Efficient method for synthesis of angucyclinone antibiotics via gold-catalyzed intramolecular [4 + 2] benzannulation: Enantioselective total synthesis of (+)-ochromycinone and (+)-rubiginone B2

Article abstract of DOI:10.1021/jo051444m

An efficient synthetic approach to angucyclinone antibiotics, (+)-ochromycinone and (+)-rubiginone B₂, is reported. The key step involves the facile formation of 2,3-dihydrophenantren-4(1H)-one skeleton, an important framework of angucyclinone

Full text of DOI:10.1021/jo051444m

Efficient Method for Synthesis of Angucyclinone Antibiotics via
Gold-Catalyzed Intramolecular [4 + 2] Benzannulation:
Enantioselective Total Synthesis of (+)-Ochromycinone and
(+)-Rubiginone B2
Kenichiro Sato, Naoki Asao,* and Yoshinori Yamamoto†
Department of Chemistry, Graduate School of Science, Tohoku University, Sendai 980-8578, Japan
asao@mail.tains.tohoku.ac.jp
Received July 13, 2005
An efficient synthetic approach to angucyclinone antibiotics, (+)-ochromycinone and (+)-rubiginone
B2, is reported. The key step involves the facile formation of 2,3-dihydrophenantren-4(1H)-one
skeleton, an important framework of angucyclinone natural products, by using gold-catalyzed
intramolecular [4 + 2] benzannulation reaction.
SCHEME 1. Anitibiotics Angucyclinone
Introduction
The family of angucyclinone exhibits a wide range of
remarkable antibiotic properties (Scheme 1).1,2 Ochro-
mycinone and rubiginones B2, first isolated by Bowie3 and
Oka4 from the strain of Streptomyces, are one of the
simple and useful angucyclinones. A group of rubiginones
has been shown to potentiate the cytotoxicity of the
chemotherapeutic agent vincristine-resistant P388 leu-
kemia and human Moser cells in vitro and in vivo.5
Ochromycinone was recently reported to have selective
anti-Helicobacter pylori activity, the major cause of
stomach ulcers and duodenal ulcer, with low activity
against other common bacteria.6 The Diels-Alder reac-
tion between juglone derivatives and the corresponding
* To whom correspondence should be addressed. Phone: +81-22-
795-6581, Fax: +81-22-795-6784.
dienes is one of the most convenient methods for the
preparation of angucyclinone frameworks.7,8 However, a
† E-mail: yoshi@yamamoto1.chem.tohoku.ac.jp.
(1) For reviews on angucyclinones, see: (a) Rohr, J.; Thiericke, R.
Nat. Prod. Rep. 1992, 9, 103-137. (b) Krohn, K.; Rohr, J. Top Curr.
Chem. 1997, 188, 128-195.
(2) (a) Liu, W.-C.; Parker, W. L.; Slusarchyk, D. S.; Greenwood, G.
L.; Graham, S. F.; Meyers, E. J. Antibiot. 1970, 23, 437-441. (b)
Imamura, N.; Kakinuma, K.; Ikekawa, N.; Tanaka, H.; Omura, S. J.
Antibiot. 1982, 35, 602-608. (c) Sezaki, M.; Kondo, S.; Maeda, K.;
Umezawa, H.; Ohno, M. Tetrahedron 1970, 26, 5171-5190.
(3) Bowie, J. H.; Johnson, A. W. Tetrahedron Lett. 1967, 16, 1449-
1452.
(4) Oka, M.; Kamei, H.; Hamagishi, Y.; Tomita, K.; Miyaki, T.;
Konishi, M.; Oki, T. J. Antibiot. 1990, 43, 967-976.
(5) Ogasawara, M.; Hasegawa, M.; Hamagishi, Y.; Kamei, H.; Oki,
T. J. Antibiot. 1992, 45, 129-132.
(6) Taniguchi, M.; Nagai, K.; Watanabe, M.; Niimura, N.; Suzuki,
K.; Tanaka, A. J. Antibiot. 2002, 55, 30-35.
(7) For total synthesis of racemic ochromycinone, see: (a) Guingant,
A.; Barreto, M. M. Tetrahedron Lett. 1987, 28, 3107-3110. (b) Gound,
S. J.; Cheng, X.-C.; Melville, C. J. Am. Chem. Soc. 1994, 116, 1800-
1804. (c) Larsen, D. S.; O’Shea, M. D. J. Chem. Soc., Chem. Commun.
