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E. Moyroud et al. / Tetrahedron 56 (2000) 1475–1484
144.25 (C(6)); 157.66 (C(2)); 158.46 (NCH); 172.08 (C(4)).
MS (FAB): 723 ([MϩK]ϩ, 7.5%); 685 ([MϩH]ϩ, 9.9%);
303 ([C–Ph(PhOCH3)2]ϩ, 100%).
6-N-((di-n-Butylamino)-methylene)-20/30-O-tert-butyldi-
methylsilyl-50-O-(4,40-dimethoxytrityl)-l -cytidine (4b/b0).
Compound 3b (92 mg, 0.14 mmol) was treated as described
above. Purification by chromatography (toluene/EtOAc
gradient from 95:5 to 30:70 (80:20 to 75:25 4b, 40:60 to
30:70 4b0)) afforded 4b (43 mg, 0.055 mmol, 40%) and 4b0
(40 mg, 0.05 mmol, 37%) as a pale yellowish foam. Rf
(CHCl3/EtOAc 6:4): 0.65 (4b), 0.32 (4b0). 1H NMR
(CDCl3) (4b): 0.19 (s, 3H, CH3); 0.32 (s, 3H, CH3); 0.90–
0.99 (m, 15H, tBu, CH3CH2); 1.26–1.38 (m, 4H, CH3CH2);
2-N-((di-n-Butylamino)-methylene)-50-O-(4,40-dimethoxy-
trityl)-l -guanosine (3c). Compound 2c (406 mg, 0.75
mmol) was treated as described above. Purification by chro-
matography (CH2Cl2/MeOH gradient 98:2 to 95:5, 0.1% v/v
pyr) gave 3c (325 mg, 0.45 mmol, 60%) as a white foam. Rf
1
(CH2Cl2/MeOH 94:6): 0.38. H NMR (CDCl3): 0.92–0.99
3
(m, 6H, CH3); 1.26–1.40 (m, 4H, CH3CH2); 1.55–1.68 (m,
4H, CH3CH2CH2); 3.30–3.73 (m, 6H, CH2N, H2C(50)); 3.75
(s, 6H, CH3O); 4.28–4.30 (m, 1H, HC(40)); 4.39–4.41 (m,
1H, HC(20)); 4.64 (d, 1H, 3J5.2 Hz, HC(30)); 5.97 (d, 1H,
3J5.8 Hz, HC(10)); 6.76–7.39 (m, 13H, Ph); 7.52 (s, 1H,
HC(8)); 8.43 (s, 1H, NH); 8.54 (s, 1H, NCH). 13C NMR
(CDCl3): 13.67, 13.78 (CH3); 19.73, 20.15 (CH3CH2);
28.95, 30.92 (CH3CH2CH2); 45.77, 52.43 (CH2N); 55.17
(CH3O); 64.03 (C(50)); 71.66 (C(30)); 74.80 (C(20)); 84.15
(C(40)); 86.40 (C–Ph(Ph–OCH3)2); 87.70 (C(10)); 119.44
(C(5)); 113.16, 126.79–136.46, 158.02 (Ph); 144.69
(C(8)); 150.63 (C(4)); 156.84, 157.70 (C(6) or C(2));
158.49 (NCH). MS (FAB): 763 ([MϩK]ϩ, 13.8%); 725
([MϩH]ϩ, 13.1%); 303 ([C–Ph(Ph–OCH3)2]ϩ, 100%).
