2584 J . Org. Chem., Vol. 67, No. 8, 2002
Fuentes et al.
dichloromethane). Anal. Calcd for C11H13NO6S: C, 45.99; H,
4.56; N, 4.88. Found: C, 46.23; H, 4.57; N, 5.13.
Hz); 13C NMR (125.7 MHz, CDCl3) δ 154.2, 151.5, 147.3,144.8,
143.5, 137.6, 129.0-127.0, 121.2, 95.2, 91.3, 87.2, 81.8, 79.4,
71.6, 60.9. Anal. Calcd for C48H40N5O3F: C, 76.47; H, 5.35; N,
9.29. Found C, 76.01; H, 5.79; N, 8.98. Compound 17: [R]26D 0
(c 0.6, dichloromethane); 1H NMR (500 MHz, CDCl3) δ 8.00
(s, 1 H), 7.96 (d, 1 H, J ) 3.4 Hz), 7.47-7.23 (m, 30 H), 7.03
(s, 1 H), 6.48 (dd, 1 H, J ) 3.1, 20.9 Hz), 4.95 (m, 1 H, J )
51.3 Hz), 4.51 (m, 1 H, J ) 16.9 Hz), 4.11 (m, 1 H), 3.48 (m, 1
H), 3.37 (dd, 1 H, J ) 5.0, 10.1 Hz); 13C NMR (125.7 MHz,
CDCl3) δ 154.1, 152.1, 148.3,144.8, 143.5, 139.3, 128.9-126.8,
120.2, 94.6, 86.9, 83.3, 82.7, 75.4, 71.4, 63.3. HRFAB MS m/z
calcd for C48H40N5O3F + Na: 776.3013. Found: 776.3023.
3-Acet yl-5-(3′-d eoxy-3′-flu or o-r-L-t h r eofu r a n osyl)-2-
m eth ylp yr r ole (18) a n d 3-Acetyl-5-(3′-d eoxy-3′-flu or o-â-
L-th r eofu r a n osyl)-2-m eth ylp yr r ole (19): From 12; m ) 100
mg (0.348 mmol); DMF, x ) 1.8 mL; y ) 98 mg (0.527 mmol);
t1 ) 12 h; t2 ) 3 h; TLC, dichloromethane/methanol (15:1).
Column chromatography, dichloromethane/methanol (15:1),
yielded 18 (33 mg 41%) and 19 (25 mg, 31%) as amorphous
Gen er a l P r oced u r e for th e P r ep a r a tion of F lu or o-
n u cleosid es 13-19. To a solution of the corresponding cyclic
sulfate 7-9, 11, or 12 (m g) in DMF or acetone (x mL) at room
temperature was added tetraethylammonium fluoride dihy-
drate (y mg). The reaction mixture was stirred for t1 h, and
the reaction was controlled by TLC. The solvent was removed
in vacuo, and the residue was stirred with THF (x mL), H2-
SO4 (50 µL/mmol), and H2O (18 µL/mmol) at room temperature
for t2 h, diluted with EtOAc, and washed with saturated
aqueous sodium hydrogencarbonate. The organic layer was
washed with water, dried (MgSO4), filtered, and evaporated
to dryness. The residue was purified by column chromatog-
raphy.
5-(3′-Deoxy-3′-flu or o-r-L-th r eofu r a n osyl)-3-eth oxyca r -
bon yl-2-m eth ylfu r a n (13): From 7; m ) 98 mg (0.308 mmol);
acetone, x ) 1.6 mL; y ) 88 mg (0.474 mmol); t1 ) 9 h; t2 ) 3
h; TLC, dichloromethane/methanol (4:1). Column chromatog-
raphy, ether/petroleum ether (1:1), yielded 50 mg (63%) as an
amorphous solid: [R]26D -60 (c 1.2, dichloromethane); 1H NMR
(500 MHz, CDCl3) δ 6.63 (s, 1 H), 5.08 (ddt, 1 H, J ) 1.4, 4.0,
52.7 Hz), 4.69-4.61 (m, 2 H), 4.27 (q, 2 H, J ) 7.1 Hz), 4.22
(ddd, 1 H, J ) 11.4, 22.2 Hz), 4.10 (ddd, 1 H, J ) 34.4 Hz),
2.56 (s, 3 H), 1.33 (t, 3 H); 13C NMR (125.7 MHz, CDCl3) δ
163.9, 159.6, 148.9, 114.2, 109.4, 97.9, 80.4, 79.3, 71.8, 60.2,
14.2, 13.7; HREI MS m/z calcd for C12H15FO5 258.0903 ([M]•+),
found 258.0902.