1995, 1019-1028. For asymmetric total synthesis of (+)-ochromycinone
via Diels-Alder reaction as a key reaction, see: (d) Larsen, D. S.;
O’Shea, M. D. Chem. Commun. (Cambridge) 1996, 203-204. (e)
Carreno, M. C.; Urbano, A.; Di Vitta, C. Chem. Commun. (Cambridge)
1999, 817-818. (f) Krohn, K.; Sohrab, M. H.; Flo¨rke, U. Tetrahedron:
Asymmetry 2004, 15, 713-718.
(8) For other examples for total synthesis of ochromycinone and (+)-
rubiginone B2, see: (a) Katsuura, K.; Snieckus, V. Tetrahedron Lett.
1985, 26, 9-12. (b) Katsuura, K.; Snieckus, V. Can. J. Chem. 1987,
65, 124-130. (c) Kalogerakis, A.; Groth, U. Synlett 2003, 1886-1888.
10.1021/jo051444m CCC: $30.25 © 2005 American Chemical Society
Published on Web 09/27/2005
J. Org. Chem. 2005, 70, 8977-8981
8977

Sato et al.
SCHEME 2. Synthetic Plan of (+)-Ochromycinone and (+)-Rubiginone B2
SCHEME 3. Synthesis of 16 for a Model Experimenta
a
Reagents and conditions: (a) p-TsOH, HO(CH2)3OH, benzene, reflux, quant. (b) BuLi, (BrCF2)2, hexane/benzene, -25 °C, 10 h, 70%.
(c) 11 N HCl, 0 °C, 30 min, quant. (d) (rac)-11, Pd2(dba) 3‚CHCl3, P(t-Bu)3, toluene, 50 °C, 4 h, 70%. (e) TBAF, AcOH, THF, rt, 30 min,
quant.
TABLE 1. Lewis Acid Catalyzed Intramolecular
Benzannulation of 16a
drawback of this methodology lies in the difficulty in
preparation of the diene parts. Recently we developed the
Lewis acid catalyzed intramolecular [4 + 2] benzannu-
lation using the tethered alkynyl enynals 7 to give the
2,3-dihydrophenanthren-4(1H)-one derivatives 8 in mod-
erate to high yields (eq 1).9 Herein, we report a new
approach to the synthesis of (+)-ochromycinone and (+)-
rubiginone B2 through the gold-catalyzed intramolecular
[4 + 2] benzannulation, in which a key step for the total
synthesis exists in the construction of 2,3-dihydrophenan-
thren-4(1H)-one skeleton.10
entry
Lewis acid
conditions
yieldb (%)
1c
2
AuBr3
AuBr3
AuCl3
PtCl2
rt, 1 h
70
77
90
83
50 °C, 1 h
50 °C, 1 h
50 °C, 1 h
3
4
a The reaction of 16 (0.5 mmol) was carried out in the presence
of 2 mol % Lewis acid in (CH2Cl)2 (0.13 M) unless otherwise noted.
b Chemical yield was determined by 1H NMR using dibro-
momethane as an internal standard. c The reaction concentration
was 0.33 M.
Results and Discussion
method, and the conversion of terminal alkyne to the
corresponding Bu3Sn-alkyne should afford 11.
Our synthetic plan of (+)-ochromycinone and (+)-
rubiginone B2 is described in Scheme 2. The previous
study suggested that the framework of 3,4-dihydrotet-
raphen-1(2H)-one skeleton of 9 would be constructed by
gold-catalyzed intramolecular benzannulation of 10, which
would be prepared by the Pd-catalyzed coupling reaction
between 11 and 12. It was thought that the chiral diyne
11 would be synthesized by the combination of known
reactions; the asymmetric conjugate addition of an or-
ganocopper reagent by using Evans’s chiral oxazolizinone,
the reduction of the resulting amide, the transformation
of the resulting aldehyde to alkyne by Cory-Fuchs
Before starting the total synthetic study of angucycli-
none antibiotics, we first performed the intramolecular
benzannulation of the tethered alkynyl enynal 16, having
two methoxy groups on the benzene ring, as a model
experiment. The substrate 16 was prepared from a
commercially available aldehyde 13 by known proce-
dures, as shown in Scheme 3.11 The selected results of
the Lewis acid catalyzed benzannulation of 16 were
summarized in Table 1. When the reaction of 16 was
carried out in the presence of 2 mol % AuBr3 at room
temperature for 1 h, the starting material was consumed
completely, and the desired product 17 was obtained in
70% yield together with small amounts of unknown
byproducts (entry 1). When the concentration of the
reaction mixture was diluted from 0.33 to 0.13 M, the
(9) Asao, N.; Sato, K.; Menggenbateer; Yamamoto, Y. J. Org. Chem.
