Uracil Nucleotide DeriVatiVes and Analogues
Journal of Medicinal Chemistry, 2006, Vol. 49, No. 24 7085
167.46. LC/ESI-MS: negative mode 499 ([M - H]-), positive
mode 501 ([M + H]+).
2-Thio-1-â-D-ribofuranosyl(3H)pyrimidine-2,4-dione 5′-Mono-
phosphate (11a).46,48,52 1H NMR (500 MHz, MeOD) δ 4.02 (m,
2H), 4.26 (m, 1H), 4.34 (m, 1H), 4.41 (m, 1H), 6.26 (d, 1H, J )
7.88 Hz), 6.71 (d, 1H, J ) 3.46 Hz), 8.36 (d, 1H, J ) 8.19 Hz).
31P NMR (202 MHz, MeOD) δ 1.62 (s). 13C NMR (125 MHz,
MeOD) δ 63.52, 70.24, 76.29, 85.10, 94.49, 107.96, 143.73, 163.84,
178.02. LC/ESI-MS: negative mode 339 ([M - H]-), positive
mode 341 ([M + H]+).
3-Methyl-1-â-D-ribofuranosyl-pyrimidine-2,4-dione 5′-Mono-
phosphate (11b).53 1H NMR (500 MHz, MeOD) δ 3.33 (s, 3H),
4.01 (m, 2H), 4.20 (q, 1H, J ) 1.78 Hz), 4.36 (m, 2H), 6.03 (m,
2H), 8.19 (d, 1H, J ) 8.19 Hz). 31P NMR (202 MHz, MeOD) δ
1.03 (s). 13C NMR (125 MHz, MeOD) δ 28.69, 65.41, 71.51, 75.69,
90.77, 98.75, 102.95, 138.96, 141.40, 149.80. LC/ESI-MS: negative
mode 337 ([M - H]-), positive mode 339 ([M + H]+).
3-Phenacyl-1-â-D-ribofuranosylpyrimidine-2,4-dione 5′-Mono-
phosphate (11c). 1H NMR (500 MHz, D2O) δ 4.10 (m, 2H), 4.29
(m, 1H), 4.33 (t, 1H, J ) 4.86 Hz), 4.37 (t, 1H, J ) 4.86 Hz), 5.51
(s, 2H), 5.98 (d, 1H, J ) 4.47 Hz), 6.07 (d, 1H, J ) 8.15 Hz),
7.60-8.09 (m, 6H). 31P NMR (202 MHz, D2O) δ 0.60 (s). 13C
NMR (125 MHz, D2O) δ 50.65, 67.53, 72.08, 76.83, 86.08, 92.31,
104.67, 131.16-137.80, 143.22, 154.65, 165.18, 188.66. LC/ESI-
MS: negative mode 441 ([M - H]-), positive mode 443 ([M +
H]+).
6-Methyl-3-â-D-ribofuranosyl(1H)pyrimidine-2,4-dione 5′-
1
Triphosphate (9f). H NMR (500 MHz, MeOD) δ 2.14 (d, 3H),
4.04 (m, 2H), 4.30 (m, 1H), 4.52 (t, 1H, J ) 6.77 Hz), 4.65 (m,
1H), 5.50 (s, 1H), 6.28 (d, 1H, J ) 3.15 Hz). 31P NMR (202 MHz,
MeOD) δ -23.79 (t, J ) 20.91 Hz), -11.57 (d, J ) 19.68 Hz),
-10.89 (d, J ) 19.68 Hz). 13C NMR (125 MHz, MeOD) δ 18.70,
67.52, 71.84, 73.60, 84.33, 89.80, 100.21, 152.80, 154.57, 165.76.
LC/ESI-MS: negative mode 497 ([M - H]-), positive mode 499
([M + H]+).
