), 120.05 (d, C-9), 125.06 (d, C-11),
132.33 (s), 136.68 (d, C-10), 139.71 (s), 145.80 (s), 161.78
(s, C-8), 186.29 (s, C-12), 189.69 (C-7). UV (CH2Cl2): lmax
(log e)ˆ276 nm (3.70), 428 (2.02). MS (EI, 70 eV), m/z
(%): 384 (82) [M1], 338 (40) [M12EtOH], 310 (36)
[M12EtOH±CO], 294 (38) [M12EtOH±CO±O], 258
(100), 229 (29). IR (KBr): n~ˆ3445 cm21 (OH), 1673
(CvO), 1645 (CvO), 1614 (CvC), 1449, 1275, 1237,
1085. Anal. Calcd for C22H24O6 (384.16) C 68.72, H 6.30;
Found: C 68.56, H 6.13.
1
reaction without further puri®cation. H NMR (200 MHz,
CDCl3): dˆ0.97 (t, Jˆ7.3 Hz; 3H, CH2CH3), 1.31 (t,
Jˆ7.0 Hz; 3H, OCH2CH3), 1.43±2.19 (m; 7H, 4-H2, 5-H,
6-H2, CH2CH3), 3.80 (q, Jˆ7.0 Hz; 2H, OCH2CH3), 4.35
0
0
(m; 1H, 1-H), 5.48 (s; 1H, 2-H), 5.58 (d, J1 ,2 ˆ12.9 Hz;
1H, 10-H), 6.55 (d, J2 ,1 ˆ12.9 Hz; 1H, 2 -H). 13C NMR
(50 MHz, CDCl3): dˆ11.66 (q, CH2CH3), 15.24 (q,
OCH2CH3), 29.70 (t, CH2CH3), 31.69 (t), 34.89 (d,
C-5), 39.69 (t), 65.82 (t, OCH2CH3), 69.07 (d, C-1),
109.13 (d, C-10), 127.11 (d, C-20), 135.37 (s, C-3), 147.35
(d, C-2).
0
0
0
(1Rp,3Rp,6Rp,6aSp,12aSp,12bRp)-1,8-Dihydroxy-6-ethoxy-
3-ethyl-1,2,3,4,6,6a,12a,12b-octahydrobenz[a]anthracene-
7,12-dione (10). A solution of the dienol 8 (0.60 g,
3.06 mmol) was added slowly at 08C to a solution of juglone
(9) (0.44 g, 2.55 mmol) and boron triacetate (0.48 g,
2.55 mmol) in dry CH2Cl2 (40 ml). The solution was stirred
for 10 min at 08C and then poured into water (50 ml). The
mixture was extracted with CH2Cl2 (2£50 ml), the
combined organic phases were washed with water
(3£50 ml), dried (MgSO4), and concentrated at reduced
pressure to ca. 20 ml. The solution was diluted with ether
(200 ml), again concentrated at reduced ca. 50 ml, and left
in the refrigerator overnight. The Diels±Alder product 11
(0.67 g, 71%) crystallized as faint yellow needles, mp: 141±
1438C. 1H NMR (200 MHz, CDCl3): dˆ0.63 (t, Jˆ7.0 Hz;
3H, CH2CH3), 0.96 (t, Jˆ7.3 Hz; 3H, OCH2CH3), 1.09 (m;
1H, 2-Ha), 1.28±1.42 (m; 2H, CH2CH3), 1.49±1.82 (m; 2H,
3-Ha, 4-Ha), 2.03 (m; 1H, 2-He), 2.11±2.26 (m; 2H, 12b-H,
1-OH), 2.42 (m; 1H, 4-He), 3.04 (m; 1H, OCH2CH3), 3.18
(m; 1H, 12a-H), 3.40 (m; 1H, OCH2CH3), 3.76 (m; 1H,
6a-H), 4.12 (m; 1H, 6-H), 4.94 (m; 1H, 1-H), 5.73 (br. s;
1H, 5-H), 7.18 (d, J9,10ˆ8.3 Hz; 1H, 9-H), 7.40 (d,
J11,10ˆ8.3 Hz; 1H, 10-H), 7.60 (t, J10,9ˆJ10,11ˆ8.3 Hz; 1H,
10-H), 12.09 (s; 1H, 8-OH). 13C NMR (50 MHz, CDCl3):
