2-amino-6-chloro-9-(3,5-di-O-benzoyl-2-deoxy-2-fluoro-α-D-arabinofuranosyl)-9H-purine | 118373-60-7

• 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: 2-amino-6-chloro-9-(3,5-di-O-benzoyl-2-deoxy-2-fluoro-α-D-arabinofuranosyl)-9H-purine
• 英文别名: 2-amino-6-chloro-9-(2-deoxy-3,5-di-O-benzoyl-2-fluoro-α-D-arabinofuranosyl)purine
• CAS: 118373-60-7
• 化学式: C₂₄H₁₉ClFN₅O₅
• 分子量: 511.897
• InChiKey: NBBXMRVTXICTEV-AWQBJMPUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.38
• 重原子数：
  36.0
• 可旋转键数：
  6.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  131.45
• 氢给体数：
  1.0
• 氢受体数：
  10.0

反应信息

• 作为产物：
  描述：

  (6-chloro-9-trimethylsilanyl-9H-purin-2-yl)-trimethylsilanyl-amine 在 四丁基氟化铵 、 氰化汞 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 10.15h， 生成 2-amino-6-chloro-9-(3,5-di-O-benzoyl-2-deoxy-2-fluoro-α-D-arabinofuranosyl)-9H-purine
  参考文献：
  名称：

  Fluorocarbocyclic nucleosides: synthesis and antiviral activity of 2'- and 6'-fluorocarbocyclic 2'-deoxyguanosines

  摘要：

  A series of four isomeric 2'- and 6'-fluorocarbocyclic guanosine analogues have been prepared and evaluated as potential anti-herpes agents. The racemic 2'-beta-fluoro isomer 2-amino-1,9-dihydro-9-[(1-alpha, 2-alpha, 3-beta, 4-alpha)-2-fluoro-3-hydroxy-4-(hydroxymethyl)cyclopenty]-6H-purin-6-one (11a, C-AFG) and its 2'-alpha-fluoro epimer 11b plus the chiral 6'-beta-fluoro isomer 2-amino-1,9-dihydro-9-[[1S-(1-alpha, 2-alpha, 3-alpha, 4-beta)]-2-fluoro-4-hydroxy-3-(hydroxymethyl)cyclopentyl]-6H-purin-6-one (11c) and its 6'-alpha-fluoro epimer 11d were prepared from their respective fluoro amino diol hydrochlorides (6a,d). For comparison, the furanosyl compound 9-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)guanine (17, AFG) was prepared by coupling 2-amino-6-chloropurine with 2-deoxy-2-fluoro-3,5-di-O-benzoyl-alpha-D-arabinofuranosyl bromide followed by base hydrolysis. The 6'-alpha-fluoro derivative 11d exhibited comparable activity to that of acyclovir (ACV) against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in vitro but was > 30-fold more active than ACV against HSV-1 and HSV-2 in vivo in the mouse systemic model. The 2'-beta-fluoro derivative (11a, C-AFG) was extremely potent in vitro against HSV-1 and HSV-2 (ID50 0.006 and 0.05-mu-g/mL) and in vivo it was greater than 2 orders of magnitude more potent than ACV against HSV-1 and 70-fold more potent against HSV-2. The 2'-alpha-fluoro 11b and 6'-beta-fluoro 11c isomers were much less active.

  DOI：

  10.1021/jm00107a006

文献信息

• Syntheses of 2′-deoxy-2′-fluoro-β-d-arabinofuranosyl purine nucleosides via selective glycosylation reactions of potassium salts of purine derivatives with the glycosyl bromide
  作者：Grigorii G. Sivets

  DOI：10.1016/j.tetlet.2015.11.091

  日期：2016.1

  Syntheses of 9-(2-deoxy-2-fluoro-β-d-arabinofuranosyl)-guanine (1) and -adenine (2) were accomplished from readily available 1,3,5-tri-O-benzoyl-2-deoxy-2-fluoro-α-d-arabinofuranose (3). A new and efficient approach for the synthesis of 1-α-bromide was developed using the mild bromination of α-1-O-benzoate (3). Selective coupling reactions of the bromosugar with purine potassium salts followed by derivatization/and

  9-（2-脱氧-2-氟-β - d-阿拉伯呋喃糖基）-鸟嘌呤（1）和-腺嘌呤（2）的合成是由容易获得的1,3,5-三-O-苯甲酰基-2-脱氧完成的-2-氟-α - d-阿拉伯呋喃糖（3）。利用α-1- O-苯甲酸酯的轻度溴化作用，开发了一种新的高效合成1-α-溴化物的方法（3）。溴糖与嘌呤钾盐的选择性偶联反应，然后对中间体封闭的2'-氟β-阿拉伯糖核苷进行衍生化和/或去保护，导致形成具有高总收率的目标化合物。
• Chemistry and Anti-HIV Activity of 2′-β-Fluoro-2′,3′-dideoxyguanosine
  作者：Harry Ford、John S. Driscoll、Maqbool Siddiqui、James A. Kelley、Hioraki Mitsuya、Takuma Shirasaka、David G. Johns、Victor E. Marquez

  DOI：10.1080/15257779408013236

  日期：1994.3

  The 2'-beta-fluoro analogue of 2',3'-dideoxyguanosine has been prepared by two synthetic routes. This compound and two analogues have anti-HIV activity in at least two of three host cell systems used (ATH8, CEM, PEL). These compounds, as well as their ddGuo parents, have been characterized with regard to their acid-stabilities, octanol-water partition coefficients, and enzyme substrate properties for adenosine deaminase and purine nucleoside phosphorylase. F-ddGuo analogues are less potent but more stable than their non-fluorinated parent compounds.