thymidine 5'-phenylphosphate | 63286-48-6

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷酸
• 英文名称: thymidine 5'-phenylphosphate
• 英文别名: [(2R,3S,5R)-3-hydroxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl phenyl hydrogen phosphate
• CAS: 63286-48-6
• 化学式: C₁₆H₁₉N₂O₈P
• 分子量: 398.309
• InChiKey: VQNFXIJIGDKLHT-BFHYXJOUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  135
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  5'-(phenylmethoxyalaninyl)phosphate thymidine 在 水 、 sodium chloride 作用下， 生成 thymidine 5'-phenylphosphate
  参考文献：
  名称：

  胸苷5'-邻-苯基-N-烷基膦酰胺酸酯的水解反应，核苷5'-单磷酸酯前药的模型。

  摘要：

  从而导致胸腺嘧啶核苷或苯酚的离开而没有任何中间体的明显积累。两种途径都代表3总体消失的一半。苯酚的离开最终导致5'-磷酸胸苷的形成。在pH> 5时，主要反应是羧酸酯键的水解，然后是羧酸根离子在分子内置换酚盐离子，然后将所得的环状混合酸酐水解成无环二酯状胸苷5'-氨基磷酸酯。后者产物定量地积累，没有任何进一步分解的迹象。原料3的氢氧根离子催化的P-OPh键断裂是副反应。与胸苷5'的比较测量

  DOI：

  10.1002/chem.200700623

文献信息

• Hydrolysis of the <i>cis</i>-Phenyl Ester of Thymidine 3‘,5‘-Cyclic Monophosphate:  pH-Dependent Competition between Depyrimidination and Phosphotriester Hydrolysis <i>via</i> CO and PO Bond Ruptures
  作者：Jaana Varila、Teemu Hankamäki、Mikko Oivanen、Leo H. Koole、Harri Lönnberg

  DOI：10.1021/jo960693v

  日期：1997.2.1

  Hydrolytic reactions of the cis-phenyl ester of thymidine 3',5'-cyclic monophosphate (In) have been followed by HPLC over a wide pH range. Under acidic conditions (pH < 4) two reactions compete: depyrimidination (cleavage of the N-glycosidic bond) and phosphotriester hydrolysis to a mixture of three phosphodiesters, viz. thymidine 3',5'-cyclic monophosphate (2) and thymidine 3'- and 5'-(phenyl phosphates) (3 and 4). Depyrimidination predominates (>80%) at pH < 1 and shows first-order dependence on acidity. The reaction is 4.5 to 5 times slower than with 2. The phosphotriester hydrolysis of 1a is acid catalyzed at pH < 2, giving all three phosphodiester products (2-4). Over a broad acidity range from pH 2 to 7, the reaction is pH-independent. In this pH region, the predominant product is 3 (up to 85%). At pH > 10, the hydrolysis is hydroxide-ion-catalyzed, yielding the three phosphodiester products in a 42:42:16 ratio ([2]:[3]:[4]). From pH 7 to 10, the pH-rate profile is nonlinear, possibly due to N3H deprotonation of the thymine moiety. In the same pH range, the site of bond cleavage appears to be changed. The product analyses of the corresponding methanolysis reactions suggest that the pH-independent reaction predominantly takes place via cleavage of the C5'O bond, while the alkaline reaction proceeds by rupture of one of the PO bonds. Consistent with this proposal, the pH-independent hydrolysis yields at high concentrations of sodium chloride 5'-chloro-5'-deoxythymidine 3'-(phenyl phosphate) and in concentrated acetate buffers 5'-O-acetylthymidin 3'-(phenyl phosphate). Accordingly, the hydrolytic reactions of 1a markedly differ from those of more simple 2-aryloxy-2-oxo-1,3,2-dioxaphosphorinanes.
• US5962291A
  申请人：——

  公开号：US5962291A

  公开（公告）日：1999-10-05
• Hydrolytic Reactions of Thymidine 5′-O-Phenyl-N-Alkylphosphoramidates, Models of Nucleoside 5′-Monophosphate Prodrugs
  作者：Mikko Ora、Jarno Ojanperä、Harri Lönnberg

  DOI：10.1002/chem.200700623

  日期：2007.10.15

  of the starting material 3 occurred as a side reaction. Comparative measurements with thymidine 5'-N-[(1S)-2-oxo-2-methoxy-1-methylethyl]phosphoramidate} (4) revealed that, under acidic conditions, this diester-like compound is hydrolyzed by P--N bond cleavage three orders of magnitude more rapidly than the triester-like 3. At pH>5, the stability order is reversed, with 3 being hydrolyzed six times

  从而导致胸腺嘧啶核苷或苯酚的离开而没有任何中间体的明显积累。两种途径都代表3总体消失的一半。苯酚的离开最终导致5'-磷酸胸苷的形成。在pH> 5时，主要反应是羧酸酯键的水解，然后是羧酸根离子在分子内置换酚盐离子，然后将所得的环状混合酸酐水解成无环二酯状胸苷5'-氨基磷酸酯。后者产物定量地积累，没有任何进一步分解的迹象。原料3的氢氧根离子催化的P-OPh键断裂是副反应。与胸苷5'的比较测量