2005, 70, 3682-3685.
(10) Recently, applications to synthesis of natural products via Au-
catalyzed cycloisomerization of o-alkynylbenzaldehyde and o-alkynyl-
aryl ketone were reported; see: (a) Zhu, J.; Germain, A. R.; Porco, J.
A., Jr. Angew. Chem., Int. Ed. 2004, 43, 1239-1243. (b) Dyker, G.;
Hildebrandt, D. J. Org. Chem. 2005, 70, 6093-6096.
(11) Li, C.; Johnson, R. P.; Porco, J. A., Jr. J. Am. Chem. Soc. 2003,
125, 5095-5106.
8978 J. Org. Chem., Vol. 70, No. 22, 2005

(+)-Ochromycinone and (+)-Rubiginone B2 Synthesis
SCHEME 4. Synthesis of the Diyne Derivative 11a
a Reagents and conditions: (a) CuBr‚DMS, BF3‚OEt2, TMSCtCCH2MgCl, THF, -40 °C, 20 h, 90%. (b) DIBALH, CH2Cl2, -78 °C, 1 h,
96%. (c) CBr4, PPh3, CH2Cl2, 0 °C, 2 h. (d) BuLi, -78 °C, 1 h, and then aq NH4Cl, rt, 1 h, 71% in two steps. (e) BuLi, -78 °C, 30 min, and
then Bu3SnCl,1 h, quant.
SCHEME 5. Synthesis of the Naphthalene Derivative 10a
a Reagents and conditions: (a) vinyl acetic acid, AgNO3, (NH4)2S2O8, CH3CN/H2O, 65 °C, 10 h, 65%. (b) SnCl2, conc HCl, EtOH, 50 °C,
30 min, and then Me2SO4, 50% aq KOH, 65 °C, 3 h, 97%. (c) KOt-Bu, THF, 4 °C, 1 h, 92%. (d) O3, MeOH, -78 °C, 20 min, and then PPh3
in CH2Cl2, rt, 1 h, 79%. (e) diyne derivative 11, Pd2(dba)3‚CHCl3, P(t-Bu)3, toluene, rt, 9 h, 97%. (f) TBAF, AcOH, THF, rt, 30 min, quant.
yield was increased to 77% yield, although it was neces-
sary to raise the temperature from room temperature to
50 °C to complete the reaction within 1 h (entry 2).
Finally we found that the chemical yield was increased
up to 90% by using AuCl3 as a catalyst. This result is
interesting because we have already reported that AuBr3
was a more effective catalyst than AuCl3 for both of the
inter- and intramolecular [4 + 2] benzannulation reaction
of o-alkynylaryl aldehydes having no methoxy group on
the benzene ring.12 In the previous papers, we proposed
that the benzannulation proceeded through the formation
of a benzopyrylium-type intermediate. Probably, in the
present case, the two methoxy groups of the aromatic ring
make the formation of the intermediate easier and
therefore less Lewis acidic AuCl3 enables induction of the
benzannulation efficiently. PtCl2 was also suitable cata-
lyst for the present reaction (entry 4).
Since the model experiments showed that the intramo-
lecular benzannulation proceeded well even with the
methoxy-substituted starting material 16, the synthetic
study of angucyclinone antibiotics was started along the
line shown in Scheme 2. First, we performed the syn-
thesis of the diyne segment as shown in Scheme 4.
According to the reported procedure, the reaction of the
organocopper reagent, derived from trimethylsilyl-sub-
stituted propargylmagnesium chloride13 and CuBr, with
the R,â-unsaturated carbonyl compound 18, having (S)-
4-phenyl oxazolidinone as a chiral auxiliary, was carried
out.14 The reaction proceeded smoothly and the conjugate
addition product 19 was obtained in 90% yield. The
diastereomeric ratio, 96% dr, was determined by GC/MS,
and it was increased up to 99% by recrystallization of
19 from EtOH. The cleavage of chiral auxiliary of 19 by
reduction with diisobutylaluminum hydride (DIBALH)
afforded the alkynyl aldehyde 20 in 96% yield,15 which
was converted to the 1,6-heptadiyne derivative 21 in 71%
yield using the Corey-Fuchs method. Treatment of 21
with BuLi, followed by addition of Bu3SnCl, gave 11
quantitatively.16
Next, we examined the preparation of the naphthalene
derivative 12 and the coupling reaction between 11 and
12 as depicted in Scheme 5. The bromonaphthoquinone
22 was prepared from 1,5-dihydronaphthalene in four
steps in 74% yield by the known procedure.17 The
introduction of the allyl group to the quinone part of 22
was carried out using vinyl acetic acid in the presence of
(13) Verkruijsse, H. D.; Brandsma, L. Synth. Commun. 1990, 20,
3375-3378.
