+
+
6658 J. Am. Chem. Soc., Vol. 118, No. 28, 1996
McDonald and Gleason
The aqueous layers were extracted with CH2Cl2, and the organic layers
were washed with brine, dried over Na2SO4, and concentrated. Silica
gel chromatography of the residue using 2.5-5% MeOH in CH2Cl2
178.0, 169.2, 168.9, 157.1 (q, J ) 37.9 Hz), 115.4 (q, J ) 285.6 Hz),
97.6, 79.9, 75.2, 63.5, 50.1, 38.8, 26.9, 20.9, 20.4.
9-(2′-O-Acetyl-3′-deoxy-3′-(trifluoroacetamido)-5′-O-(trimeth-
ylacetyl)-â-D-ribofuranosyl)-N-6-benzoyladenine (43A). N-Bz-
(TMS)2-adenine34a,b (154.1 mg, 0.4017 mmol) was added to flame-
dried 3 Å molecular sieves (52 mg). Diacetate 42 (49.8 mg, 0.120
mmol; dried by azeotropic evaporation from toluene, 3×) was added
via cannula in ClCH2CH2Cl (3.0 mL). TMSOTf (0.028 mL, 0.14
mmol) was added at 20 °C. The mixture was heated to reflux for 4 h.
The reaction was quenched by dilution with CH2Cl2, and washing with
saturated NaHCO3. The aqueous layer was extracted with CH2Cl2. The
organic layers were washed with brine, dried over Na2SO4, and
concentrated. Purification by silica gel chromatography using 1-1.5%
gave 35A (53.0 mg, 42%): colorless glass; [R]23 -2° (CHCl3, c )
D
0.456); IR (thin film) 3289, 3067, 2976, 1688, 1609, 1447, 1272, 1159,
1
1093, 1036, 954, 893, 710 cm-1; H NMR (300 MHz, CDCl3) δ 9.40
(1 H, br s), 8.66 (1 H, s), 8.23 (1 H, s), 7.99 (2 H, d J ) 7.2 Hz), 7.57
(1 H, t, J ) 7.4 Hz), 7.47 (2 H, t, J ) 7.4 Hz), 7.13 (1 H, br d, J ) 7.3
Hz), 6.43 (1 H, t, J ) 5.9 Hz), 4.73 (1 H, m), 4.39-4.25 (3 H, m),
2.85 (1 H, ddd, J ) 13.4, 5.4, 2.5 Hz), 2.68 (1 H, ddd, J ) 13.4, 6.8,
6.4 Hz), 2.00 (3 H, s), 1.16 (9 H,s); 13C NMR (75 MHz, CDCl3) δ
178.2, 170.5, 165.0, 152.3, 151.1, 149.4, 141.2, 133.4, 132.8, 128.8,
127.8, 123.5, 84.4, 82.7, 64.0, 50.2, 38.7, 37.8, 27.1, 23.1; HRMS
(LSIMS) calcd for C24H28 N6O5 [(M + H)+] 480.2121, found 480.2131.
MeOH in CH2Cl2 gave 43A (65.0 mg, 90%): colorless glass; [R]23
D
+33.1° (CHCl3, c ) 0.652); IR (thin film) 3294, 3074, 2978, 1726,
7-(3′-Acetamido-2′,3′-dideoxy-5′-O-(trimethylacetyl)-â-D-ribo-
furanosyl)-N-2-acetylguanine (35G*). Thioglycoside 37 (37.9 mg,
0.108 mmol) was dissolved in dry EtCN (3.0 mL) and added via cannula
to 3 Å molecular sieves (44 mg, flame dried) and N-Ac-(TMS)3-
guanine36 (115 mg, 0.281 mmol). The mixture was chilled to -78
°C. NIS (81.8 mg, 0.345 mmol) was added followed by dropwise
addition of TfOH (0.012 mL, 0.13 mmol). After 3 h at -78 °C, the
mixture was warmed to 0 °C. The reaction was quenched by dilution
with EtOAc (20 mL), and washing with 10% Na2S2O5 (1 × 10 mL)
and saturated NaHCO3 (1 × 10 mL). The aqueous layers were extracted
with EtOAc (4 × 15 mL), and the organic layers were washed with
brine (15 mL), dried over Na2SO4, and concentrated. Silica gel
chromatography (4-5% MeOH in CH2Cl2) gave 35G* as a 7.3:1
mixture of isomers (16.3 mg, 35% combined). This mixture was
1
1612, 1514, 1456, 1223, 1161, 897, 797, 705 cm-1; H NMR (300
MHz, CDCl3) δ 9.17 (1 H, br s), 8.77 (1 H, s), 8.12 (1 H, s), 8.01 (2
H, d, J ) 7.2 Hz), 7.60 (1 H, t, J ) 7.4 Hz), 7.51 (2 H, t, J ) 7.4 Hz),
7.18 (1 H, br d, J ) 8.4 Hz), 6.12 (1 H, d, J ) 2.7 Hz), 5.83 (1 H, dd,
J ) 6.6, 2.4 Hz), 5.52-5.47 (1 H, m), 4.48-4.42 (2 H, m), 4.32 (1 H,
dd, J ) 12.9, 5.4 Hz), 2.17 (3 H, s), 1.17 (9H, s); 13C NMR (75 MHz,
CDCl3) δ 178.2, 169.4, 164.7, 157.2 (q, J ) 37.6 Hz), 152.9, 151.2,
149.7, 142.0, 133.3, 132.9, 128.9, 127.8, 123.6, 115.5 (q, J ) 287 Hz),
88.5, 80.0, 75.1, 62.9, 50.3, 38.8, 27.0, 20.4; HRMS (LSIMS) calcd
for C26H27N6O7F3Na [(M + Na)+] 615.1791, found 615.1812.
