Helvetica Chimica Acta Vol. 85(2002)
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HÀC(1')); 7.75( s, HÀC(6)). 13C-NMR (CD3OD): 12.4 (Me); 28.7 (C(3')); 37.2 (C(2')); 61.3 (C(5')); 84.7
(C(4')); 86.8 (C(1')); 111.4 (C(5)); 120.0 (CN); 138.2 (C(6)); 152.1 (C(2)); 166.4 (C(4)).
Without further purification, 13 was treated with dimethylammonium azide [16] (500 mg, 6 mmol) in DMF
(80 ml) at 1008. Every 6 h, dimethylammonium azide (1 equiv., 250 mg) was added. After 30 h, the solvent was
removed in vacuo, the residue was dissolved in H2O and carefully acidified by addition of 10% HCl to pH 1 2.
After 30 min, the solvent was removed in vacuo, and the residue was purified by CC (silica gel; CH2Cl2/MeOH
1
0 ! 10%) to afford 8 (663 mg, 74%). Rf 0.05. H-NMR (CD3OD): 1.82 (s, Me); 2.50 2.70 (m, CH2(2')); 3.52
(m, HÀC(3')); 3.70 (m, HaÀC(5')); 3.90 (m, HbÀC(5')); 4.24 (m, HÀC(4')); 4.80 (m, NH, OH); 6.20
(m, HÀC(1')); 7.95( s, HÀC(6)). 13C-NMR (CD3OD): 12.4 (Me); 34.4 (C(3')); 38.8 (C(2')); 61.8 (C(5')); 86.1
(C(4')); 86.7 (C(1')); 111.1 (C(5)); 138.5 (C(6)); 152.2 (C(2)); 158.1 (C(tetrazole)); 166.6 (C(4)). HR-MS:
317.096 ([M Na] , C11H14N6NaO4 ; calc. 317.096).
4. 3'-Deoxy-3'-[2-(5'-deoxythymidin-5'-yl)-2H-tetrazol-5-yl]thymidine (4). Compound 9 (830 mg, 1.1 mmol)
was heated in 80% aq. AcOH at 808, until the starting compound disappeared on TLC. After 18 h, the solvent
was removed in vacuo, the residue was dissolved in 100 ml H2O/CH2Cl2 (50 :50), and the org. layer was
extracted with H2O (3 Â 25ml). The combined H 2O extracts were evaporated under reduced pressure, and two
compounds, 10 and 4, were separated by CC (silica gel; CH2Cl2/MeOH 0 ! 10%).
Data of 5'-O-Acetyl-3'-deoxy-3'-[2-(5'-deoxythymidin-5-yl)-2H-tetrazol-5-yl]thymidine (10): 280 mg
(46%). Rf 0.37. 1H-NMR (CD3OD): 1.89 (s, Me); 1.92 (s, Me); 2.08 (s, Me); 2.30 (m, CH2(2')); 2.68
(m, HbÀC(2'')); 2.85( m, HaÀC(2'')); 3.93 (m, HÀC(3')); 4.35( m, HÀC(4'), HÀC(4'')); 4.42 (m, CH2(5'));
4.52 (m, HÀC(3'')); 4.80 (s, 2 NH, 2 OH); 5.00 (d, J 5.9, CH2(5'')); 6.17 (t, J 7.0, HÀC(1'')); 6.23 (dd, J 4.1,
7.6, HÀC(1')); 7.39 (s, HÀC(6)); 7.65( s, HÀC(6)). 13C-NMR (CD3OD): 12.5(Me); 12.6 (Me); 20.8 ( MeCO);
37.2 (C(3')); 38.1 (C(2')); 39.9 (C(2'')); 55.7 (C(5'')); 64.7 (C(5')); 72.8 (C(3'')); 83.3 (C(4')); 85.2 (C(4'')); 87.2
(C(1'')); 87.4 (C(1')); 111.5, 111.8 (2 C(5)); 138.0, 138.2 (2 C(6)); 152.1, 152.2 (2 C(2)); 166.2, 166.3 (2 C(4));
166.6 (C(tetrazole)); 172.3 (MeCO). HR-MS: 583.182 ([M Na] , C23H28NaO9 ; calc. 583.187).
