尿苷5-单磷酸 → Diuridine tetraphosphate tetraammonium salt

HRID 429715

反应方程式

HRID 429715 反应方程式
[P:1]([O:5][CH2:6][C@H:7]1[O:11][C@@H:10]([N:12]2[CH:19]=[CH:18][C:16](=[O:17])[NH:15][C:13]2=[O:14])[C@H:9]([OH:20])[C@@H:8]1[OH:21])([OH:4])([OH:3])=[O:2].[P:22]([O:34][CH2:35][C@H:36]1[O:40][C@@H:39]([N:41]2[CH:48]=[CH:47][C:45](=[O:46])[NH:44][C:42]2=[O:43])[C@H:38]([OH:49])[C@@H:37]1[OH:50])([O:25][P:26]([O:29][P:30](O)([OH:32])=[O:31])([OH:28])=[O:27])(=[O:24])[OH:23].C([NH+:55](CCCC)CCCC)CCC>CN(C=O)C.C(N(CCCC)CCCC)CCC>[NH4+:12].[NH4+:41].[NH4+:55].[NH4+:12].[O-:4][P:1]([O:5][P:30]([O:29][P:26]([O:25][P:22]([OH:24])([OH:34])=[O:23])([O-:28])=[O:27])([O-:32])=[O:31])(=[O:2])[O-:3].[C@@H:10]1([N:12]2[CH:19]=[CH:18][C:16](=[O:17])[NH:15][C:13]2=[O:14])[O:11][C@H:7]([CH2:6][OH:5])[C@@H:8]([OH:21])[C@H:9]1[OH:20].[C@@H:39]1([N:41]2[CH:48]=[CH:47][C:45](=[O:46])[NH:44][C:42]2=[O:43])[O:40][C@H:36]([CH2:35][OH:34])[C@@H:37]([OH:50])[C@H:38]1[OH:49]

参与物

6

反应物 3

HCID 6030尿苷5-单磷酸HCID 6133尿苷5'-三磷酸酯HCID 3724478Tributylammonium

产物 1

HCID 131722997Diuridine tetraphosphate tetraammonium salt收率 30%

试剂、催化剂与溶剂 2

HCID 6228N,N-二甲基甲酰胺溶剂2 次HCID 7622三正丁胺溶剂2 次

反应条件

温度
50 °C

实验过程

Uridine 5′-monophosphate (Sigma, Milwaukee, 3.0 g, 9.26 mmol) was dissolved in dry DMF (10 mL) and tributylamine (Aldrich, 2 mL). The solution was evaporated in vacuo at 40° C. to an oil. The residue was dissolved in dry DMF (Aldrich, 8 mL) to form a solution. Carbonyldilmidazole (Aldrich, 1.65 g, 10.18 mmol) was added to this solution. The reaction was heated at 50° C. for one hour. Uridine 5′-triphosphate (Yamasa, 5.60 g, 10.18 mmol) prepared as the anhydrous tributylammonium salt in DMF (5 mL) and tributylamine (2 mL), as described in Example 3 below, was added to the reaction solution. The mixture was allowed to stir at 50° C. for three days when the solution was evaporated in vacuo to an oil, redissolved in water (5 mL) and purified by column (300×50 mm) chromatography (Sephadex DEAE-A25, 40-120μ, Aldrich, pre-swollen in 1.0 M NaHCO3 and washed with 2 column volumes of deionized H2O (H2O→0.03 M NH4HCO3 gradient). The pure fractions were concentrated in vacuo at 35° C., and H2O added and reevaporated 5 times to obtain diuridine tetraphosphate tetraammonium salt as a white solid (2.37 g, 30% yield): 92.11% pure by HPLC with the same retention time as the standard. In addition, the tetraammonium salt was analyzed by FABMS to give a mass of [C18H25N4O23P4 (M−H+)−: calculated 788.9860] 788.9857, confirming a parent formula of C18H26N4O23P4 for the free acid].

后处理

  1. customThe solution was evaporated in vacuo at 40° C. to an oil
  2. dissolutionThe residue was dissolved in dry DMF (Aldrich, 8 mL)
  3. customto form a solution
  4. additionCarbonyldilmidazole (Aldrich, 1.65 g, 10.18 mmol) was added to this solution
  5. additionwas added to the reaction solution
  6. customwas evaporated in vacuo to an oil
  7. dissolutionredissolved in water (5 mL)
  8. custompurified by column (300×50 mm) chromatography (Sephadex DEAE-A25, 40-120μ, Aldrich
  9. washpre-swollen in 1.0 M NaHCO3 and washed with 2 column volumes of deionized H2O (H2O→0.03 M NH4HCO3 gradient)
  10. concentrationThe pure fractions were concentrated in vacuo at 35° C.
  11. additionH2O added
  12. customreevaporated 5 times

来源与证据

ORD记录
ord-189bb935407a498e9d666b45cdf15497
来源数据集
uspto-grants-2001_11
专利号
US06319908B1

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