Dai et al.
Benzo[a]pyrene-6-boronic acid (4): yield 52%. Trimethylborate
6 equiv) was used instead of triisopropylborate. H NMR (500.1
130.63, 130.31, 128.62(3), 127.41, 127.37, 127.31, 126.73, 126.25,
126.0, 125.70, 125.57, 125.10, 124.87, 124.25, 124.15, 123.78,
1
(
+
MHz, DMSO-d
d, 1H, J ) 7.5 Hz), 8.29 (d, 1H, J ) 7.5 Hz), 8.31 (d, 1H, J ) 7.5
Hz), 8.33 (d, 1H, J ) 8.0 Hz), 8.42 (d, 1H, J ) 9.0 Hz), 8.97 (br,
6
) δ 7.84-7.90 (m, 2H), 8.02-8.08 (m, 3H), 8.18
123.66; APCI-MS m/e 336.1 [M ].
1
(
8-Phenylguanine: yield 83%. H NMR (500.1 MHz, DMSO-
d ) δ 6.41 (br s, 2H), 7.44-7.48 (m, 3H), 7.98 (J ) 7.2 Hz, d,
6
13
13
2
(
1
1
H), 9.24 (d, 1H, J ) 8.0 Hz), 9.25 (d, 1H, J ) 9.0 Hz); C NMR
125.8 MHz, DMSO-d ) δ 122.5, 123.5, 124.7, 124.7, 125.4, 126.0,
26.3, 126.6, 127.1, 127.2, 127.4, 129.2, 129.7, 130.5, 131.0, 131.1,
2H), 10.59 (br s, 1H), 12.82 (br s, 1H); C NMR (125.8 MHz,
DMSO-d
125.5, 117.61, 129.1; HRMS calcd for C19
found 312.1254.
6
6
) δ 157.03, 157.73, 153.60, 145.0, 130.28, 129.03, 126.5,
+
H
14 5
N [M ] 312.1249,
-
32.5; HRMS calcd for C20
12 1 2
H B O [M ] 295.0930, found 295.0924.
8
1
General Procedure for Synthesis of C -PAH-2′-deoxyadenos-
ine or C -PAH-2′-deoxyguanosine Adducts by the Suzuki-
Miyaura Coupling Method. To a 150 mL pyrex culture tube
8-(1-Pyrenyl)guanine (2b): yield 91%. H NMR (500.1 MHz,
8
DMSO-d
(m, 7H), 9.52 (d, 1H, J ) 7.1 Hz), 10.69 (br s, 1H), 13.05 (br s,
1H); 13C NMR (125.8 MHz, DMSO-d
) δ 156.89, 153.70, 153.29,
6
6
) δ 6.48 (br s, 2H), 8.12 (t, 1H, J ) 7.6 Hz), 8.20-8.43
containing 10 mL of acetonitrile/H
PAH-boronic acid (1.12 mmol), NaCO
TPPTS (29.6 mg, 0.052 mmol), Pd(OAc)
2
O (1:2, v/v) were added the
3
(160 mg, 1.5 mmol),
(4.4 mg, 0.02 mmol),
145.08, 131.29, 130.99, 130.69, 128.60, 128.50, 127.71, 127.65,
2
126.98, 126.59, 126.11, 125.78, 125.44, 125.14, 124.71, 124.56,
+
and 8-bromo-2′-deoxyadenosine or 8-bromo-2′-deoxyguanosine (1.1
mmol). The tube was sealed and heated overnight at 80 °C with
124.11, 118.17; HRMS calcd for C21
H N O
14 5 1
[M ] 352.1198, found
352.1216.
7-Benz[a]anthracenecarboxaldehyde (15).34 1H NMR (500.1
stirring. Water (10 mL) and 10% KH
2
PO
4
(20 mL) were added,
and the mixture was heated at 90 °C for 2 h. The solution was
allowed to cool to room temperature, and further cooled in an ice
bath for several hours. The precipitate was filtered and washed
sequentially with 50 mL each of water, hexane, ether, and EtOAc,
6
MHz, DMSO-d ) δ 11.48 (s, 1H), 9.89 (s, 1H), 9.09 (d, J ) 8.1
Hz, 1H), 9.01 (d, 1H, J ) 8.8 Hz), 8.79 (d, 1H, J ) 9.6 Hz), 8.39
(d, 1H, J ) 8.2 Hz), 8.04 d, 1H, J ) 7.7 Hz), 8.01 (d, 1H, J ) 9.7
1
3
Hz), 7.79-7.82 (m, 2H), 7.73-7.77 (m, 2H); C NMR (125.8
then dried in air.
MHz, DMSO-d
6
) δ 193.6, 132.0, 131.2, 131.0, 131.0, 130.8, 130.1,
1
8-(1-Naphthyl)-2′-deoxyadenosine (7a): yield 58%. H NMR
129.4, 128.9, 128.9, 128.6, 128.2, 127.6, 127.6, 126.1, 125.9, 123.6,
122.8, 121.5; HRMS calcd for C19
257.0966.
