DNA Lesion
293 301
(300 MHz, CDCl3): d 0.94 1.00 (m, 28H, iPr), 2.12 (s, 3H, CH3), 2.23 (s,
Compound 10a: Rf 0.50 (ethyl acetate/MeOH 20:1); m.p. 97 998C; IR
(KBr): nÄ 1039, 1073, 1134, 1247, 1334, 1507, 1521, 1540, 1559, 1577, 1653,
3
3H, CH3), 3.88 3.99 (m, 3H, C4'H, C5'H), 4.38 (dd, J(C3'H,C4'H) 8.0,
3
1
3J(C3'H,C2'H) 5.0 Hz, 1H, C3'H), 5.35 (d, J(C2'H,C3'H) 5.0 Hz, 1H,
1683, 1734, 2869, 2947, 3447 cmÀ1; H NMR (300 MHz, CDCl3): d 0.96
C2'H), 5.52 (d, 3J(C1'H,NH) 5.8 Hz, 1H, C1'H), 8.68 (s, 1H, NH), 9.35 (d,
3J(NH,C1'H) 5.8 Hz, 1H, NH), 11.30 (s, 1H, NH); 13C NMR (50 MHz,
CDCl3): d 12.60, 12.67, 12.99, 13.34, 16.85, 16.90, 16.98 (2 Â CH3CSi),
17.16 (3 Â CH3CSi), 17.29, 20.93, 24.41, 60.92, 69.29, 73.47, 77.13, 81.64, 85.94,
1.01 (m, 28H, iPr), 2.14 (s, 3H, CH3CO), 3.82 3.92 (m, 2H, C5'H), 3.97
4.00 (m, 1H, C4'H), 4.44 (dd, 3J(C3'H,C4'H) 8.3, 3J(C3'H,C2'H) 4.9 Hz,
1H, C3'H), 5.71 (t, 3J(C1'HC2'HC3'H,C1'HC2'HC3'H) 4.9 Hz, 1H,
C2'H), 6.04 (dd, 3J(C1'H,NHC1') 9.0, 3J(C1'H,C2'H) 4.9 Hz, 1H,
C1'H), 7.33 (d, 3J(NHC1',C1'H) 9.0 Hz, 1H, NHC1'), 7.55 (t,
3J(CarH,CarH) 8.0 Hz, 1H, CarH), 7.78 (d, 3J(CarH,CarH) 8.0 Hz, 1H,
CarH), 7.86 (d, 3J(CHONH,CHO) 1.7 Hz, 1H, CHONH), 8.02 (d,
3J(CHO,HNCHO) 1.7 Hz, 1H, CHO), 8.30 (d, 3J(CarH,CarH) 8.0 Hz,
1H, CarH), 8.35 (s, 1H, CarH), 9.14 (s, 1H, NH), 11.52 (s, 1H, NH); 13C NMR
(50 MHz, CDCl3): d 12.53, 12.75, 12.95, 13.32, 16.57, 16.61, 16.79, 16.81,
16.98 (2C), 17.16, 17.26, 24.12, 60.66, 70.56, 77.13, 80.01, 80.46, 98.92, 123.81
(q, 1J 273 Hz), 126.76 (q, 3J 4 Hz), 129.42, 130.03 (q, 3J 4 Hz), 130.05,
131.38 (q, 2J 33 Hz), 133.21, 146.51, 152.57, 157.75, 159.99, 164.03, 171.85;
149.82, 154.22, 157.55 (2C), 170.96, 171.96; MS (ESI ): m/z (%): 630.2 (100)
[MH] ; HR-MS (ESIÀ): calcd for [C25H43N5O10Si2 À H]À: 628.2470, found:
628.2083.
