diethyl {(1'SR,4'RS)-1'-[[(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)]-3'-methyl-2'-oxa-3'-aza-cyclopent-4'-yl]}methylphosphonate

• 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: diethyl {(1'SR,4'RS)-1'-[[(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)]-3'-methyl-2'-oxa-3'-aza-cyclopent-4'-yl]}methylphosphonate
• 英文别名: 1-[(3S,5R)-3-(diethoxyphosphorylmethyl)-2-methyl-isoxazolidin-5-yl]-5-methyl-pyrimidine-2,4-dione；1-[(3S,5R)-3-(diethoxyphosphorylmethyl)-2-methyl-1,2-oxazolidin-5-yl]-5-methylpyrimidine-2,4-dione
• 化学式: C₁₄H₂₄N₃O₆P
• 分子量: 361.335
• InChiKey: MVAZAYVUDUJZAB-NWDGAFQWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  97.4
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  diethyl 2-[methyl(oxido)imino]ethylphosphonate 在 牛血清白蛋白 作用下， 以 乙腈 为溶剂， 反应 30.25h， 生成 diethyl {(1'SR,4'RS)-1'-[[(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)]-3'-methyl-2'-oxa-3'-aza-cyclopent-4'-yl]}methylphosphonate
  参考文献：
  名称：

  Synthesis of Phosphonated Carbocyclic 2‘-Oxa-3‘-aza-nucleosides:  Novel Inhibitors of Reverse Transcriptase

  摘要：

  Phosphonated carbocyclic 2'-oxa-3'-aza-nucleosides have been synthesized in good yields by 1,3-dipolar cycloaddition methodology. The cytotoxicity and the reverse transcriptase inhibitory activity of the obtained compounds have been investigated. Phosphonated carbocyclic 2'-oxa-3'-aza-nucleosides, while showing low levels of cytotoxicity, exert a specific inhibitor activity on two different reverse transcriptases, which is comparable with that of AZT, opening new perspectives on their possible use as therapeutic agents, in anti-retroviral and anti-HBV chemotherapy.

  DOI：

  10.1021/jm049399i

文献信息

• Enantiomerically Pure Phosphonated Carbocyclic 2'-Oxa-3'-Azanucleosides: Synthesis and Biological Evaluation
  作者：Roberto Romeo、Caterina Carnovale、Salvatore Giofrè、Giulia Monciino、Maria Chiacchio、Claudia Sanfilippo、Beatrice Macchi

  DOI：10.3390/molecules190914406

  日期：——

  Starting from enantiomeric pure 1-[(3S,5R)- and 1-[(3R,5S)-3-(hydroxymethyl)-2-methylisoxazolidin-5-yl]-5-methylpyrimidine-2,4(1H,3H)-diones (−)7a and (+)7b, obtained by lipase-catalyzed resolution, pure diethyl[(3S,5R)-2-methyl-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)isoxazolidin-3-yl]methyl}phosphonate (−)12a and diethyl[(3R,5S)-2-methyl-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)isoxazolidin-3-yl]methyl}phosphonate (+)12b have been synthesized. The obtained compounds showed no cytotoxic activity versus the U937 cell line in comparison with AZT, and were poorly able to inhibit HIV infection in vitro.

  从脂肪酶催化分解得到的对映体纯品1-[(3S,5R)-和1-[(3R,5S)-3-(羟甲基)-2-甲基异恶唑烷-5-基]-5-甲基嘧啶-2,4(1H,3H)-二酮(-)7a和(+)7b开始，纯品二乙基[(3S,5R)-2-甲基-5-(5-甲基-2、(3R,5S)-2-甲基-5-(5-甲基-2,4-二氧代-3,4-二氢嘧啶-1(2H)-基)异恶唑烷-3-基]甲基}膦酸二乙酯 (-)12a 和二乙基[(3R,5S)-2-甲基-5-(5-甲基-2,4-二氧代-3,4-二氢嘧啶-1(2H)-基)异恶唑烷-3-基]甲基}膦酸二乙酯 (+)12b 合成。与 AZT 相比，所获得的化合物对 U937 细胞系没有细胞毒性活性，对体外 HIV 感染的抑制能力也很差。
• Phosphonated Carbocyclic 2‘-Oxa-3‘-azanucleosides as New Antiretroviral Agents
  作者：Ugo Chiacchio、Antonio Rescifina、Daniela Iannazzo、Anna Piperno、Roberto Romeo、Luisa Borrello、Maria Teresa Sciortino、Emanuela Balestrieri、Beatrice Macchi、Antonio Mastino、Giovanni Romeo

  DOI：10.1021/jm070285r

  日期：2007.7.1

  Phosphonated carbocyclic 2'-oxa-3'-azanucleosides have been synthesized and tested for their antiretroviral activity. The obtained results have shown that some of the compounds were as powerful as azydothymidine in inhibiting the reverse transcriptase activity of the human retrovirus T-cell leukemia/lymphotropic virus type 1 and in protecting human peripheral blood mononuclear cells against human retrovirus T-cell leukemia/lymphotropic virus type 1 transmission in vitro. These data indicate that phosphonated carbocyclic 2'-oxa-3'-azanucleosides possess the necessary requirements to efficiently counteract infections caused by human retroviruses.
• Synthesis of Phosphonated Carbocyclic 2‘-Oxa-3‘-aza-nucleosides:  Novel Inhibitors of Reverse Transcriptase
  作者：Ugo Chiacchio、Emanuela Balestrieri、Beatrice Macchi、Daniela Iannazzo、Anna Piperno、Antonio Rescifina、Roberto Romeo、Monica Saglimbeni、M. Teresa Sciortino、Vincenza Valveri、Antonio Mastino、Giovanni Romeo

  DOI：10.1021/jm049399i

  日期：2005.3.1

  Phosphonated carbocyclic 2'-oxa-3'-aza-nucleosides have been synthesized in good yields by 1,3-dipolar cycloaddition methodology. The cytotoxicity and the reverse transcriptase inhibitory activity of the obtained compounds have been investigated. Phosphonated carbocyclic 2'-oxa-3'-aza-nucleosides, while showing low levels of cytotoxicity, exert a specific inhibitor activity on two different reverse transcriptases, which is comparable with that of AZT, opening new perspectives on their possible use as therapeutic agents, in anti-retroviral and anti-HBV chemotherapy.