6-Propyl-3-â-D-ribofuranosyl(1H)pyrimidine-2,4-dione 5′-
Triphosphate (9g). 1H NMR (500 MHz, D2O) δ 0.92 (t, 3H, J )
6.62 Hz), 1.60 (m, 2H), 2.39 (t, 2H, J ) 7.56 Hz), 4.10 (m, 2H),
4.26 (q, 1H, J ) 6.41 Hz), 4.51 (t, 1H, J ) 6.62 Hz), 4.74 (m,
1H), 5.67 (s, 1H), 6.24 (d, 1H, J ) 2.20 Hz). 31P NMR (202 MHz,
D2O) δ -22.05 (t, J ) 19.68 Hz), -10.64 (d, J ) 19.68 Hz), -7.13
(d, J ) 19.68 Hz). 13C NMR (125 MHz, D2O) δ 15.33, 22.99,
36.64, 68.22, 72.05, 74.31, 84.49, 90.51, 101.50, 155.00, 160.91,
168.33. LC/ESI-MS: negative mode 525 ([M - H]-), positive
mode 527 ([M + H]+).
2-Thio-1-â-D-ribofuranosyl(3H)pyrimidine-2,4-dione 5′-Diphos-
phate (10a).48 1H NMR (500 MHz, MeOD) δ 4.26 (m, 2H), 4.29
(m, 1H), 4.34 (m, 1H), 4.41 (m, 1H), 6.25 (d, 1H, J ) 8.19 Hz),
6.64 (d, 1H, J ) 3.46 Hz), 8.25 (d, 1H, J ) 7.88 Hz). 31P NMR
(202 MHz, MeOD) δ -11.51 (d, J ) 14.76 Hz), -9.55 (d, J )
14.76 Hz). 13C NMR (125 MHz, MeOD) δ 64.91, 69.68, 76.20,
84.36, 94.56, 107.88, 143.43, 163.72, 177.45. LC/ESI-MS: negative
mode 419 ([M - H]-), positive mode 421 ([M + H]+).
3-Methyl-1-â-D-ribofuranosylpyrimidine-2,4-dione 5′-Diphos-
phate (10b).49 1H NMR (500 MHz, MeOD) δ 3.33 (s, 3H), 4.18
(m, 2H), 4.27 (q, 1H, J ) 4.25 Hz), 4.32 (m, 1H), 4.44 (t, 1H, J )
5.35 Hz), 5.97 (m, 2H), 8.11 (d, 1H, J ) 8.19 Hz). 31P NMR (202
MHz, MeOD) δ -11.26 (d, J ) 14.76 Hz), -7.17 (d, J ) 14.76
Hz). 13C NMR (125 MHz, MeOD) δ 28.41, 65.49, 70.65, 76.19,
84.89, 91.52, 102.57, 141.16, 153.23, 165.91. LC/ESI-MS: negative
mode, 417 ([M - H]-), positive mode 419 ([M + H]+).
3-Phenacyl-1-â-D-ribofuranosylpyrimidine-2,4-dione 5′-Diphos-
phate (10c). 1H NMR (500 MHz, D2O + NaOD) δ 3.42 (m, 2H),
3.77 (m, 2H), 3.90 (m, 1H), 5.28 (m, 2H), 5.32 (m, 2H), 7.27-
7.76 (m, 5H), 8.11 (m, 1H). 31P NMR (202 MHz, D2O + NaOD)
δ -14.72 (d, J ) 19.68 Hz), -10.21 (d, J ) 19.68 Hz). 13C NMR
(125 MHz, D2O) δ 50.36, 66.53, 72.01, 75.80, 85.47, 91.83, 104.09,
131.27-137.91, 142.92, 154.18, 166.84, 187.73. LC/ESI-MS:
negative mode 521 ([M - H]-), positive mode 523 ([M + H]+).