6-(3'-O,5'-O-[1,1,3,3-Tetraisopropyldisiloxane-1,3-diyl]-2'-O-[4-trifluoro-
methyl-benzoyl]-b-d-ribofuranose-1-yl)amino-2-acetylamino-5-nitro-3H-
pyrimidine-4-one (9): Silyl protected sugar 8 (1.5 g, 2.6 mmol) and DMAP
(780 mg, 6.4 mmol, 2.5 equiv) were dissolved in CH2Cl2 (15 mL).3-(Tri-
fluoromethyl)benzoyl chloride (0.4 mL, 2.6 mmol, 1.0 equiv) was added
dropwise at 08C.After stirring for 30 min, ethyl acetate was added
(150 mL) and the reaction mixture was three times extracted with 1n HCl
(20 mL), sat.NaHCO 3 (20 mL) and sat.NaCl (20 mL).After drying of the
organic phase over MgSO4 and removal of the solvent in vacuo, compound
9 was obtained as a yellowish powder (1.8 g, 2.4 mmol, 95%). Rf 0.44
(ethyl acetate/MeOH 20:1); m.p. 195 1978C; IR (KBr): nÄ 3460, 2947,
2869, 1733, 1683, 1620, 1584, 1539, 1465, 1436, 1384, 1336, 1250, 1169, 1134,
1073, 1039, 994, 885, 695 cmÀ1; 1H NMR (300 MHz, CDCl3): d 1.01 1.09
(m, 28H, iPr), 2.25 (s, 3H, CH3CO), 4.05 4.10 (m, 3H, C4'H, C5'H), 4.56
(dd, 3J(C3'H,C4'H) 8.0, 3J(C3'H,C2'H) 5.0 Hz, 1H, C3'H), 5.65 (d,
3J(C2'H,C3'H) 5.0 Hz, 1H, C2'H), 5.83 (d, 3J(C1'H,NH) 6.3 Hz, 1H,
C1'H), 7.60 7.65 (m, 1H, CarH), 7.84 7.86 (m, 1H, CarH), 8.23 8.34 (m,
2H, CarH), 9.35 (s, 1H, NH), 9.47 (d, 3J(NH,C1'H) 6.3 Hz, 1H, NH),
11.46 (s, 1H, NH); 13C NMR (50 MHz, CDCl3): d 12.78, 12.81, 13.19,
13.53, 17.14 (8 C), 24.54, 61.17, 70.04, 77.93, 82.03, 85.89, 113.78, 123.79 (q,
1J 272 Hz), 126.74 (q, 3J 4 Hz), 129.58, 130.30 (q, 3J 4 Hz), 131.10,
131.93 (q, 2J 33 Hz), 133.20, 150.15, 154.61, 157.71, 164.49, 172.66; 19F
19F NMR (188 MHz, CDCl3): d À63.21; MS (ESI ): m/z (%): 788 (36)
[MNa] , 758 (100) [MH] ; HR-MS (ESIÀ): calcd for [C32H46F3N5O8Si2 À
H]À: 756.2708, found 756.2709.
a
and b-6-(3'-O,5'-O-[1,1,3,3-Tetraisopropyldisiloxane-1,3-diyl]-2'-deoxy-
d-ribofuranose-1'-yl)amino-2-acetylamino-5-formylamino-3H-pyrimidine-
4-one (11): The sugar 10 (100 mg, 0.13 mmol), MgClO4 Â 6H2O (9 mg,
0.04 mmol, 0.3 equiv) and 9-ethyl-3,6-dimethylcarbazole (5 mg, 0.02 mmol,
0.15 equiv) were dissolved in a mixture of isopropanol/water (9:1, 10 mL)
After purging of the solution with N2 for 45 min, the solution was irradiated
with a medium pressure mercury lamp in a pyrex reaction vial for 15 h at
158C.The solvent was removed in vacuo and the residual material purified
by flash chromatography.Compound 11 was obtained as a yellowish
powder as a mixture of the two anomers (yield 60%).Separation of the
anomers was possible, with a small amount (12 mg) of the obtained
material, by HPLC. 11a (minor anomer): Rf 0.38 (ethyl acetate/MeOH
10:1); 1H NMR (400 MHz, CDCl3): d 1.02 1.05 (m, 28H, iPr), 2.00 2.05
(m, 1H, C2'Ha), 2.22 (s, 3H, CH3CO), 2.48 2.53 (m, 1H, C2'Hb), 3.71 3.76
(m, 1H, C5'Ha), 3.92 3.94 (m, 1H, C4'H), 3.99 4.02 (m, 1H, C5'Hb),
4.42 4.46 (m, 1H, C3'H), 5.87 5.91 (m, 1H, C1'H), 7.06 (d,
3J(NH,C1'H) 8.1 Hz, 1H, NHC1'), 7.38 (s, 1H, NHCHO), 8.07 (s, 1H,
NH), 8.23 (s, 1H, CHO), 11.41 (s, 1H, NH); 13C NMR (100 MHz, CDCl3):
d 12.21, 12.62, 13.00, 13.13, 16.60, 16.71 (3C), 16.90, 17.01, 17.04, 17.13,
23.97, 39.49, 62.16, 71.65, 80.38, 83.26, 146.00, 152.74, 157.33, 159.27, 170.84,
170.89. HRMS (ESIÀ): calcd for [C24H43N5O7Si2 À H]À: 568.2623, found
568.2613.