dˆ11.72 (q, CH2CH3), 14.93 (q, OCH2CH3), 29.71 (t,
CH2CH3), 36.18 (d, C-3), 40.63 (t), 42.36 (t), 43.98 (d,
C-12b), 47.69 (d, C-12a), 55.00 (d, C-6a), 65.31 (t,
OCH2CH3), 70.01 (d, C-1), 72.69 (d, C-6), 116.97 (d,
C-5), 119.02 (s), 119.74 (d, C-9), 122.30 (d, C-11), 136.91
(d, C-10), 139.95 (s), 141.86 (s), 161.58 (s, C-8), 197.13 (s,
C-12), 205.80 (C-7). MS (EI, 70 eV), m/z (%): 370 (3) [M1],
324 (100) [M12EtOH], 278 (90), 263 (45), 214 (44), 195
(58), 165 (51), 134 (69). IR (KBr): n~ˆ3487 cm21 (OH),
1698 (CvO), 1620 (CvO). Anal. Calcd for C22H26O5
(370.18) C 71.32, H 7.08; Found: C 71.12, H 6.89.
(1Rp,3Rp)-1-Acetoxy-3-ethyl-8-hydroxy-1,2,3,4-tetrahydro-
benz[a]anthracene-7,12-dione (12). A solution of the
epoxide 11 (100 mg, 0.260 mmol) in dry THF (10 ml) was
treated with boron triacetate (1.5 g) and the mixture was
stirred at 208C for 15 h. The solution was then poured into
1N HCl (100 ml) and extracted with CH2Cl2 (3£30 ml). The
combined organic phases were washed with water
(3£50 ml), dried (MgSO4), and concentrated at reduced
pressure. The residue was puri®ed by chromatography on
silica (diethyl ether/petroleum ether, 1:4) to afford the
aromatic monoacetate 12 (22 mg, 23%) as a yellow solid;
1
mp: 145±1478C. H NMR (200 MHz, CDCl3): dˆ1.03 (t,
Jˆ7.2 Hz; 3H, CH2CH3), 1.32±1.61 (m; 3H, 2-Ha CH2CH3),
1.89±2.03 (m; 1H, 3-H), 2.08 (s; 3H, Ac), 2.40±2.59 (m;
2H, 2-He, 4-Ha), 3.13 (m; 1H, 4-He), 6.80 (m; 1H, 1-H), 7.28
(d, J9,10ˆ8.1 Hz; 1H, 9-H), 7.50±7.78 (m; 3H, 5-H, 10-H,
11-H), 8.27 (d, J6,5ˆ8.1 Hz; 1H, 6-H), 12.45 (s; 1H, 8-OH).
13C NMR (50 MHz, CDCl3): dˆ11.54 (q, CH2CH3), 21.60
(q, Ac), 29.36 (t, CH2CH3), 29.70 (d, C-3), 35.22 (t), 37.92
(t), 68.11 (d, C-1), 115.64 (s), 120.20 (d, C-9), 123.68 (d,
C-11), 127.67 (d, C-5), 132.16 (s), 133.73 (s), 135.17 (d,
C-10), 135.70 (s), 136.00 (s), 137.17 (d, C-6), 147.69 (s),
162.12 (s, C-8), 170.78 (s, Ac), 184.01 (s, C-12), 188.63 (s,
C-7). UV (CH2Cl2): lmax (log e)ˆ272 nm (4.26), 284
(3.51), 354 (1.14), 405 (1.82). MS (EI, 70 eV), m/z (%):
364 (4) [M1], 321 (100) [M12Ac], 275 (40). IR (KBr):
n~ˆ3439 cm21 (OH), 1743 (CvO), 1634 (CvO), 1460,
1368, 1270, 1237. HRMS: Calcd for C22H20O5: 364.1311;
Found: 364.1311^3 ppm.
rac-3-Ethyl-8-hydroxy-3,4-dihydro-2H-benz[a]anthra-
cene-1,7,12-trione (2) (6-deoxybrasiliquinone B). Method
A: A solution of the acetate 12 (20 mg, 0.055 mmol) in THF
(2 ml) was treated with NaOMe in methanol (2N, 2 ml).