1.51–1.64 (m, 4H, CH3CH2CH2); 2.44 (d, 1H, J8.7 Hz,
HOC(30)); 3.29–3.58 (2m, 6H, CH2N, H2C(50)); 3.80 (s, 6H,
CH3O); 4.05–4.09 (m, 1H, HC(40)); 4.28–4.32 (m, 2H,
3
HC(20), HC(30)); 5.74 (d, 1H, J7.2 Hz, HC(5)); 5.94 (d,
3
1H, J1.2 Hz, HC(10)); 6.73–7.45 (m, 13H, Ph); 8.07 (d,
1H, 3J7.2 Hz, HC(6)); 8.86 (s, 1H, NCH). 13C NMR
(CDCl3) (4b): Ϫ5.50, Ϫ4.39 ((CH3)2Si); 13.65, 13.74
(CH3); 18.07 (C(CH3)3); 19.76, 20.04 (CH3CH2); 25.86
((CH3)3C); 29.06, 31.00 (CH3CH2CH2); 45.40, 52.11
(CH2N); 55.18 (CH3O); 61.94 (C(50)); 69.49 (C(30));
76.67 (C(20)); 82.89 (C(40)); 86.77 (C–Ph(Ph–OCH3)2);
90.52 (C(10)); 113.08–141.28, 158.32 (Ph); 144.43 (C(6));
156.25 (C(2)); 158.55 (NCH); 171.94 (C(4)). 1H NMR
(CDCl3) (4b0): Ϫ0.07 (s, 3H, CH3); 0.04 (s, 3H, CH3);
0.82 (s, 9H, tBu); 0.88–0.97 (m, 6H, CH3CH2); 1.26–1.40
(m, 4H, CH3CH2); 1.52–1.64 (m, 4H, CH3CH2CH2); 2.62 (t,
20/30-O-tert-Butyldimethylsilyl-50-O-(4,40-dimethoxytri-
tyl)-l -uridine (4a/a0). Compound 3a (169 mg, 0.31 mmol)
and imidazole (84 mg, 1.24 mmol) were coevaporated three
times with anhydrous pyr under Ar. Abs. pyr (1.6 ml)
followed by TBDMSCl (51 mg, 0.34 mmol) were added.
The mixture was stirred overnight at room temperature.
After evaporation to dryness, CH2Cl2 (100 ml) was added
washed by sat. NaHCO3 solution (15 ml). After drying over
Na2SO4 and evaporation, purification by chromatography
(toluene/EtOAc gradient from 95:5 to 50:50 (85:15 to
82:18 for 4a, 70:30 to 50:50 for 4a0)) afforded 4a (94 mg,
0.14 mmol, 46%) and 4a0 (88 mg, 0.12 mmol, 43%) as a
white foam. Rf (CHCl3/EtOAc 6:4): 0.64 (4a) 0.44 (4a0).
1H NMR (CDCl3) (4a): 0.16 (s, 3H, CH3); 0.19 (s, 3H,
CH3); 0.93 (s, 9H, tBu); 2.58 (br s, 1H, HOC(30)); 3.46–
3.55 (m, 2H, H2C(50)); 3.79 (s, 6H, CH3O); 4.10–4.12 (m,
1H, HC(40)); 4.33–4.36 (m, 2H, HC(20), HC(30)); 5.29 (d,
3
1H, J7.3 Hz, HOC(20)); 3.24–3.61 (2m, 6H, CH2N,
H2C(50)); 3.79 (s, 6H, CH3O); 4.12–4.17 (m, 2H, HC(20),
3
HC(40)); 4.35 (t, 1H, J5.5 Hz, HC(30)); 5.83 (d, 1H,
3
3J7.5 Hz, HC(5)); 6.03 (d, 1H, J3.3 Hz, HC(10));
3
6.82–7.42 (m, 13H, Ph); 8.05 (d, 1H, J7.5 Hz, HC(6));
8.84 (s, 1H, NCH). 13C NMR (CDCl3) (4b0): Ϫ5.01, Ϫ4.76
((CH3)2Si); 13.66, 13.96 (CH3); 18.01 (C(CH3)3); 19.76,
20.05 (CH3CH2); 25.65 ((CH3)3C); 29.06, 30.98
(CH3CH2CH2); 45.39, 52.10 (CH2N); 55.20 (CH3O); 62.07
(C(50)); 71.25 (C(30)); 75.98 (C(20)); 83.57 (C(40)); 86.74
(C–Ph(Ph–OCH3)2); 91.18 (C(10)); 113.19–141.29, 158.28
(Ph); 144.18 (C(6)); 156.75 (C(2)); 158.60 (NCH); 172.00
(C(4)). MS (FAB): 838 ([MϩK]ϩ, 2.0%); 800 ([MϩH]ϩ,
16.6%); 799 ([M]ϩ, 31.1%); 303 ([C–Ph(Ph–OCH3)2]ϩ,
100%).
