10458 J. Am. Chem. Soc., Vol. 121, No. 45, 1999
De Riccardis et al.
MHz, CDCl3) δ -5.5 (× 2), -4.7 (× 2), 17.9, 18.3, 25.7 (× 3), 25.9
(× 3), 41.6, 62.5, 68.8, 71.4, 84.0, 87.8, 110.6, 118.1, 121.0, 122.9,
124.1, 125.1, 128.1 (× 2), 128.5 (× 2), 130.8, 133.6, 134.6, 135.6,
136.2, 139.9, 141.7, 143.0, 149.2, 152.2, 152.8, 160.3, 189.7; FABMS
m/z 809 [M + 1]+. Anal. Calcd for C42H52N6O7Si2: C, 62.35; H, 6.48;
N, 10.39. Found: C, 62.10; H, 6.01; N, 9.90.
CH3CO), 2.25 (1H, m, H-2′), 2.90 (1H, m, H′-2′), 3.45 (2H, m, H-5′),
3.73 (1H, m, H-4′), 3.87 (2H, s, C13H8), 4.29 (1H, m, H-3′), 6.11 (1H,
t, J ) 6.6 Hz, H-1′), 7.30 (2H, m, C13H8), 7.56 (1H, d, C13H8), 7.62
(1H, s, C13H8), 7.76 (1H, d, C13H8), 7.97 (1H, s, H-8), 8.11 (1H, s,
N-H), 8.36 (1H, s, C13H8), 9.66 (1H, s, N-H), 11.27 (1H, s, N-H);
13C NMR (62.5 MHz, DMSO-d6), δ -5.5 (× 2), -5.4 (× 2), 17.9,
18.4, 23.3, 25.7 (× 3), 26.0 (× 3), 36.72, 41.9, 62.8, 71.7, 84.7, 88.1,
114.5, 118.3, 119.6, 124.7, 125.0, 126.6, 126.9, 128.7, 132.9, 136.8,
139.3, 140.5, 141.8, 144.1, 150.6, 151.1, 158.8, 170.7; FABMS m/z
717 [M + 1]+.
N2-(2-Acetylaminoaryl)-3′,5′-bis-O-(tert-butyldimethylsilyl)-2′-
deoxyguanosine (5a-e). General Procedure. To a solution of 3a-e
(0.1 mmol) in ethyl acetate/ethanol (1:1, 10 mL) was added a 10%
palladium-on-carbon catalyst. The flask was evacuated (50 Torr) and
flushed with hydrogen three times. The reaction mixture was hydro-
genated for 16 h at 50 psi with stirring. It was then filtered through a
pad of Celite and concentrated under reduced pressure. The residue
was dried for 6 h in a vacuum oven, the crude product was redissolved
in methylene chloride (10 mL), and acetic anhydride (10 equiv) was
added. Stirring was continued at room temperature for 16 h. Concentra-
tion under vacuum and purification by flash chromatography (silica
gel, 0-20% methanol in ethyl acetate) afforded the desired compound.
N2-(2-Acetylaminophenyl)-3′,5′-bis-O-(tert-butyldimethylsilyl)-2′-
deoxyguanosine (5a): white solid (0.060 g, 96%); mp 148-150 °C;
1H NMR (250 MHz, CDCl3) δ 0.03 (6H, s, CH3Si), 0.04 (6H, s, CH3-
Si), 0.81 (9H, s, (CH3)3C), 0.82 (9H, s, (CH3)3C), 1.96 (3H, s, CH3-
CO), 2.21 (1H, m, H-2′), 2.35 (1H, m, H′-2′), 3.68 (2H, m, H-5′), 3.89
(1H, m, H-4′), 4.43 (1H, m, H-3′), 6.22 (1H, t, J ) 6.3 Hz, H-1′), 7.02
(1H, t, J ) 7.5 Hz, -C6H4), 7.18 (2H, m, -C6H4), 7.99 (1H, s, H-8),
8.21 (1H, d, J ) 8.0 Hz, -C6H4), 9.41 (1H, s, N-H), 10.72 (1H, s,
H-8), 11.33 (1H, s, N-H); 13C NMR (62.5 MHz, CDCl3) δ -4.9 (×
2), -4.6 (× 2), 17.9, 18.4, 22.8, 25.7 (× 3), 25.9 (× 3), 42.5, 62.5,
72.3, 84.4, 87.8, 117.6, 121.6, 123.7, 127.4, 127.9, 129.7, 135.5, 136.7,
149.7, 150.7, 158.4, 171.4; FABMS m/z 629 [M + 1]+.