The mixture was stirred for 15 min at 208C, the alkaline
solution was acidi®ed by addition of 0.5N HCl (10 ml)
and the product extracted with ethyl acetate (3£10 ml).
The combined organic phases were washed with water
(3 ml), dried (MgSO4), and the solvent was removed at
(1Rp,3Rp,4aSp,5Rp,6Sp,12bSp)-1,8-Dihydroxy-4a,5-epoxy-
6-ethoxy-3-ethyl-1,2,3,4,6,6a,12a,12b-octahydrobenz-
[a]anthracene-7,12-dione (11). A solution of the Diels±
Alder product 10 (250 mg, 0.675 mmol) in CH2Cl2
(50 ml) was treated at 08C with a ca. 0.08 M solution of
dimethyldioxirane in acetone (25 ml, ca. 2 mmol).32 The
solution was kept for 15 h at 08C and then concentrated at

K. Krohn et al. / Tetrahedron 56 (2000) 4753±4758
4757
reduced pressure. The residue was redissolved in CH2Cl2
(12 ml) and exposed to diffuse sunlight for 12 h in 4 NMR
tubes. The combined solutions were concentrated at reduced
pressure and puri®ed by preparative TLC on silica gel
(CH2Cl2) to afford 6-deoxybrasiliquinone B (2), (9 mg,
52%), mp: 143±1448C. 1H NMR (200 MHz, CDCl3):
dˆ1.12 (t, Jˆ7.2 Hz; 3H, CH2CH3), 1.46±1.75 (q; 2H,
CH2CH3), 2.35±2.56 (m; 1H, 3-H), 2.59±2.71 (m; 2H,
2-Ha, 4-Ha), 2.93±3.10 (m; 2H, 2-He, 4-He), 7.27 (d,
J9,10ˆ7.6 Hz; 1H, 9-H), 7.56 (d, J5,6ˆ8.0 Hz, 1H, 5-H),
7.61±7.73 (m; 2H, 10-H, 11-H), 8.28 (d, J6,5ˆ8.0 Hz; 1H,
6-H), 12.28 (s; 1H, 8-OH). 13C NMR (50 MHz, CDCl3):
dˆ11.80 (q, CH2CH3), 29.96 (t, CH2CH3), 31.72 (d, C-3),
38.72 (t, C-4), 43.05 (t, C-2), 115.13 (s), 119.28 (d, C-9),
123.21 (d, C-11), 128.98 (d, C-5), 129.54 (s), 133.28 (s),
134.74 (s), 134.97 (d, C-10), 135.88 (s), 136.73 (d, C-6),
147.17 (s), 161.56 (s, C-8), 184.22 (s, CvO), 187.09 (s,
CvO), 197.63 (s, C-1). UV (CH2Cl2): lmax (log e)ˆ265 nm
(4.31), 405 (3.43). MS (EI, 70 eV), m/z (%): 320 (31) [M1],
292 (59) [M12CO], 279 (100), 262 (35), 250(55). IR
(KBr): n~ˆ3446 cm21 (OH), 1702 (CvO), 1668 (CvO),
1638 (CvO), 1458, 1366, 1272, 1228. HRMS: Calcd for
C20H16O4: 320.1049; Found: 320.1049^3 ppm. Anal. Calcd
for C20H16O4: 320.34: C 74.99, H 5.03; Found: C 74,37, H
4.77.