(14) William, D. R.; Kissel, W. S.; Li, J. J. Tetrahedron Lett. 1998,
39, 8593-8596.
(15) Bull, S. D.; Davis, S. G.; Nicholson, R. L.; Sanganee, H. J.;
Smith, A. D. Org. Biomol. Chem. 2003, 1, 2886-2899.
(16) Buffet, M. F.; Dixon, D. J.; Ley, S. V.; Reynolds, D. J.; Storer,
R. I. Org. Biomol. Chem. 2004, 2, 1145-1154.
(17) (a) Nguyen Van, T.; De Kimpe, N. Tetrahedron 2003, 59, 5941-
5946. (b) Heinzman, S. W.; Grunwell, J. R. Tetrahedron Lett. 1980,
21, 4305-4308.
(12) (a) Asao, N.; Takahashi, K.; Lee, S.; Kasahara, T.; Yamamoto,
Y. J. Am. Chem. Soc. 2002, 124, 12650-12651. (b) Asao, N.; Nogami,
T.; Lee, S.; Yamamoto, Y. J. Am. Chem. Soc. 2003, 125, 10921-10925.
J. Org. Chem, Vol. 70, No. 22, 2005 8979

Sato et al.
SCHEME 6. Total Synthesis of (+)-Ochromycinone (1) and (+)-Rubiginone B2 (5)a
a Reagents and conditions: (a) 2 mol % AuCl3, (CH2Cl)2, 50 °C, 1 h, 84%. (b) CAN, CH3CN/H2O, rt, 1 h, 97%. (c) BCl3, CH2Cl2, -78 °C,
1 h, 89%.
silver nitrate, ammonium persulfate, and 23 was ob-
(1) was prepared in 89% yield from 5 by demethylation
using BCl3. The synthetic (+)-rubiginone B2 5 and (+)-
ochromycinone 1 exhibited physical and spectroscopic
data identical to those reported previously.23
tained in 65% yield.18,19 Reduction to the hydroquinone
of 23 using SnCl2 and concentrated HCl in EtOH,
followed by treatment of the resulting 1,4-dihydroxy-
naphthalene with Me2SO4 under basic conditions gave
24 in 97% yield. The terminal olefin on the allyl group of
24 was isomerized to the internal one by KOt-Bu in
tetrahydrofuran (THF) and 25 was obtained in 92% yield
as a 95:5 mixture of trans and cis isomers.19 Interestingly,
while the oxidative cleavage of olefin group of 25 by
ozonolysis in CH2Cl2 gave only a trace amount of 12, the
chemical yield was dramatically improved by using
MeOH as a solvent and 12 was obtained in 79% yield.
We next examined the coupling reaction between 12 and
the diyne part. Unfortunately, the desired compound 26
was not obtained under the Sonogashira coupling condi-
tions using 21 as a diyne part, and most of the starting
material was recovered.20 However, we found that the
reaction of 12 with the alkynyl stannane 11, instead of
21, proceeded well under the Stille coupling conditions
and the coupling product 26 was obtained in 97% yield.21
The trimethylsilyl (TMS) group at the terminus of the
acetylene group of 26 was removed by tetrabutylammo-
nium fluoride (TBAF) in the presence of AcOH in THF
and 10 was obtained almost quantitatively.
Conclusion
The total synthesis of (+)-ochromycinone and (+)-
rubiginone B2 was accomplished via the AuCl3-catalyzed
intramolecular [4 + 2] benzannulation reaction as the
key step. This result indicates that the intramolecular
benzannulation is useful for construction of 2,3-dihydro-
phenanthren-4(1H)-one skeleton, an important structural
framework in a wide rage of bioactive compounds, such
as tanshinone family containing the activity to ischemia
disease.24 Further study to apply the present methodology
for the synthesis of other natural products is in progress
in our laboratory.
