Sp-(exo)-2',3'-cyclic-UMPS | 30802-43-8

• 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: Sp-(exo)-2',3'-cyclic-UMPS
• 英文别名: (S_P)-uridine 2',3'-cyclic phosphoromonothioate；Sp-(exo)-uridine 2',3'-cyclic phosphorothioate
• CAS: 30802-43-8
• 化学式: C₉H₁₁N₂O₇PS
• 分子量: 322.235
• InChiKey: OIDQHQCLWHMGIL-JTVQEINNSA-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：

  Sp-(exo)-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 Sp-(exo)-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

• Addressing regio- and stereo-specificity challenges in the synthesis of nucleoside 2′,3′-cyclic monophosphate analogs – a rapid and facile synthesis of nucleoside-2′,3′-<i>O</i>,<i>O</i>-phosphoro-thioate or -selenoate, and elucidation of the origin of the rare specificity
  作者：Molhm Nassir、Lara Balaom、Bilha Fischer

  DOI：10.1039/d0cc02886j

  日期：——

  A new facile, rapid, stereo- and regio-selective one-pot synthesis of nucleoside-2′,3′-O,O-phosphorothioate and selenoate analogs has been developed. This method avoids the need for protection strategies and chiral reagents, chiral metal catalysts, or chiral separations. This synthetic method has been applied to all natural nucleosides (U/A/G/C/T). Furthermore, we have deciphered the origin of the

  已经开发了一种新的简便，快速，立体和区域选择性的核苷2'，3'- O，O-硫代磷酸酯和硒酸酯类似物的一锅合成方法。该方法避免了保护策略和手性试剂，手性金属催化剂或手性分离的需要。该合成方法已应用于所有天然核苷（U / A / G / C / T）。此外，我们已经破译了反应的立体选择性和区域选择性的起源。