9-(2′-O-Acetyl-3′-deoxy-3′-(trifluoroacetamido)-5′-O-(trimeth-
ylacetyl)-â-D-ribofuranosyl)-N-6,N-6-dimethyladenine (43A′). TMS-
6-(dimethylamino)purine37 (0.40 mmol) was added to flame-dried 3 Å
molecular sieves (50 mg). Diacetate 42 (59.7 mg, 0.144 mmol; dried
by azeotropic evaporation from toluene, 3×) was added via cannula in
ClCH2CH2Cl (3.0 mL). TMSOTf (0.056 mL, 0.29 mmol) was added
at 20 °C. The mixture was heated to reflux for 4 h. The reaction was
quenched by dilution with CH2Cl2, and washing with saturated
NaHCO3. The aqueous layer was extracted with CH2Cl2. The organic
layers were washed with brine, dried over Na2SO4, and concentrated.
Purification by silica gel chromatography using 2-4% MeOH in CH2-
Cl2) gave 43A′ (53.2 mg, 71%): colorless glass; [R]23D +32° (CHCl3,
c ) 0.472); IR (thin film) 3314, 3063, 2973, 2880, 1739, 1622, 1552,
characterized as follows: colorless glass; [R]23 +54° (CHCl3, c )
D
0.358); IR (thin film) 3267, 3185, 3068, 2965, 1684, 1610, 1549, 1456,
1370, 1256, 1161, 1098, 969, 780 cm-1; 1H NMR (300 MHz, CDCl3,
major isomer) δ 11.18 (1 H, br s), 8.21 (1 H, s), 7.15 (1 H, br d, J )
7.4 Hz), 6.61 (1 H, t, J ) 5.4 Hz), 4.68-4.58 (1 H, m), 4.47-4.37 (2
H, m), 4.28 (1 H, ddd, J ) 6.3, 4.4, 3.9 Hz), 2.86 (1 H, ddd, J ) 14.1,
7.2, 6.5 Hz), 2.67 (1 H, ddd, J ) 13.8, 7.5, 5.0 Hz), 2.41 (3 H, s), 2.02
(3 H, s), 1.20 (9 H, s); 13C NMR (75 MHz, CDCl3, major isomer) δ
178.3, 173.7, 170.6, 157.7, 152.9, 148.0, 140.6, 110.9, 86.9, 83.2,
63.9,49.2, 40.1, 38.8, 27.2, 24.5, 23.1; HRMS (LSIMS) calcd for
C19H27N6O6 [(M + H)+] 435.1992, found 435.1982.
1
1415, 1269, 1232, 1160, 1064, 918, 738 cm-1; H NMR (300 MHz,
CDCl3) δ 8.06 (1 H, s), 7.97 (1 H, s), 6.69 (1 H, br d, J ) 7.6 Hz),
5.97 (1 H, d, J ) 1.7 Hz), 5.80 (1 H, dd, J ) 6.6, 1.9 Hz), 5.82-5.74
(1 H, m), 4.55-4.49 (1 H, m) 4.41-4.33 (2 H, m), 3.96 (3 H, br s),
3.39 (3 H, br s), 2.21 (3 H, s), 1.22 (9H, s); 13C NMR (75 MHz, CDCl3)
δ 178.3, 169.5, 157.1 (q, J ) 38 Hz), 153.2, 152.4, 148.3, 139.7, 121.3,
115.5 (q, J ) 286 Hz), 93.6, 80.8, 75.4, 63.2, 50.2, 39.9, 38.8, 38.1,
27.1, 20.5; HRMS (LSIMS) calcd for C21H28N6O6F3 [(M + H)+]
517.2022, found 517.2047.
Data for 9-(3′-acetamido-2′,3′-dideoxy-5′-O-(trimethylacetyl)-â-
D-ribofuranosyl)-N-2-acetylguanine (35G): 1H NMR (300 MHz,
acetone-d6) δ 12.04 (1 H, br s), 10.78 (1 H, br s), 8.00 (1 H, s), 7.65
(1 H, br d, J ) 5.8 Hz), 6.26 (1 H, dd, J ) 7.2, 5.1 Hz), 4.76-4.67 (1
H, m), 4.34 (1 H, dd, J ) 12.0, 3.4 Hz), 4.23 (1 H, dd, J ) 11.8, 5.8
Hz), 4.17-4.11 (1 H, m), 2.92-2.83 (1 H, m), 2.62-2.53 (1 H, m),
2.29 (3 H, s), 1.92 (3 H, s), 1.14 (9 H, s).