Experimental Section
(S)-7,8,12-Trimethoxy-3-methyl-3,4-dihydrotetraphen-
1(2H)-one (9). To AuCl3 (12 mg, 0.04 mmol) was added a
solution of 10 (0.70 g, 2.0 mmol) in (ClCH2)2 (20 mL) at room
temperature under an argon atmosphere. The reaction mixture
was stirred for 1 h at 50 °C and then transferred to a silica
gel column. The solvent was removed under reduced pressure
to give a crude product, which was purified by silica gel column
chromatography using hexane/ethyl acetate ) 3/1 as eluent
to give 9 as a yellow solid (0.59 g, 1.68 mmol) in 84% yield:
1H NMR (CDCl3, 400 MHz) δ 8.42 (d, J ) 8.8 Hz, 1H), 7.98 (d,
J ) 8.6 Hz, 1H), 7.41 (dd, J ) 7.6, 8.6 Hz, 1H), 7.18 (d, J )
8.8 Hz, 1H), 6.83 (d, J ) 7.6 Hz, 1H), 4.07 (s, 3H), 3.99 (s,
3H), 3.73 (s, 3H), 3.09-2.97 (m, 2H), 2.81-2.74 (m, 1H), 2.62-
2.50 (m, 2H), 1.25 (d, J ) 5.9 Hz, 3H); 13C NMR (CDCl3, 100
MHz) δ 197.2, 156.1, 149.1, 148.3, 145.1, 129.9, 129.4, 128.1,
125.9, 125.6, 119.9, 118.5, 115.7, 104.2, 104.2, 63.8, 61.2, 56.1,
47.6, 39.0, 30.9, 21.3; IR (KBr) 2835, 1676, 1599, 1553, 1452,
1256, 1221, 1090, 1003, 812, 565 cm-1; MS (EI) m/z 350 (M+,
54). HRMS (ESI). Calcd for C22H22O4Na (M+ + Na): 373.1410.
On the basis of the results shown in Table 1, we
examined the intramolecular benzannulation reaction of
10 in the presence of 2 mol % AuCl3 in (CH2Cl)2 at 50 °C
for 1 h as shown in Scheme 6. As expected, the reaction
proceeded smoothly and the dihydrotetraphenone deriva-
tive 9 was obtained in 84% yield. Rubiginone B2 (5) was
produced in 97% yield by oxidation of 9 using ceric
ammonium nitrate (CAN).22 Finally, (+)-ochromycinone
(18) (a) Jacobsen, N.; Torsell, K. Acta Chem. Scand. 1973, 27, 3211-
3216. (b) Aldersley, M. F.; Christi, S. H.; Dean, F. M.; Douglas, M. E.;
Ennis, D. S. J. Chem. Soc., Perkin Trans. 1 1990, 2163-2174.
(19) Kesteleyn, B.; Kimpe, N. D.; Puyvelde, L. V. J. Org. Chem. 1999,
64, 1173-1179.
Found: 373.1410. mp ) 204-208 °C. [R]31 + 172.9 (c 0.05,
D
CHCl3).
(20) Hundertmark, T.; Littke, A. F.; Buchwald, S. L.; Fu, G. C. Org.
Lett. 2000, 2, 1729-1731.
(21) Littke, A. F.; Schwarz, L.; Fu, G. C. J. Am. Chem. Soc. 2002,
124, 6343-6348.
(23) The RD value of synthetic 1 {[R]20D + 98.4 (c 0.08, CHCl3), 99%
ee} was identical to that of (+)- ochromycinone {[R]25 + 96 (c 0.08,
D
(22) The RD value of synthetic 5 {[R]19 + 79.6 (c 0.5, CHCl3)} was
CHCl3), 99% ee} synthesized by Krohn and co-workers.7f
identical to that of natural (+)-rubiginDone B2 {[R]20 + 78 (c 0.5,
(24) Takeo, S.; Tanonaka, K.; Hirai, K.; Kawaguchi, K.; Ogawa, M.;
Yagi, A.; Fugimoto, K. Biochem. Pharmacol. 1990, 40, 1137-1143.
