Rp-(endo)-2',3'-cyclic-UMPS | 30802-06-3

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: Rp-(endo)-2',3'-cyclic-UMPS
• 英文别名: (R_P)-uridine 2',3'-cyclic phosphoromonothioate；Rp-(endo)-uridine 2',3'-cyclic phosphorothioate
• CAS: 30802-06-3
• 化学式: C₉H₁₁N₂O₇PS
• 分子量: 322.235
• InChiKey: OIDQHQCLWHMGIL-VQAIERIMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.75
• 重原子数：
  20.0
• 可旋转键数：
  2.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  119.85
• 氢给体数：
  3.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  Rp-(endo)-2',3'-cyclic-UMPS 在 zinc(II) nitrate sodium nitrate 、 HEPES buffer 作用下， 生成 uridine 2',3'-cyclic phosphate 、 1-[(2R,3R,4R,5R)-3-dihydroxyphosphinothioyloxy-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione 、 uridine 3'-O-phosphorothioate
  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：

  1-{(3aR,4R,6R,6aR)-6-[Bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-2-oxo-tetrahydro-2λ⁵-furo[3,4-d][1,3,2]dioxaphosphol-4-yl}-1H-pyrimidine-2,4-dione 在 二氯乙酸 、 1,2,3,4,5,6,7,8-八硫杂环辛烷 作用下， 以 二硫化碳 、 二氯甲烷 为溶剂， 生成 Rp-(endo)-2',3'-cyclic-UMPS
  参考文献：
  名称：

  Synthesis and separation of diastereomers of uridine 2′,3′-cyclic boranophosphate

  摘要：

  The first boron-containing 2',3'-cyclic phosphate-modified analogue, uridine 2',3'-cyclic boranophosphate (2',3'-cyclic-UMPB), was synthesized. 5'-O-Protected uridine was cyclophosphorylated by diphenyl H-phosphonate to yield uridine 2',3'-cyclic H-phosphonate, which upon silylation followed by boronation and subsequent acid treatment gave 2',3'-cyclic-UMPB in high yield. The two diastereomers of 2',3'-cyclic-UMPB were separated by HPLC. An alternative method for synthesis of uridine 2',3'-cyclic phosphorothioate (2',3'-cyclic-UMPS) via H-phosphonate was also described. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00700-9

文献信息

• Metal-Ion-Promoted Cleavage, Isomerization, and Desulfurization of the Diastereomeric Phosphoromonothioate Analogues of Uridylyl(3‘,5‘)uridine
  作者：Mikko Ora、Markku Peltomäki、Mikko Oivanen、Harri Lönnberg

  DOI：10.1021/jo972112n

  日期：1998.5.1

  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.
• Synthesis and separation of diastereomers of uridine 2′,3′-cyclic boranophosphate
  作者：Kaizhang He、Barbara Ramsay Shaw

  DOI：10.1016/s0960-894x(00)00700-9

  日期：2001.3

  The first boron-containing 2',3'-cyclic phosphate-modified analogue, uridine 2',3'-cyclic boranophosphate (2',3'-cyclic-UMPB), was synthesized. 5'-O-Protected uridine was cyclophosphorylated by diphenyl H-phosphonate to yield uridine 2',3'-cyclic H-phosphonate, which upon silylation followed by boronation and subsequent acid treatment gave 2',3'-cyclic-UMPB in high yield. The two diastereomers of 2',3'-cyclic-UMPB were separated by HPLC. An alternative method for synthesis of uridine 2',3'-cyclic phosphorothioate (2',3'-cyclic-UMPS) via H-phosphonate was also described. (C) 2001 Elsevier Science Ltd. All rights reserved.