9-(3-O-acetyl-5-O-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-9H-purine-2,6-diamine | 103885-02-5

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 9-(3-O-acetyl-5-O-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-9H-purine-2,6-diamine
• 英文别名: [(2R,3R,4S,5R)-3-acetyloxy-5-(2,6-diaminopurin-9-yl)-4-fluorooxolan-2-yl]methyl benzoate
• CAS: 103885-02-5
• 化学式: C₁₉H₁₉FN₆O₅
• 分子量: 430.395
• InChiKey: FLUVLPDHKBHHTP-DMVWFOPNSA-N

物化性质

• 沸点：
  705.7±70.0 °C(Predicted)
• 密度：
  1.66±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.01
• 重原子数：
  31.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  157.47
• 氢给体数：
  2.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  9-(3-O-acetyl-5-O-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-9H-purine-2,6-diamine 在 sodium hydroxide 、 水 作用下， 以 甲醇 为溶剂， 反应 38.0h， 生成 9-(2-脱氧-2-氟阿拉伯呋喃基)鸟嘌呤
  参考文献：
  名称：

  9-(2-Deoxy-2-fluoro-.beta.-D-arabinofuranosyl)guanine: a metabolically stable cytotoxic analogue of 2'-deoxyguanosine

  摘要：

  The synthesis of 9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)guanine (1b) from 1,3-di-O-acetyl-5-O-benzoyl-2-deoxy-2-fluoro-D-arabinofuranose (2a) and 2,6-dichloropurine in six steps using an enzymatic deamination as the last step is reported. The target compound was found to be stable to purine nucleoside phosphorylase cleavage and was cytotoxic in two cell lines, one a T-cell line. Incubation of L1210 cells with 1b results in an inhibition of DNA synthesis as judged by the reduced incorporation of labeled thymidine into DNA, while RNA and protein syntheses were unaffected.

  DOI：

  10.1021/jm00161a041
• 作为产物：
  描述：

  2,6-二氯嘌呤 在 palladium on activated charcoal sodium azide 、 4 A molecular sieve 、 氢气 作用下， 以 乙醇 、 1,2-二氯乙烷 为溶剂， 反应 21.5h， 生成 9-(3-O-acetyl-5-O-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-9H-purine-2,6-diamine
  参考文献：
  名称：

  9-(2-Deoxy-2-fluoro-.beta.-D-arabinofuranosyl)guanine: a metabolically stable cytotoxic analogue of 2'-deoxyguanosine

  摘要：

  The synthesis of 9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)guanine (1b) from 1,3-di-O-acetyl-5-O-benzoyl-2-deoxy-2-fluoro-D-arabinofuranose (2a) and 2,6-dichloropurine in six steps using an enzymatic deamination as the last step is reported. The target compound was found to be stable to purine nucleoside phosphorylase cleavage and was cytotoxic in two cell lines, one a T-cell line. Incubation of L1210 cells with 1b results in an inhibition of DNA synthesis as judged by the reduced incorporation of labeled thymidine into DNA, while RNA and protein syntheses were unaffected.

  DOI：

  10.1021/jm00161a041

文献信息

• Synthesis and biological activity of 2'-fluoro-2-halo derivatives of 9-.beta.-D-arabinofuranosyladenine
  作者：John A. Montgomery、Anita T. Shortnacy-Fowler、Sarah D. Clayton、James M. Riordan、John A. Secrist

  DOI：10.1021/jm00080a029

  日期：1992.1

  The synthesis of 2-halo-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)adenines (4b and 4d) by coupling the 2,6-dihalopurine with 3-acetyl-5-benzoyl-2-deoxy-2-fluoro-D-arabinofuranosyl bromide (2) followed by replacement of the 6-halogen with concomitant removal of the acyl blocking groups is described. 2-Fluoroadenine derivative 4g had to be prepared by the diazotization-fluorination of 2-aminoadenine

  通过将2,6-二卤代嘌呤与3-乙酰基-5-苯甲酰基-2-脱氧偶合，合成2-卤代9-（2-脱氧-2-氟-β-D-阿拉伯呋喃糖基）ni啶（4b和4d）描述了-2-氟-D-阿拉伯呋喃糖基溴化物（2），然后取代6-卤素并同时去除了酰基保护基团。必须通过2-氨基腺嘌呤核苷4e的重氮化-氟化来制备2-氟鸟嘌呤衍生物4g。所有三种核苷均能使接种P388白血病的小鼠的寿命延长。当在白血病细胞植入后第1、5和9天每3h x 8给予化合物时，可获得最佳结果。通过4f脱乙酰基化并在4h脱氧后再去除5a的苯甲酰基制得的2'，3'-二脱氧核苷5b在细胞培养中对HIV具有轻微的活性。