2-(3'-O-acetyl-2'-deoxythymidin-5'-yl)-4H-1,3,2-benzodioxaphosphorin-4-one | 208115-15-5

• 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: 2-(3'-O-acetyl-2'-deoxythymidin-5'-yl)-4H-1,3,2-benzodioxaphosphorin-4-one
• 英文别名: [(2R,3S,5R)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)-2-[(4-oxo-1,3,2-benzodioxaphosphinin-2-yl)oxymethyl]oxolan-3-yl] acetate
• CAS: 208115-15-5；316356-96-4；316356-97-5
• 化学式: C₁₉H₁₉N₂O₉P
• 分子量: 450.342
• InChiKey: JFQXIFGVXCCODT-AXWAUASUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  130
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2-(3'-O-acetyl-2'-deoxythymidin-5'-yl)-4H-1,3,2-benzodioxaphosphorin-4-one 在 三正丁胺 、 三丁基焦磷酸铵 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.17h， 生成 [(2R,3S,5R)-2-[(4,6-dioxido-4,6-dioxo-1,3,5,2,4lambda5,6lambda5-trioxatriphosphinan-2-yl)oxymethyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl] acetate
  参考文献：
  名称：

  2'-脱氧核糖核苷5'-（α - P-硼烷）三磷酸酯的简便合成

  摘要：

  一类新的核苷酸已显示出在DNA测序中的潜在应用，该类核苷酸在α-磷上的两个非桥键氧之一被硼烷（BH 3）基团取代。我们已经开发了一种方便的方法来合成2'-脱氧-5'-（α-P-硼烷）三磷酸腺苷，鸟苷，胞苷，胸苷和尿苷（6a-e），与之相比，该方法既省时又节省成本以前报告的方法。用2-氯-4 H -1,3,2-苯并二氧杂磷酰基-4-酮将适当的碱/糖保护的核苷1磷酸化，得到相应的环状中间体2-（2'-脱氧核糖核苷-5'- O-） -4 H -1,3,2-苯并二氧杂磷酰基-4-酮（2）。这2与焦磷酸盐的原位反应生成P 2，P 3-二氧代-P 1-（2'-脱氧核糖核苷-5'-）环三亚磷酸酯（3）。3与N，N-二异丙基乙胺-硼烷络合物的后续反应产生P 1-硼烷- （2'-脱氧核糖核苷-5'）环三磷酸酯（4），在温和条件下水解后可得到经碱/糖保护的2'-脱氧核糖核苷- 5′-（α - P-硼烷）三磷酸酯（5）。治疗5用氨：甲醇（2∶1v

  DOI：

  10.1016/s0040-4020(98)00251-8
• 作为产物：
  描述：

  2-氯-1,3,2-苯并二氧磷杂环己烷-4-酮 、 3'-O-acetylthymidine 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.17h， 生成 2-(3'-O-acetyl-2'-deoxythymidin-5'-yl)-4H-1,3,2-benzodioxaphosphorin-4-one
  参考文献：
  名称：

  Synthesis of a novel triphosphate analogue: nucleoside α-P-borano, α-P-thiotriphosphate

  摘要：

  第一个硫代三磷酸硼化合物，胸苷 5-[α-P-硼烷，α-P-硫代]三磷酸盐， 其中硼烷和硫取代了两个非桥接氧 天然三磷酸核苷（NTP）中的α-磷酸盐，已被 合成的；这种硼烷硫的一些化学性质 已经研究了二取代核苷三磷酸类似物。这 这里报告的合成方法应该适用于制备 任何α-硼烷、α-硫代修饰的 NTP 或脱氧 NTP；潜在的 讨论了应用。

  DOI：

  10.1039/b005059h

文献信息

• Synthesis of α-P-Modified Nucleoside Diphosphates with Ethylenediamine
  作者：Ping Li、Zhihong Xu、Hongyan Liu、Charlotta K. Wennefors、Mikhail I. Dobrikov、János Ludwig、Barbara Ramsay Shaw

  DOI：10.1021/ja055179y

  日期：2005.12.1

  a one-pot synthesis of α-P-borano-, α-P-thio-, and α-P-seleno-modified nucleoside diphosphate analogues that are otherwise difficult to obtain. The key step involves the intramolecular nucleophilic attack by an amino group in 5 to remove the γ-phosphate. The absolute configurations of P-diastereomers were confirmed by analysis of their 1H NMR. Affinity studies revealed that the nucleoside boranodiphosphates