D
CHCl3)}.4
8980 J. Org. Chem., Vol. 70, No. 22, 2005

(+)-Ochromycinone and (+)-Rubiginone B2 Synthesis
(S)-8-Methoxy-3-methyl-3,4-dihydrotetraphene-1,7,12-
(2H)-trione [(+)-Rubiginone B2 (5)]. To a solution of 9 (0.35
g, 1.0 mmol) in acetonitrile (8 mL) at 0 °C was added a solution
of CAN (1.64 g, 3.0 mmol) in H2O (20 mL), and the reaction
mixture was allowed to warm to room temperature over 30
min and stirred for 1 h additionally. The resulting mixture
was extracted with CH2Cl2 twice and dried over MgSO4. The
solvent was removed under reduced pressure to give a crude
product, which was purified by recrystallization from EtOH
to give 5 as a yellow solid (0.31 g, 0.97 mmol) in 97% yield:
1H NMR (CDCl3, 400 MHz) δ 8.26 (d, J ) 8.2 Hz, 1H), 7.77
(dd, J ) 1.0, 7.6 Hz, 1H), 7.70 (dd, J ) 7.6, 8.5 Hz, 1H), 7.50
(d, J ) 8.2 Hz, 1H), 7.29 (dd, J ) 1.0, 8.5 Hz, 1H), 4.04 (s,
3H), 3.03-2.95 (m, 2H), 2.68 (dd, J ) 10.8, 16.6 Hz, 1H), 2.56
(dd, J ) 11.2, 15.9 Hz, 1H), 2.47 (m, 1H), 1.20 (d, J ) 6.6 Hz,
3H); 13C NMR (CDCl3, 100 MHz) δ 198.7, 184.3, 181.4, 159.7,
149.0, 137.6, 135.2, 135.0, 134.9, 132.9, 132.9, 129.5, 120.6,
119.6, 117.1, 56.5, 47.6, 38.4, 30.9, 21.5; IR (KBr) 2957, 1707,
1676, 1560, 1508, 1267, 1040, 1015, 968, 826 cm-1; MS (EI)
h. Methanol (3 mL) was added, the resulting mixture was
allowed to warm to room temperature over 1 h, and then a
solution of aqueous NaHCO3 (10 mL) was added. The mixture
was extracted with CH2Cl2 twice and dried over MgSO4. The
solvent was removed under reduced pressure to give a crude
product, which was purified by recrystallization from EtOH
to give (1) as a yellow solid (82 mg, 0.27 mmol) in 89% yield:
1H NMR (CDCl3, 400 MHz) δ 12.29 (s, 1H), 8.29 (d, J ) 8.0
Hz, 1H), 7.70-7.64 (m, 2H), 7.55 (d, J ) 8.0 Hz, 1H), 7.27 (m,
1H), 3.06-2.99 (m, 2H), 2.69 (dd, J ) 11.0, 16.6 Hz, 1H), 2.58
(dd, J ) 11.0, 15.2 Hz, 1H), 2.52-2.44 (m, 1H), 1.22 (d, J )
6.6 Hz, 3H); 13C NMR (CDCl3, 100 MHz) δ 198.8, 187.3, 182.7,
161.9, 150.2, 136.9, 136.4, 135.7, 134.9, 133.3, 132.9, 128.8,
123.5, 119.4, 115.3, 47.5, 38.4, 30.8, 21.5; IR (KBr) 2974, 1705,
1668, 1636, 1454, 1364, 1281, 1157, 829, 600 cm-1; MS (EI)
m/z 306 (M+, 43). HRMS (ESI). Calcd for C19H14O4Na (M+
+
+
Na): 329.0784. Found: 329.0786. mp ) 166-167 °C. [R]20
98.4 (c 0.08, CHCl3), 99% ee.
D
m/z 320 (M+, 100). HRMS (ESI). Calcd for C20H16O4Na (M+
+
Supporting Information Available: Preparation meth-
ods of 19-21, 11, 23-25, 12, 26, and 10 and spectroscopic and
analytical data for 16, 17, 19-21, 11, 23-25, 12, 26, 10, 9, 5,
and 1 (PDF). This material is available free of charge via the
Internet at http://pubs.acs.org.
Na): 343.0941. Found: 343.0941. [R]19D + 79.6 (c 0.5, CHCl3).
(S)-8-Hydroxy-3-methyl-3,4-dihydrotetraphene-1,7,12-
(2H)-trione [(+)-Ochromycinone (1)]. To a solution of 5 (96
mg, 0.3 mmol) in CH2Cl2 (15 mL) at -78 °C under an argon
atmosphere was added dropwise a solution of BCl3 in heptane
(1.80 mL, 1.80 mmol, 1 M), and the mixture was stirred for 1
JO051444M
J. Org. Chem, Vol. 70, No. 22, 2005 8981