7434 J . Org. Chem., Vol. 61, No. 21, 1996
Clive et al.
shaken with hydrogen (50 psi) for 4 h. The mixture was
filtered and evaporated. Flash chromatography of the residue
over silica gel (1 × 30 cm), using 5:3:2 MeCN-CH2Cl2-PhMe,
gave N-acetyl-2′,3′-dideoxy-5′-O-(triphenylmethyl)cytidine (30
mg, 61%) as a colorless oil: FTIR (CH2Cl2, cast) 3229, 2925,
J ) 12.0, 4.0 Hz, 1 H), 4.38-4.48 (m, 1 H), 5.70-5.80 (apparent
t, J ) 5.0 Hz, 1 H), 6.08-6.18 (apparent t, J ) 5.0 Hz, 1 H),
6.32-6.38 (d, J ) 5.0 Hz, 1 H), 6.60-6.76 (br s, 2 H), 8.22 (s,
1 H), 8.25 (s, 1 H); 13C NMR (acetone-d6, 50.3 MHz) δ -5.40
(two overlapping signals), 18.94, 26.28 (three overlapping
signals), 38.67 (two overlapping signals), 62.29, 76.20, 78.31,
83.50, 87.15, 120.89, 140.49, 150.50, 153.96, 157.36; mass
(FAB) m/ z calcd for C18H32N5O8S2Si (M + H) 538, found 538.
5′-O-[(1,1-Dim eth yleth yl)dim eth ylsilyl]-2′,3′-dideh ydr o-
2′,3′-d id eoxya d en osin e (14a ) fr om Dim esyla te 14. The
general procedure was followed, using Te powder (200 mesh,
113 mg, 0.887 mmol), Et3BHLi (1 M in THF, 2.0 mL, 2.0
mmol), an initial reaction time of ca. 6 h, dimesylate 14 (200
mg, 0.372 mmol) in THF (2 mL), and a reaction time of 20 h.
The mixture was washed out of the flask with CH2Cl2 and
evaporated at room temperature. Flash chromatography of
the residue over silica gel (2 × 15 cm), using 1:19 MeOH-
CH2Cl2, gave 14a 56 (101 mg, 78%) as a colorless oil: FTIR (CH2-
1
1717, 1663, 1493 cm-1; H NMR (CD2Cl2, 300 MHz) δ 1.88-
1.98 (m, 2 H), 2.09-2.20 (m, 4 H), 2.41-2.55 (m, 1 H), 3.36
(dd, J ) 4.5, 4.5 Hz, 1 H), 3.49 (dd, J ) 2.7, 2.7 Hz, 1 H), 4.22-
4.32 (m, 1 H), 6.03 (dd, J ) 2.0, 2.0 Hz, 1 H), 7.10 (d, J ) 7.5
Hz, 1 H), 7.25-7.49 (m, 15 H), 8.31 (d, J ) 7.5 Hz, 1 H), 9.12
(br s, 1 H); 13C NMR (CD2Cl2, 75 MHz) δ 25.08 (q′), 25.17 (t′),
38.87 (t′), 64.38 (t′), 82.20 (d′), 87.63 (s′), 88.32 (d′), 95.48 (d′),
127.67 (d′), 128.38 (d′), 129.05 (d′), 144.02 (s′), 145.31 (d′),
155.36 (s′), 162.71 (s′), 170.50 (s′) (several signals of the trityl
group overlap); mass (FAB) m/ z calcd for C30H30N3O4 (M +
H) 496.2, found 496.1.
5′-O-Acet ylu r id in e 2′,3′-Bis(m et h a n esu lfon a t e) (13).
MeSO2Cl (0.90 mL, 11.60 mmol) in CH2Cl2 (1.6 mL) was added
dropwise to a stirred and cooled (ice bath) solution of 5′-O-
acetyluridine52,53 (332 mg, 1.16 mmol) and pyridine (1.50 mL,
18.5 mmol) in CH2Cl2 (3 mL). The ice bath was removed, and
stirring was continued for 24 h. The mixture was evaporated
at room temperature, and flash chromatography of the residue
over silica gel (3.5 × 30 cm), using 3:97 MeOH-CH2Cl2, gave,
after a second chromatography under the same conditions, 13
(417 mg, 81%): FTIR (MeOH, cast) 1365, 1180 cm-1; 1H NMR
(acetone-d6, 200 MHz) δ 2.07 (s, 3 H), 3.26 (s, 3 H), 3.32 (s, 3
H), 4.30-4.60 (m, 3 H), 5.48 (t, J ) 6.0 Hz, 1 H), 5.55-5.80
(m, 2 H), 6.00 (d, J ) 3.0 Hz, 1 H), 7.76 (d, J ) 8.0 Hz, 1 H),
10.23 (br s, 1 H); 13C NMR (acetone-d6, 50.3 MHz) δ 20.61,
38.66, 38.74, 62.58, 75.14, 78.61, 80.24, 91.11, 103.34, 141.93,
Cl2 cast) 3292, 3164, 2927, 1601, 1085, 837 cm-1 1H NMR
;
(CD2Cl2, 400 MHz) δ 0.04 (s, 3 H), 0.05 (s, 3 H), 0.89 (s, 9 H),
3.82 (d, J ) 4.0 Hz, 2 H), 4.94-5.00 (m, 1 H), 5.91 (br s, W1/2
) 17 Hz, 2 H), 6.04 (ddd, J ) 6.0, 4.0, 2.0 Hz, 1 H), 6.41 (dt J
) 6.0, 2.0, 2.0 Hz, 1 H), 7.04-7.08 (m, J ) 2.0, 1 H), 8.08 (s,
1 H), 8.30 (s, 1 H); 13C (CD2Cl2, 75 MHz) δ -5.17 (q′), -5.06
(q′) (two overlapping signals), 18.95 (s′), 26.29 (q′) (three
overlapping signals), 65.45 (t′), 88.27 (d′), 88.68 (d′), 120.19
(s′), 126.06 (d′), 134.96 (d′), 139.81 (d′), 150.44 (s′), 153.58 (d′),
156.01 (s′); exact mass m/ z calcd for C16H25N5O2Si 347.1778,
found 347.1776.
