Synthesis of Benzopicene and its Putative Carcinogenic trans-3,4-Dihydrodiol and Fjord Region anti-Diol Epoxide Metabolites

Full text of DOI:10.1021/jo9806613

J . Org. Chem. 1998, 63, 6405-6408
6405
A practical synthetic route to benzo[s]picene was
recently reported,5 making it readily available for chemi-
cal and biological investigations. In connection with
studies on the metabolic activation and tumorigenicity
of benzo[s]picene, samples of its potential carcinogenic
metabolites were required as authentic standards. Con-
venient syntheses of the bis-dihydrodiol metabolite (2)
and the corresponding bis-anti-diol epoxide metabolite
(3) were recently described.6 We now report a new
synthesis of benzo[s]picene and efficient syntheses of its
3,4-dihydrodiol, trans-3,4-dihydroxy-3,4-dihydrobenzo[s]-
picene (4) and the corresponding anti-diol epoxide, trans-
3,4-dihydroxy-anti-1,2-epoxy-1,2,3,4-tetrahydrobenzo[s]-
picene (5), implicated as its proximate and ultimate
carcinogenic metabolites, respectively.
Syn th esis of Ben zo[s]p icen e a n d its
P u ta tive Ca r cin ogen ic
tr a n s-3,4-Dih yd r od iol a n d F jor d Region
a n ti-Diol Ep oxid e Meta bolites
R. G. Harvey,* J .-T. Zhang, E. Luna, and J . Pataki
Ben May Institute, University of Chicago,
Chicago, Illinois 60637
Received April 9, 1998
The chemistry of the polycyclic aromatic hydrocarbon
benzo[s]picene (1) has been relatively unexplored as a
consequence of its relative synthetic inaccessibility.1
Resu lts a n d Discu ssion
The successful synthetic route to 1 entails two oxida-
tive photocyclizations (Scheme 1) in the key steps. Wittig
reaction of 2-acetylnaphthalene with benzyltriphenylphos-
phonium chloride and NaH gave the expected olefin 6,
1
shown by the complexity of its H NMR spectrum to be
a mixture of Z- and E-isomers. Although the pure
isomers were separable by recrystallization, it was more
efficient to employ the mixture directly in the next step
because photocatalyzed interconversion of the Z- and
E-isomers occurs with facility.7 Photocyclodehydrogena-
tion of 6 took place smoothly in the presence of I2 and
epoxybutane8 to furnish 6-methylbenzo[c]phenanthrene
(7a ) arising from regiospecific bond formation in the more
reactive 1-position of the naphthalene ring. Bromination
of 7a with N-bromosuccinimide and benzoyl peroxide in
refluxing CCl4 provided 6-bromomethylbenzo[c]phenan-
threne (7b). Reaction of 7b with triphenylphosphine
gave the corresponding phosphonium salt 6-(benzo[c]-
phenanthryl)methyltriphenylphosphonium bromide (7c).
The phosphonium salt 7c was employed as the starting
compound for the synthesis of benzo[s]picene (1) and its
3,4-dihydrodiol (4) and diol epoxide (5) derivatives.
Wittig reaction of 7c with benzaldehyde furnished â-(6-
benzo[c]phenanthryl)styrene (8) as a mixture of E- and
Z-isomers in approximately 1:1 ratio. Photocyclization
of 8 in the presence of I2 and epoxybutane took place
smoothly to furnish 1 in good overall yield. Wittig
reaction of 7c with 2,3-dimethoxybenzaldehyde furnished
the dimethoxy-substituted derivative of the olefin 8 (9),
predominantly as the Z-isomer with only a trace of the
E-isomer detectable by NMR analysis. The strong pref-
erence for formation of the Z-isomer in the Wittig reaction
of 2,3-dimethoxybenzaldehyde versus benzaldehyde ac-
cords with previous observations.9 Although direct evi-
dence concerning the reason for this difference is lacking,
it is reasonable to suggest that the methoxy group may
interact with the positively charged phosphorus atom in
the reaction intermediate to favor elimination to form this
isomer.
