DNA Oligomers Containing 2′-Deoxynucleoside N-Oxide DeriVatiVes
29.3, 30.7, 41.8, 42.0, 47.1, 61.7, 69.8, 87.1, 87.7, 102.7, 128.5,
1H, J ) 7.3 Hz), 7.79-7.83 (m, 2H), 7.95-7.98 (m, 2H), 8.63 (d,
1H, J ) 7.3 Hz); 13C NMR (CDCl3) δ -5.5, -5.4, -4.9, -4.5,
18.0, 18.4, 25.7, 25.7, 25.90, 25.94, 42.1, 61.5, 69.4, 87.5, 87.9,
100.4, 124.4, 131.5, 135.1, 145.4, 154.7, 159.1, 165.1; HRMS (ESI)
m/z (M + H) calcd for C29H44N3O6Si2+ 586.2763, found 586.2762.
Stability of 10a,b and 11a-c under Conditions for N-
Oxidation. The conditions used for these experiments are shown
in Table 2. Typical procedure: The compound (0.10 mmol) was
dissolved in MeOH (1 mL), and m-CPBA (22.4 mg, 0.10 mmol;
77% purity) was added. After being stirred at room temperature
for 24 h, the reaction mixture was diluted with CHCl3 (10 mL)
and washed with aqueous NaHCO3. The organic phase was
collected, dried over Na2SO4, filtered, and evaporated under reduced
pressure. The residue was chromatographed on a column of silica
gel with CHCl3-MeOH (100:0-95:5, v/v) to give the fractions
containing starting material. The fractions were collected and
evaporated under reduced pressure to give starting material. The
recovery yields of 10a,b and 11a-c are listed in Table 2.
151.5, 154.4, 159.6; HRMS (ESI) m/z (M + H) calcd for
+
C30H59N4O5Si2 611.4019, found 611.4010.
Synthesis of Compound 7. To a solution of compound 5
(1.22 g, 2.0 mmol) in dry THF (10 mL) were added triethylamine
trihydrofluoride (977 µL, 6.0 mmol) and triethylamine (836 µL).
After being stirred at room temperature for 2 h, the reaction was
quenched by addition of H2O. The mixture was partitioned between
CHCl3/i-PrOH (3:1, v/v) and H2O. The organic phase was collected,
dried over Na2SO4, filtered, and evaporated under reduced pressure.
Subsequently, the residue was rendered anhydrous by repeated
coevaporation with dry pyridine (1 mL × 1) and dissolved in dry
pyridine (20 mL). To the solution was added DMTrCl (813 mg,
2.4 mmol), and the mixture was stirred at room temperature for
2 h. The reaction was quenched by addition of saturated aqueous
NaHCO3. The mixture was partitioned between CHCl3 and H2O.
The organic phase was collected, dried over Na2SO4, filtered, and
evaporated under reduced pressure. The residue was chromato-
graphed on a column of silica gel with CHCl3-MeOH (100:0-
95:5, v/v) containing 0.5% Et3N to give the fractions containing 7.
The fractions were collected and evaporated under reduced pressure.