+
(
500.1 MHz, DMSO-d
H), 3.64 (m, 1H), 3.74 (br s, 1H), 4.32 (br, 1H), 5.09 (br, 1H),
.74 (m, 2H), 7.51 (br s, 2H), 7.55-7.58 (m, 1H), 7.61-7.65 (m,
H), 7.69-7.74 (m, 2H), 8.09 (J ) 8 Hz, d, 1H), 8.19 (J ) 9 Hz,
6
) δ 2.00 (br, 1H), 3.15 (br, 1H), 3.47 (br,
13 1
H O [M ] 257.0966, found
1
5
2
6-Benzo[a]pyrenecarboxaldehyde (17). To a solution of benzo-
[a]pyrene35 (1 g, 4 mmol) in DMF (10 mL) in a 150 mL pyrex
+
d, 1H), 8.20 (s, 1H); HRMS calcd for C20
found 378.1562.
H N O
20 5 3
[M ] 378.1566,
3
culture tube were added POCl (1.2 g) and N-methylformanilide
(1.2 g). The screw cap was sealed, and the reaction tube was heated
at 90 °C overnight. The reaction mixture was cooled and washed
with 40 mL of diethyl ether. The red slurry was recovered and
mixed with Na CO (2.5 g/50 mL water) in a 150 mL beaker. The
2 3
green precipitate that formed was filtered, washed with a copious
1
8-(9-Phenanthryl)-2′-deoxyadenosine (8a): yield 80%. H NMR
(
1
6
500.1 MHz, DMSO-d ) δ 1.99 (br, 1H), 3.47 (br, 1H), 3.64 (br,
H), 3.72 (s, 1H), 4.30 (br, 1H), 5.05 (br, 1H), 5.78 (br, 2H), 7.55
(
br, 2H), 7.66-7.69 (m, 2H), 7.73-7.81 (m, 2H), 7.83-7.86 (m,
1
1
4
H), 8.14 (d, 1H), 8.15 (s, 1H), 8.22 (s, 1H), 8.96 (J ) 8.5 Hz, d,
amount of water, and dried in the air to furnish 16 essentially
+
1
H), 9.00 (J ) 8.5 Hz, d, 1H); HRMS calcd for C24
H
21
N
5
O
3
[M ]
quantitatively: H NMR (500.1 MHz, DMSO-d
6
) δ 7.96-7.98 (m,
28.1723, found 428.1736.
2H), 8.18 (t, 1H, J ) 7.6 Hz), 8.34 (d, 1H, J ) 9.6 Hz), 8.41 (d,
1H, J ) 7.3 Hz), 8.54 (d, 1H, J ) 7.7 Hz), 8.68 (d, 1H, J ) 9.1
Hz), 9.06 (d, 1H, J ) 9.6 Hz), 9.27-9.30 (m, 1H), 9.35-9.39 (m,
1
8
-(1-Pyrenyl)-2′-deoxyguanosine (2a): yield 65%. H NMR
500.1 MHz, DMSO-d ) δ 1.94 (m, 1H), 3.02 (br s, 1H), 3.39 (m,
H), 3.47 (m, 1H), 3.62 (s, 1H), 4.14 (s, 1H), 5.00 (br, 1H), 5.15
(
1
6
2H), 11.61 (s, 1H); 13C NMR (125.8 MHz, DMSO-d
6
) δ 194.9,
(
8
br, 1H), 5.80 (br, 1H), 6.84 (br s, 2H), 8.02 (d, 1H, J ) 9 Hz),
131.7, 131.4, 131.3, 131.1, 130.7, 129.7, 128.9, 128.4, 127.9, 127.4,
127.3, 127.1, 126.8, 124.7, 124.0, 123.8, 123.48, 122.8, 122.6,
.13-8.17 (m, 2H), 8.25-8.33 (m, 3H), 8.37 (d, 1H, J ) 7.5 Hz),
.40 (d, 1H, J ) 7.5 Hz), 8.43 (J ) 8 Hz, d, 1H), 11.82 (br s, 1H);
+
+
8
121.8; EI-MS m/e 280.1 [M ]; HRMS calcd for C21
H O
12 1
[M ]
1
3
C NMR (125.8 MHz, DMSO-d
6
) δ 158.0, 154.4, 152.1, 145.6,
280.0888, found 280.0872
1
1
6
4
32.0, 131.2, 130.7, 130.5, 129.0, 128.9, 128.9, 127.6, 127.1, 126.4,
10-Dibenzo[def,p]chrysenecarboxaldehyde (18). To a solution
of dibenzo[def,p]chrysene36 (100 mg, 0.33 mmol) in 1,2-dichlo-
robenzene (0.5 mL) in a 10 mL pyrex culture tube were added
26.2, 125.3, 125.0, 124.8, 124.1, 123.9, 118.0, 88.2, 85.3, 71.6,
+
2.5, 37.5; HRMS calcd for C26
H N O
22 5 4
[M ] 468.1672, found
68.1651.
