1-[(2R,3R,4R,5R)-3-dihydroxyphosphinothioyloxy-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione | 166533-21-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-[(2R,3R,4R,5R)-3-dihydroxyphosphinothioyloxy-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione
• CAS: 166533-21-7
• 化学式: C₉H₁₃N₂O₈PS
• 分子量: 340.251
• InChiKey: GKCMCEMMYAEKQO-XVFCMESISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.4
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  181
• 氢给体数：
  5
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  1-[(2R,3R,4R,5R)-3-dihydroxyphosphinothioyloxy-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione 在 zinc(II) nitrate sodium nitrate 、 HEPES buffer 作用下， 生成 uridine 2',3'-cyclic phosphate 、 尿嘧啶核苷
  参考文献：
  名称：

  Metal-Ion-Promoted Cleavage, Isomerization, and Desulfurization of the Diastereomeric Phosphoromonothioate Analogues of Uridylyl(3‘,5‘)uridine

  摘要：

  Metal-ion-promoted hydrolytic reactions of the S-P and R-P diastereomers of the phosphoromonothioate analogues of uridylyl(3',5')uridine [3',5'-Up(s)U] and their cleavage products, diastereomeric uridine 2',3'-cyclic phosphates [2',3'-cUMPS], were followed by HPLC, as a function of pH (4.7-5.6) and metal ion concentration (1-10 mmol L-1). With 3',5'-Up(s)U, three reactions compete: (i) cleavage to 2',3'-cUMPS, (ii) isomerization to 2',5'-Up(s)U, and (iii) desulfurization to an equilibrium mixture of 2',5'- and 3',5'-UpU. Of these, the cleavage to 2',3'-cUMPS is markedly accelerated by Zn2+ Cd2+, and Gd3+, the rate enhancements observed with the S-P isomer at [Mz+] = 5 mmol L-1 and pH 5.6 (T = 363.2 K) being 410-, 3600-, and 2000-fold, respectively. The effect of Mn2+ and Mg2+ on the cleavage rate is, in turn, modest (6- and 1.7-fold acceleration, respectively). The rate-accelerations are almost equal with the S-P and R-P diastereomers. The metal-ion-promoted reaction is first-order in both the hydroxide and metal ion concentration, and it proceeds by inversion of configuration at phosphorus, consistent with an in-line displacement mechanism. The isomerization and desulfurization are much less susceptible to metal ion catalysis: 6.4- and 7.7-fold accelerations were observed with Zn2+, respectively. Gd3+ does not promote these reactions at all. The isomerization proceeds by retention of configuration at phosphorus, consistent with formation of a pentacoordinated thiophosphorane intermediate having the entering 2'-hydroxy group apical and the leaving 3'-hydroxy equatorial, and subsequent pseudorotation posing the leaving group apical. The hydrolysis of 2',3'-cUMPS is accelerated by metal ions slightly more efficiently than the cleavage of 3',5'-Up(s)U to 2',3'-cUMPS. In striking contrast to the reactions of 3',5'-Up(s)U, the hydrolytic desulfurization to 2',3'-cUMP is accelerated as efficiently as its endocyclic hydrolysis to uridine 2'- and 3'-phosphoromonothioates [2'- and 3'-UMPS]. Somewhat unexpectedly, the latter compounds were observed to undergo metal-ion-promoted cyclization/desulfurization to 2',3'-cUMP. The hydrolysis of 2'- or 3'-UMPS to uridine was, in turn, observed to be retarded by metal ions. The mechanisms of the partial reactions are discussed.

  DOI：

  10.1021/jo972112n
• 作为产物：
  描述：

  Thiophosphoric acid O-(4-cyano-phenyl) ester O'-[(2R,3S,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-hydroxy-2-hydroxymethyl-tetrahydro-furan-3-yl] ester 在 Carbonate buffer 、 hydroxide 、 羟基甲酸酯 作用下， 生成 uridine 3'-O-phosphorothioate 、 1-[(2R,3R,4R,5R)-3-dihydroxyphosphinothioyloxy-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione
  参考文献：
  名称：

  尿苷 3'-（芳基硫代磷酸酯）分子内醇解中的碱催化和离开基团依赖性

  摘要：

  还研究了尿苷 3'-(芳基硫代磷酸酯) (Up(S)Ar) 中碱催化的分子内酯交换反应对离去芳氧基 (pKa 7.1-10) 共轭酸酸度的依赖性关于催化剂的碱度 (pKa(BH) = 7-10.2)。所研究的硫代磷酸酯的合成是通过使用基于受保护的尿苷 3'-H-膦酸酯与适当的酚类缩合的方法来完成的。氢氧化物和咪唑催化的速率常数（25°C，0.25 M 离子强度）服从布朗斯台德线性自由能关系，获得的 β 离去基团 (βlg) 值分别为 -0.55 和 -0.63。4-硝基苯氧化物从相应的硫代磷酸酯中的一般碱催化释放也遵循与催化剂碱度有关的布朗斯台德关系 (β = 0.59)。

  DOI：

  10.1021/ja953399d

文献信息

• Hydrolytic dethiophosphorylation and desulfurization of the monothioate analogues of uridine monophosphates under acidic conditions
  作者：Mikko Ora、Mikko Oivanen、Harri Lönnberg

  DOI：10.1039/p29960000771

  日期：——

  The hydrolytic reactions of uridine 2'-, 3'- and 5'-phosphoromonothioates (2'-, 3'- and 5'-UMPS) under acidic and neutral conditions have been followed by HPLC. Under slightly acidic conditions (pH 2-5), only pa-independent dethiophosphorylation to uridine takes place. This reaction is 200- to 300-fold as fast as dephosphorylation of the corresponding uridine monophosphates (UMP), presumably due to higher stability of the thiometaphosphate monoanion compared to metaphosphate anion. At pH > 5, i.e. at pH > pK(a2) of the thiophosphate moiety, the dethiophosphorylation is retarded with increasing basicity of the solution. At pH < 1, acid-catalysed desulfurization of 2'- and 3'-UMPS to an isomeric mixture of 2'/3'-UMP competes with their dethiophosphorylation. This reaction is suggested to proceed by a nucleophilic attack of the neighbouring hydroxy group on phosphorus. No such reaction occurs with 5'-UMPS. In contrast to 2'- and 3'-UMP, no sign of interconversion of 2'- and 3'-UMPS is detected.