(1'S,2'S,5'R)-tert-butyl{[4-(5-methyl-2,4-dioxo-1,3-dihydropyrimidinyl)bicyclo[3.1.0]hex-3-en-2-enyl]methyl}phosphate | 577991-21-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机磷酸及其衍生物
• 英文名称: (1'S,2'S,5'R)-tert-butyl{[4-(5-methyl-2,4-dioxo-1,3-dihydropyrimidinyl)bicyclo[3.1.0]hex-3-en-2-enyl]methyl}phosphate
• 英文别名: ditert-butyl [(1R,4S,5S)-4-(5-methyl-2,4-dioxopyrimidin-1-yl)-1-bicyclo[3.1.0]hex-2-enyl]methyl phosphate
• CAS: 577991-21-0
• 化学式: C₂₀H₃₁N₂O₆P
• 分子量: 426.45
• InChiKey: NHHSLDVDFQIRLQ-QEEYODRMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  94.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (1'S,2'S,5'R)-tert-butyl{[4-(5-methyl-2,4-dioxo-1,3-dihydropyrimidinyl)bicyclo[3.1.0]hex-3-en-2-enyl]methyl}phosphate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 (1',2'S,5'R)-5-methyl-1-{5-[(phosphoryloxy)methyl]bicyclo[3.1.0]hex-3-en-2-yl}-1,3-dihydropyrimidine-2,4-dione
  参考文献：
  名称：

  A Conformationally Locked Analogue of the Anti-HIV Agent Stavudine. An Important Correlation between Pseudorotation and Maximum Amplitude

  摘要：

  The synthesis and biological evaluation of a bicyclo[3.1.0]hexene nucleoside designed as a conformational mimic of the anti-HIV agent stavudine (1, D4T) is described. The unsaturated methanocarbocyclic pseudosugar of N-MCD4T (2) was constructed from an iodo-substituted precursor by a DBU-catalyzed olefination reaction. Mitsunobu coupling with N-3-benzoylthymine afforded the desired target after deprotection. Both D4T and N-MCD4T are in the North (N) hemisphere of the pseudorotational cycle but 70degrees away from a perfect N (P = 0degrees) conformation toward the East and West hemispheres, respectively. Despite this large difference, the double bond reduces the puckering amplitude (v(max)) of N-MCD4T to 6.81degrees, and the superposition of both structures showed a RMS deviation of only 0.039 Angstrom. The combined structural analysis of P and vmax shows that while the value of P may differ substantially, the low v(max) resolves the differences and becomes the dominant pseudorotational. parameter. N-MCD4T is active against HIV-1 and HIV-2 in CEM, MT-2, and MT-4 cells, and while it is somewhat less potent than D4T, it also appears to be less toxic. The triphosphate (N-MCD4TTP) inhibits HIV reverse transcriptase with a 10-fold higher IC50 than D4TTP. By virtue of its carbocyclic nature, N-MCD4T (2) is a more robust molecule stable to conditions that would cleave D4T.

  DOI：

  10.1021/jm030116g
• 作为产物：
  描述：

  N-3-benzoylthymine 在 四氮唑 、 ammonium hydroxide 、 四丁基氟化铵 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 5.5h， 生成 (1'S,2'S,5'R)-tert-butyl{[4-(5-methyl-2,4-dioxo-1,3-dihydropyrimidinyl)bicyclo[3.1.0]hex-3-en-2-enyl]methyl}phosphate
  参考文献：
  名称：

  A Conformationally Locked Analogue of the Anti-HIV Agent Stavudine. An Important Correlation between Pseudorotation and Maximum Amplitude

  摘要：

  The synthesis and biological evaluation of a bicyclo[3.1.0]hexene nucleoside designed as a conformational mimic of the anti-HIV agent stavudine (1, D4T) is described. The unsaturated methanocarbocyclic pseudosugar of N-MCD4T (2) was constructed from an iodo-substituted precursor by a DBU-catalyzed olefination reaction. Mitsunobu coupling with N-3-benzoylthymine afforded the desired target after deprotection. Both D4T and N-MCD4T are in the North (N) hemisphere of the pseudorotational cycle but 70degrees away from a perfect N (P = 0degrees) conformation toward the East and West hemispheres, respectively. Despite this large difference, the double bond reduces the puckering amplitude (v(max)) of N-MCD4T to 6.81degrees, and the superposition of both structures showed a RMS deviation of only 0.039 Angstrom. The combined structural analysis of P and vmax shows that while the value of P may differ substantially, the low v(max) resolves the differences and becomes the dominant pseudorotational. parameter. N-MCD4T is active against HIV-1 and HIV-2 in CEM, MT-2, and MT-4 cells, and while it is somewhat less potent than D4T, it also appears to be less toxic. The triphosphate (N-MCD4TTP) inhibits HIV reverse transcriptase with a 10-fold higher IC50 than D4TTP. By virtue of its carbocyclic nature, N-MCD4T (2) is a more robust molecule stable to conditions that would cleave D4T.

  DOI：

  10.1021/jm030116g