Acetyl 2-O-Acetyl-3-deoxy-3-(trifluoroacetamido)-5-O-(trimethyl-
acetyl)-D-ribofuranoside (42). Glycal 30 (192.6 mg, 0.7982 mmol)
was dissolved in 16 mL of CH2Cl2 and chilled to 0 °C. Peracetic acid
(32 wt % in dilute AcOH, 0.25 mL, 1.2 mmol) was added dropwise.
The mixture was allowed to warm to 20 °C. After 1.5 h, the mixture
was diluted with EtOAc and washed with 10% Na2SO3 and saturated
NaHCO3. The aqueous layers were extracted with EtOAc, and the
organic layers were washed with brine, dried over Na2SO4, and
concentrated to give 41. The crude hydroxy acetate 41 was dissolved
in 7.0 mL of dry CH2Cl2. Pyridine (0.39 mL, 4.8 mmol), Ac2O (0.23
mL, 2.4 mmol), and DMAP (1 mg) were added, and the mixture was
stirred at 20 °C for 24 h. The volatiles were evaporated, and the residue
was purified by silica gel chromatography using 2% MeOH in CH2Cl2
to yield 42 as an inseparable mixture of anomers (278.3 mg, 97%
combined over two steps). This mixture was characterized as fol-
lows: colorless oil; [R]23D +25.3° (CHCl3, c ) 0.900); IR (neat) 3328,
2972, 1737, 1553, 1482, 1374, 1284, 1232, 1154, 1074, 1026, 973,
1-(3′-Deoxy-3′-(trifluoroacetamido)-5′-O-(trimethylacetyl)-â-D-ri-
bofuranosyl)thymine (43T). Glycal 30 (70.4 mg, 0.238 mmol) was
dissolved in 35 mL of dry CH2Cl2 and chilled to 0 °C. Dimethyldiox-
irane (5.7 mL, 0.059 M solution in acetone) was added dropwise over
10 min. The mixture was stirred at 0 °C for 1 h. The CH2Cl2 was
reduced in volume to 2 mL by evaporation with a stream of N2. Dry
MeCN (10 mL) was added and the volume reduced to 4 mL by
evaporation with a stream of N2. (TMS)2-thymine32 (269 mg, 0.994
mmol) was added, and the mixture was stirred at room temperature
for 19 h. The mixture was diluted with CH2Cl2 and washed with
saturated NaHCO3. The aqueous layer was extracted with CH2Cl2. The
organic layers were washed with brine, dried over Na2SO4, and
concentrated. The residue was dissolved in THF (1.5 mL), H2O (1.5
mL), and Ac2O (4.5 mL) and stirred at 20 °C for 1.5 h. The volatiles
were evaporated, and the residue was purified by silica gel chroma-
tography using 3% MeOH in CH2Cl2 to give 43T (90 mg, 86%):
colorless glass; [R]23D +18.3° (acetone, c ) 1.19); IR (thin film) 3427,
3196, 3054, 2978, 1710, 1536, 1470, 1368, 1262, 1213, 1164, 912,
1
900, 736 cm-1; H NMR (300 MHz, CDCl3, major isomer) δ 6.50 (1
H, br d, J ) 9.0 Hz), 6.18 (1 H, s), 5.20 (1 H, d, J ) 5.0 Hz), 4.89 (1
H, ddd, J ) 8.6, 8.5, 5.1 Hz), 4.33-4.22 (3 H, m), 2.19 (3 H, s), 2.13
(3 H, s), 1.23 (9 H, s); 13C NMR (75 MHz, CDCl3, major isomer) δ
1
792 cm-1; H NMR (300 MHz, acetone-d6) δ 10.27 (1 H, br s), 8.45
(1 H, br s), 7.56 (1 H, d, J ) 1.2 Hz), 5.92 (1 H, d, J ) 2.8 Hz),
4.69-4.63 (2 H, m), 4.44-4.35 (3 H, m), 3.09 (1 H, br s), 1.90 (3 H,
s), 1.26 (9H, s); 13C NMR (75 MHz, acetone-d6) δ 177.6, 164.0, 157.2
(36) (a) Shabarova, Z. A.; Polyakova, Z. P.; Prokofev, M. A. Zh. Obshch.
Khim. 1959, 29, 215; J. Gen. Chem. USSR 1959, 29, 218; Chem. Abstr.
1959, 53, 21998a. (b) Azuma, T.; Isono, K. Chem. Pharm. Bull. 1977, 25,
3347.
(37) Motawia, M. S.; El-Torgoman, A. M.; Pedersen, E. B. Liebigs Ann.
Chem. 1991, 879.