2-amino-9-(3,5-di-O-benzoyl-2-deoxy-β-D-erythro-pentofuranosyl)-6-O-(4-methylbenzenesulfonyl)purine | 500225-57-0

• 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-9-(3,5-di-O-benzoyl-2-deoxy-β-D-erythro-pentofuranosyl)-6-O-(4-methylbenzenesulfonyl)purine
• 英文别名: [(2R,3S,5R)-5-[2-amino-6-(4-methylphenyl)sulfonyloxypurin-9-yl]-3-benzoyloxyoxolan-2-yl]methyl benzoate
• CAS: 500225-57-0
• 化学式: C₃₁H₂₇N₅O₈S
• 分子量: 629.65
• InChiKey: VXDFYVBKEONVIA-ISJGIBHGSA-N

物化性质

• 沸点：
  860.0±75.0 °C(Predicted)
• 密度：
  1.49±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  45
• 可旋转键数：
  11
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  183
• 氢给体数：
  1
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  2-amino-9-(3,5-di-O-benzoyl-2-deoxy-β-D-erythro-pentofuranosyl)-6-O-(4-methylbenzenesulfonyl)purine 在 亚硝酸苄基三乙基铵 、 氨 、 乙酰氯 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 7.08h， 生成 克拉屈滨
  参考文献：
  名称：

  Efficient Syntheses of 2-Chloro-2‘-deoxyadenosine (Cladribine) from 2‘-Deoxyguanosine¹

  摘要：

  We report efficient syntheses of the clinical agent cladribine (2-chloro-2'-deoxyadenosine, CldAdo), which is the drug of choice against hairy-cell leukemia and other neoplasms, from 2'-deoxyguanosine. Treatment of 3',5'-di-O-acetyl- or benzoyl-2'-deoxyguanosine (1) with 2,4,6-triisopropyl- or 4-methylbenzenesulfonyl chloride gave high yields of the 6-O-arylsulfonyl derivatives 2 or 2%. Deoxychlorination at C6 of 1 also proceeded to give the 2-amino-6-chloropurine derivative 5 in excellent yields. The nonaqueous diazotization/chloro dediazoniation (acetyl chloride/benzyltriethylammonium nitrite) of 2, 2%, and 5 gave the 2-chloropurine derivatives 3, 3'b, and 6, respectively. The selective ammonolysis at C6 (arylsulfonate with 3 or chloride with 6) and accompanying deprotection of the sugar moiety gave CldAdo (64-75% overall yield from 1).

  DOI：

  10.1021/jo020644k
• 作为产物：
  描述：

  3',5'-di-O-benzoyl-2'-deoxyguanosine 、 对甲苯磺酰氯 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 氯仿 为溶剂， 反应 15.0h， 以89%的产率得到2-amino-9-(3,5-di-O-benzoyl-2-deoxy-β-D-erythro-pentofuranosyl)-6-O-(4-methylbenzenesulfonyl)purine
  参考文献：
  名称：

  Efficient Syntheses of 2-Chloro-2‘-deoxyadenosine (Cladribine) from 2‘-Deoxyguanosine¹

  摘要：

  We report efficient syntheses of the clinical agent cladribine (2-chloro-2'-deoxyadenosine, CldAdo), which is the drug of choice against hairy-cell leukemia and other neoplasms, from 2'-deoxyguanosine. Treatment of 3',5'-di-O-acetyl- or benzoyl-2'-deoxyguanosine (1) with 2,4,6-triisopropyl- or 4-methylbenzenesulfonyl chloride gave high yields of the 6-O-arylsulfonyl derivatives 2 or 2%. Deoxychlorination at C6 of 1 also proceeded to give the 2-amino-6-chloropurine derivative 5 in excellent yields. The nonaqueous diazotization/chloro dediazoniation (acetyl chloride/benzyltriethylammonium nitrite) of 2, 2%, and 5 gave the 2-chloropurine derivatives 3, 3'b, and 6, respectively. The selective ammonolysis at C6 (arylsulfonate with 3 or chloride with 6) and accompanying deprotection of the sugar moiety gave CldAdo (64-75% overall yield from 1).

  DOI：

  10.1021/jo020644k

文献信息

• Efficient Syntheses of 2-Chloro-2‘-deoxyadenosine (Cladribine) from 2‘-Deoxyguanosine¹
  作者：Zlatko Janeba、Paula Francom、Morris J. Robins

  DOI：10.1021/jo020644k

  日期：2003.2.1

  We report efficient syntheses of the clinical agent cladribine (2-chloro-2'-deoxyadenosine, CldAdo), which is the drug of choice against hairy-cell leukemia and other neoplasms, from 2'-deoxyguanosine. Treatment of 3',5'-di-O-acetyl- or benzoyl-2'-deoxyguanosine (1) with 2,4,6-triisopropyl- or 4-methylbenzenesulfonyl chloride gave high yields of the 6-O-arylsulfonyl derivatives 2 or 2%. Deoxychlorination at C6 of 1 also proceeded to give the 2-amino-6-chloropurine derivative 5 in excellent yields. The nonaqueous diazotization/chloro dediazoniation (acetyl chloride/benzyltriethylammonium nitrite) of 2, 2%, and 5 gave the 2-chloropurine derivatives 3, 3'b, and 6, respectively. The selective ammonolysis at C6 (arylsulfonate with 3 or chloride with 6) and accompanying deprotection of the sugar moiety gave CldAdo (64-75% overall yield from 1).