Our interest in 1 was stimulated by its potential carci-
nogenicity; that is, it has two fjord regions, a structural
feature characteristic of some of the most potent carci-
nogenic hydrocarbons known (e.g. dibenzo[def,p]chry-
sene2 and benzo[g]chrysene3). Like both of these pol-
yarenes, 1 is presumed to be distorted from planarity due
to steric interference between the fjord region atoms.4
(1) Harvey, R. G. Polycyclic Aromatic Hydrocarbons, Wiley-VCH:
New York, 1997.
(2) Higginbotham, S.; Ramakrishna, N. V. S.; J ohansson, S. I.;
Rogan, E. G.; Cavalieri, E. L. Carcinogenesis 1993, 14, 875. Dibenzo-
[def,p]chrysene is the name for this hydrocarbon in the widely
employed IUPAC nomenclature, cf Harvey, R. G. Polycyclic Aromatic
Hydrocarbons, Wiley-VCH: New York, 1997. It is commonly referred
to as dibenzo[a,l]pyrene in the biological literature.
(3) Szeliga, J .; Lee, H.; Harvey, R. G.; Page, J . E.; Ross, H. L.;
Routledge, M. N.; Hilton, B. D.; Dipple, A. Chem. Res. Toxicol. 1994,
7, 420.
(4) Deviation from planarity is associated with carcinogenicity, and
it has been proposed that this effect may have its basis in increased
binding of the active diol epoxide metabolites to deoxyadenosine sites
in DNA; see, Dipple, A. In DNA Adducts: Identification and Biological
Significance; Hemminki, K.; Dipple, A.; Segerba¨ck, D.; Kadlubar, F.
F.; Shuker, D.; Bartsch, H., Eds.; IARC: Lyon, France, 1994; pp 107-
129; Szeliga, J .; Lee, H.; Harvey, R. G.; Page, J . E.; Ross, H. L.;
Routledge, M. N.; Hilton, B. D.; Dipple, A. Chem. Res. Toxicol. 1994,
7, 420.
(5) Tang, X.-Q.; Harvey, R. G. J . Org. Chem. 1995, 60, 3568.
(6) Zhang, F.-J .; Harvey, R. G. J . Org. Chem. 1998, 63, 1168.
(7) Mallory, F. B.; Mallory, C. W. Org. Reactions 1984, 30, 1.
(8) Epoxybutane serves to prevent competing secondary reactions,
principally reduction of the olefin by HI, by scavenging the HI
produced; see, Liu, L. B.; Yang, B. W.; Katz, T. J .; Poindexter, M. K.
J . Org. Chem. 1991, 56, 3769.
(9) Zhang, J .-T.; Dai, W.; Harvey, R. G. J . Org. Chem. 1998, 63, 0000.
S0022-3263(98)00661-6 CCC: $15.00 © 1998 American Chemical Society
Published on Web 08/08/1998

6406 J . Org. Chem., Vol. 63, No. 18, 1998
Notes
Sch em e 1
Sch em e 2
ing separation. If significant activity is found, the
isomers may be resolved by the methods devised for the
separation of other similar types of compounds, such as
resolution on a chiral column,11 and the individual
enantiomers can then be tested for activity.
Exp er im en ta l Section
Mater ials an d Meth ods. Benzyltriphenylphosphonium chlo-
ride was purchased from Aldrich. m-Chloroperbenzoic acid
(Aldrich) was purified by washing with pH 7.4 phosphate buffer
and drying under reduced pressure. N-Bromosuccinimide (NBS)
was purified by recrystallization from water. Tetrahydrofuran
(THF) was distilled from sodium benzophenone ketyl. The 1H
NMR spectra were recorded on 400 or 500 MHz spectrometers
in CDCl3 with tetramethylsilane as internal standard unless
stated otherwise; integration was consistent with the structural
assignments. All melting points are uncorrected. Ca u tion :
Although benzo[s]picene is not an established carcinogen, it and
its dihydrodiol and diol epoxide metabolites are potentially
hazardous and should be handled in accordance with “NIH
Guidlines for the Laboratory Use of Chemical Carcinogens.”
