Efficient Synthesis of CDP-Choline and Its Analogs
385
NMR (100 MHz, D O): δ 166.0, 151.6, 141.1, 102.2, 88.0, 82.8, 73.3, 69.2,
2
31
6
2
1
5.4, 64.5, 59.4, 53.5 ppm; P NMR (162 MHz, D O): δ –11.6 (d, J
=
2
P-α,P-β
3673, 2983, 2904,
1.0 Hz, 1P), –12.3 (d, J P-α,P-β = 21.0 Hz, 1P) ppm; IR: ν
max
−
1
689, 1463, 1395, 1237, 1082, 770, 608, 536 cm ; HRMS (ESI–): m/z calcd
−
for C H N O P [M–H] 488.0841; found 488.0853.
14
24
3
12
2
ꢁ
Adenosine 5 -diphosphate choline, sodium salt (8): Starting from adeno-
ꢁ
sine 5 -phosphoropiperidate (52 mg, 0.1 mmol), compound 8 was synthe-
sized according to the general procedure. Ion-exchange chromatography
1
afforded 8 (42 mg, 78%) as a white solid; H NMR (400 MHz, D O): δ 8.40 (s,
2
1
4
H), 8.15 (s, 1H), 6.05 (d, J = 4 Hz, 1H), 4.54−4.44 (m, 2H), 4.43−4.42 (m,
13
H), 4.30−4.28 (m, 2H), 3.55 (s, 2H), 3.10 (s, 9H) ppm; C NMR (100 MHz,
D O): δ 155.2, 152.5, 148.7, 139.3, 118.1, 86.4, 83.4, 73.7, 69.9, 65.4, 64.8,
2
31
5
1
1
9.4, 53.4 ppm; P NMR (162 MHz, D O): δ –11.5 (d, J
= 20.9 Hz,
2
P-α,P-β
P), –12.3 (d, J P-α,P-β = 20.9 Hz, 1P) ppm; IR: νmax 3332, 2981, 2491, 1651,
−
1
477, 1409, 1331, 1235, 1118, 944, 873, 817, 784, 710, 646, 561 cm ; HRMS
−
(ESI–): m/z calcd for C H N O P [M–H] 511.1113; found 511.1126.
1
5
25
6
10 2
ꢁ
Guanosine 5 -diphosphate choline, sodium salt (9): Starting from guano-
ꢁ
sine 5 -phosphoropiperidate (53 mg, 0.1 mmol), compound 9 was synthe-
sized according to the general procedure. Ion-exchange chromatography
1
afforded 9 (43 mg, 78%) as a white solid; H NMR (400 MHz, D O): 8.10
2
(
2
1
s, 1H), 5.93 (s, 1H), 4.51 (s, 1H), 4.25−4.40 (m, 4H), 4.20 (s, 2H), 3.62 (s,
13
H), 3.17 (s, 9H); C NMR (100 MHz, D O): δ 159.9, 154.7, 151.9, 137.4,
2
31
16.4, 86.7, 83.7, 73.6, 70.4, 66.0, 65.3, 59.8, 53.9 ppm; P NMR (162 MHz,
= 20.8 Hz, 1P), –12.1 (d, J = 20.8 Hz, 1P)
D O): δ –11.3 (d, J
ppm; IR: νmax 3668, 2986, 2313, 1667, 1530, 1481, 1237, 1080, 1047, 939, 917,
7
2
P-α,P-β
P-α,P-β
−
1
−
78, 642, 571 cm ; HRMS (ESI–): m/z calcd for C H N O P [M–H]
15 25 6 11 2
5
27.1062; found 527.1077.
ꢁ
ꢁ
2
-Deoxycytidine 5 -diphosphate choline, sodium salt (10): Starting from
ꢁ
ꢁ
2
-deoxycytidine 5 -phosphoropiperidate (48 mg, 0.1 mmol), compound 10
was synthesized according to the general procedure. Ion exchange chro-
1
matography afforded 10 (40 mg, 81%) as a white solid; H NMR (400 MHz,
D O): δ 7.81 (d, J = 8.1 Hz, 1H), 6.21 (t, J = 7.3 Hz, 1H), 5.98 (d, J = 7.2 Hz,
2
1
2
1
H), 4.45 (s, 1H), 4.26 (s, 2H), 4.07−4.05 (m, 3H), 3.55 (s, 2H), 3.09 (s, 9H),
13
.32−2.26 (m, 1H), 2.21−2.14 (m, 1H) ppm; C NMR (100 MHz, D O): δ
2
31
66.3, 157.7, 141.7, 96.6, 86.1, 85.5, 70.9, 66.1, 65.5, 60.0, 54.1, 39.5 ppm; P
NMR (162 MHz, D2O): δ –10.9, –11.7 ppm; IR: ν
3680, 2979, 2909, 1682,
max
−
1
1
498, 1402, 1248, 1078, 794, 653, 628, 564 cm ; HRMS (ESI–): m/z calcd
−
for C H N O P [M–H] 471.3172; found 471.3165.
14
25
4
10 2
FUNDING
The authors thank the National Natural Science Foundation of China
No. 21262014), Major Science and Technology Project of Jiangxi Province
(