NMR (188 MHz, CDCl3): d À63.01; MS (ESI ): m/z (%): 782 (6)
[MNa] , 760 (18) [MH] , 261 (63), 186 (100); HR-MS (ESI ): calcd for
[C31H44N5O10Si2H] : 760.2680, found 760.2679.
a- and b-6-(3'-O,5'-O-[1,1,3,3-Tetraisopropyldisiloxane-1,3-diyl]-2'-O-
[4-trifluoromethyl-benzoyl]-d-ribofuranose-1-yl)amino-2-acetylamino-5-
formylamino-3H-pyrimidine-4-one (10a and 10b): Sugar
9 (500 mg,
0.66 mmol) was dissolved in ethyl acetate (0.5 mL). Under argon, Pd/C
(10%, 500 mg) was added and the reaction mixture was diluted with
MeOH (5 mL).The solution was then stirred under an H atmosphere.
2
Compound 11b (major anomer): Rf 0.38 (ethyl acetate/MeOH 10:1);
1H NMR (400 MHz, CDCl3): d 1.02 1.10 (m, 28H, iPr), 2.16 2.19 (m,
1H, C2'Ha), 2.23 (s, 3H, CH3CO), 2.30 2.37 (m, 1H, C2'Hb), 3.78 3.80 (m,
2H, C5'Ha, C4'H), 3.98 4.04 (m, 1H, C5'Hb), 4.54 4.58 (m, 1H, C3'H),
5.83 5.90 (m, 1H, C1'H), 7.44 (d, 3J(NH,C1'H) 8.7 Hz, 1H, NHC1'), 7.59
(s, 1H, NHCHO), 8.00 (s, 1H, NH), 8.16 (s, 1H, CHO), 11.45 (s, 1H, NH);
13C NMR (100 MHz, CDCl3): d 12.21, 12.50, 13.00, 13.13, 16.62, 16.70
(2C), 16.77, 16.93, 17.01, 17.08, 17.17, 24.01, 40.43, 64.19, 72.59, 80.07, 84.35,
145.57, 152.74, 157.06, 158.99, 170.86, 170.89; MS (ESIÀ): m/z (%): 604
(101), 658 (100) [M À H]À; HR-MS (ESIÀ): calcd for [C24H43N5O7Si2 À H]À:
568.2623, found 568.2613.
After 7 min, diisopropylethylamine (0.5 mL) was added and the hydro-
genation was continued for another 7 min.The reaction mixture was
filtered through Celite and the filtrate was evaporated to dryness in vacuo.