Photoreaction of 9 took place readily to afford the
cyclized product 3,4-dimethoxybenzo[s]picene (10a ) in
excellent yield. As in the synthesis of 7a , interconversion
of the Z- and E-isomers took place with facility during
the photocyclization of both 8 and 9.
Conversion of 10a to the 3,4-dihydrodiol (4) was
accomplished via initial demethylation with BBr3 to 3,4-
dihydroxybenzo[s]picene (10b). In view of the well-
known air sensitivity of polycyclic aromatic hydroquino-
nes, 10b was isolated and characterized as its diacetate
(10c).10 Reduction of 10c with NaBH4 with O2 bubbling
through the solution (Scheme 2) took place smoothly with
concurrent deacetylation to provide trans-3,4-dihydroxy-
3,4-dihydrobenzo[s]picene (4) free of the corresponding
cis-diastereomer.11 The coupling constant for the carbinol
protons of 4 was 11 Hz, indicating existence of the
dihydrodiol in solution predominantly as the trans
diequatorial conformer, consistent with previous findings
for other sterically unrestricted trans-dihydrodiols.11
Conversion of 4 to the corresponding anti-diol epoxide
(5) took place stereospecifically on treatment with m-
chloroperbenzoic acid (m-CPBA). It was shown in previ-
ous studies that epoxidation with m-CPBA of trans-
dihydrodiols free to adopt the diequatorial conformation
generally takes place stereoselectively to afford the anti-
diastereomeric diol epoxides.11
â-Meth yl-â-(2-n a p h th yl)styr en e (6). Benzyltriphenylphos-
phonium chloride (25.20 g, 64.8 mmol) was added in three
portions to a stirred suspension of NaH (2.60 g, 65.0 mmol, 60%
in mineral oil) under argon. The suspension was stirred for 1 h
at room temperature, then 2-acetylnaphthalene (10.00 g, 59
mmol) was added, and the resulting orange mixture was heated
at 70 °C for 2 h. The reaction mixture was cooled and poured
onto ice, stirred for 1 h, then extracted with ether (3 × 500 mL).
The organic layer was washed with water, dried over MgSO4,
and evaporated to dryness. Chromatography of the residue on
a silica gel column eluted with hexanes-CH2Cl2 (9:1) afforded
6 (10.57 g, 83%) as a mixture of Z- and E-isomers. Recrystal-
lization of this mixture from EtOAc-hexane afforded the pure
E-isomer of 6 (7.76 g) as white crystals, mp 144-145 °C (lit.12
137-138 °C); recrystallization of the residue from the filtrate
from hexane gave an additional 1.25 g of 6 (E-isomer with traces
of Z-isomer). Evaporation of the filtrate gave essentially pure
Z-isomer (2.93 g) as a white solid, mp 68-70 °C. E-isomer: 1H
NMR δ 7.94 (s, 1H), 7.86 (d, J ) 8.7 Hz, 1H), 7.84 (d, J ) 8.8
Hz, 2H), 7.72 (dd, J ) 1.8, 8.6 Hz, 1H), 7.38-7.51 (m, 6H), 7.25-
7.28 (m, 1H), 7.01 (s, 1H), 2.39 (s, 3H); Z-isomer: 1H NMR δ
7.81 (dd, J ) 3.4, 6.0 Hz, 1H), 7.76 (dd, J ) 3.4, 6.0 Hz, 1H),
7.72 (d, J ) 8.9 Hz, 1H), 7.71 (s, 1H), 7.46 (dd, J ) 6.2, 6.3 Hz,
2H), 7.28 (dd, J ) 1.5, 8.4 Hz, 1H), 7.05-7.09 (m, 3H), 6.98-
6.99 (m, 2H), 6.58 (s, 1H), 2.31 (s, 3H).
As a consequence of their mode of synthesis, the trans-
dihydrodiol (4) and the anti-diol epoxide (5) are racemic.
Although separation of the enantiomers at this stage is
possible, it is more convenient to assay the mixture for
biological activity prior to attempting their time-consum-
(10) The crude 10a obtained as a white solid darkened quickly on
exposure to air.