solids. Compound 18: [R]23 -56 (c 0.8, dichloromethane); 1H
D
NMR (300 MHz, CDCl3) δ 8.52 (bs, 1 H), 6.43 (d, 1 H, J ) 2.6
Hz), 5.09 (m, 1 H, J ) 52.1 Hz), 4.73 (d, 1 H, J ) 3.3 Hz), 4.40
(bd, 1 H, J ) 16.9 Hz), 4.26 (dd, 1 H, J ) 11.4, 21.9 Hz), 4.06
(ddd, 1 H, J ) 3.0, 38.7 Hz), 3.37 (bs, 1 H), 2.48 (s, 3 H), 2.35
(s, 3 H).13C NMR (75.4 MHz, CDCl3) δ 195.4, 135.9 (C-5), 127.0,
120.7, 108.9, 98.1, 81.6, 80.1, 71.8, 28.2, 14.0; HREI MS m/z
calcd for C11H14NO3F 227.0958 ([M]•+), found 227.0957. Com-
1
pound 19: [R]25 -53 (c 0.7, dichloromethane); H NMR (300
D
5-(3′-Deoxy-3′-flu or o-â-L-th r eofu r a n osyl)-3-eth oxyca r -
bon yl-2-m eth ylfu r a n (14): From 8; m ) 83 mg (0.261 mmol);
acetone, x ) 1.3 mL; y ) 75 mg (0.404 mmol); t1 ) 6 h; t2 ) 0.5
h; TLC, dichloromethane/methanol (4:1). Column chromatog-
raphy, ether/petroleum ether (1:1), yielded 14 (27 mg, 40%)
and 20 (11 mg, 20%). Compound 14 was an amorphous solid:
[R]23D -15 (c 0.9, dichloromethane); 1H NMR (500 MHz, CDCl3)
δ 6.71 (s, 1 H), 5.14 (dd, 1 H, J ) 3.5, 51.8 Hz), 5.02 (bt, 1 H,
J ) 3.1 Hz), 4.38 (dd, 1 H, J ) 11.0 Hz), 4.34 (ddd, 1 H, J )
11.3, 40.2 Hz), 4.28 (c, 2 H, J ) 7.1 Hz), 4.05 (dd, 1 H, J )
27.8 Hz), 2.56 (s, 3 H), 1.32 (t, 3 H); 13C NMR (125.7 MHz,
CDCl3) δ 163.7, 159.8, 146.9, 114.5, 110.8, 96.4, 76.7, 75.3, 71.7,
60.2, 14.2, 13.7. Anal. Calcd for C12H15FO5: C, 55.81; H, 5.85.
Found: C, 55.80; H, 5.78.
MHz, CDCl3) δ 8.91 (bs, 1 H), 6.46 (d, 1 H, J ) 2.6 Hz), 5.16
(dd, 1 H, J ) 3.8, 51.7 Hz), 5.00 (dd, 1 H, J ) 3.2, 3.4 Hz),
4.35 (bd, 1 H, J ) 8.7 Hz), 4.35 (ddd, 1 H, J ) 11.3, 40.7 Hz),
4.04 (dd, 1 H, J ) 30.7 Hz), 3.03 (bs, 1 H), 2.46 (s, 3 H), 2.35
(s, 3 H); 13C NMR (75.4 MHz, CDCl3) δ 195.1, 135.8 (C-5),
123.7, 120.7, 110.0, 96.7, 76.8, 75.9, 71.4, 28.2, 13.9; HREI MS
m/z calcd for C11H14NO3F 227.0958 ([M]•+), found 227.0962.
Gen er a l P r oced u r e for th e P r ep a r a tion of th e Azid o
Com p ou n d s 23-29. To a solution of the corresponding cyclic
sulfate 7-9, 11, or 12 (m g) in DMF (x mL) under argon and
at room temperature was added sodium azide (y mg). The
reaction mixture was stirred for t1 min and controlled by TLC
(dichloromethane). The solvent was removed in vacuo, and the
residue was stirred with 36 N H2SO4 (40 µL/mmol) and H2O
(16 µL/mmol) at room temperature for t2 min, diluted with
EtOAc, and washed with saturated aqueous sodium hydro-
gencarbonate. The organic layer was washed with water, dried
(MgSO4), filtered, and evaporated to dryness. The residue was
purified by column chromatography.
1
3-Eth oxyca r bon yl-5-(fu r -2′-yl)-2-m eth ylfu r a n (20): H
NMR (500 MHz, CDCl3) δ 7.41 (d, 1 H, J ) 1.7 Hz), 6.77 (s, 1
H), 6,54 (d, 1 H, J ) 3.3 Hz), 6.45 (dd, 1 H), 4.30 (q, 2 H, J )
7.1 Hz), 2.63 (s, 3 H), 1.36 (t, 3 H); 13C NMR (125.7 MHz,
CDCl3) δ 163.8, 158.4, 145.7, 144.3, 142.0, 115.1, 111.3, 105.5,
60.2, 14.3, 13.8; HREI MS m/z calcd for C12H12O4 220.0736
([M]•+), found 220.0735.
5-(3′-Azid o-3′-d eoxy-r-L-th r eofu r a n osyl)-3-eth oxyca r -
bon yl-2-m eth ylfu r a n (23): From 7; t1 ) 90 min; t2 ) 15 min;
m ) 750 mg (2.358 mmol); x ) 13.3 mL; y ) 305 mg (4.753
mmol). Column chromatography, ether/petroleum ether (1:1),
yielded 583 mg (88%) as an amorphous solid; [R]29D -43 (c 1.0,
dichloromethane). For FAB MS, IR, and NMR data, see Table
1 and Supporting Information. Anal. Calcd for C12H15N3O5: C,
51.24; H, 5.38; N, 14.94. Found: C, 51.20; H, 5.35; N, 14.81.