N2-(2-Acetylaminoaryl)-2′-deoxyguanosine (6a-e). General Pro-
cedure. A solution of 5a-e (0.1 mmol) in tetrahydrofuran (3 mL) was
stirred with a 1 M solution of tetrabutylammonium fluoride in
tetrahydrofuran (0.22 mL, 0.22 mmol) at room temperature. After 1 h,
the solvent was removed under reduced pressure. The residue was then
purified by flash chromatography (silica gel, 10-20% methanol in
methylene chloride) to afford the desired compound.
N2-(2-Acetylaminophenyl)-2′-deoxyguanosine (6a): white solid
1
(0.037 g, 94%); mp 190-193 °C; H NMR (250 MHz, DMSO-d6) δ
1.84 (3H, s, CH3CO), 2.24 (1H, m, H-2′), 2.55 (1H, m, H-2′), 3.47
(2H, m, H-5′), 3.79 (1H, m, H-4′), 4.29 (1H, m, H-3′), 4.85 (1H, br s,
5′-OH), 5.27 (1H, s, 4′-OH), 6.12 (1H, t, J ) 6.8 Hz, H-1′), 7.09 (1H,
t, J ) 7.5 Hz, -C6H4), 7.27 (2H, m, -C6H4), 8.00 (3H, s, -C6H4,
H-8, N-H), 9.60 (1H, s, N-H), 11.26 (1H, s, N-H); 13C NMR (62.5
MHz, DMSO-d6) δ 23.3, 40.4, 61.7, 70.7, 82.9, 87.7, 118.3, 123.1,
123.7, 125.7, 126.1, 129.4, 132.5, 136.5, 149.5, 149.8, 156.6, 169.2;
FAB HRMS: exact mass calculated for C18H21N6O5 (M + 1)+,
401.1573; found, 401.1584.
N2-(2-Acetylamino-3-methylphenyl)-2′-deoxyguanosine (6b): white
solid (0.039 g, 95%); mp 195-198 °C; 1H NMR (250 MHz, CD3OD)
δ 2.25 (3H, s, CH3CO), 2.29 (3H, s, CH3-Ph), 2.42 (1H, m, H-2′),
2.74 (1H, m, H′-2′), 3.65 (2H, m, H-5′), 3.99 (1H, m, H-4′), 4.45 (1H,
m, H-3′), 6.30 (1H, t, J ) 6.8 Hz, H-1′), 7.13 (1H, d, J ) 7.5 Hz,
-C6H3), 7.30 (1H, dd, J ) 8.1, 7.5 Hz, -C6H3),7.93 (1H, d, J ) 8.1
Hz, -C6H3) 8.07 (1H, s, H-8); 13C NMR (62.5 MHz, CD3OD) δ 18.4,
22.8, 41.2, 63.2, 72.5, 85.5, 89.2, 119.2, 122.5, 127.5, 128.6, 129.0,
136.0, 137.5, 138.7, 151.6, 159.2, 173.2; FAB HRMS: exact mass
calculated for C19H23N6O5 (M + 1)+, 415.1730; found, 415.1719.