(11) The trans-stereoselectivity of these reductions is well estab-
lished; see Harvey, R. G. Polycyclic Aromatic Hydrocarbons: Chemistry
and Carcinogenesis, Cambridge University: Cambridge, England,
1991; Chapter 13.
(12) Nagel, D. L.; Kupper, R.; Antonson, K.; Wallcave, L. J . Org.
Chem. 1977, 42, 3626.

Notes
6-Meth ylben zo[c]p h en a n th r en e (7a ). Argon was bubbled
J . Org. Chem., Vol. 63, No. 18, 1998 6407
1H), 6.47-6.49 (m, 2H), 3.91 (s, 3H), 3.84 (s, 3H). Anal. Calcd
for C28H22O2: C, 86.12; H, 5.68. Found: C, 85.95; H, 5.70.
through a stirred solution of 6 (2.0 g, 8.2 mmol) and I2 (2.1 g,
8.3 mmol) in 700 mL of Et2O-cyclohexane (1:1) for 30 min before
12 mL of 1,2-epoxybutane was added. The solution was irradi-
ated by UV light generated from a Hanovia 400-W medium-
pressure lamp using a Vycor filter, maintaining the argon flow
throughout the procedure. After 4 h, NMR analysis showed
consumption of 6 to be complete. Removal of the solvent under
reduced pressure and passage of the residue through a short
silica gel column eluted with hexane gave 7a (1.90 g, 96%) as a
white solid, mp 76-77 °C (lit.10 76.8-77.6 °C): 1H NMR δ 9.11
(d, J ) 8.2 Hz, 1H), 9.04 (d, J ) 9.4 Hz, 1H), 8.05 (d, J ) 8.8 Hz,
1H), 8.03 (d, J ) 8.4 Hz, 1H), 7.95 (t, J ) 8.8 Hz, 1H), 7.94 (d,
J ) 9.4 Hz, 1H), 7.75 (s, 1H), 7.58-7.67 (m, 4H), 2.83 (s, 3H).
3,4-Dim eth oxyben zo[s]p icen e (10a ). Photocyclization of
9 (205 mg, 0.53 mmol) was carried out by the procedure
employed for the synthesis of 7a (reaction time 2 h). The usual
workup and chromatography through a short Florisil column
gave 10a (196 mg, 96%) as a white solid, mp 211-213 °C
(hexanes-EtOAc): 1H NMR δ 9.01 (d, J ) 8.4 Hz, 1H), 8.97
(dd, J ) 5.2, 7.0 Hz, 1H), 8.92 (dd, J ) 5.2, 6.9 Hz, 1H), 8.76 (d,
J ) 9.3 Hz, 1H), 8.64 (d, J ) 9.0 Hz, 2H), 8.38 (d, J ) 9.2 Hz,
1H), 8.05 (d, J ) 8.8 Hz, 2H), 8.04 (d, J ) 7.5 Hz, 1H), 7.68 (t,
J ) 7.1, 8.3 Hz, 1H), 7.60-7.65 (m, 3H), 7.44 (d, J ) 9.3 Hz,
1H), 4.10 (s, 3H), 4.09 (s, 3H). Anal. Calcd for C28H20O2: C,
86.57; H, 5.19. Found: C, 86.51; H, 5.20.
6-Br om om eth ylben zo[c]p h en a n th r en e (7b). A solution
of 7a (8.50 g, 35.1 mmol), NBS (6.50 g, 36.5 mmol), and benzoyl
peroxide (180 mg) in 250 mL of CCl4 was heated at reflux for 2
h. The reaction mixture was cooled to room temperature,
filtered, and evaporated to dryness. Chromatography of the
product on a Florisil column eluted with hexanes-EtOAc (99:
1) afforded 7b (10.27 g, 91%) as a yellow solid, mp 77-79 °C
(EtOAc-hexane): 1H NMR δ 9.07 (d, J ) 9.2 Hz, 1H), 9.05 (d,
J ) 9.2 Hz, 1H), 8.19 (d, J ) 8.8 Hz, 1H), 8.05 (d, J ) 7.7 Hz,
1H), 8.03 (d, J ) 8.8 Hz, 1H), 7.99 (t, J ) 10.0 Hz, 1H), 7.98 (s,
1H), 7.61-7.70 (m, 4H), 5.09 (s, 2H); MS (m/e) 320 (M+, 20), 241
(M+,-Br 100) (based on Br, 79); HRMS: calcd for C19H13Br:
320.0201. Found: 320.0194.
3,4-Dih yd r oxyben zo[s]p icen e (10b). To a solution of 10a
(210 mg, 0.54 mmol) in 200 mL of CH2Cl2 was added in a
dropwise manner 5.4 mL of a solution of BBr3 (1.0 M solution
in CH2Cl2) at 0 °C. Stirring was continued at this temperature
for 40 min, and then the reaction was quenched by addition of
water. The solvent was evaporated under reduced pressure,
EtOAc was added, and the organic layer was washed with water,
dried over Na2SO4, and evaporated to dryness to yield 10b (194
mg) as a white solid that darkened quickly in air: 1H NMR (CD3-
COCD3) δ 9.01 (d, J ) 8.5 Hz, 1H), 8.99 (d, J ) 9.6 Hz, 1H),
8.97 (d, J ) 9.5 Hz, 1H), 8.96 (d, J ) 9.5 Hz, 1H), 8.80 (d, J )
9.0 Hz, 1H), 8.72 (d, J ) 9.3 Hz, 1H), 8.45 (d, J ) 9.1 Hz, 1H),
8.44 (d, J ) 9.0 Hz, 1H), 8.15 (d, J ) 8.9 Hz, 1H), 8.13 (d, J )
8.0 Hz, 1H), 7.73 (t, J ) 7.7 Hz, 1H), 7.64-7.69 (m, 2H), 7.40
(d, J ) 9.0 Hz, 1H). In view of the air sensitivity of 10b, it was
isolated and characterized as the diacetate (10c).
6-(Ben zo[c]p h en a n th r yl)m eth yltr ip h en ylp h osp h on iu m
br om id e (7c). A solution of 7b (4.94 g, 15.4 mmol) and PPh3
(4.45 g, 17.0 mmol) in 65 mL of toluene was heated at reflux
overnight. The usual workup gave 7c (8.09 g, 90%) as a white
solid, mp 284-286 °C: 1H NMR δ 8.87 (d, J ) 8.3 Hz, 1H), 8.83
(d, J ) 8.5 Hz, 1H), 7.94 (d, J ) 4.0 Hz, 1H), 7.78 (d, J ) 7.7 Hz,
1H), 7.42-7.75 (m, 21H), 7.34 (d, J ) 8.9 Hz, 1H), 6.02 (d, J )
14.0 Hz, 2H). Anal. Calcd for C37H28BrP: C, 76.16; H, 4.84;
Br, 13.69. Found: C, 76.09; H, 4.83; Br, 13.76.
3,4-Acetoxyben zo[s]p icen e (10c). The crude 10b was
dissolved in 7.0 mL of Ac2O and 5.0 mL of pyridine, and the
solution was stirred overnight at room temperature. The usual
workup afforded 10c (220 mg, 91%) as a white solid, mp 220-
222 °C (hexanes-EtOAc): 1H NMR δ 9.02 (d, J ) 8.3 Hz, 1H),
8.96-8.97 (m, 1H), 8.92 (d, J ) 9.3 Hz, 1H), 8.89-8.91 (m, 1H),
8.70 (d, J ) 9.3 Hz, 1H), 8.61 (d, J ) 8.9 Hz, 1H), 8.06 (d, J )
8.8 Hz, 2H), 8.05 (d, J ) 6.5 Hz, 1H), 7.63-7.71 (m, 4H), 7.53
(d, J ) 9.3 Hz, 1H), 2.55 (s, 3H), 2.41 (s, 3H). Anal. Calcd for
C30H20O4: C, 81.06; H, 4.54. Found: C, 80.78; H, 4.53.
