The C8-(2′-Deoxyribofuranoside) of 7-Deazaguanine
J . Org. Chem., Vol. 66, No. 10, 2001 3311
1.84 mmol) was dried by coevaporation with pyridine (2 × 10
mL). The residue was suspended in pyridine (5 mL), and Me3-
SiCl (3.0 mL, 23.6 mmol) was added at room temperature.
After 15 min of stirring, the solution was treated with
isobutyric anhydride (0.6 mL, 3.82 mmol) and maintained at
room temperature for 6 h. The solution was cooled in an ice
bath, H2O (3 mL) and subsequently (5 min later) a 25%
aqueous NH3 solution (3 mL) was added, and stirring was
continued for 15 min. The solution was evaporated to dryness,
dissolved in H2O (20 mL), and washed with Et2O (2 × 10 mL).
The aqueous layer was evaporated to dryness again and
coevaporated at first with toluene (2 × 10 mL) and then with
MeOH (2 × 10 mL). The residue was applied to FC (column
10 × 2 cm, CH2Cl2/MeOH 8:2, v/v) to yield the title compound
7 as a pale yellow powder (470 mg, 72%): TLC (CH2Cl2/MeOH
8:2, v/v) 0.3; UV (MeOH) 275 (16600), 294 (15000 sh.); 1H NMR
(d6-DMSO) 1.11 (6H, d, J ) 6.8, Me2), 2.76 (1H, h, J ) 6.8,
CH), 3.51 (1H, m, 5′-H), 3.57 (1H, m, 5′′-H), 3.78 (1H, m, 4′-
H), 3.97 (2H, m, 2′-H, 3′-H), 4.62 (1H, d, J ) 6.3, 1′-H), 4.91
(1H, d, J ) 4.6, 3′-OH), 4.92 (1H, t, J ) 5.8, 5′-OH), 5.06 (1H,
d, J ) 5.8, 2′-OH), 6.39 (1H, d, J ) 1.4, 5-H), 11.34 (1H, s,
NH), 11.60 (1H, s, NH), and 11.78 (1H, s, NH). Anal. Calcd
for C15H20N4O6: C, 51.13; H, 5.72; N, 15.90. Found: C, 51.23;
H, 5.82; N, 15.95.
2-Isob u t yr yla m in o-6-[3,5-(1,1,3,3-t et r a isop r op yl-1,3-
d isiloxa n -1,3-yl)-â-D-r ibofu r a n osyl]-7H-p yr r olo[2,3-d ]p y-
r im id in -4(3H)-on e (8). To a solution of compound 7 (500 mg,
1.42 mmol) in anhydrous pyridine (6 mL) was added 1,3-
dichloro-1,1,3,3-tetraisopropyldisiloxane (0.55 mL, 1.75 mmol)
under an argon atmosphere. The reaction mixture was stirred
at room temperature overnight, and extracted twice with a
5% aqueous NaHCO3 solution (25 mL) followed by brine (25
mL). The organic layer was dried (Na2SO4), filtered, evapo-
rated, and coevaporated twice with toluene (20 mL). The
residue was purified by FC (silica gel, 4 × 10 cm, CH2Cl2/
MeOH 95:5, v/v) to yield the title compound 8 as a colorless
foam (485 mg, 57%): TLC (CH2Cl2/MeOH 95:5) 0.5; UV
(MeOH) 275 (17200), 293 (15700 sh.); 1H NMR (d6-DMSO)
0.89-1.04 (28H, m, (CHMe2)4), 1.12 (6H, d, J ) 6.7, Me2), 2.77
(1H, h, J ) 6.7, CH), 3.87 (1H, m, 5′′-H), 3.91 (1H, m, 5′-H),
3.94 (1H, m, 4′-H), 4.15 (1H, d't′, J ) 5.0, J ) 3.5, 2′-H), 4.24
(1H, dd, J ) 6.0, J ) 6.7, 3′-H), 4.71 (1H, d, J ) 3.0, 1′-H),
5.03 (1H, d, J ) 5.3, 2′-OH), 6.35 (1H, s, 5-H), 11.34 (1H, br.
s, NH), 11.67 (1H, s, NH), and 11.74 (1H, br. s, NH). Anal.
Calcd for C27H46N4O7Si2: C, 54.52; H, 7.79; N, 9.42. Found:
C, 54.51; H, 7.88; N, 9.51.