  本报告描述了 α-P-硼烷-、α-P-硫代-和 α-P-硒修饰的核苷二磷酸类似物的一锅合成，否则很难获得。关键步骤涉及 5 中的氨基进行分子内亲核攻击以去除 γ-磷酸盐。P-非对映异构体的绝对构型通过其 1H NMR 分析得到证实。亲和力研究表明，核苷硼二磷酸在抗病毒研究中可能有用。
• Synthesis of nucleoside 5'-O-(1,3-dithiotriphosphates) and 5'-O-(1,1-dithiotriphosphates)
  作者：Janos Ludwig、Fritz Eckstein

  DOI：10.1021/jo00005a023

  日期：1991.3

  The synthesis of 3'-deoxy-3'-azidothymidine 5'-O-(1,3-dithiotriphosphate) (5) as the first example of a nucleoside 5'-O-(1,3-dithiotriphosphate) is described. 2-Chloro-4H-1,3,2-benzodioxaphosphorin-4-one phosphitylates the 5'-hydroxy group of 3'deoxy-3'-azidothymidine to form intermediate 1. Reaction of 1 with thiopyrophosphate (9) and sulfur results in the formation of an unseparable mixture of 3'-deoxy-3'-azidothymidine 5'-O-(1,3-dithiotriphosphate) (5) and 3'-deoxy-3'-azidothymidine 5'-O-(1,2-dithiotriphosphate) (3). Selective hydrolysis of 5 allows isolation of 3. However, reaction of 1 with P1-O-(cyanoethyl)-P1-thiopyrophosphate (8) and sulfur produced the diastereomers of 5 in good yield. Compound 8 is prepared by reaction of 3-hydroxyproprionitrile with 2-chloro-4H-1,3,2-benzodioxaphosphorin-4-one, pyrophosphate, and sulfur to yield 10, which is ring opened to 8 by reaction with ethylenediamine. Hydrolysis of this compound leads to 9. An alternative route to nucleoside 5'-O-(1,3-dithiotriphosphates) consists of reacting a nucleoside 5'-O-(1-thiocyclotriphosphate) such as 13 with Li2S. This reaction, when performed in pyridine/dioxane, leads to a mixture of the nucleoside 5'-O-(1,3-dithiotriphosphate) and the nucleoside 5'-O-(1,1-dithiotriphosphate). The latter is the only nucleotide product when the reaction is carried out in DMF.
• Convenient Synthesis of Nucleoside Borane Diphosphate Analogues:  Deoxy- and Ribonucleoside 5‘-<i>P</i>^α-Boranodiphosphates
  作者：Ping Li、Barbara Ramsay Shaw

  DOI：10.1021/jo049094b

  日期：2004.10.1

  The nucleoside boranophosphates, having one of the nonbridging phosphate oxygens substituted with a borane (BH3) group, have shown potential therapeutical applications as aptamers, antisense agents, and antiviral prodrugs. An oxathiaphospholane approach, which does not require exocyclic amine protection of the nucleobase, has been successfully developed to efficiently synthesize 5'-P-alpha-boranodiphosphates of 2'-deoxythymidine, adenosine, guanosine, and uridine. The approach involves a key intermediate, the borane complex of nucleoside 5'-O-1,3,2-oxathiaphospholane 16, that undergoes a ring-opening reaction catalyzed by 1,4-diazabicyclo[5.4.0]-undec-7-ene to form the protected nucleoside 5'-P-alpha-boranodiphosphate 18. Treatment of 18 with ammonium hydroxide yielded diastereoisomeric mixtures of nucleoside 5'-P-alpha-boranodiphosphates 5. This oxathiaphospholane approach ensures the availability of nucleoside 5'-P-alpha-boranodiphosphate analogues needed for antiviral drug research.
• Rapid and efficient synthesis of nucleoside 5'-0-(1-thiotriphosphates), 5'-triphosphates and 2',3'-cyclophosphorothioates using 2-chloro-4H-1,3,2-benzodioxaphosphorin-4-one
  作者：Janos Ludwig、Fritz Eckstein

  DOI：10.1021/jo00264a024

  日期：1989.2
• SYNTHESIS AND PROPERTIES OF NOVEL TRIPHOSPHATE ANALOGUES: RIBONUCLEOSIDE AND DEOXYRIBONUCLEOSIDE (α-<i>P</i>-BORANO, α-<i>P</i>-THIO)TRIPHOSPHATES
  作者：Jinlai Lin、Kenneth W. Porter、Barbara Ramsay Shaw

  DOI：10.1081/ncn-100002482

  日期：2001.3.31

  The first ribo- and deoxyribo-nucleoside (alpha -P-borano, alpha -P-thio)triphosphates have been synthesized. The chemical and biochemical properties of adenosine (alpha -P-borano, alpha -P-thio)triphosphate and thymidine (alpha -P-borano, alpha -P-thio) triphosphate have been investigated.