â-(6-Ben zo[c]p h en a n th r yl)styr en e (8). To a solution of the
phosphonium salt 7c (1.50 g, 2.6 mmol), benzaldehyde (285 mg,
2.7 mmol), and a catalytic amount of 18-crown-6 in 45 mL of
CH2Cl2 was added to 4.7 mL of a 50% aqueous solution of NaOH,
and stirring was continued overnight. The usual workup
followed by chromatography on a silica gel column eluted with
hexane gave 8 (762 mg, 91%) as a mixture of Z- and E-isomers
(∼1:1). Z-isomer, white semisolid: 1H NMR δ 9.14 (d, J ) 8.4
Hz, 1H), 9.10 (d, J ) 8.5 Hz, 1H), 8.15 (d, J ) 8.8 Hz, 1H), 8.03
(dd, J ) 1.6, 8.0 Hz, 1H), 7.91 (t, J ) 8.8 Hz, 1H), 7.83 (d, J )
7.9 Hz, 1H), 7.78 (s, 1H), 7.62-7.71 (m, 3H), 7.56 (t, J ) 7.4 Hz,
1H), 7.03-7.16 (m, 6H), 6.93 (d, J ) 12 Hz, 1H). Anal. Calcd
tr a n s-3,4-Dih yd r oxy-3,4-d ih yd r ob en zo[s]p icen e (4).
A
suspension of 10c (67 mg, 0.15 mmol) and NaBH4 (200 mg, 5.35
mmol) in 150 mL of EtOH with O2 bubbling through the solution
was stirred at ambient temperature for 24 h. EtOH was
removed under reduced pressure, water was added, and the
aqueous suspension was extracted with EtOAc-ether. The
combined organic extracts were washed with brine, dried over
Na2SO4, and evaporated to dryness. Chromatography of the
product on a short Florisil column eluted with hexane-THF (1:
1) gave 4 (47 mg 86%) as a white solid, mp 238-241 °C
(triturated with acetone): 1H NMR (DMSO-d6) δ 8.83 (d, J )
8.3 Hz, 1H), 8.68-8.72 (m, 3H), 8.11 (d, J ) 8.6 Hz, 2H), 7.92
(d, J ) 8.3 Hz, 1H), 7.71 (t, J ) 7.0, 8.3 Hz, 1H), 7.61-7.68 (m,
3H), 7.14 (dd, J ) 2.2, 10.0 Hz, 1H), 6.22 (dd, J ) 2.2, 10.0 Hz,
1H), 5.71 (d, J ) 5.9 Hz, 1H, exchangeable with D2O), 5.38 (d,
J ) 5.0 Hz, 1H, exchangeable with D2O), 4.59-4.61 (m, 1H, after
addition of D2O changed to doublet, J ) 11.0 Hz), 4.50-4.53
(m, 1H, after addition of D2O changed to doublet, J ) 11.0 Hz);
MS (m/e) 362 (M+, 15); HRMS: Calcd for C26H18O2: 362.1307.
Found: 362.1312. UV (EtOH) λmax (ꢀ): 214 (3.87 × 104), 288
(8.77 × 104) nm.
for C26H18
: C, 94.51; H, 5.49. Found: C, 94.55; H, 5.49.
E-isomer, white semisolid: 1H NMR δ 9.10 (d, J ) 8.2 Hz, 1H),
9.05 (d, J ) 9.0 Hz, 1H), 8.21 (d, J ) 8.8 Hz, 1H), 8.11 (s, 1H),
8.03-8.06 (m, 2H), 7.95 (d, J ) 8.8 Hz, 1H), 7.93 (d, J ) 16 Hz,
1H), 7.61-7.70 (m, 6H), 7.43 (t, J ) 7.4, 7.8 Hz, 2H), 7.34 (t, J
) 7.4 Hz, 1H), 7.25 (d, J ) 16 Hz, 1H). Anal. Calcd for C26H18
C, 94.51; H, 5.49. Found: C, 94.61; H, 5.45.
