(R_P)-uridylyl(3',5')uridine phosphoromonothioate | 143344-32-5

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: (R_P)-uridylyl(3',5')uridine phosphoromonothioate
• CAS: 143344-32-5
• 化学式: C₁₈H₂₃N₄O₁₃PS
• 分子量: 566.439
• InChiKey: QZPKUYPXYHEYMQ-ILIYZMILSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -4.42
• 重原子数：
  37.0
• 可旋转键数：
  8.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  247.79
• 氢给体数：
  7.0
• 氢受体数：
  15.0

反应信息

• 作为反应物：
  描述：

  (R_P)-uridylyl(3',5')uridine phosphoromonothioate 在 zinc(II) nitrate sodium nitrate 、 HEPES buffer 作用下， 生成 2',5''-Uridyluridine 、 尿苷酰基-(3',5')-尿苷 、 Rp-(endo)-2',3'-cyclic-UMPS 、 (R_P)-uridylyl(2',5')uridine phosphoromonothioate
  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：

  在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 生成 (R_P)-uridylyl(3',5')uridine phosphoromonothioate
  参考文献：
  名称：

  氧杂磷腈法立体控制合成寡核糖核苷硫代磷酸酯

  摘要：

  在固体载体上合成了在磷原子上立体定义的寡核糖核苷硫代磷酸酯（PS-ORN）。所得PS-ORN的热变性实验表明，由（S p）-PS键和立体随机PS键组成的主链对PS-ORN-ORN双链体的稳定作用出乎意料地大，而由（- [R p）-PS-键略微稳定双链体。

  DOI：

  10.1021/ol802910k

文献信息

• Hydrolytic Reactions of the Phosphorodithioate Analogue of Uridylyl(3‘,5‘)uridine:  Kinetics and Mechanisms for the Cleavage, Desulfurization, and Isomerization of the Internucleosidic Linkage
  作者：Mikko Ora、Johanna Järvi、Mikko Oivanen、Harri Lönnberg

  DOI：10.1021/jo991632a

  日期：2000.5.1

  2 K. Under acidic and neutral conditions, three reactions compete: (i) desulfurization to a mixture of the (Rp)- and (Sp)-diastereomers of the corresponding 3',5'- and 2',5'-phosphoromonothioates [3',5'- and 2',5'-Up(s)U], which are subsequently desulfurized to a mixture of uridylyl(3',5')- and -(2',5')uridine [3',5'- and 2',5'-UpU], (ii) isomerization to 2',5'-Up(s)2U, and (iii) cleavage to uridine

  在363.2 K的宽pH范围内，通过HPLC对uridylyl（3'，5'）尿苷[3'，5'-Up（s）2U]的二硫代磷酸酯类似物进行水解反应。在酸性和中性条件下，三个反应竞争：（i）脱硫为相应的3'，5'-和2'，5'-磷酸一硫代磷酸酯（3'，5'-和2'）（Rp）-和（Sp）-非对映异构体的混合物， 5'-Up（s）U]，随后将其脱硫成尿嘧啶（3'，5'）-和-（2'，5'）尿苷[3'，5'-和2'，5' -UpU]，（ii）异构化为2'，5'-Up（s）2U和（iii）裂解成尿苷，很可能是通过2'，3'-环状二硫代磷酸酯（2'，3'-cUMPS2 ）。在碱性条件下（pH> 8），只有氢氧根离子通过2'，3'催化水解为尿苷 -cUMPS2发生。在pH 3-7时，所有三个反应均与pH无关，脱硫比裂解和异构化快约1个数量级。在pH <3时，所有反应均被水合氢离子催化。在变成非常酸性的溶液时
• Oxathiaphospholane Method of Stereocontrolled Synthesis of Diribonucleoside 3‘,5‘-Phosphorothioates
  作者：Agnieszka Sierzchała、Andrzej Okruszek、Wojciech J. Stec

  DOI：10.1021/jo960811e

  日期：1996.1.1