50%), and from the polar fraction, the phenol 14a (56 mg,
7%), mp: 2568C.
rac-3-Ethyl-5,8-dihydroxy-3,4-dihydro-2H-benzo[a]-
anthracene-1,7,12-trione (14a). Mp: 2568C (decomp.). 1H
NMR (200 MHz, D6-acetone): dˆ1.06 (t, Jˆ7.4 Hz; 3H,
CH2CH3), 1.62 (q; 2H, CH2CH3), 2.2 (m; 1H, 3-H), 2.41±
2.67 (m; 2H, 2-Ha, 2-Ha), 2.9 (m; 1H, 4-He), 23.27 (dd, 1H,
4-He), 7.30 (d, J9,10ˆ8.3 Hz; 1H, 10-H), 7.59 (d,
J8,9ˆ7.7 Hz, 1H, 8-H), 7.78 (s, 1H, 6-H), 7.81 (t; 1H,
9-H), 12.29 (s; 1H, 11-OH). UV (CH2Cl2): lmax
(log e)ˆ283 nm (4,13), 329 (3.47), 389 (3.60). IR (KBr):
n~ˆ3391 cm21 (OH), 1701 (CvO), 1654 (CvO), 1575
(CvC), 1456, 1363, 1285. MS (EI, 70 eV), m/z (%):
336.1 (78) [M1], 308.1 (62), 281.0 (76), 280.0 (100),
279.1 (78), 252.0 (31), 224.1 (24), 168.1 (56), 139.1 (68);
Anal. Calcd for C20H16O5: 336.34: C 71.42, H 4.79; Found:
71.22, H 4.68.
rac-5-Acetoxy-3-ethyl-8-hydroxy-3,4-dihydro-2H-
benzo[a]anthracene-1,7,12-trione (14b). A suspension of
the phenol 14a (17 mg, 0.05 mmol) in CH2Cl2 (2 ml) was
treated with 0.2 ml of acetic anhydride and 0.1 ml of
pyridine. After 20 min stirring at 208C, the phenol was
dissolved and the reaction quenched by addition of 2N
HCl (1 ml). Excess acetic anhydride was hydrolyzed by
stirring the mixture for 30 min. The phases were separated,
the organic phase was dried (MgSO4), and the solvent
removed at reduced pressure. The residue was puri®ed by
®ltration through a short column of silica gel (2 g, CH2Cl2)
and the acetate was isolated from the nonpolar fraction and
crystallized from diethyl ether to yield yellow plates of 14b
rac-4-(5-Hydroxy-9,10-dioxo-9,10-dihydroanthracen-2-
ylmethyl)-3-pentanal (13). The ®nely ground epoxide 11
(35 mg, 0.091 mmol) was sublimed at 0.8 Torr by external
heating with hot air. The sublimate was puri®ed by TLC
chromatography on silica gel (CH2Cl2) to yield the open
chain aldehyde 13 as a yellow solid (17 mg, 57%); mp:
95±968C. 1H NMR (200 MHz, CDCl3): dˆ0.99 (t,
Jˆ7.2 Hz; 3H, CH2CH3), 1.38±1.44 (m; 2H, CH2CH3),
2.36±2.53 (m; 3H, 2-H2, 3-H), 2.72±2.94 (m; 2H, 4-H2),
1
(20 mg, 96%); mp: 1488C. H NMR (200 MHz, CDCl3):
dˆ1.05 (t, Jˆ7.4 Hz; 3H, CH2CH3), 1.59 (q; 2H,
CH2CH3), 2.2 (m; 1H, 3-H), 2,45 (s, 3H, COCH3), 2.4±
2.7 (m; 2H, 2-Ha, 4-Ha), 2.95±3.12 (m; 2H, 2-He), 23.27
(dd, 1H, 4-He), 7.30 (t, J9,10ˆ8.3 Hz; 1H, 10-H), 7.66±7.74
(m, 2H, 8-H, 9-H), 7.88 (s, 1H, 6-H), 7.81 (t; 1H, 9-H),