Data of 4: 110 mg, 20%. M.p. 2348 (MeOH). Rf 0.21. 1H-NMR (CD3OD): 1.90 (s, 2 Me); 2.30
(m, CH2(2')); 2.64 (m, HbÀC(2'')); 2.86 (m, HaÀC(2'')); 3.83 (dd, J 3.1, 12.3, HaÀC(5')); 3.90 (m, HÀC(3'),
HbÀC(5')); 4.29 (dt, J 8.5, 2.7, HÀC(4')); 4.37 (dd, J 5.9, 9.4, HÀC(4'')); 4.53 (m, HÀC(3'')); 4.80 (s, 2 NH,
2 OH); 5.00 (d, J 5.9, CH2(5'')); 6.21 (t, J 7.0, HÀC(1'')); 6.28 (dd, J 3.7, 7.0, HÀC(1')); 7.42 (s, HÀC(6));
8.08 (s, HÀC(6)). 13C-NMR (CD3OD): 12.5(2 Me); 35.6 (C(3 ')); 38.9 (C(2')); 39.6 (C(2'')); 55.7 (C(5'')); 61.9
(C(5')); 72.8 (C(3'')); 82.3 (C(4')); 86.6 (C(4''), C(1'')); 87.4 (C(1')); 111.2, 111.8 (2 C(5)); 138.2, 138.4 (2 C(6));
152.1, 152.3 (2 C(2)); 166.2, 166.3 (2 C(4)); 167.0 (C(tetrazole)). HR-MS: 541.181 ([M Na] , C21H26N8NaO8
;
calc. 541.177).
From 10. Compound 10 (77 mg, 0.14 mmol) was dissolved in 25% aq. NH3 (5ml). After stirring at r.t. for
1.5h, the solvent was removed in vacuo, the residue was purified by CC (silica gel; CH2Cl2/MeOH 0 ! 10%) to
give 4 (71 mg, 100%).
From 8. Compound 8 (663 mg, 2.3 mmol), 6 (952 mg, 2.7 mmol), and Et3N (312 ml, 2.3 mmol) in DMF
(40 ml) were heated at 1108 for 18 h. After cooling, the solvent was removed in vacuo. The residue was co-
evaporated with toluene (2 Â 30 ml) and purified by CC (silica gel; CH2Cl2/MeOH 0 ! 10%) to afford 4
(533 mg, 46%).
5. 3'-Deoxy-3'-[2-(5'-deoxythymidin-5'-yl)-2H-tetrazol-5-yl]-5'-O-(4,4'-dimethoxytrityl)thymidine (11).
Thymidine dimer 4 (70 mg, 0.14 mmol) was dissolved in anh. pyridine (3 ml) and DMTCl (70 mg, 0.21 mmol)
was added under N2. After 18 h, more DMTCl (70 mg, 0.21 mmol) was added to complete the reaction. After
4 h, anal. TLC showed no more starting material, and the reaction was quenched with MeOH (1 ml). The
solvent was removed under reduced pressure, and the residue was dissolved in CH2Cl2 (10 ml) and extracted
with sat. aq. NaHCO3 (3 Â 5ml). The org. layer was dried (Na 2SO4), and evaporated in vacuo, and the product
was purified by CC (silica gel; CH2Cl2/MeOH 0 ! 10%) to afford 11 as a foam (78 mg, 70%), which was used in
the next step without further purification. Rf 0.36. 1H-NMR (CDCl3): 1.50 (s, Me); 1.95( s, Me); 2.30
(m, CH2(2')); 2.65( m, HbÀC(2'')); 2.89 (m, HaÀC(2'')); 3.13 (br. s, OH); 3.39 (d, J 8.6, HaÀC(5')); 3.60
(d, J 8.6, HbÀC(5')); 3.70 (m, HÀC(3')); 3.80 (s, 2 MeO), 4.36 (m, HÀC(4')); 4.46 (m, HÀC(4'')); 4.52
(m, HÀC(3'')); 4.90 (m, CH2(5'')); 6.10 (t, J 6.7, HÀC(1'')); 6.28 (t, J 5.5, HÀC(1')); 6.79 (d, J 8.8, 2 H,
DMT); 6.81 (d, J 9.1, 2 H, DMT); 7.03 (s, HÀC(6)); 7.20 7.45( m, 10 H, DMT); 7.74 (s, HÀC(6)); 9.80
(s, 2 NH). 13C-NMR (CDCl3): 11.9 (Me); 12.4 (Me); 35.5 (C(3')); 38.3 (C(2')); 39.2 (C(2'')); 54.4 (C(5'')); 55.2
(MeO); 62.7 (C(5')); 71.5(C(3 '')); 83.4 (C(4')); 83.5(C(4 '')); 85.1 (C(Ar3)); 86.4 (C(1'')); 86.7 (C(1')); 110.9,
111.0 (2 C (5)); 113.1, 127.0, 127.9, 128.0, 130.0, 138.7 (Ar); 135.3, 135.4 (2 C(6)); 144.3 (Ar); 150.2, 150.5 (2
C(2)); 158.5 (Ar); 163.9, 164.0 (2 C(4)); 165.7 (C(tetrazole)). HR-MS: 843.288 ([M Na] , C42H44N8NaO10
;
calc. 843.284).