3
N-methylformanilide (0.11 g) and POCl (0.11 g). The mixture was
8
8
Synthesis of C -Aryladenine and C -Arylguanine Adducts.
heated at 90 °C for 8 h and monitored by TLC. The mixture was
poured into water (2 mL) and extracted with EtOAc (500 mL),
and the organic layer was washed with water (3 × 100 mL) and
Deglycosylation of 2′-deoxyribonucleoside adducts was conducted
by the procedure reported in ref 23b.
1
2 4
dried over anhydrous Na SO . Evaporation of most of the solvent
8
-(1-Naphthyl)adenine (7b): yield 83%. H NMR (500.1 MHz,
DMSO-d ) δ 7.24 (br s, 2H), 7.61-7.63 (m, 2H), 7.66 (t, 1H, J )
.0 Hz), 7.97 (d, 1H, J ) 7.0 Hz), 8.04 (d, 1H, J ) 8.5 Hz), 8.08
d, 1H, J ) 8.0 Hz), 8.17 (s, 1H), 9.05 (d, 1H, J ) 7.5 Hz), 13.32
followed by filtration of the solid precipitate afforded 17 (96 mg,
6
1
8
88%) sufficiently pure for reaction: H NMR (500.1 MHz, DMSO-
(
(
6
d ) δ 11.58 (s, 1 H), 9.31 (d, J ) 8.0 Hz, 1 H), 9.25 (d, J ) 8.0
s, 1H); 1 C NMR (125.8 MHz, DMSO-d
3
Hz, 1 H), 9.16 (d, J ) 8.0 Hz, 1 H), 9.07 (dd, J ) 8.0 and 5.0 Hz,
2 H), 8.94 (d, J ) 8.0 Hz, 1 H), 8.39 (d, J ) 8.0 Hz, 1 H), 8.29 (d,
J ) 10.0 Hz, 1 H), 8.20 (t, J ) 8.0 Hz, 1 H), 7.98 (d, J ) 8.0 Hz,
1 H), 7.94 (d, J ) 8.0 Hz, 1 H), 7.86 (d, J ) 8.0 Hz, 1 H), 7.84 (d,
6
) δ 155.69, 152.62,
1
1
2
51.26, 148.19, 133.55, 130.36, 130.16, 128.37, 127.97, 127.09,
26.36(2), 125.23, 119.70; HRMS calcd for C15
+
12 5
H N [M ]
62.1093, found 262.1105.
1
3
1
J ) 8.0 Hz, 1 H); C NMR (125.8 MHz, DMSO-d ) δ 194.6, 132.1,
8-(9-Phenanthryl)adenine (8b): yield 98%. H NMR (DMSO-
6
1
31.8, 131.7, 131.5, 131.1, 129.4, 129.0, 128.8, 128.7, 128.3, 128.1,
d
6
) δ 7.30 (br s, 2H), 7.68-7.75 (m, 2H), 7.77-7.85 (m, 2H), 8.09
1
27.7, 127.3, 126.3, 124.7, 124.6, 124.0, 123.2, 122.9, 122.6, 122.3;
(
d, 1H, J ) 8 Hz), 8.19 (s, 1H), 8.33 (s, 1H), 8.91 (d, 1H, J ) 8
+
HRMS calcd for C25
H14O [MH ] 331.1123, found 331.1135.
Hz), 8.96 (d, 1H, J ) 8 Hz), 9.00 (d,1H, J ) 8.5 Hz), 13.44 (br s,
1
1
1
H); 13C NMR (125.8 MHz, DMSO-d
48.17, 130.38, 130.24, 129.57, 129.23, 129.00, 128.26, 127.46,
6
) δ 155.75, 152.74, 151.24,
(
34) Lee, H.; Harvey, R. G. J. Org. Chem. 1988, 53, 4587-4589. Fieser,
L. F.; Hartwell, J. L. J. Am. Chem. Soc. 1938, 60, 2555-2559.
35) Harvey, R. G.; Lim, K.; Dai, Q. J. Org. Chem. 2004, 69, 1372-
373.
36) Sharma, A. K.; Kumar, S.; Amin, S. J. Org. Chem. 2004, 69, 3979-
3982.
27.31, 127.05, 126.12, 123.29, 123.01, 119.68.
(
1
8
-(1-Pyrenyl)adenine (3b): yield 68%. H NMR (500.1 MHz,
1
DMSO-d
6
) δ 7.38 (br s, 2H), 8.13-8.51 (m, 9H), 9.41 (J ) 9.3
(
Hz, d, 1H); 13C NMR (125.8 MHz, DMSO-d
) δ 152.60, 130.89,
6
4862 J. Org. Chem., Vol. 72, No. 13, 2007