5-(3′-Azid o-3′-d eoxy-â-L-t h r eofu r a n osyl)-3-et h oxyca r -
bon yl-2-m eth ylfu r a n (24): From 8; t1 ) 45 min; t2 ) 15 min;
m ) 125 mg (0.393 mmol); x ) 2.2 mL; y ) 51 mg (0.794 mmol).
Column chromatography, ether/petroleum ether (1:1f3:1),
4-(3′-Deoxy-3′-flu or o-r-L-th r eofu r a n osyl)-1,3-d ih yd r o-
3-m eth yl-1-p-tolyl-2H-im id a zole-2-th ion e (15): From 9; m
) 100 mg (0.271 mmol); acetone, x ) 1.4 mL; y ) 76 mg (0.409
mmol); t1 ) 3 h; t2 ) 2 h; TLC, dichloromethane/methanol (20:
1). Column chromatography, dichloromethane/methanol (40:
1), yielded 50 mg (60%) as an amorphous solid: [R]27 -15 (c
D
1.0, dichloromethane); 1H NMR (500 MHz, CDCl3) δ 7.39-7.25
(m, 4 H), 6.83 (s, 1 H), 5.04 (dd, 1 H, J ) 3.4, 51.9 Hz), 4.67 (d,
1 H, J ) 4.1 Hz), 4.45 (bd, 1 H, J ) 18.0 Hz), 4.22 (dd, 1 H, J
) 11.5, 21.9 Hz), 4.07 (ddd, 1 H, J ) 3.4, 37.0 Hz), 3.68 (s, 3
H), 3.43 (bs, 1 H), 2.38 (s, 3 H); 13C NMR (125.7 MHz, CDCl3)
δ 163.7, 138.5-125.7, 127.7, 116.3, 97.9, 79.1, 78.8, 71.9, 32.8,
21.0; HREI MS m/z calcd for C15H17FN2O2S 308.0995 ([M]•+),
found 308.0983.
yielded 97 mg (88%) as an amorphous solid; [R]29 -43 (c 1.0,
D
dichloromethane). For FAB MS, IR, and NMR data, see Table
1 and Supporting Information. Anal. Calcd for C12H15N3O5: C,
51.24; H, 5.38; N, 14.94. Found: C, 51.12; H, 5.37; N, 14.64.
4-(3′-Azid o-3′-d eoxy-r-L-th r eofu r a n osyl)-1,3-d ih yd r o-3-
m eth yl-1-p-tolyl-2H-im id a zole-2-th ion e (25): From 9; TLC,
dichloromethane/methanol (20:1); t1 ) 120 min; t2 ) 30 min;
m ) 675 mg (1.833 mmol); x ) 10.0 mL; y ) 196 mg (3.023
mmol). Column chromatography, dichloromethane/methanol
(60:1), yielded 449 mg (74%) as an amorphous solid; [R]29D -39
(c 1.0, dichloromethane). For FAB MS, IR, and NMR data, see
9-(3′-Deoxy-3′-flu or o-5′-O-tr ityl-â-D-xylofu r a n osyl)-N6-
tr ityla d en in e (16) a n d 9-(2′-Deoxy-2′-flu or o-5′-O-tr ityl-â-
D-a r a bin ofu r a n osyl)-N6-tr ityla d en in e (17): From 11; m )
100 mg (0.123 mmol); DMF, x ) 0.8 mL; y ) 35 mg (0.188
mmol); t1 ) 1.5 h; t2 ) 4.5 h; TLC, dichloromethane/methanol
(4:1). Column chromatography, dichloromethane/methanol
(100:1), yielded 16 (72 mg, 72%) and 17 (6 mg, 6.5%) as
amorphous solids. Compound 16: [R]23 -33 (c 1.1, dichlo-
Table 1 and Supporting Information. Anal. Calcd for C15H17-
D
1
romethane); H NMR (500 MHz, CDCl3) δ 7.94 (s, 1 H), 7.82
N5O2S: C, 54.36; H, 5.17; N, 21.13. Found: C, 54.21; H, 5.34;
N, 20.60.
(s, 1 H), 7.50-7.22 (m, 30 H), 7.13 (s, 1 H), 6.07 (s, 1 H), 5.04
(m, 1 H, J ) 50.8 Hz), 4.66 (m, 1 H, J ) 29.7 Hz), 4.58 (bd, 1
H, J ) 14.5 Hz), 3.63 (m, 1 H), 3.49 (dd, 1 H, J ) 5.2, 10.0
9-(3′-Azid o-3′-d eoxy-5′-O-t r it yl-â-D-xylofu r a n osyl)-N6-
tr ityla d en in e (26) a n d 9-(2′-Azid o-2′-d eoxy-5′-O-tr ityl-â-