5-Bromo-1-â-D-ribofuranosyl(3H)pyrimidine-2,4-dione 5′-
Diphosphate (10d).50,51 1H NMR (500 MHz, D2O) δ 4.21 (m, 2H),
4.25 (m, 1H), 4.37 (m, 2H), 5.92 (d, 1H, J ) 4.72 Hz), 8.24 (s,
1H). 31P NMR (202 MHz, D2O) δ -10.94 (d, J ) 22.14 Hz), -7.90
(d, J ) 17.22 Hz). 13C NMR (125 MHz, D2O) δ 67.21, 72.01,
76.72, 86.12, 91.88, 99.84, 143.76, 154.16, 165.05. LC/ESI-MS:
negative mode 481 and 483 ([M - H]-), positive mode 483 and
485 ([M + H]+).
6-Methyl-3-â-D-ribofuranosyl(1H)pyrimidine-2,4-dione 5′-
Diphosphate (10f). 1H NMR (500 MHz, D2O) δ 2.15 (s, 3H), 3.97
(m, 2H), 4.08 (m, 1H), 4.50 (t, 1H, J ) 6.46 Hz), 4.66 (m, 1H),
5.64 (s, 1H), 6.22 (d, 1H, J ) 2.83 Hz). 31P NMR (202 MHz, D2O)
δ -10.50 (d, J ) 17.22 Hz), -8.42 (d, J ) 19.68 Hz). 13C NMR
(125 MHz, D2O) δ 20.71, 67.96, 72.15, 74.33, 84.47, 90.52, 102.08,
157.39, 160.76, 168.15. LC/ESI-MS: negative mode 417 ([M -
H]-), positive mode 419 ([M + H]+).
6-Propyl-3-â-D-ribofuranosyl(1H)pyrimidine-2,4-dione 5′-
Diphosphate (10g). 1H NMR (500 MHz, MeOD) δ 1.03 (t, 3H, J
) 7.25 Hz), 1.65 (m, 2H), 2.38 (t, 2H, J ) 7.56 Hz), 4.0 (m, 2H),
4.24 (m, 1H), 4.58 (t, 1H, J ) 6.77 Hz), 4.66 (m, 1H), 5.67 (s,
1H), 6.29 (d, 1H, J ) 2.83 Hz). 31P NMR (202 MHz, MeOD) δ
-11.20 (d, J ) 17.22 Hz), -10.02 (d, J ) 19.68 Hz). 13C NMR
(125 MHz, MeOD) δ 15.29, 22.97, 36.58, 68.12, 72.27, 74.32,
84.51, 90.53, 101.38, 155.00, 160.76, 168.33. LC/ESI-MS: negative
mode 445 ([M - H]-), positive mode 447 ([M + H]+).
5-Bromo-1-â-D-ribofuranosyl(3H)pyrimidine-2,4-dione 5′-
Monophosphate (11d).54 1H NMR (500 MHz, D2O) δ 4.07 (m,
2H), 4.28 (m, 1H), 4.32 (t, 1H, J ) 4.73 Hz), 4.36 (t, 1H, J ) 5.13
Hz), 5.95 (d, 1H, J ) 4.99 Hz), 8.26 (s, 1H). 31P NMR (202 MHz,
D2O) δ 1.09 (s). 13C NMR (125 MHz, D2O) δ 66.83, 72.57, 76.79,
86.46, 91.71, 99.89, 143.78, 154.09, 164.88. LC/ESI-MS: negative
mode 401 ([M - H]-), 423 ([(M - H + Na) - H]-), positive mode
403 ([M + H]+).
1-â-D-Ribofuranosyl(3H)pyrimidine-2,4,6-trione 5′-Mono-
phosphate (11e).55 1H NMR (500 MHz, D2O) δ 3.86 (m, 2H), 3.98
(m, 3H), 4.39 (m, 2H), 6.159 (d, 1H, J ) 3.15 Hz). 31P NMR (202
MHz, D2O) δ 1.56 (s). 13C NMR (125 MHz, D2O) δ 47.35, 66.34,
69.56, 72.08, 81.32, 87.98, 153.68, 167.46. LC/ESI-MS: negative
mode 339 ([M - H]-), positive mode 441 ([M + H]+).
