9292 J . Org. Chem., Vol. 64, No. 25, 1999
Notes
4.08 (m, 1 H), 3.94 (m, 3 H), 1.40 (s, 9 H); 13C NMR (10% CD3-
OD in CDCl3) δ 165.54, 156.52, 154.86, 154.07, 140.58, 134.02,
128.79, 128.44, 128.39, 94.91, 91.52, 83.46, 80.65, 74.59, 71.10,
70.92, 51.75, 27.64; IR (neat) 3345, 1791, 1652 cm-1; HRFABMS
calcd for C22H29N4O9 (M + H)+ 493.1935, found 493.1944.
3,5′-An h yd r ogu a n osin e (15). Compound 15 was prepared
by method A in a THF (10 mL) and DMSO (2 mL) solution as a
white solid in 90% yield: mp 180 °C (dec); 1H NMR (DMSO-d6)
δ 7.72 (s, 1 H), 6.14 (s, 1 H), 4.50 (br, 1 H), 4.42 (d, J ) 13.8 Hz,
yield: 1H NMR (CDCl3) δ 7.55 (s, 1 H), 7.52-7.49 (m, 2 H), 7.39-
7.28 (m, 8 H), 5.76 (d, J ) 5.7 Hz, 1 H), 5.47 (s, 2 H), 5.26 (br,
2 H), 5.17 (s, 2 H), 4.78 (t, J ) 5.4 Hz, 1 H), 4.34-4.29 (m, 1 H),
4.23-4.20 (m, 1 H), 4.07-3.91 (m, 2 H), 1.34 (s, 9 H); 13C NMR
(CDCl3) δ 160.36, 159.19, 155.03, 154.43, 152.56, 138.28, 136.14,
134.17, 128.82, 128.57, 128.47, 128.21, 128.08, 115.16, 90.02,
83.36, 82.04, 73.24, 72.30, 71.13, 68.23, 51.69, 27.81; IR (neat)
3359, 1786, 1717, 1616, 1590, 1259, 1219 cm-1; HRFABMS calcd
for C30H35N6O9 (M + H)+ 623.2466, found 623.2465.
5′-Deoxy-5′-N-(N-ter t-b u t oxyca r b on yl)h yd r oxyla m in o-
a d en osin e (21). Compound 21 was prepared by method B as a
clear oil in 95% yield: 1H NMR (10% CD3OD in CDCl3) δ 8.21
(s, 1 H), 7.94 (s, 1 H), 5.76 (d, J ) 6.0 Hz, 1 H), 4.55 (t, J ) 5.7
Hz, 1 H), 4.32-4.25 (m, 2 H), 4.03 (dd, J ) 3.3 Hz, 15.3 Hz, 1
H), 3.71 (dd, J ) 4.2 Hz, 15.3 Hz, 1 H), 1.44 (s, 9 H); 13C NMR
(10% CD3OD in CDCl3) δ 157.11, 155.45, 152.30, 148.14, 140.12,
119.42, 89.15, 83.18, 81.70, 73.24, 71.28, 52.28, 27.97; IR (neat)
3335, 1652 cm-1; HRFABMS calcd for C15H23N6O6 (M + H)+
383.1679, found 383.1666.
1 H), 4.18 (m, 1 H), 3.93 (d, J ) 13.5 Hz, 1H), 3.87 (m, 1 H); 13
C
NMR (DMSO-d6) δ 164.27, 153.89, 138.60, 133.15, 121.61, 92.42,
83.13, 75.54, 70.58, 53.38; IR (KBr) 3350, 1634 cm-1; HRFABMS
calcd for C10H12N5O4 (M + H)+ 266.0889, found 266.0891.