The residue was dissolved in pyridine (5 mL) under argon and DCC
(270 mg, 1.32 mmol, 2 equiv) was added. After cooling to 08C, HCOOH
(50 mL, 1.32 mmol, 2 equiv) was added. The reaction mixture was allowed
to warm to r.t. over 12 h. The mixture was diluted with ethyl acetate
(60 mL) and extracted two times with 1n HCl (15 mL), sat.NaHCO
3
(15 mL) and sat.NaCl (15 mL).Drying of the organic phase over MgSO
4
and removal of the solvent in vacuo afforded crude 10.Both anomers were
separated by flash chromatography (CHCl3, 1 4% MeOH). 10b (240 mg,
0.3 mmol, 47%) and 10a (50 mg, 0.07 mmol, 10%) were obtained as
yellowish powders.Compound 10b: Rf 0.48 (ethyl acetate/MeOH 20:1);
m.p. 94 968C; IR (KBr): nÄ 605, 695, 1038, 1073, 1135, 1251, 1335, 1422,
a- and b-6-(3'-O,5'-O-[1,1,3,3-Tetraisopropyldisiloxane-1,3-diyl]-2'-O-ace-
tyl-b-d-ribofuranose-1'-yl)amino-2-acetylamino-5-formylamino-3H-pyri-
midine-4-one (12): Sugar 13b (253 mg, 0.40 mmol) was dissolved in
degassed ethyl acetate (0.2 mL) under argon. Pd/C (250 mg) was added
and the mixture was diluted with MeOH (2.5 mL). The solution was stirred
under an H2 atmosphere for 5 min and diisopropylethylamine (0.2 mL) was
added.The hydrogenation was continued for another 10 min.The reaction
mixture was filtered through Celite and the filtrate was concentrated to
dryness in vacuo.The residual material was dissolved in degassed pyridine
(2.5 mL). DCC (165 mg, 0.8 mmol, 2 equiv) was added and at 08C,
HCOOH (30 mL, 0.8 mmol, 2 equiv) was added. The reaction was allowed
to warm to r.t. over 12 h and was diluted with ethyl acetate (50 mL). The
organic phase was extracted two times with 1n HCl (15 mL), sat.NaHCO 3
(15 mL) and sat.NaCl (15 mL) and dried over MgSO 4.After removal of
the solvent in vacuo and separation of 12a and 12b by flash chromatog-
raphy (CHCl3, 1 4% MeOH) were both compounds obtained in form of
yellowish powders. 12b: (104 mg, 0.16 mmol, 41%). Rf 0.38 (CHCl3/
MeOH 10:1); m.p. 122 1248C; IR (KBr): nÄ 702, 1039, 1075, 1154, 1237,
1467, 1530, 1552, 1643, 1727, 2869, 2947, 3454 cmÀ1 1H NMR (400 MHz,
;
CDCl3): d 0.83 1.11 (m, 28H, iPr), 2.22 (s, 3H, CH3CO), 3.96 4.04 (m,
3H, C4'H, C5'H), 4.57 4.62 (m, 1H, C3'H), 5.55 (dd, 3J(C2'H,C3'H) 5.0,
3J(C2'H,C1'H) 1.3 Hz, 1H, C2'H), 5.78 (dd, 3J(C1'H,NHC1') 8.0,
3J(C1'H,C2'H) 1.3 Hz, 1H, C1'H), 7.61 (t, 3J(CarH,CarH) 8.0 Hz, 1H,
Car5H), 7.73 (d, 3J(NHC1',C1'H) 8.0 Hz, 1H, NHC1'), 7.81 7.86 (m, 2H,
HNCHO, Car6H), 8.16 (d, 3J(CHO,HNCHO) 2 Hz, 1H, CHO), 8.25 (d,
3J(C4H,C5H) 8.0 Hz, 1H, Car4H), 8.32 (s, 1H, Car2H), 8.45 (s, 1H, NH),
11.54 (s, 1H, NH); 13C NMR (50 MHz, CDCl3): d 12.54, 12.58, 12.99,
13.16, 16.63, 16.87, 16.93 (2C), 17.17, 17.23 (2C), 17.31, 24.11 (CH3CON),
62.51 (C5'), 71.30 (C3'), 77.91 (C1'), 81.36 (C2'), 84.53 (C4'), 99.11, 123.84 (q,
1J 273 Hz), 126.84 (q, 3J 4 Hz), 129.43, 130.00, 130.02 (q, 3J 4 Hz),
131.40 (q, 2J 33 Hz), 133.24, 146.16, 151.60, 157.48, 159.59, 164.44, 171.82;
19F NMR (188 MHz, CDCl3): d À63.21; MS (ESI ): m/z (%): 788 (36)
[MNa] , 758 (100) [MH] ; HR-MS (ESIÀ): calcd for [C32H46F3N5O8Si2 À
H]À: 756.2708, found 756.2709.
1384, 1467, 1555, 1591, 1649, 1656, 1741, 1753, 2868, 2946, 3417 cmÀ1
;
Chem. Eur. J. 2002, 8, No. 1
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
0947-6539/02/0801-0299 $ 17.50+.50/0
299