N-[(Dim et h yla m in o)m et h ylen e]-5′-O-[b is(4-m et h oxy-
p h en yl)p h en ylm et h yl]a d en osin e 2′,3′-Bis(m et h a n esu l-
fon a te) (15). MeSO2Cl (0.37 mL, 4.8 mmol) in CH2Cl2 (5 mL)
was added dropwise to a stirred and cooled (0 °C) solution of
N-[(dimethylamino)methylene]-5′-O-[bis(4-methoxyphenyl)-
phenylmethyl]adenosine,57 (1.001 g, 1.602 mmol), and Et3N
(1.34 mL, 9.61 mmol) in CH2Cl2 (8 mL). The mixture was
stirred at 0 °C for 30 min, poured onto ice (ca. 200 g), and
extracted with CH2Cl2 (2 × 150 mL). The organic extract was
washed with water (1 × 100 mL), saturated aqueous NaHCO3
(1 × 100 mL), and water (1 × 100 mL), dried (MgSO4), and
evaporated. Flash chromatography of the residue over silica
gel (3 × 30 cm), using 49:30:20:1 CH2Cl2-PhMe-MeCN-Et3N,
151.33, 163.36, 170.57; mass (HRFAB) m/ z calcd for (C13H18
N2O11S2 + H) 443.0431, found 443.0398.
-
5′-O-Acetyl-2′,3′-d id eh yd r o-2′,3′-d id eoxyu r id in e (13a )
fr om Dim esyla te 13. The general procedure was followed,
using Te powder (200 mesh, 61 mg, 0.475 mmol), Et3BHLi (1
M in THF, 1.17 mL, 1.17 mmol), dimesylate 13 (100 mg, 0.226
mmol) in THF (3 mL), and a reaction time of 96 h. The
mixture was washed out of the flask with CH2Cl2 and
evaporated at room temperature. Flash chromatography of
the residue over silica gel (1 × 30 cm), using 3:97 MeOH-
CH2Cl2, gave 13a (7.7 mg, 14%), spectroscopically identical to
an authentic9b,54 sample.
gave 15 (1.089 g, 87%): FTIR (CH2Cl2, cast) 1365, 1180 cm-1
;
1H NMR (acetone-d6, 200 MHz) δ 3.10-3.30 (m, 12 H), 3.40
(dd, J ) 11.0, 4.0 Hz, 1 H), 3.62 (dd, J ) 11.0, 3.5 Hz, 1 H),
3.75 (s, 3 H), 3.76 (s, 3 H), 4.40-4.60 (m, 1 H), 5.85-6.00 (m,
1 H), 6.30-6.55 (m, 2 H), 6.70-6.90 (m, 4 H), 7.10-7.38 (m, 7
H), 7.38-7.55 (m, 2 H), 8.30 (s, 1 H), 8.31 (s, 1 H), 8.85-9.00
(br s, 1 H); 13C NMR (acetone-d6, 50.3 MHz) δ 35.02, 38.74,
38.80, 41.13, 55.60 (two overlapping signals), 62.99, 77.08,
77.47, 82.51, 87.67, 87.86, 114.06, 127.68, 128.63, 129.14,
131.04, 136.53, 136.65, 145.76, 152.45, 153.25, 159.14, 159.82,
161.16 (several signals of DMT group overlap); mass (HRFAB)
m/ z calcd for (C36H40N6O10S2 + H) 781.2328, found 781.2337.