3,5′-An h yd r o-4-N-t r ip h en ylp h osp h or a n ylid en egu a n o-
sin e (16). Compound 16 was prepared by method A in a THF
(5 mL) and DMSO (5 mL) solution as a white solid in 35%
yield: mp 180 °C (dec); 1H NMR (10% CD3OD in CDCl3) δ 7.76-
7.69 (m, 6 H), 7.49-7.34 (m, 10 H), 5.95 (s, 1 H), 5.33 (d, J )
12.9 Hz, 1 H), 4.67 (m, 1 H), 4.20 (m, 1 H), 4.07 (dd, J ) 2.4 Hz,
14.7 Hz, 1 H), 3.86 (m, 1 H); 13C NMR (10% CD3OD in CDCl3)
δ 165.92, 156.91, 140.06, 133.19, 133.05, 132.64, 132.43, 132.39,
128.59, 128.42, 127.52, 126.15, 121.16, 92.70, 84.48, 75.35, 70.54,
54.25; 31P NMR (10% CD3OD in CDCl3) 21.87; IR (KBr) 3370,
1597, 1435 cm-1; HRFABMS calcd for C28H25N5O4P (M + H)+
526.1644, found 526.1652.
6-O-Ben zyl-2′,3′,5′-O-t r i-ter t-b u t yld im et h ylsilylgu a n o-
sin e (18). Guanosine 8 (1.45 g, 5 mmol) was suspended in dry
DMF (30 mL) and treated with imidazole (2.7 g, 40 mmol) and
TBSCl (4.5 g, 30 mmol). The reaction mixture was stirred at
room temperature overnight. Then DMF was removed under
reduced pressure. The residue was diluted with ethyl acetate
(100 mL) and was washed with water (3 × 50 mL), saturated
aqueous ammonium chloride (NH4Cl) solution (2 × 50 mL), and
brine (50 mL). The organic layer was dried over anhydrous
sodium sulfate, filtered, and evaporated to give a white foam
(3.0 g). This white foam was further evacuated overnight under
high vacuum and dissolved in anhydrous THF (40 mL). Triph-
enylphosphine (1.97 g, 7.5 mmol) was added, followed by benzyl
alcohol (1.03 mL, 10 mmol). The mixture was cooled to 0 °C and
diisopropyl azodicarboxylate (DIAD) (1.48 mL, 7.5 mmol) was
added dropwise. The solution then was stirred at room temper-
ature for 4 h and the solvent was removed in vacuo. The residue
was purified by flash column chromatography (hexanes/EtOAc
) 8:1) to give 18 (2.1 g, 2 steps, 59%) as a white solid: mp 95-
97 °C; 1H NMR (CDCl3) δ 7.96 (s, 1 H), 7.51-7.48 (m, 2 H), 7.38-
7.26 (m, 3 H), 5.96 (d, J ) 6.0 Hz, 1 H), 5.55 (s, 2 H), 5.49 (br,
2 H), 4.46 (m, 1 H), 4.28 (m, 1 H), 4.11 (m, 1 H), 3.96 (dd, J )
3.3 Hz, 11.4 Hz, 1 H), 3.78 (dd, J ) 2.4 Hz, 11.1 Hz, 1 H), 0.95
(s, 18 H), 0.79 (s, 9 H), 0.16 (s, 3 H), 0.14 (s, 3 H), 0.13 (s, 3 H),
0.125 (s, 3 H), -0.038 (s, 3 H), -0.18 (s, 3 H); 13C NMR (CDCl3)
δ 160.84, 159.35, 153.91, 137.40, 136.43, 128.25, 128.13, 127.80,
115.46, 87.13, 85.42, 76.57, 72.27, 67.80, 62.71, 26.02, 25.84,
25.61, 18.44, 18.04, 17.88, -4.29, -4.78, -4.80, -5.13, -5.44,
-5.50; IR (neat) 3322, 3203, 1635, 1579 cm-1; HRFABMS calcd
for C35H62N5O5Si3 (M + H)+ 716.4059, found 716.4041.