2-Isob u t yr yla m in o-6-[2-O-p h en oxyt h ioca r b on yl-3,5-
(1,1,3,3-tetr a isop r op yl-1,3-d isiloxa n -1,3-yl)-â-D-r ibofu r a -
n osyl]-7H-p yr r olo[2,3-d ]p yr im id in -4(3H)-on e (9a ). To a
suspension of compound 8 (1.71 g, 2.88 mmol) and 4-(dim-
ethylamino)pyridine (2.1 g, 17.2 mmol) in anhydrous MeCN
(65 mL) was added phenylchlorothionoformiate (0.48 mL, 3.48
mmol) under an argon atmosphere. After the reaction mixture
was stirred overnight at room temperature, it was evaporated
to dryness and dissolved with CH2Cl2 (50 mL). The organic
phase was washed twice with cold 1.0 M hydrochloric acid (20
mL), H2O (20 mL), and a saturated aqueous NaHCO3 solution
(20 mL). The organic layer was dried (Na2SO4), and the solvent
was evaporated. The residue, which was a mixture of two
major compounds, was purified by FC (silica gel, 4 × 10 cm,
CH2Cl2/acetone 9:1, v/v). The slower moving major product
yielded a colorless foam and was characterized as the title
compound 9a (1.0 g, 48%): TLC (CH2Cl2/acetone 9:1) 0.6; UV
(MeOH) 274 (18000), 294 (16200 sh.); 1H NMR (d6-DMSO)
0.95-1.03 (28H, m, (CHMe2)4), 1.11 (6H, d, J ) 6.9, Me2), 2.77
(1H, h, J ) 6.9, CH), 3.90 (1H, m, 5′′-H), 4.00 (2H, m, 5′-H,
4′-H), 4.66 (1H, d“t”, J ) 6.4, 3′-H), 5.14 (1H, d, J ) 2.8, 1′-H),
5.90 (1H, “t”, J ) 4.2, 1′-H), 7.12 (2H, d, J ) 7.9, arom. H),
7.33 (1H, t, J ) 7.2, arom. H), 7.48 (2H, t, J ) 7.5, arom. H),
11.36 (1H, s, NH), 11.81 (1H, s, NH), and 11.87 (1H, s, NH).
Anal. Calcd for C34H50N4O8SSi2: C, 55.86; H, 6.89; N, 7.66.
Found: C, 56.00; H, 6.82; N, 7.60.
4(3H)-on e (9b). The faster moving byproduct of the synthesis
procedure described above was obtained as a yellow powder
(250 mg, 10%) and was characterized as compound 9b: TLC
(CH2Cl2/acetone 9:1) 0.8; UV (MeOH) 272 (20900), 295 (15600
sh.); 1H NMR (d6-DMSO) 0.97-1.08 (28H, m, (CHMe2)4), 1.13
(6H, d, J ) 6.4, Me2), 2.85 (1H, d, J ) 6.8, CH), 3.93 (1H, d, J
) 8.9, 4′-H), 4.01 (1H, d, J ) 12.1, 5′-H), 4.20 (1H, d, J ) 12.7,
5′′-H), 4.65 (1H, dd, J ) 8.9, J ) 4.5, 3′-H), 5.78 (1H, s, 1′-H),
6.14 (1H, d, J ) 4.5, 2′-H), 6.72 (2H, d, J ) 7.6, arom. H), 6.88
(1H, s, 5-H), 7.29 (1H, t, J ) 7.3, arom. H), 7.38 (2H, d, J )
8.3, arom. H), 7.41 (2H, t, J ) 8.0, arom. H), 7.45 (1H, t, J )
8.3, arom. H), 7.57 (2H, t, J ) 7.6, arom. H), 11.44 (1H, br. s,
NH), and 12.18 (1H, br. s, NH). Anal. Calcd for C41H54N4O9S2-
Si2: C, 56.79; H, 6.28; N, 6.46. Found: C, 56.89; H, 6.16; N,
6.41.
2-Isob u t yr yla m in o-6-[3,5-(1,1,3,3-t et r a isop r op yl-1,3-
d isiloxa n -1,3-yl)-(2-d eoxy-â-D-er yt h r o-p en t ofu r a n osyl]-
7H-p yr r olo[2,3-d ]p yr im id in -4(3H)-on e (10). To a solution
of compound 9a (1.06 g, 1.45 mmol) in anhydrous toluene (60
mL) was added 2,2′-azobis(isobutyronitrile) (AIBN, 120 mg,
0.73 mmol) and tri-n-butyltin(IV) hydride (3.8 mL, 14.1 mmol)
under an argon atmosphere. The reaction flask was placed in
a preheated oil bath (70 °C). After 2 h, the mixture was cooled
to room temperature, and the solvent was evaporated. The oily
residue was applied to FC (silica gel, 4 × 10 cm, CH2Cl2/MeOH
95:5, v/v) to yield the title compound 10 as a colorless foam
(755 mg, 90%): TLC (CH2Cl2/MeOH) 0.4; UV (MeOH) 274
(17200), 293 (15500); 1H NMR (d6-DMSO) 0.99-1.02 (28H, m,
(CHMe2)4), 1.11 (6H, d, J ) 6.6, Me2), 2.18 (1H, m, 2′-HR), 2.41
(1H, m, 2′-Hâ), 2.76 (1H, h, J ) 6.5, CH), 3.75 (2H, m, 5′-H2),
3.95 (1H, m, 4′-H), 4.51 (1H, m, 3′-H), 5.02 (1H, t, J ) 7.2,
1′-H), 6.37 (1H, s, 5-H), 11.36 (1H, br. s, NH), 11.70 (1H, br. s,
NH), and 11.77 (1H, s, NH). Anal. Calcd for C27H46N4O6Si2:
C, 56.02; H, 8.01; N, 9.68. Found: C, 56.21; H, 8.15; N, 9.63.