:
Ben zo[s]p icen e (1). Photocyclization of 8 (232 mg, 0.74
mmol) was carried out by the procedure employed for the
synthesis of 7a (reaction complete in 2 h by NMR). Chroma-
tography of the product on a short Florisil column furnished 1
(220 mg, 95%) as a white solid, mp 204-205 °C (EtOAc) (lit.5
198-199 °C): 1H NMR δ 9.02 (d, J ) 8.3 Hz, 2H), 8.97 (dd, J )
6.2, 6.2 Hz, 2H), 8.65 (d, J ) 9.0 Hz, 2H), 8.06 (d, J ) 8.8 Hz,
2H), 8.04 (dd, J ) 1.3, 7.8 Hz, 2H), 7.61-7.71 (m, 6H).
â-(6-Ben zo[c]ph en an th r yl)-2,3-dim eth oxystyr en e (9). Wit-
tig reaction of the phosphonium salt 7c (4.95 g, 8.5 mmol) with
2,3-dimethoxybenzaldehyde (1.42 g, 8.5 mmol), was conducted
by the procedure employed for the preparation of 8. The usual
workup and chromatography on a column of silica gel eluted with
hexanes-EtOAc (95:5) gave a yellow semisolid product identified
as the Z-isomer of 9 (3.12 g, 94%) with only a trace amount of
the E-isomer: 1H NMR δ 9.13 (d, J ) 8.7 Hz, 1H), 9.08 (d, J )
8.5 Hz, 1H), 8.16 (d, J ) 8.7 Hz, 1H), 8.03 (d, J ) 7.8 Hz, 1H),
7.92 (d, J ) 8.8 Hz, 1H), 7.80 (d, J ) 7.9 Hz, 1H), 7.72 (s, 1H),
7.69 (t, J ) 7.0, 8.4 Hz, 1H), 7.61-7.65 (m, 2H), 7.54 (t, J ) 7.2,
7.7 Hz, 1H), 7.20 (d, J ) 3.2 Hz, 2H), 6.65 (dd, J ) 6.3, 6.2 Hz,
tr a n s-3,4-Dih ydr oxy-a n ti-1,2-epoxy-1,2,3,4-tetr ah ydr oben -
zo[s]p icen e (5). To a solution of 4 (51 mg, 0.14 mmol) in freshly
distilled THF (6 mL) was added m-CPBA (242 mg, 1.4 mmol).
Stirring was continued for 2 h, then the solution was diluted
with THF and ether, and washed with cold aqueous 10% NaOH,
water, and dried over Na2SO4. The solvent was removed under
reduced pressure without heating and triturated with ether to
yield 5 (48 mg, 90%) as a white solid, mp 213-215 °C: 1H NMR
(DMSO-d6) δ 8.85 (d, J ) 8.5 Hz, 1H), 8.79 (d, J ) 8.6 Hz, 1H),
8.75 (dd, J ) 3.6, 8.9 Hz, 1H), 8.73 (d, J ) 9.0 Hz, 1H), 8.51-
8.53 (m, 1H), 8.14 (d, J ) 9.0 Hz, 1H), 8.13 (d, J ) 7.8 Hz, 1H),
7.98 (d, J ) 8.4 Hz, 1H), 7.69-7.74 (m, 3H), 7.66 (t, J ) 7.1, 7.6
Hz, 1H), 5.85 (d, J ) 6.4 Hz, 0.6H, exchangeable with D2O), 5.68
(d, J ) 5.0 Hz, 0.6H, exchangeable with D2O), 4.71 (d, J ) 4.3

6408 J . Org. Chem., Vol. 63, No. 18, 1998
Notes
Hz, 1H), 4.67 (t, J ) 6.9, 8.4 Hz, 1H), 3.77 (t, J ) 5.6, 8.6 Hz,
1H), 3.74 (d, J ) 4.4 Hz, 1H), MS (m/e) 378 (M+, 5), 154 (11);
HRMS: Calcd for C26H18O2: 378.1256. Found: 378.1256. UV
(EtOH) λmax (ꢀ): 209 (4.96 × 104), 270 (6.61 × 104), 279 (8.07 ×
104), 289 (8.14 × 104) nm.
Ack n ow led gm en t. This research was supported by
grants from the American Cancer Society (CN-22) and
the National Cancer Institute (CA 67937).
J O9806613