((2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl)methyl phenyl phosphonate | 834918-59-1

• 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: ((2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl)methyl phenyl phosphonate
• CAS: 834918-59-1
• 化学式: C₁₆H₁₈N₅O₆P
• 分子量: 407.323
• InChiKey: FBYLFEMOCZDJHZ-BFHYXJOUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  28.0
• 可旋转键数：
  7.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  148.38
• 氢给体数：
  1.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  ((2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl)methyl phenyl phosphonate 在 吡啶 、 RPMI 1640 、 N,N-二异丙基乙胺 、 fetal bovine serum 作用下， 以 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 0.17h， 生成 3'-azido-3'-deoxythymidin-5'-yl α-hydroxy(4-chlorophenyl)methylphosphonate triethylammonium salt
  参考文献：
  名称：

  Aryl nucleoside H-phosphonates. Part 15: Synthesis, properties and, anti-HIV activity of aryl nucleoside 5′-α-hydroxyphosphonates

  摘要：

  Aryl nucleoside 5'-H-phosphonates 4 bearing AZT or 2',3'-dideoxyuridine moieties were subjected to reaction with various aromatic aldehydes to produce nucleoside 5'-alpha-hydroxyphosphonate derivatives 2 as potential anti-HIV agents. Stability of the title compounds in cell culture media was investigated and three distinct decomposition pathways were identified. The anti-HIV activity of hydroxyphosplionates 2 correlates well with the type and extent of their chemical or enzymatic degradation in Culture medium (RPMI 1640 containing 10% FBS), suggesting that aryl nucleoside 5'-hydroxyphosphonates 2 act as depot forms of the parent antiviral nucleosides. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.10.048
• 作为产物：
  描述：

  在 水 、 三乙胺 、 氯磷酸二苯酯 作用下， 以 吡啶 、 二氯甲烷 、 乙腈 为溶剂， 反应 2.0h， 生成 ((2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl)methyl phenyl phosphonate
  参考文献：
  名称：

  芳基膦酸酯。14.具有膦酸酯-磷酸核苷间键合的新核苷酸类似物的合成。

  摘要：

  [反应：见正文]分别由适当的H-膦酸酯1和酰基膦酸酯单酯2原位生成的芳基核苷H-膦酸酯3和芳基核苷P-酰基膦酸酯4在叔胺存在下迅速反应，以高收率生产扩展的焦磷酸盐类似物，二芳基二核苷膦酸酯磷酸酯衍生物6。根据膦酸酯部分的α-碳上的取代基，将其转化为二核苷膦酸酯磷酸酯7或提供核苷H-膦酸酯8和芳基核苷。磷酸盐9。

  DOI：

  10.1021/ol035166u

文献信息

• One-Pot Synthesis of Aryl Phosphoramidate Derivatives of AZT/d4T as Anti-HIV Prodrugs
  作者：Hua Fu、Peng Jiang、Xin Guo、Yuyang Jiang、Yufen Zhao

  DOI：10.1055/s-2005-917085

  日期：——

  Arbuzov reaction of aryl phosphorodichloridite with mixture of one equivalent of AZT or d4T and one equivalent of tert-butyl alcohol led to the corresponding AZT/d4T aryl H-phosphonate diesters, and the following reactionof the H-phosphonate diesters with amino acid methyl esters in the presence of N-chloro-succinimide (NCS) produced membrane-soluble anti-HIV prodrugs AZT/d4T aryl phosphoramidate derivatives

  芳基二氯化磷与一当量 AZT 或 d4T 和一当量叔丁醇的混合物的 Arbuzov 反应产生相应的 AZT/d4T 芳基 H-膦酸二酯，H-膦酸二酯与氨基酸甲酯的以下反应N-氯-琥珀酰亚胺 (NCS) 的存在以良好的产率产生了膜溶性抗 HIV 前药 AZT/d4T 芳基氨基磷酸酯衍生物。
• New and Efficient Approach to Aryl Phosphoramidate Derivatives of AZT/d4T as Anti-HIV Prodrugs
  作者：Hua Fu、Xueshu Li、Yuyang Jiang、Yufen Zhao、Jinyong Liu

  DOI：10.1055/s-2004-834800

  日期：——

  Ester exchange of diaryl phosphite with AZT or d4T produced aryl AZT/d4T H-phosphonate, and the following reaction with amino acid esters in the presence of hexachloroethane and triethylamine yielded membrane-soluble anti-HIV prodrugs aryl phosphoramide derivatives of AZT and d4T in good yields.

  二芳基磷酸酯与AZT或d4T的酯交换反应产生了芳基AZT/d4T H-磷酸酯，随后在六氯乙烷和三乙胺的存在下与氨基酸酯反应，得到膜可溶的抗HIV前药芳基磷酰胺衍生物AZT和d4T，产率良好。
• Aryl nucleoside H-phosphonates. Part 16: Synthesis and anti-HIV-1 activity of di-aryl nucleoside phosphotriesters
  作者：Joanna Romanowska、Agnieszka Szymańska-Michalak、Jerzy Boryski、Jacek Stawiński、Adam Kraszewski、Roberta Loddo、Giuseppina Sanna、Gabriella Collu、Barbara Secci、Paolo La Colla

  DOI：10.1016/j.bmc.2009.02.033

  日期：2009.5

  Di-aryl nucleoside phosphotriesters have been explored as a new type of pronucleotides for the purpose of anti-HIV-1 therapy and efficient synthetic protocols, based on H-phosphonate chemistry, have been developed for the preparation of this class of compounds. It was found that anti-HIV-1 activity of the phosphotriesters bearing an antiviral nucleoside moiety (AZT, ddA) and also ddU was due, at least partially, to intracellular conversion into the corresponding nucleoside 5'-monophosphates, and their efficiency correlated well with the pK(a) values of the aryloxy groups present. (C) 2009 Elsevier Ltd. All rights reserved.
• Xiao, Qiang; Sun, Jing; Sun, Qi, Synthesis, 2003, # 1, p. 107 - 111
  作者：Xiao, Qiang、Sun, Jing、Sun, Qi、Ju, Yong、Zhao, Yu-fen、Cui, Yu-xin

  DOI：——

  日期：——
• Novel approach to the synthesis of AZT 5′-O-hydrogen phospholipids
  作者：Qiang Xiao、Jing Sun、Yong Ju、Yu-fen Zhao、Yu-xin Cui

  DOI：10.1016/s0040-4039(02)01045-6

  日期：2002.7

  A series of AZT 5'-O-hydrogen phospholipids were synthesized by a tandem transesterification of diphenyl phosphite with AZT and a long-chain alcohol. The method possesses the merits of case of operation and high yields. It can also be extended to synthesize other biological phospholipids. (C) 2002 Elsevier Science Ltd. All rights reserved.