(1'S,4'R)-9-<4'-(phosphonomethoxy)cyclopent-2'-enyl>adenine | 162119-14-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: (1'S,4'R)-9-<4'-(phosphonomethoxy)cyclopent-2'-enyl>adenine
• CAS: 162119-14-4
• 化学式: C₁₁H₁₄N₅O₄P
• 分子量: 311.237
• InChiKey: XZODRISOVMXWBO-SFYZADRCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.43
• 重原子数：
  21.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  136.38
• 氢给体数：
  3.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  (1'S,4'R)-9-<4'-(phosphonomethoxy)cyclopent-2'-enyl>adenine 在 三丁基焦磷酸铵 、 N,N'-羰基二咪唑 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (1'S,4'R)-9-<4'-(diphosphorylphosphonomethoxy)cyclopent-2'-enyl>adenine
  参考文献：
  名称：

  Synthesis of Four Stereoisomers of Carbocyclic 5'-NOR D4A and Evaluation of Their Triphosphates as Substrates for DNA Polymerases

  摘要：

  A method was developed for synthesis of the four stereoisomeric enantiomerically pure 5'-nor carbocyclic nucleosides 4b, ent-4b, 10 and ent-10 starting from the common enantiomerically pure allylic monoacetate 1. Nucleoside analogues were converted to the corresponding triphosphate derivatives 6, ent-6, 12, and ent-12. The substrate properties of the latters towards different DNA polymerases were evaluated.

  DOI：

  10.1080/15257779508012458
• 作为产物：
  描述：

  (1R,4S)-4-(6-aminopurin-9-yl)cyclopent-2-en-1-ol 在 三甲基溴硅烷 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (1'S,4'R)-9-<4'-(phosphonomethoxy)cyclopent-2'-enyl>adenine
  参考文献：
  名称：

  立体合成碳环2'，3'-二脱氧-2'，3'-二氢-5'-芥子苷的四个立体异构体二膦酰基膦酸酯

  摘要：

  已经开发了从常见的对映体纯的烯丙基单乙酸酯3开始的四个立体异构对映体纯的5'-去碳环腺苷类似物4b，ent - 4b，5b和ent - 5b的灵活合成。将每个核苷类似物分别转化为相应的4'-膦酸酯，然后分别转化为二磷酸基膦酸酯4e，ent - 4e，5e和ent - 5e。

  DOI：

  10.1016/0040-4020(94)00986-5

文献信息

• New modified nucleoside 5′-triphosphates: synthesis, properties towards DNA polymerases, stability in blood serum and antiviral activity
  作者：Alexander V. Shipitsin、Lyubov S. Victorova、Elena A. Shirokova、Natalya B. Dyatkina、Lyudmila E. Goryunova、Robert Sh. Beabealashvilli、Chris J. Hamilton、Stanley M. Roberts、Alexander Krayevsky

  DOI：10.1039/a900336c

  日期：——

  A series of new nucleoside 5′-triphosphate mimetics, 2, 3, 5, 6, 8–10, modified at the glycone and all three phosphate residues, have been synthesised and studied. These compounds only bear the enzymatically labile anhydride bond between the α and β phosphorus atoms. The preparative chemistry involved the preparation of phosphonic salts 30, 31 and 32 and coupling of these species to the morpholidate 33. The mechanism of formation of some of the intermediates ‘en route’ to 27 and 28 is discussed. All of the target compounds demonstrated high stability in human blood serum with half lives towards hydrolysis of up to 4.5 days. Some of these nucleoside triphosphonates have been shown to be selective inhibitors of DNA synthesis catalysed by retroviral reverse transcriptases and terminal deoxynucleotidyl transferases. They inhibited replication of the artificial virus containing Moloney murine leukemia virus reverse transcriptase in infected cell culture, probably due to the inhibition of a reverse transcription step of a genomic RNA. Compared to the triphosphonates, the corresponding monophosphonates demonstrated decreased antiviral activity by 1–2 orders of magnitude. This implies that the triphosphonates inhibit virus replication directly, rather than by a two-step mechanism based on their hydrolysis to the monophosphonates and subsequent intracellular diphosphorylation. Being totally independent of the enzymatic phosphorylation pathways of the host cell, the compounds under study may also be able to inhibit retrovirus reproduction both in kinase deficient cell lines and in the intercellular blood media.

  一系列新的核苷5'-三磷酸盐类似物2、3、5、6、8-10在糖基和所有三个磷酸盐残基处进行了修饰，已被合成并研究。这些化合物仅具有α和β磷原子之间的酶促不稳定的酐键。涉及的制备化学包括制备膦酸盐30、31和32以及将这些物种与吗啉代33耦合。讨论了形成一些中间体形成27和28的机制。所有目标化合物在人体血清中表现出高稳定性，水解半衰期长达4.5天。一些这些核苷三磷酸盐已被证明是对逆转录病毒逆转录酶和终端脱氧核苷酸转移酶催化的DNA合成的选择性抑制剂。它们抑制了感染细胞培养中包含Moloney鼠白血病病毒逆转录酶的人工病毒的复制，这可能是由于基因组RNA的逆转录步骤被抑制。与三磷酸盐相比，相应的单磷酸盐的抗病毒活性降低了1-2个数量级。这意味着三磷酸盐直接抑制病毒复制，而不是通过先水解为单磷酸盐然后细胞内二磷酸化的两步机制。由于完全独立于宿主细胞的酶促磷酸化途径，所研究的化合物也可能在缺乏激酶的细胞系和细胞间血液介质中抑制逆转录病毒的繁殖。
• Preparation of carbocyclic phosphonate nucleosides
  作者：Gerhard Jähne、Armin Müller、Herbert Kroha、Manfred Rösner、Otto Holzhäuser、Christoph Meichsner、Matthias Helsberg、Irvin Winkler、Günther Rieß

  DOI：10.1016/s0040-4039(00)79086-1

  日期：1992.9

  A versatile and high-yielding synthesis of racemic carbocyclic phosphonate nucleosides of adenine, hypoxanthine, guanine, cytosine, uracil, and thymine has been developed. These newly prepared compounds are isosteric (and isoelectronic) with (carbo)cyclic 2,3-dideoxy- and 2,3-dideoxy-2',3'-didehydronucleoside monophosphates.
• Modified triphosphates of carbocyclic nucleoside analogues: Synthesis, stability towards alkaline phosphatase and substrate properties for some DNA polymerases
  作者：Natalya Dyatkina、Elena Shirokova、Fritz Theil、Stanley M. Roberts、Alexander Krayevsky

  DOI：10.1016/s0960-894x(96)00482-9

  日期：1996.11

  New triphosphate derivatives of carbocyclic nucleoside analogues have been synthesized and shown to be potent substrates for terminal deoxynucleotidyltransferase and/or HIV reverse transcriptase; the compounds are stable to dephosphorylation with human placental alkaline phosphatase. Copyright (C) 1996 Elsevier Science Ltd
• Shirokova, Elena A.; Dyatkina, Natalia B., Collection of Czechoslovak Chemical Communications, 1996, vol. 61, p. S158 - S160
  作者：Shirokova, Elena A.、Dyatkina, Natalia B.

  DOI：——

  日期：——