3
3
1H, J8.2 Hz, HC(5)); 5.95 (d, 1H, J3.0 Hz, HC(10));
6.81–7.40 (2m, 13H, Ph); 7.95 (d, 1H, 3J8.1 Hz, HC(6));
9.14 (br s, 1H, NH). 13C NMR (CDCl3) (4a): Ϫ5.19, Ϫ4.65
((CH3)2Si); 18.02 (C(CH3)3); 25.67 (C(CH3)3); 55.25
(CH3O); 62.32 (C(50)); 70.46 (C(30)); 76.34 (C(20)); 83.56
(C(40)); 87.21 ((C–Ph(Ph–OCH3)2); 88.71 (C(10)); 102.28
(C(5)); 113.32–135.17, 158.72, 158.75 (Ph); 140.25 (C(6));
2-N-((di-n-Butylamino)-methylene)-20/30-O-tert-butyldi-
methylsilyl-50-O-(4,40-dimethoxytrityl)-l -guanosine (4c/c0).
3c (480 mg, 0.66 mmol) was treated as described as above.
Purification by chromatography (toluene/EtOAc gradient
from 50:50 to 20:80) afforded 4c (194 mg, 0.23 mmol,
35%) and 4c0 (188 mg, 0.22 mmol, 34%) as a yellowish
foam. Rf (CHCl3/EtOAc 6:4): 0.25 (4c), 0.12 (4c0). 1H
NMR (CDCl3) (4c): Ϫ0.13 (s, 3H, CH3); 0.03 (s, 3H,
CH3); 0.85 (s, 9H, tBu); 0.94–0.99 (m, 6H, CH3CH2);
1.29–1.39 (m, 4H, CH3CH2); 1.55–1.68 (m, 4H,
1
150.22 (C(2)); 163.18 (C(4)). H NMR (CDCl3) (4a0):
Ϫ0.03 (s, 3H, CH3); 0.07 (s, 3H, CH3); 0.0.85 (s, 9H,
tBu); 3.34–3.56 (m, 2H, H2C(50)); 3.79 (s, 6H, CH3O);
4.07–4.09 (m, 1H, HC(40)); 4.17–4.20 (m, 2H, HC(20));
3
CH3CH2CH3CH2); 2.75 (d, 1H, J3.9 Hz, HOC(30));
3
3
4.40 (t, 1H, J5.4 Hz, HC(30)); 5.40 (d, 1H, J6.3 Hz,
3.26–3.50 (m, 6H, CH2N, H2C(50)); 3.79 (s, 6H, CH3O);
4.19–4.25 (m, 1H, HC(40)); 4.28–4.32 (m, 1H, HC(30));
3
HC(5)); 5.98 (d, 1H, J3.0 Hz, HC(10)); 6.83–7.41 (2m,
13H, Ph); 7.88 (d, 1H, 3J6.0 Hz, HC(6)). 13C NMR
(CDCl3) (4a0): Ϫ4.93, Ϫ4.89 ((CH3)2Si); 17.89 (C(CH3)3);
25.58 (C(CH3)3); 55.12 (CH3O); 61.65 (C(50)); 71.10
(C(30)); 75.09 (C(20)); 83.66 (C(40)); 86.98 ((C–Ph(Ph–
OCH3)2); 89.54 (C(10)); 102.39 (C(5)); 113.17–135.06,
143.96, 158.86 (Ph); 140.11 (C(6)); 150.55 (C(2)); 163.33
(C(4)). MS (FAB): 699 ([MϩK]ϩ, 5.3%); 661 ([MϩH]ϩ,
1.7%); 303 ([C–Ph(Ph–OCH3)2]ϩ, 100%).
4.66 (t, 1H, J5.4 Hz, HC(20)); 6.00 (d, 1H, J5.7 Hz,
HC(10)); 6.80–7.44 (m, 13H, Ph); 7.80 (s, 1H, HC(8)); 8.49
(br s, 1H, NH); 8.57 (s, 1H, NCH). 13C NMR (CDCl3) (4c):
Ϫ5.17, Ϫ4.99 ((CH3)2Si); 13.67, 13.77 (CH3CH2); 17.88
(C(CH3)3); 19.73, 20.11 (CH3CH2); 25.56 ((CH3)3C);
28.95, 30.98 (CH3CH2CH2); 45.64, 52.20 (CH2N); 55.24
(CH3O); 63.64 (C(50)); 71.72 (C(30); 77.20 (C(20)); 83.78
(C(40)); 86.69 (C(10)); 86.74 (C-Ph(PhOCH3)2); 120.42
3
3