2-Isobu tyr yla m in o-6-(2-d eoxy-â-D-er yth r o-p en tofu r a -
n osyl)-7H-p yr r olo[2,3-d ]p yr im id in -4(3H)-on e (11). To a
solution of compound 10 (865 mg, 1.5 mmol) in THF (10 mL)
was added a 1.0 N solution of (n-Bu)4NF (8 mL, 8 mmol) in
THF. The mixture was stirred at room temperature for 3 h,
and the solvent was evaporated. The resulting residue was
applied to FC (silica gel, 4 × 10 cm, CH2Cl2/MeOH 9:1, v/v) to
yield the title compound 11 as a colorless powder (410 mg,
82%): TLC (CH2Cl2/MeOH 9:1) 0.25; UV (MeOH) 272 (15900),
1
291 (14200); H NMR (d6-DMSO) 1.11 (6H, d, J ) 6.9, Me2),
2.01 (1H, m, 2′-HR), 2.11 (1H, m, 2′-Hâ), 2.76 (1H, h, J ) 7.0,
CH), 3.45 (2H, m, 5′-H2), 3.74 (1H, m, 4′-H), 4.20 (1H, m, 3′-
H), 4.79 (1H, t, J ) 4.2, 5′-OH), 5.02 (1H, dd, J ) 10.1, J )
5.7, 1′-H), 5.08 (1H, d, J ) 3.5, 3′-OH), 6.35 (1H, s, 5-H), 11.33
(1H, br. s, NH), 11.63 (1H, br. s, NH), and 11.76 (1H, s, NH).
Anal. Calcd for C15H20N4O5: C, 53.56; H, 5.99; N, 16.66.
Found: C, 53.54; H, 5.94; N, 16.63.
2-Isobu tyr yla m in o-6-[2-d eoxy-5-O-(4,4′-d im eth oxytr i-
tyl)-â-D-er yth r o-p en tofu r a n osyl]-7H-p yr r olo[2,3-d ]p yr i-
m id in -4(3H)-on e (12). Compound 11 (350 mg, 1.04 mmol) was
dried by repeated coevaporation with anhydrous pyridine (2
× 10 mL) and dissolved in dry pyridine (15 mL). Then, 4,4′-
dimethoxytriphenylmethyl chloride (407 mg, 1.2 mmol) was
added, and the solution was stirred for 3 h under argon at
room temperature. MeOH (3 mL) was added, and the mixture
was stirred for another 30 min. Then the solution was reduced
to half of the volume, diluted with CH2Cl2 (50 mL), and
extracted twice with a 5% aqueous NaHCO3 solution (25 mL)
followed by brine (25 mL). The organic layer was dried (Na2-
SO4), filtered, evaporated, and coevaporated with toluene (20
mL twice). The residue was purified by FC (silica gel, 4 × 10
cm, CH2Cl2/MeOH 9:1, v/v) to yield the title compound 12 as
a colorless foam (480 mg, 72%): TLC (CH2Cl2/MeOH 95:5, v/v)
0.2; UV (MeOH) 272 (15700), 294 (13200); 1H NMR (d6-DMSO)
1.11 (6H, d, J ) 6.6, Me2), 2.10 (1H, m, 2′-HR), 2.18 (1H, m,
2′-Hâ), 2.76 (1H, h, J ) 6.6, CH), 3.02 (2H, m, 5′-H2), 3.72 (6H,
s, Me2), 3.91 (1H, m, 4′-H), 4.16 (1H, m, 3′-H), 5.10 (1H, dd, J
) 9.0, J ) 6.4, 1′-H), 5.16 (1H, d, J ) 3.5, 3′-OH), 6.36 (1H, s,
5-H), 6.82-6.87 (4H, m, arom. H), 7.17-7.39 (9H, m, arom.
H), 11.38 (1H, br. s, NH), 11.77 (1H, br. s, NH), and 11.79
2-Isobu tyr yla m in o-7-p h en oxyth ioca r bon yl-6-[2-O-p h e-
n oxyth iocar bon yl-3,5-(1,1,3,3-tetr aisopr opyl-1,3-disiloxan -
1,3-yl)-â-D-r ib ofu r a n osyl]-7H -p yr r olo[2,3-d ]p yr im id in -