5′-Deoxy-5′-N-(N-ter t-b u t oxyca r b on yl)h yd r oxyla m in o-
u r id in e (22). Compound 22 was prepared by method B as a
1
white solid in 96% yield. Mp 179 °C (dec); H NMR (10% CD3-
OD in CDCl3) δ 7.66 (d, J ) 7.8 Hz, 1 H), 5.83 (d, J ) 4.5 Hz, 1
H), 5.73 (d, J ) 8.1 Hz, 1 H), 4.22-4.18 (m, 2 H), 4.12 (m, 1 H),
3.88-3.76 (m, 2 H), 1.48 (s, 9 H); 13C NMR (10% CD3OD in
CDCl3) δ 164.09, 156.64, 150.42, 140.64, 101.44, 89.75, 81.00,
80.60, 73.15, 70.66, 51.53, 27.23; IR (neat) 3234, 1686 cm-1
;
HRFABMS calcd for C14H22N3O8 (M + H)+: 360.1407, found
360.1381.
5′-Deoxy-5′-N-(N-ter t-b u t oxyca r b on yl)h yd r oxyla m in o-
cytid in e (23). Compound 23 was prepared by method B as a
1
white solid in 94% yield: mp 174 °C (dec); H NMR (20% CD3-
OD in CDCl3) δ 7.66 (d, J ) 7.5 Hz, 1 H), 5.87 (d, J ) 7.5 Hz, 1
H), 5.74 (d, J ) 3.0 Hz, 1 H), 4.21 (m, 1 H), 4.12 (m, 1 H), 4.04
(m, 1 H), 3.80 (m, 2 H), 1.44 (s, 9 H); 13C NMR (20% CD3OD in
CDCl3) δ 165.51, 156.62, 156.36, 140.82, 94.48, 91.25, 81.34,
80.94, 73.94, 70.64, 51.48, 27.21; IR (KBr) 3344, 1651 cm-1
;
HRFABMS calcd for C14H23N4O7 (M + H)+ 359.1567, found
359.1558.
5′-Deoxy-5′-N-(N-ter t-b u t oxyca r b on yl)h yd r oxyla m in o-
gu a n osin e (24). Compound 24 was prepared by method B as a
white solid in 88% yield: mp 205 °C (dec); 1H NMR (DMSO-d6)
δ 10.69 (s, 1H), 9.39 (s, 1H), 7.89 (s, 1 H), 6.49 (s, 2 H), 5.68 (d,
J ) 6.0 Hz, 1 H), 5.47 (d, J ) 5.1 Hz, 1 H), 5.21 (br, 1 H), 4.45
(m, 1 H), 4.10-4.05 (m, 2 H), 3.71-3.55 (m, 2 H), 1.33 (s, 9 H);
13C NMR (DMSO-d6) δ 156.77, 155.88, 153.70, 151.33, 135.77,
116.79, 86.35, 80.97, 79.73, 72.98, 71.36, 53.00, 27.95; IR (KBr)
3415, 1694 cm-1; HRFABMS calcd for C15H23N6O7 (M + H)+
399.1628, found 399.1610.
5′-Deoxy-5′-N-h yd r oxyla m in oa d en osin e (1). Compound 1
was prepared by method C as a white solid in 95% yield: mp
110 °C (dec); 1H NMR (CD3OD) δ 8.45 (s, 1 H), 8.39 (s, 1 H),
6.08 (d, J ) 5.4 Hz, 1 H), 4.86 (t, J ) 5.1 Hz, 1 H), 4.51-4.44
(m, 2 H), 3.87 (dd, J ) 9.3 Hz, 13.5 Hz, 1 H), 3.60 (dd, J ) 2.7
Hz, 12.9 Hz, 1 H); 13C NMR (CD3OD) δ 153.64, 150.17, 147.94,
144.20, 121.81, 91.73, 79.86, 74.58, 73.06, 54.11; IR (KBr) 3337,
1684 cm-1; HRFABMS calcd for C10H15N6O4 (M + H)+ 283.1155,
found 283.1148.