12.29 (s; 1H, 11-OH). 13C NMR (50 MHz, CDCl3):
dˆ11.52 (q, CH2CH3), 21.22 (q, COCH3), 29.42 (t,
CH2CH3), 31.90 (4-CH2), 37.25 (d, C-3), 45.39 (t, 2-CH2),
115.82 (s, C-5), 120.23 (d, C-8), 122.54 (s, C-6), 124.17 (d,
C-10), 133.68, 134,74, 135.32, 137.66 (s, C-9), 139.10 (s,
C-4a), 143.30 (s, C-12b), 151.95 (s, C-5), 162.35 (s, C-11),
168.61(s, ester CvO), 182.40 (s, CvO), 187.17 (s, CvO),
199.23 (s, C-1). UV (CH2Cl2): lmax (log e)ˆ283 nm (4,13),
329 (3.47), 389 (3.60). IR (KBr): n~ˆ3447 cm21 (OH), 1768
(ester CvO), 1702 (CvO), 1653 (CvO), 1636 (CvO),
1592 (CvC), 1472, 1359, 1214, 1188. MS (EI, 70 eV),
m/z (%): 378.1 (69) [M1], 350.1 (42), 336.1 (66), 308.1
(76), 280.0 (100), 251.0 (26), 224.0 (22), 196.0 24), 168.1
(41), 139.1 (77); Anal. Calcd for C22H18O6: (378.38): C
69.83, H 4.79; Found: C 69.75, H 4.51.
0
0
0
0
7.34 (d, J6 ,7 ˆ8.3 Hz; 1H, 6 -H), 7.63±7.75 (m; 2H, 4 -H,
70-H), 7.86 (d, J8 ,7 ˆ7.5 Hz; 1H, 8 -H), 8.11 (s; 1H, 1 -H),
0
0
0
0
0
0
0
8.28 (d, J4 ,3 ˆ8.0 Hz; 1H, 3 -H), 9.77 (m; 1H, 1-H), 12.68
(s; 1H, 8-OH). 13C NMR (50 MHz, CDCl3): dˆ11.48 (q,
CH2CH3), 26.82 (t, CH2CH3), 36.59 (d, C-3), 40.84 (t, C-4),
47.75 (t, C-2), 116.54 (s), 119.99 (d, C-60), 124.86 (d, C-80),
127.74 (d, C-10), 128.26 (d, C-40), 131.92 (s), 133.91 (s),
134.03 (s), 135.54 (d, C-30), 137.08 (d, C-70), 148.75 (s,
C-20), 162.95 (s, C-50), 183.09 (s, C-90), 188.91 (s, C-100),
202.36 (d, C-1). UV (CH2Cl2): lmax (log e)ˆ248 nm (4.19),
338 (1.09), 405 (1.85). MS (EI, 70 eV), m/z (%): 322 (31)
[M1],
278
(100)
[M12CH3CHO],
263
(33)
[M12CH3CHO±Me], 149 (32). IR (KBr): n~ˆ3467 cm21
(OH), 1721 (CvO), 1672 (CvO), 1634 (CvO), 1590
(CvC), 1449, 1357, 1291, 1264. HRMS: Calcd for
C20H18O4: 322.1205; Found: 322.1205^3 ppm.
rac-3-Ethyl-8-hydroxy-3,4-dihydro-2H-benz[a]anthra-
cene-1,7,12-trione (2) (rac-6-deoxybrasiliquinone B).
Method B: A solution of juglone (9) (503 mg, 0.29 mmol),
the crude mixture of the dienes 6 and 7 (ratio ca. 1:6,
600 mg, ca. 0.25 mmol by NMR) and boron triacetate
(0.56 g, 30 mmol) in CH2Cl2 (20 ml) was stirred at 208C
for 15 h. The mixture was washed with water (2£20 ml),
the organic phase was dried (MgSO4), and the solvent was
removed at reduced pressure. Column chromatography of
the residue on silica gel (CH2Cl2) afforded from the major
nonpolar fraction 6-deoxybrasiliquinone B (2) (417 mg,
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