1-[(2R,5S)-5-[(6-chloro-2-oxo-4H-1,3,2$l^{5}-benzodioxaphosphinin-2-yl)oxymethyl]-2,5-dihydrofuran-2-yl]-5-methyl-pyrimidine-2,4-dione | 188548-78-9

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷酸
• 英文名称: 1-[(2R,5S)-5-[(6-chloro-2-oxo-4H-1,3,2$l^{5}-benzodioxaphosphinin-2-yl)oxymethyl]-2,5-dihydrofuran-2-yl]-5-methyl-pyrimidine-2,4-dione
• 英文别名: 1-[(2R,5S)-5-[(6-chloro-2-oxo-4H-1,3,2λ5-benzodioxaphosphinin-2-yl)oxymethyl]-2,5-dihydrofuran-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 188548-78-9
• 化学式: C₁₇H₁₆ClN₂O₇P
• 分子量: 426.75
• InChiKey: RVLRBHLDPAIIAN-NQMRZEFVSA-N

物化性质

• 密度：
  1.58±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-[(2R,5S)-5-[(6-chloro-2-oxo-4H-1,3,2$l^{5}-benzodioxaphosphinin-2-yl)oxymethyl]-2,5-dihydrofuran-2-yl]-5-methyl-pyrimidine-2,4-dione 以 水 为溶剂， 生成 5-氯-2-羟基苯甲醇 、 3'-deoxy-2',3'-didehydro-5'-O-dihydroxyphosphoryl thymidine
  参考文献：
  名称：

  Cyclic saligenyl phosphotriesters of 2′,3′-dideoxy-2′,3′-didehydrothymidine (d4T) — a new pro-nucleotide approach

  摘要：

  The synthesis of a new pro-nucleotide approach for d4TMP 2 based on cycloSal-d4TMP 3a-d is described. Phosphotriesters 3 release d4TMP 2 selectively by a controlled, chemically induced tandem reaction. CycloSal-phosphotriesters 3 exhibited high biological activity against HIV-1/HIV-2 in CEM cells which was retained in CEM TK- cells. (C) 1997, Published by Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(96)00597-5
• 作为产物：
  描述：

  5-氯代水杨酸 在 叔丁基过氧化氢 、 lithium aluminium tetrahydride 、 N,N-二异丙基乙胺 、 三氯化磷 作用下， 以 吡啶 、 异丙醇 为溶剂， 反应 2.83h， 生成 1-[(2R,5S)-5-[(6-chloro-2-oxo-4H-1,3,2$l^{5}-benzodioxaphosphinin-2-yl)oxymethyl]-2,5-dihydrofuran-2-yl]-5-methyl-pyrimidine-2,4-dione
  参考文献：
  名称：

  Cyclic saligenyl phosphotriesters of 2′,3′-dideoxy-2′,3′-didehydrothymidine (d4T) — a new pro-nucleotide approach

  摘要：

  The synthesis of a new pro-nucleotide approach for d4TMP 2 based on cycloSal-d4TMP 3a-d is described. Phosphotriesters 3 release d4TMP 2 selectively by a controlled, chemically induced tandem reaction. CycloSal-phosphotriesters 3 exhibited high biological activity against HIV-1/HIV-2 in CEM cells which was retained in CEM TK- cells. (C) 1997, Published by Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(96)00597-5

文献信息

• <i>cyclo</i>Sal-2‘,3‘-dideoxy-2‘,3‘-didehydrothymidine Monophosphate (<i>cyclo</i>Sal-d4TMP):  Synthesis and Antiviral Evaluation of a New d4TMP Delivery System
  作者：Chris Meier、Martina Lorey、Erik De Clercq、Jan Balzarini

  DOI：10.1021/jm970664s

  日期：1998.4.1

  The synthesis, hydrolysis, and antiviral evaluation of novel, lipophilic cycloSal-d4TMP derivatives 3a-h of the anti-HIV dideoxynucleoside 2',3'-dideoxy-2',3'-didehydrothymidine (d4T, 1) are reported. This pro-nucleotide concept has been designed to deliver d4TMP (2) by selective chemical hydrolysis. All compounds 3a-h were synthesized using phosphorus(III) chemistry in good yields and in somewhat

  报告了抗HIV双脱氧核苷2'，3'-二脱氧-2'，3'-二脱氢胸苷（d4T，1）的新型亲脂性cycloSal-d4TMP衍生物3a-h的合成，水解和抗病毒评估。该前核苷酸概念已被设计为通过选择性化学水解来递送d4TMP（2）。所有化合物3a-h都是使用磷（III）化学方法合成的，产率很高，而使用磷（V）化学方法则是从取代的水杨醇6a-h开始以较低的产率合成的。相对于在磷中心作为1：1非对映异构体混合物的构型，在没有立体化学偏爱的情况下获得了磷酸三酯3。但是，一些三酯3可以通过半制备HPLC分离为非对映异构体。在1-辛醇/磷酸盐缓冲液混合物中，从其Pa值判断，所有化合物3的亲脂性都比d4T高9-100倍（1）。此外，在水解研究中3在温和的碱性水溶液中分解，仅按照设计的串联反应顺序释放d4TMP（2）和二醇6。观察到由取代基引入的电子性质与三酯3的半衰期的相关性。因此，通过改变取代基，可以在仍
• Meier, Chris, Angewandte Chemie, 1996, vol. 108, # 1, p. 77 - 79
  作者：Meier, Chris

  DOI：——

  日期：——
• <i>Cyclo</i>-saligenyl-2′,3′-dideoxy-2′,3′-didehydroythymidinemonophosphate (<i>cyclo</i>Sal-d4TMP) — A New Pro-Nucleotide Approach
  作者：Chris Meier、Martina Lorey、Eric De Clercq、Jan Balzarini

  DOI：10.1080/07328319708006176

  日期：1997.7

  The synthesis of cycloSal-d4TMP 3a-g as new pro-nucleotide approach for d4TMP 2 is described. Phosphotriesters 3 release the d4TMP 2 selectively by a controlled, chemically induced tandem reaction. CycloSal-phosphotriesters 3 exhibited high biological activity against HIV-1/HIV-2 in CEM cells which was completely retained in CEM TK- cells.
• Cyclic saligenyl phosphotriesters of 2′,3′-dideoxy-2′,3′-didehydrothymidine (d4T) — a new pro-nucleotide approach
  作者：Chris Meier、Martina Lorey、E. De Clercq、Jan Balzarini

  DOI：10.1016/s0960-894x(96)00597-5

  日期：1997.1

  The synthesis of a new pro-nucleotide approach for d4TMP 2 based on cycloSal-d4TMP 3a-d is described. Phosphotriesters 3 release d4TMP 2 selectively by a controlled, chemically induced tandem reaction. CycloSal-phosphotriesters 3 exhibited high biological activity against HIV-1/HIV-2 in CEM cells which was retained in CEM TK- cells. (C) 1997, Published by Elsevier Science Ltd.