The residue was evaporated by repeated coevaporation three times
each with toluene and CHCl3 to remove the last traces of Et3N to
give 7 (979 mg, 71%): 1H NMR (CDCl3) δ 0.93 (t, 6H, J ) 7.2
Hz), 1.26-1.36 (m, 2H), 1.54-1.65 (m, 2H), 2.21-2.30 (m, 1H),
2.62-2.71 (m, 1H), 3.36-3.50 (m, 4H), 3.73-3.78 (m, 8H), 4.18-
4.20 (m, 1H), 4.49-4.55 (m, 1H), 5.75 (d, 1H, J ) 7.7 Hz), 6.33
(t, 1H, J ) 5.5 Hz), 6.83 (d, 4H, J ) 8.7 Hz), 7.26-7.42 (m, 9H),
7.66 (d, 1H, J ) 7.7 Hz), 10.43 (s, 1H); 13C NMR (CDCl3) δ 13.7,
19.8, 29.1, 30.6, 41.9, 44.5, 52.1, 55.1, 62.9, 70.4, 86.4, 86.5, 87.8,
102.5, 113.1, 126.8, 127.8, 128.1, 129.4, 130.0, 130.1, 130.3, 130.5,
144.5, 151.4, 154.7, 158.4, 159.5; HRMS (ESI) m/z (M + H) calcd
Synthesis of Compound 12. 2′-Deoxycytidine monohydride
(2.27 g, 10.0 mmol) was rendered anhydrous by repeated coevapo-
ration with dry pyridine (2 mL × 1) and dissolved in dry pyridine
(36 mL). To the solution was added chlorotrimethylsilane (3.16
mL, 25.0 mmol), and the mixture was stirred for 1 h. Then DMAP
(10 mg) was added, and phthaloyl chloride (2.16 mL, 15.0 mmol)
in dioxane (4 mL) was added dropwise at 0 °C for 15 min. After
being stirred at room temperature for 1 h, the mixture was
hydrolyzed with ice-water, and stirring was continued for 15 min.
The mixture was partitioned between 10% pyridine in CHCl3 and
H2O. The organic phase was extracted with H2O (50 mL), and the
combined aqueous phases were washed twice with 10% pyridine
in CHCl3 (50 mL). The organic phase was collected, dried over
Na2SO4, filtered, and evaporated under reduced pressure. The
residue was evaporated by repeated coevaporation with toluene and
CH3CN to remove pyridine. The residue was washed with CH2Cl2
to give 12 (2.13 g, 60%): 1H NMR (DMSO) δ 2.10-2.16 (m,
1H), 2.36-2.43 (m, 1H), 3.57-3.68 (m, 2H), 3.90-3.94 (m, 1H),
4.21-4.28 (m, 1H), 5.11 (t, 1H, J ) 5.2 Hz), 5.30 (d, 1H, J ) 4.3
Hz), 6.11 (t, 1H, J ) 6.2 Hz), 6.71 (d, 1H, J ) 7.1 Hz), 7.92-8.03
(m, 4H), 8.63 (d, 1H, J ) 7.3 Hz); 13C NMR (DMSO) δ 40.9,
60.7, 69.7, 87.1, 88.3, 101.1, 124.0, 131.2, 135.4, 146.0, 154.2,
+
for C39H49N4O7 685.3596, found 685.3593.
Deoxygenation of 5 by Use of Various Phosphorus Reagents.
The conditions used for these experiments are shown in Scheme
3. Typical procedure: Compound 5 (61.1 mg, 0.10 mmol) was
dissolved in CH3CN (1 mL), and this solution was treated with a
phosphorus agent for an appropriate time. The reaction was
monitored by TLC analysis. The reaction mixture was diluted with
CHCl3 (10 mL) and washed once with aqueous NaHCO3. The
organic phase was collected, dried over Na2SO4, filtered, and
evaporated under reduced pressure. The residue was chromato-
graphed on a column of silica gel with CHCl3-MeOH (100:0-
95:5, v/v) to give the fractions containing 9. The fractions were
+
158.9, 165.1; HRMS (ESI) m/z (M + H) calcd for C17H16N3O6
358.1034, found 358.1038.
