(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

文献信息

• A Conformationally Locked Analogue of the Anti-HIV Agent Stavudine. An Important Correlation between Pseudorotation and Maximum Amplitude
  作者：Yongseok Choi、Clifford George、Maria J. Comin、Joseph J. Barchi,、Hak Sung Kim、Kenneth A. Jacobson、Jan Balzarini、Hiroaki Mitsuya、Paul L. Boyer、Stephen H. Hughes、Victor E. Marquez

  DOI：10.1021/jm030116g

  日期：2003.7.1

  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.