2,4-dichloro-7-β-D-ribofuranosyl-5H-pyrrolo[3,2-d]pyrimidine

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2,4-dichloro-7-β-D-ribofuranosyl-5H-pyrrolo[3,2-d]pyrimidine
• 英文别名: (2S,3R,4S,5R)-2-(2,4-dichloro-5H-pyrrolo[3,2-d]pyrimidin-7-yl)-5-(hydroxymethyl)oxolane-3,4-diol
• 化学式: C₁₁H₁₁Cl₂N₃O₄
• 分子量: 320.132
• InChiKey: ADJZZTSZRVRUDY-GXTPVXIHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  112
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  1-乙酰基-三-苄氧基-罗伯糖 在 palladium dihydroxide 亚硝酸特丁酯 、 苄基三乙基氯化铵 、 sodium methylate 、 三氯化锑 、 四氯化锡 、 N,N-二甲基苯胺 、 环己烯 、 三氯氧磷 作用下， 以 甲醇 、 硝基甲烷 、 乙醇 、 1,2-二氯乙烷 、 乙腈 为溶剂， 反应 11.5h， 生成 2,4-dichloro-7-β-D-ribofuranosyl-5H-pyrrolo[3,2-d]pyrimidine
  参考文献：
  名称：

  Synthesis and Biological Evaluation of 2- and 7-Substituted 9-Deazaadenosine Analogues

  摘要：

  A series of 2-halogen and 7-alkyl substituted analogues of 9-deazaadenosine and 2'-deoxy-9-deazaadenosine was synthesized by new efficient methodology involving transformation of corresponding 9-deazaguanosine and 2'-deoxyguanosine, which in turn were synthesized by direct C-gocosylation of 1-benzyl-9-deazaguanine with 1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose and methyl 2-deoxy-3,5-di-O-(p-toluoyl)-D-ribofuranoside, respectively. Deoxychlorination of C6 and diazotization/chloro- or fluoro-dediazoniation of the sugar-protected 9-deazaguanosine, followed by selective ammonolysis at C6 and deprotection of the sugar moiety, gave 2-chloro- and 2-fluoro-9-deazaadenosine (6 and 9). Substitution of the 7-position of the dihalogen-intermediate with alkyl groups, followed by ammonolysis and deprotection, provided 2-chloro-7-alkyl-9-deazaadenosines (13a-e) and 2-fluoro-7-benzyl-9-deazaadenosine (13f). Catalytic hydrogenation of 13a-e gave 7-alkyl-9-deazaadenosines 14a-e. Similarly, 2-chloro-2'-deoxy-9-deazaadenosine (21), 2-chloro-2'-deoxy-7-methyl-9-deazaadenosine (25), 2'-deoxy-9-deazaadenosine (22), and 2'-deoxy-7-methyl-9-deazaadenosine (26) were Prepared from sugar-protected 2'-deoxy-9-deazaguanosine. Among these compounds, 7-benzyl-9-deazaadenosine (14b) showed the most potent cytotoxic activity, with IC50 values of 0.07, 0.1, 0.2 and 1.5 muM, while both 7-methyl-9-deazaadenosine (14a) and 2-fluoro-9-deazaadenosine (9) also demonstrated significant cytotoxic activity with IC50 values of 0.4, 0.7, 0.3, and 1.5 muM, and 1.5, 0.9, 0.3, and 5 muM against L 12 10 leukemia, P388 leukemia, CCRF-CEM lymphoblastic leukemia, and B16F10 melanoma cells, respectively.

  DOI：

  10.1081/ncn-200046784

文献信息

• Synthesis and Biological Evaluation of 2- and 7-Substituted 9-Deazaadenosine Analogues
  作者：Mao-Chin Liu、Mei-Zhen Luo、Diane Mozdziesz、Alan Sartorelli

  DOI：10.1081/ncn-200046784

  日期：2005.1.1

  A series of 2-halogen and 7-alkyl substituted analogues of 9-deazaadenosine and 2'-deoxy-9-deazaadenosine was synthesized by new efficient methodology involving transformation of corresponding 9-deazaguanosine and 2'-deoxyguanosine, which in turn were synthesized by direct C-gocosylation of 1-benzyl-9-deazaguanine with 1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose and methyl 2-deoxy-3,5-di-O-(p-toluoyl)-D-ribofuranoside, respectively. Deoxychlorination of C6 and diazotization/chloro- or fluoro-dediazoniation of the sugar-protected 9-deazaguanosine, followed by selective ammonolysis at C6 and deprotection of the sugar moiety, gave 2-chloro- and 2-fluoro-9-deazaadenosine (6 and 9). Substitution of the 7-position of the dihalogen-intermediate with alkyl groups, followed by ammonolysis and deprotection, provided 2-chloro-7-alkyl-9-deazaadenosines (13a-e) and 2-fluoro-7-benzyl-9-deazaadenosine (13f). Catalytic hydrogenation of 13a-e gave 7-alkyl-9-deazaadenosines 14a-e. Similarly, 2-chloro-2'-deoxy-9-deazaadenosine (21), 2-chloro-2'-deoxy-7-methyl-9-deazaadenosine (25), 2'-deoxy-9-deazaadenosine (22), and 2'-deoxy-7-methyl-9-deazaadenosine (26) were Prepared from sugar-protected 2'-deoxy-9-deazaguanosine. Among these compounds, 7-benzyl-9-deazaadenosine (14b) showed the most potent cytotoxic activity, with IC50 values of 0.07, 0.1, 0.2 and 1.5 muM, while both 7-methyl-9-deazaadenosine (14a) and 2-fluoro-9-deazaadenosine (9) also demonstrated significant cytotoxic activity with IC50 values of 0.4, 0.7, 0.3, and 1.5 muM, and 1.5, 0.9, 0.3, and 5 muM against L 12 10 leukemia, P388 leukemia, CCRF-CEM lymphoblastic leukemia, and B16F10 melanoma cells, respectively.