5′-Deoxy-5′-N-h yd r oxyla m in ou r id in e (2). Compound 2
was prepared by method C as a white solid in quantitative
yield: mp 143 °C (dec); 1H NMR (CD3OD) δ 7.81 (d, J ) 8.1 Hz,
1 H), 5.83 (d, J ) 5.1 Hz, 1 H), 5.74 (d, J ) 8.1 Hz, 1 H), 4.35-
4.32 (m, 1 H), 4.19 (m, 2 H), 3.22 (m, 2 H); 13C NMR (DMSO-d6)
δ 163.06, 150.76, 141.40, 101.89, 87.94, 81.44, 72.52, 71.25, 55.76;
IR (KBr) 3403, 1683 cm-1; HRFABMS calcd for C9H14N3O6 (M
+ H)+ 260.0883, found 260.0840.
6-O-Ben zylgu a n osin e (19). A stirred solution of compound
18 (700 mg, 0.98 mmol) in THF (15 mL) was treated with TBAF
(1.28 g, 4.89 mmol). The reaction mixture was stirred at room
temperature for 0.5 h and concentrated in vacuo. The residue
was redissloved in ethyl acetate (100 mL) and was washed with
saturated aqueous NH4Cl (5 × 50 mL). The ethyl acetate layer
was dried over sodium sulfate, filtered, and evaporated. The
residue was purified by flash column chromatography (CH2Cl2/
MeOH ) 10:1) to give 19 (334 mg, 92%) as a white solid: mp
86-88 °C; 1H NMR (10% CD3OD in CDCl3) δ 7.60 (s, 1 H), 7.49-
7.45 (m, 2 H), 7.38-7.30 (m, 3 H), 5.70 (d, J ) 7.5 Hz, 1 H), 5.59
(d, J ) 12.6 Hz, 1 H), 5.44 (br, 1 H), 5.38 (d, J ) 12.3 Hz, 1 H),
4.96 (dd, J ) 5.4 Hz, 7.5 Hz, 1 H), 4.31 (d, J ) 5.1 Hz, 1 H), 4.25
(s, 1 H), 3.92 (dd, J ) 2.1 Hz, 12.9 Hz, 1 H), 3.72 (dd, J ) 1.2
Hz, 12.6 Hz, 1 H); 13C NMR (10% CD3OD in CDCl3) δ 160.52,
158.80, 151.62, 139.42, 135.73, 128.26, 127.96, 115.53, 91.02,
5′-Deoxy-5′-N-h yd r oxyla m in ocyt id in e (3). Compound 3
was prepared by method C as a clear oil in 93% yield: 1H NMR
(CD3OD) δ 8.06 (d, J ) 8.1 Hz, 1 H), 6.21 (d, J ) 7.8 Hz, 1 H),
5.77 (d, J ) 4.2 Hz, 1 H), 4.45 (dd, J ) 3.9 Hz, 5.7 Hz, 1 H),
4.40-4.33 (m, 1 H), 4.18 (t, J ) 6.0 Hz, 1 H), 3.73 (dd, J ) 9.9
Hz, 13.2 Hz, 1 H), 3.57 (dd, J ) 2.4 Hz, 13.2 Hz, 1 H); 13C NMR
(CD3OD) δ 161.29, 148.37, 147.98, 95.50, 95.22, 78.81, 74.13,
72.64, 54.17; IR (neat) 3117, 1679 cm-1; HRFABMS calcd for
C9H15N4O5 (M + H)+ 259.1042, found 259.1025.
86.96, 72.59, 72.22, 68.12, 62.93; IR (KBr) 3357, 1616, 1591 cm-1
;
HRFABMS calcd for C17H20N5O5 (M + H)+ 374.1464, found
374.1480.
6-O-Ben zyl-5′-d eoxy-5′-N-(N-ter t-bu toxyca r bon yl-O-ben -
zyloxyca r bon yl)-h yd r oxyla m in ogu a n osin e (20). Compound
20 was prepared by method A in THF as a clear oil in 91%
5′-Deoxy-5′-N-h yd r oxyla m in ogu a n osin e (4). Compound 4
was prepared by method C as a white solid in 96% yield: mp