6-Methyl-3-â-D-ribofuranosyl(1H)pyrimidine-2,4-dione 5′-
Monophosphate (11f).56 1H NMR (500 MHz, MeOD) δ 2.15 (s,
3H), 3.98 (m, 2H), 4.14 (m, 1H), 4.40 (t, 1H, J ) 6.46 Hz), 4.65
(m, 1H), 5.51 (s, 1H), 6.27 (d, 1H, J ) 3.15 Hz). 31P NMR (202
MHz, MeOD) δ -1.70 (s). 13C NMR (125 MHz, MeOD) δ 18.70,
67.52, 72.32, 73.44, 84.33, 89.80, 100.21, 152.80, 154.57, 165.76.
LC/ESI-MS: negative mode: 337 ([M - H]-), positive mode: 339
([M + H]+).
6-Propyl-3-â-D-ribofuranosyl(1H)pyrimidine-2,4-dione 5′-
1
Monophosphate (11g). H NMR (500 MHz, MeOD) δ 1.01 (t,
3H, J ) 7.40 Hz), 1.64 (m, 2H), 2.36 (t, 2H, J ) 7.72 Hz), 3.98
(m, 2H), 4.14 (m, 1H), 4.43 (t, 1H, J ) 6.46 Hz), 4.67 (m, 1H),
5.51 (s, 1H), 6.28 (d, 1H, J ) 3.15 Hz). 31P NMR (202 MHz,
MeOD) δ 0.47 (s). 13C NMR (125 MHz, MeOD) δ 13.98, 22.16,
35.47, 67.19, 72.38, 73.43, 84.44, 89.75, 99.52, 152.97, 158.09,
165.95. LC/ESI-MS: negative mode 365 ([M - H]-), positive
mode 367 ([M + H]+).
6-Propyl-3-â-D-ribofuranosyl(1H)pyrimidine-2,4-dione 2′,3′-
1
(Cyclic phosphate) 5′-Triphosphate (12). H NMR (500 MHz,
MeOD) δ 1.02 (t, 3H, J ) 7.40 Hz), 1.65 (m, 2H), 2.38 (t, 2H, J
) 7.72 Hz), 4.17 (m, 2H), 4.41 (q, 1H, J ) 5.88 Hz), 5.06 (m,
1H), 5.23 (m, 1H), 5.53 (s, 1H), 6.54 (s, 1H). 31P NMR (202 MHz,
MeOD) δ -23.40 (t, J ) 20.91 Hz), -11.69 (d, J ) 19.68 Hz),
-10.73 (d, J ) 19.68 Hz), 19.02 (d, J ) 14.76 Hz). 13C NMR
(125 MHz, MeOD) δ 14.04, 22.13, 35.59, 67.60, 80.46, 82.60,
86.65, 88.79, 99.45, 152.81, 158.42, 163.39. LC/ESI-MS: negative
mode 587 ([M - H]-), positive mode 589 ([M + H]+).
3-Phenacyl-1-â-D-ribofuranosylpyrimidine-2,4-dione 2′-Mono-
phosphate 5′-Triphosphate (13). 1H NMR (500 MHz, MeOD) δ
4.32 (m, 2H), 4.49 (m, 1H), 5.04 (m, 2H), 5.44 (d, 2H, J ) 3.15
Hz), 5.99 (d, 1H, J ) 8.19 Hz), 6.19 (d, 1H, J ) 3.46 Hz), 7.57-
8.11 (m, 6H). 31P NMR (202 MHz, MeOD) δ -22.50 (t, J ) 18.45
Hz), -11.60 (d, J ) 19.68 Hz), -9.67 (d, J ) 17.22 Hz), 18.43 (t,