N2-(2-Acetylaminonaphth-1-yl)-2′-deoxyguanosine (6c): white
N2-(2-Acetylamino-3-methylphenyl)-3′,5′-bis-O-(tert-butyldimeth-
ylsilyl)-2′-deoxyguanosine (5b): white solid (0.061 g, 95%); mp 154-
156 °C; 1H NMR (250 MHz, CDCl3) δ 0.07 (6H, s, CH3Si), 0.11 (6H,
s, CH3Si), 0.90 (9H, s, (CH3)3C), 0.93 (9H, s, (CH3)3C), 2.11 (3H, s,
CH3CO), 2.33 (3H, s, CH3-Ph), 2.34 (1H, m, H-2′), 2.44 (1H, m, H′-
2′), 3.81 (2H, m, H-5′), 4.01 (1H, m, H-4′), 4.50 (1H, m, H-3′), 6.33
(1H, t, J ) 6.3 Hz, H-1′), 7.02 (1H, t, J ) 7.5 Hz, -C6H3), 7.20 (1H,
dd, J ) 8.0, 7.5 Hz, -C6H3), 7.95 (1H, s, H-8), 8.17 (1H, d, J ) 8.0
Hz, -C6H3), 9.57 (1H, s, N-H), 10.77 (1H, s, N-H), 11.36 (1H, s,
N-H); 13C NMR (62.5 MHz, CDCl3) δ -5.4 (× 2), -4.7 (× 2), 17.9,
18.3, 22.8, 25.7 (× 3), 25.9 (× 3), 42.6, 62.8, 72.1, 84.5, 88.0, 117.4,
119.0, 125.0, 126.7, 127.2, 135.9, 136.2, 137.4, 149.7, 150.8, 158.4,
171.1; FABMS m/z 643 [M + 1]+.
1
solid (0.040 g, 90%); mp 200-203 °C; H NMR (250 MHz, DMSO-
d6) δ 1.86 (1H, m, H-2′), 2.08 (3H, s, CH3CO), 2.27 (1H, m, H′-2′),
3.11 (2H, m, H-5′), 3.59 (1H, m, H-3′) 3.88 (1H, m, H-4′), 4.58 (1H,
s, 5′-OH), 5.00 (1H, s, 4′-OH), 5.75 (1H, t, J ) 6.8 Hz, H-1′), 7.48
(2H, m, C10H6), 7.85-7.94 (5H, m, C10H6 and H-8), 8.60 (1H, s, N-H),
9.77 (1H, s, N-H), 11.25 (1H, s, N-H); 13C NMR (62.5 MHz, DMSO-
d6) δ 23.6, 40.5, 61.5, 70.7, 82.8, 87.6, 118.0, 123.2, 123.3, 124.1,
125.2, 126.4, 126.9, 128.0, 130.8, 131.2, 132.6, 136.3, 150.1, 151.9,
168.9. FABMS m/z 451 [M + 1]+; FAB HRMS: exact mass calculated
for C22H23N6O5 (M + 1)+, 451.1730; found, 451.1738.
N2-(2-Acetylaminonaphth-1-yl)-3′,5′-bis-O-(tert-butyldimethylsi-
lyl)-2′-deoxyguanosine (5c): yellow amorphous solid (0.060 g, 88%);
1H NMR (250 MHz, CDCl3) δ -0.07 (6H, s, CH3Si), -0.06 (6H, s,
CH3Si), 0.78 (9H, s, (CH3)3C), 0.80 (9H, s, (CH3)3C), 1.90 (1H, m,
H-2′), 2.07 (1H, m, H′-2′), 2.13 (3H, s, CH3CO), 3.40 (2H, m, H-5′),
3.74 (1H, m, H-4′), 4.11 (1H, m, H-3′), 5.79 (1H, t, J ) 6.3 Hz, H-1′),
7.39 (3H, m, -C10H6), 7.78 (2H, m, -C10H6), 7.80 (1H, s, H-8), 7.95
(1H, m, -C10H6), 8.19 (1H, m, -C10H6), 8.92 (1H, s, N-H); 13C NMR
(62.5 MHz, CDCl3) δ -5.6 (× 2), -4.8 (× 2), 17.8, 18.1, 24.5, 25.6
(× 6), 40.3, 62.8, 72.0, 84.5, 87.8, 117.7, 122.6 (× 2), 123.4, 124.9,
126.1, 127.5, 127.9, 130.8, 131.4, 133.1, 136.1, 150.3, 151.7, 159.3,
169.2; FABMS m/z 679 [M + 1]+.
