(2R,3S,5R)-5-(7,8-dihydroimidazo[2,1-f]purin-3-yl)-2-(hydroxymethyl)oxolan-3-ol | 210689-69-3

• 分子结构分类: 有机化合物
• 英文名称: (2R,3S,5R)-5-(7,8-dihydroimidazo[2,1-f]purin-3-yl)-2-(hydroxymethyl)oxolan-3-ol
• CAS: 210689-69-3
• 化学式: C₁₂H₁₅N₅O₃
• 分子量: 277.283
• InChiKey: AMHOZHHZMYGEHZ-DJLDLDEBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  95.5
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2R,3S,5R)-5-(7,8-dihydroimidazo[2,1-f]purin-3-yl)-2-(hydroxymethyl)oxolan-3-ol 在 2,6-二甲基吡啶 、 lithium carbonate 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 7.5h， 生成 3-[[(2R,3S,5R)-2-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-5-(7,8-dihydroimidazo[2,1-f]purin-3-yl)oxolan-3-yl]oxy-[di(propan-2-yl)amino]phosphanyl]oxypropanenitrile
  参考文献：
  名称：

  Synthesis of 1,N⁶-Ethano-2‘-deoxyadenosine, a Metabolic Product of 1,3-Bis(2-chloroethyl)nitrosourea, and Its Incorporation into Oligomeric DNA

  摘要：

  1,N-6-Ethano-2'-deoxyadenosine (1) is one of the adducts formed during DNA reaction with the antitumor agent, 1,3-bis(2-chloroethyl)nitrosourea (BCNU), and was synthesized and incorporated into a site-specific deoxyoligonucleotide for the first time. The product 6-chloropurine-2'-deoxyriboside (11) was prepared in high yield by the reaction of 2'-deoxyinosine (6) with SOCl2, which then was derivatized to give compound 12 using tert-butyldimethylsilyl chloride, which was then reacted with 2-hydroxyethylamine to produce compound 13 in 86% yield. Reaction of 13 with (PhO)(8)P+MeI- in DMF gave the cyclized 1,N-6-ethano derivative 10 in 67% yield. Desilylation of 10 with triethylamine trihydrofluoride in THF gave 1,N-6-ethano-dA (1) in 91% yield. Tritylation of compound 1 with DMT+BF4- gave the 5'-O-DMT product 14 in 62% yield, which then was phosphitylated with 2-cyanoethyl N,N-diisopropylchlorophosphoramidite, which yielded a 1:1 mixture of the diastereoisomers 15 in 71% yield. This fully protected compound 15 was incorporated site-specifically into a 25-mer oligonucleotide. The coupling efficiency of ethano-dA phosphoramidite was 93%. Enzymatic hydrolysis and analysis by HPLC confirmed the incorporation of ethano-dA and base composition of the DNA oligomer. The latter is now under investigation for its biochemical and physical properties.

  DOI：

  10.1021/jo980170i
• 作为产物：
  描述：

  N⁶-(2-hydroxyethyl)-3',5'-bis-O-(tert-butyldimethylsilyl)-2'-deoxyadenosine 在 triethylamine trihydrofluoride 、 甲基三苯氧基碘磷 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.75h， 生成 (2R,3S,5R)-5-(7,8-dihydroimidazo[2,1-f]purin-3-yl)-2-(hydroxymethyl)oxolan-3-ol
  参考文献：
  名称：

  Synthesis of 1,N⁶-Ethano-2‘-deoxyadenosine, a Metabolic Product of 1,3-Bis(2-chloroethyl)nitrosourea, and Its Incorporation into Oligomeric DNA

  摘要：

  1,N-6-Ethano-2'-deoxyadenosine (1) is one of the adducts formed during DNA reaction with the antitumor agent, 1,3-bis(2-chloroethyl)nitrosourea (BCNU), and was synthesized and incorporated into a site-specific deoxyoligonucleotide for the first time. The product 6-chloropurine-2'-deoxyriboside (11) was prepared in high yield by the reaction of 2'-deoxyinosine (6) with SOCl2, which then was derivatized to give compound 12 using tert-butyldimethylsilyl chloride, which was then reacted with 2-hydroxyethylamine to produce compound 13 in 86% yield. Reaction of 13 with (PhO)(8)P+MeI- in DMF gave the cyclized 1,N-6-ethano derivative 10 in 67% yield. Desilylation of 10 with triethylamine trihydrofluoride in THF gave 1,N-6-ethano-dA (1) in 91% yield. Tritylation of compound 1 with DMT+BF4- gave the 5'-O-DMT product 14 in 62% yield, which then was phosphitylated with 2-cyanoethyl N,N-diisopropylchlorophosphoramidite, which yielded a 1:1 mixture of the diastereoisomers 15 in 71% yield. This fully protected compound 15 was incorporated site-specifically into a 25-mer oligonucleotide. The coupling efficiency of ethano-dA phosphoramidite was 93%. Enzymatic hydrolysis and analysis by HPLC confirmed the incorporation of ethano-dA and base composition of the DNA oligomer. The latter is now under investigation for its biochemical and physical properties.

  DOI：

  10.1021/jo980170i