Synthesis of Compound 13. Compound 12 (715 mg, 2.0 mmol)
was rendered anhydrous by repeated coevaporation with dry
pyridine (1 mL × 1) and dissolved in dry pyridine (20 mL). To
the solution was added DMTrCl (813 mg, 2.4 mmol), and the
mixture was stirred at room temperature for 3 h. The reaction was
quenched by addition of saturated aqueous NaHCO3. The mixture
was partitioned between CHCl3 and H2O. The organic phase was
collected, dried over Na2SO4, filtered, and evaporated under reduced
pressure. The residue was chromatographed on a column of silica
gel with hexane-ethyl acetate (25:75, v/v) containing 1% pyridine
to give the fractions containing 13. The fractions were collected
and evaporated under reduced pressure. The residue was finally
evaporated by repeated coevaporation three times each with toluene
and CHCl3 to remove the last traces of pyridine to give 13 (920
mg, 70%): 1H NMR (CDCl3) δ 2.36-2.40 (m, 1H), 2.67-2.77
(m, 1H), 3.42 (dd, 1H, J ) 3.4 Hz, J ) 11.3 Hz), 3.52 (dd, 1H, J
) 2.7 Hz, J ) 11.1 Hz), 3.75 (s, 6H), 4.12-4.13 (m, 1H), 4.54-
4.60 (m, 1H), 6.21 (t, 1H, J ) 5.4 Hz), 6.37 (d, 1H, J ) 7.1 Hz),
6.81 (d, 4H, J ) 8.7 Hz), 7.11-7.37 (m, 9H), 7.75-7.79 (m, 2H),
7.90-7.93 (m, 2H), 8.54 (d, 1H, J ) 7.1 Hz); 13C NMR (CDCl3)
δ 41.7, 55.1, 62.1, 69.6, 86.3, 86.6, 87.7, 100.5, 113.2, 124.2, 126.9,
127.9, 128.1, 129.9, 131.1, 135.0, 135.3, 135.4, 144.1, 145.5, 155.0,
158.4, 159.0, 164.8; HRMS (ESI) m/z (M + H) calcd for
1
collected and evaporated under reduced pressure to give 9: H NMR
(CDCl3) δ 0.00-0.07 (m, 12H), 0.83-0.91 (m, 24H), 1.26-1.34
(m, 2H), 1.49-1.60 (m, 2H), 2.06-2.12 (m, 1H), 2.36-2.46 (m,
1H), 3.21-3.32 (m, 2H), 3.43-3.54 (m, 2H), 3.73 (dd, 1H, J )
2.3 Hz, J ) 11.5 Hz), 3.82-3.93 (m, 2H), 4.31-4.38 (m, 1H),
5.95 (d, 1H, J ) 7.3 Hz), 6.27 (t, 1H, J ) 5.5 Hz), 8.06 (d, 1H, J
) 7.3 Hz), 8.78 (s, 1H); 13C NMR (CDCl3) δ -5.59, -5.55, -5.0,
-4.6, 13.6, 13,7, 17.9, 18.3, 19.7, 20.0, 25.7, 25.9, 29.0, 30.9, 42.2,
45.2, 52.0, 61.7, 69.7, 86.0, 87.1, 102.4, 141.3, 156.3, 158.1, 171.8;
+
HRMS (ESI) m/z (M + H) calcd for C30H59N4O4Si2 595.4069,
found 595.4069.
Synthesis of Compound 11c. Compound 2 (228 mg, 0.50 mmol)
was rendered anhydrous by repeated coevaporation with dry
pyridine (1 mL × 1) and dissolved in dry pyridine (5 mL). To the
solution was added phthaloyl chloride (86.4 mg, 0.6 mmol), and
the mixture was stirred at room temperature for 30 min. The reaction
mixture was diluted with CHCl3 (10 mL) and washed with aqueous
NaHCO3. The organic phase was collected, dried over Na2SO4,
filtered, and evaporated under reduced pressure. The residue was
chromatographed on a column of silica gel with CHCl3-MeOH
(100:0-98:2, v/v) to give the fractions containing 11c. The fractions
were collected and evaporated under reduced pressure to give 11c
(246 mg, 84%): 1H NMR (CDCl3) δ 0.05-0.11 (m, 12H), 0.86-
0.91 (m, 18H), 2.20-2.23 (m, 1H), 2.53-2.63 (m, 1H), 3.76-
4.01 (m, 2H), 4.34-4.42 (m, 1H), 6.19-6.23 (m, 1H), 6.61 (d,
+
C38H34N3O8 660.2340, found 660.2349.
Synthesis of Compound 14. Compound 13 (990 mg, 1.5 mmol)
was rendered anhydrous by repeated coevaporation with dry
pyridine (1 mL × 3), dry toluene (1 mL × 1), and dry CH3CN (1
J. Org. Chem, Vol. 73, No. 4, 2008 1223