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N. Joubert et al. / Tetrahedron 64 (2008) 4444e4452
H-40), 5.32 (dd, J¼4.4, 53.4 Hz, 1H, H-30), 6.33 (dd, J¼5.3,
9.1 Hz, 1H, H-10), 6.75e7.50 (m, 14H, MMTr), 8.01 (s, 1H,
H-6), 9.20 (br s, 1H, NH); 13C NMR (CDCl3) d: 12.1 (CCI),
39.8 (d, J¼86.6 Hz, C-20), 55.4 (OCH3), 63.4 (d, J¼40.9 Hz,
C-50), 84.2 (C), 84.9 (d, J¼101.1 Hz, C-40), 86.0 (C-10), 87.8
(C), 94.5 (d, J¼707.6 Hz, C-30), 101.0 (C), 113.6 (CH),
127.5 (CH), 127.9 (C), 128.1 (CH), 128.2 (CH), 130.4 (CH),
134.6 (C), 143.5 (C), 143.7 (C-6), 143.8 (C), 149.2 (C]O),
159.0 (C), 161.6 (C); HRMS: C31H26N2O5FINa, calcd m/z
675.0768; found m/z 675.0771.
[a]2D0 þ13.0 (c 0.6, CH3OH); mp 107 ꢀC; UV (MeOH) lmax
1
296 nm; H NMR (CD3OD) d: 2.14e2.47 (m, 1H, H-20a),
2.52e2.78 (m, 1H, H-20b), 3.80 (d, J¼3.0 Hz, 2H, H-50),
4.31 (td, J¼2.9, 27.0 Hz, 1H, H-40), 5.30 (dd, J¼4.7,
53.7 Hz, 1H, H-30), 6.36 (dd, J¼5.6, 9.0 Hz, 1H, H-10), 7.30
(s, 1H, CH alkene), 8.36 (s, 1H, H-6); 13C NMR (CD3OD)
d: 40.3 (d, C-20), 62.7 (d, C-50), 83.2 (CH alkene), 87.0
(C-10), 87.3 (d, C-40), 87.3 (C), 96.0 (d, C-30), 115.5 (C),
116.0 (C), 143.9 (C-6), 151.5 (C]O), 161.8 (C]O); HRMS:
C11H11N2O4FBrINa, calcd m/z 482.8829; found m/z 482.8838.
5.3.2. 1-{4-Azido-5-[(4-methoxy-phenyl)-diphenyl-
methoxymethyl]-tetrahydrofuran-2-yl}-5-iodoethynyl-
1H-pyrimidine-2,4-dione (17)
5.4.3. 5-(1-Chloro-2-iodo-vinyl)-1-(4-fluoro-5-hydroxy-
methyl-tetrahydrofuran-2-yl)-1H-pyrimidine-2,4-dione (10c)
Prepared from compound 9c, using the typical procedure
described before to give 10c (76%) as an orange solid. [a]D20
þ17.0 (c 0.7, CH3OH); mp 87 ꢀC; UV (MeOH) lmax
Prepared from compound 14 using the typical procedure
described before to give 17 (74%) as a pale yellow solid.
1
[a]2D0 þ32 (c 1.0, CH3OH); mp 95 ꢀC; H NMR (CDCl3) d:
1
274 nm; H NMR (CD3OD) d: 2.13e2.48 (m, 1H, H-20a),
2.37e2.47 (m, 1H, H-20a), 2.52e2.62 (m, 1H, H-20b), 3.36e
3.48 (m, 2H, H-50), 3.81 (s, 3H, OCH3), 4.01e4.05 (m, 1H,
H-40), 4.28e4.38 (m, 1H, H-30), 6.15 (t, J¼6.1 Hz, 1H,
H-10), 6.85e6.89 (m, 2H, MMTr), 7.22e7.47 (m, 12H,
MMTr), 8.02 (s, 1H, H-6); 13C NMR (CDCl3) d: 12.9 (C),
39.3 (C-20), 56.0 (OCH3), 61.2 (C-30), 63.5 (C-50), 84.8
(C-40), 86.4 (C-10), 88.2 (C), 101.4 (C), 114.2 (CH), 128.0
(CH), 128.8 (CH), 128.9 (CH), 131.0 (CH), 135.4 (C), 144.3
(C-6), 149.6 (C), 159.5 (C), 162.1 (C); HRMS:
C31H26N5O5INa, calcd m/z 698.0876; found m/z 698.0871.
2.52e2.75 (m, 1H, H-20b), 3.80 (d, J¼2.8 Hz, 2H, H-50),
4.30 (td, J¼2.8, 26.8 Hz, 1H, H-40), 5.30 (dd, J¼4.6,
53.5 Hz, 1H, H-30), 6.37 (dd, J¼5.7, 8.8 Hz, 1H, H-10), 7.06
(s, 1H, CH alkene), 8.38 (s, 1H, H-6); 13C NMR (CD3OD)
d: 40.2 (d, J¼84.2 Hz, C-20), 62.7 (d, J¼43.3 Hz, C-50), 81.1
(CH alkene), 87.0 (C-10), 87.4 (d, J¼93.9 Hz, C-40), 96.2 (d,
J¼698.0 Hz, C-30), 114.5 (C), 128.9 (C), 146.0 (C-6), 151.2
(C]O), 164.2 (C]O); HRMS: C11H11N2O4FClINa, calcd
m/z 438.9334; found m/z 438.9340.