2′,3′-Did e h yd r o-2′,3′-d id e oxy-N -[(d im e t h yla m in o)-
m et h ylen e]-5′-O-[b is(4-m et h oxyp h en yl)p h en ylm et h yl]-
a d en osin e (15a ) fr om Dim esyla te 15. The general proce-
dure was followed, using Te powder (200 mesh, 20 mg, 0.156
mmol), Et3BHLi (1 M in THF, 0.33 mL, 0.33 mmol), dimesylate
15 (58 mg, 0.074 mmol) in THF (2 mL), and a reaction time of
16 h. The mixture was washed out of the flask with CH2Cl2,
and evaporated at room temperature. Flash chromatography
of the residue over silica gel (1 × 30 cm), using 29:20:50:1 CH2-
Cl2-PhMe-MeCN-Et3N, gave 15a (39 mg, ca. 89%), contain-
ing trace impurities (1H NMR, 200 MHz): 1H NMR (acetone-
d6, 200 MHz) δ 3.02-3.30 (m, 6 H), 3.30-3.46 (m, 1 H), 3.46-
3.65 (m, 1 H), 3.74 (s, 3 H), 3.75 (s, 3 H), 5.02-5.18 (m, 1 H),
6.15-6.30 (m, 1 H), 6.48-6.60 (m, 1 H), 6.60-6.90 (m, 4 H),
7.00-7.32 (m, 8 H), 7.32-7.50 (m, 2 H), 8.01 (s, 1 H), 8.42 (s,
1 H), 8.86-9.05 (s, 1 H). For characterization the material
was processed as described in the next experiment.
5′-O-[(1,1-Dim eth yleth yl)d im eth ylsilyl]a d en osin e 2′,3′-
Bis(m eth a n esu lfon a te) (14). MeSO2Cl (0.57 mL, 7.3 mmol)
in CH2Cl2 (2 mL) was added dropwise to a stirred and cooled
(0 °C) solution of 5′-O-[(1,1-dimethylethyl)dimethylsilyl]ad-
enosine55 (700 mg, 1.84 mmol) in a mixture of CH2Cl2 (2 mL)
and pyridine (8.3 mL). After 1 h, the ice bath was removed,
and stirring was continued for 24 h; the mixture was then
poured onto ice, EtOAc (200 mL) was added, and the organic
layer was dried (MgSO4) and evaporated. Flash chromatog-
raphy of the residue over silica gel (3 × 20 cm), using 1:19
MeOH-CH2Cl2, gave 14 (773 mg, 78%) as a colorless oil: FTIR
(CH2Cl2, cast) 3315, 3148 cm-1; 1H NMR (acetone-d6, 200 MHz)
δ 0.07 (s, 3 H), 0.08 (s, 3 H), 0.88 (s, 9 H), 3.25 (s, 3 H), 3.32
(s, 3 H), 3.92-4.02 (dd, J ) 12.0, 4.0 Hz, 1 H), 4.02-4.15 (dd,
(52) Fromageot, H. P. M.; Griffin, B. E.; Reese, C. B.; Sulston, J . E.
Tetrahedron 1967, 23, 2315.
(53) 2′,3′-O-Isopropylideneuridine, prepared (91%) by the reported
procedure (ref 52), except that the product was isolated by flash
chromatography (silica gel, 1:19 MeOH-CH2Cl2), had: FTIR (CH2Cl2,
cast) 3600-3300, 3300-3140, 1692 cm-1 1H NMR (acetone-d6, 200
;
MHz) δ 1.33 (s, 3 H), 1.53 (s, 3 H), 3.72-3.82 (apparent t, J ) 7.6, 3.8
Hz, 2 H), 4.00-4.40 (m, including br s at δ 4.23, 2 H in all), 4.82-5.00
(m, 2 H), 5.55-5.65 (m, 1 H), 5.88-5.95 (d, J ) 3.6 Hz, 1 H), 7.85-
7.88 (d, J ) 8.0 Hz, 1 H), 9.60-10.30 (br s, 1 H); 13C NMR (acetone-d6,
50.3 MHz) δ 25.57, 27.52, 63.06, 67.97, 80.96, 84.49, 87.43, 95.58,
102.90, 142.96, 150.90, 160.13; exact mass m/ z calcd for C12H16N2O6
284.1008, found 284.1011. 5′-O-Acetyluridine, prepared from 2′,3′-O-
isopropylideneuridine, had: 1H NMR (acetone-d6, 200 MHz) δ 2.08 (s,
3 H), 4.10-4.38 (m, 5 H), 4.38-4.58 (br s, 1 H), 4.60-4.85 (br s, 1 H),
5.60-5.70 (d, J ) 8.0 Hz, 1 H), 5.82-5.92 (d, J ) 4.0 Hz, 1 H), 7.62-
7.72 (d, J ) 8.0 Hz, 1 H), 9.75-10.25 (br s, 1 H).
(54) Amino, Y.; Iwagami, H. Chem. Pharm. Bull. 1991, 39, 622.
(55) We thank Dr. G. A. Angoh (Raylo Chemicals) for a gift of this
compound. Cf. Imbach, J . L.; Gosselin, G. PCT Int. Appl. WO 93 12,128,
24 J un 1993; Chem. Abstr. 1994, 120, 135074u.
(56) RajanBabu, T. V.; Nugent, W. A. J . Am. Chem. Soc. 1994, 116,
986.
(57) Vinayak, R.; Anderson, P.; McCollum, C.; Hampel, A. Nucleic
Acids Res. 1992, 20, 1265.