N2-(2-Acetylamino-5-(phenyl)phenyl)-2′-deoxyguanosine (6d): white
solid (0.044 g, 92%); mp 245 °C dec; 1H NMR (250 MHz, DMSO-d6)
δ 2.12 (3H, s, CH3CO), 2.27 (1H, m, H-2′), 2.60 (1H, m, H′-2′), 3.47
(2H, m, H-5′), 3.87 (1H, m, H-4′), 4.29 (1H, m, H-3′), 4.88 (1H, t, J
) 5.1 Hz, 5′-OH), 5.30 (1H, d, J ) 3.4 Hz, 4′-OH), 6.27 (1H, t, J )
7.2 Hz, H-1′), 7.32-7.54 (5H, m, -C12H8), 7.69 (2H, m, -C12H8),
8.09 (2H, s, N-H and H-8) 8.51 (1H, s, -C12H8), 9.67 (1H, s, N-H),
11.32 (1H, s, N-H); 13C NMR (62.5 MHz, DMSO-d6) δ 23.4, 40.5,
61.7, 70.8, 82.7, 87.9, 118.2, 120.6, 121.5, 126.5 (× 3), 126.8, 127.4,
128.1, 129.2 (× 2), 133.2, 136.1, 137.7, 139.6, 149.7, 156.7, 169.4;
FAB HRMS: exact mass calculated for C24H25N6O5 (M + 1)+,
477.1886; found, 476.1871.
N2-(2-Acetylamino-5-(phenyl)phenyl)-3′,5′-bis-O-(tert-butyldi-
methylsilyl)-2′-deoxyguanosine (5d): white solid (0.067 g, 96%); mp
161-163 °C; 1H NMR (250 MHz, CDCl3) δ 0.04 (6H, s, CH3Si), 0.11
(6H, s, CH3Si), 0.85 (9H, s, (CH3)3C), 0.94 (9H, s, (CH3)3C), 2.10 (3H,
s, CH3CO), 2.41 (2H, m, H-2′), 3.79 (2H, m, H-5′), 3.92 (1H, m, H-4′),
4.52 (1H, m, H-3′), 6.30 (1H, t, J ) 6.3 Hz, H-1′), 7.39 (5H, m,
-C12H8), 7.63 (2H, m, -C12H8), 8.21 (1H, s, H-8), 8.60 (1H, m,
-C12H8), 9.61 (1H, s, N-H), 10.77 (1H, s, N-H), 11.50 (1H, s, N-H);
13C NMR (62.5 MHz, CDCl3) δ -4.9 (× 2), -4.6 (× 2), 17.9, 18.4,
23.1, 25.7 (× 3), 26.0 (× 3), 42.2, 61.9, 70.0, 84.0, 87.4, 117.6, 120.7,
122.4, 127.0 (× 2), 127.3, 128.7 (× 3), 129.8, 135.4, 137.0, 140.3,
140.9, 149.8, 150.6, 158.4, 171.4; FABMS m/z 705 [M + 1]+.
N2-(2-Acetylaminofluoren-3-yl)-3′,5′-bis-O-(tert-butyldimethylsi-
lyl)-2′-deoxyguanosine (5e):29 yellow amorphous solid (0.031 g, 43%);
1H NMR (250 MHz, DMSO-d6) δ -0.05 (6H, s, CH3Si), -0.10 (6H,
s, CH3Si), 0.74 (9H, s, (CH3)3C), 0.75 (9H, s, (CH3)3C), 2.11 (3H, s,
N2-(2-Acetylaminofluoren-3-yl)-2′-deoxyguanosine (6e): yellow
1
amorphous solid (0.045 g, 92%); H NMR (250 MHz, DMSO-d6) δ
2.11 (3H, s, CH3), 2.26 (1H, m, H-2′), 2.60 (1H, m, H′-2′), 3.42 (2H,
m, H-5′), 3.79 (1H, m, H-4′), 3.89 (2H, s, -C13H8), 4.25 (1H, m, H-3′),
4.84 (1H, t, J ) 5.4 Hz, 5′-OH), 5.27 (1H, d, J ) 3.6 Hz, 4′-OH), 6.18
(1H, t, J ) 6.6 Hz, H-1′), 7.34 (2H, m, -C13H8), 7.57 (2H, m, -C13H8),
7.81 (1H, m, -C13H8), 8.04 (1H, s, H-8) 8.08 (1H, s, N-H), 8.58 (1H,
s, -C13H8), 9.63 (1H, s, N-H), 11.28 (1H, br s, N-H); 13C NMR
(62.5 MHz, DMSO-d6) δ 23.3, 36.0, 61.6, 70.7, 83.1, 87.8, 114.2, 118.2,
119.7, 122.5, 125.0, 126.6, 126.9, 128.4, 131.5, 136.0, 138.3, 138.7,