5.4.4. 1-(4-Fluoro-5-hydroxymethyl-tetrahydrofuran-2-yl)-
5-iodoethynyl-1H-pyrimidine-2,4-dione (12)
5.4. General procedure for deprotection
Prepared from compound 11, using the typical procedure
described before to give 12 (47%) as a yellow solid. [a]D20
ꢂ1.5 (c 1.0, CH3OH); mp 140 ꢀC; UV (MeOH) lmax 233,
A solution of the protected nucleoside (0.3 mmol) in acetic
acid (80%, 30 mL) is stirred at rt until completion (checked by
TLC, typically 18 h). After evaporation of the solvent, the
crude product was submitted to a flash silica gel column chro-
matography (eluent: hexanes/EtOAc, 2:8) to give the desired
deprotected nucleoside.
1
298 nm; H NMR (CD3OD) d: 2.11e2.45 (m, 1H, H-20a),
2.46e2.75 (m, 1H, H-20b), 3.79 (d, J¼3.2 Hz, 2H, H-50),
4.29 (td, J¼2.9, 27.0 Hz, 1H, H-40), 5.27 (dd, J¼4.9,
53.9 Hz, 1H, H-30), 6.28 (dd, J¼5.5, 8.9 Hz, 1H, H-10), 8.30
(s, 1H, H-6); 13C NMR (CD3OD) d: 15.8 (CCI), 39.8 (d,
J¼81.8 Hz, C-20), 62.5 (d, J¼43.3 Hz, C-50), 85.2 (C), 87.0
(C-10), 87.3 (d, J¼96.3 Hz, C-40), 96.0 (d, J¼700.4 Hz,
C-30), 101.5 (C), 146.0 (C-6), 151.1 (C]O), 164.4 (C]O);
HRMS: C11H11N2O4FBrINa, calcd m/z 402.9567; found m/z
402.9571.
5.4.1. 5-(1,2-Diiodo-vinyl)-1-(4-fluoro-5-hydroxymethyl-
tetrahydrofuran-2-yl)-1H-pyrimidine-2,4-dione (10a)
Prepared from compound 9a, using the typical procedure
described before to give 10a (51%) as a yellow solid. [a]D20
þ16.0 (c 1.0, CH3OH); mp 112 ꢀC; UV (MeOH) lmax 232,
1
274 nm; H NMR (CD3OD) d: 2.13e2.47 (m, 1H, H-20a),
2.50e2.77 (m, 1H, H-20b), 3.80 (d, J¼2.8 Hz, 2H, H-50),
4.32 (td, J¼2.9, 27.0 Hz, 1H, H-40), 5.30 (dd, J¼4.6,
53.7 Hz, 1H, H-30), 6.36 (dd, J¼5.6, 9.0 Hz, 1H, H-10), 7.53
(s, 1H, CH alkene), 8.28 (s, 1H, H-6); 13C NMR (CD3OD)
d: 40.3 (d, J¼81.9 Hz, C-20), 62.7 (d, J¼43.3 Hz, C-50), 87.0
(C-10), 87.3 (d, J¼96.3 Hz, C-40), 87.3 (C), 88.1 (CH alkene),
96.0 (d, J¼698.0 Hz, C-30), 119.2 (C), 142.2 (C-6), 151.5
(C]O), 161.8 (C]O); HRMS: C11H11N2O4FI2Na, calcd
m/z 530.8690; found m/z 530.8687.
5.4.5. 5-Ethynyl-1-(4-fluoro-5-hydroxymethyl-tetrahydro-
furan-2-yl)-1H-pyrimidine-2,4-dione (13)
Prepared from compound 8, using the typical procedure de-
scribed before to give 13 (50%) as a pale yellow solid. [a]D20
þ0.5 (c 1.0, CH3OH); mp 209 ꢀC; UV (MeOH) lmax
1
287 nm; H NMR (CD3OD) d: 2.13e2.45 (m, 1H, H-20a),
2.47e2.71 (m, 1H, H-20b), 3.56 (s, 1H, H alkyne), 3.79 (d,
J¼3.2 Hz, 2H, H-50), 4.30 (td, J¼3.0, 27.0 Hz, 1H, H-40),
5.27 (dd, J¼4.9, 53.8 Hz, 1H, H-30), 6.29 (dd, J¼5.5,
8.9 Hz, 1H, H-10), 8.38 (s, 1H, H-6); 13C NMR (CD3OD) d:
39.8 (d, J¼84.2 Hz, C-20), 62.6 (d, J¼43.3 Hz, C-50), 75.9
(CH alkyne), 82.9 (C), 87.0 (C-10), 87.4 (d, J¼96.3 Hz, C-40),
96.0 (d, J¼698 Hz, C-30), 100.0 (C), 146.0 (C-6), 151.2
5.4.2. 5-(1-Bromo-2-iodo-vinyl)-1-(4-fluoro-5-hydroxy-
methyl-tetrahydrofuran-2-yl)-1H-pyrimidine-2,4-dione (10b)
Prepared from compound 9b, using the typical procedure
described before to give 10b (52%) as a pale yellow solid.