2-amino-7-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-5H-pyrrolo<3,2-d>pyrimidin-4(3H)-one | 864155-80-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-amino-7-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-5H-pyrrolo<3,2-d>pyrimidin-4(3H)-one
• 英文别名: 2-amino-7-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-5H-pyrrolo[3,2-d]pyrimidin-4(3H)-one；[(2R,3R,4S,5S)-5-(2-amino-4-oxo-3,5-dihydropyrrolo[3,2-d]pyrimidin-7-yl)-3,4-dibenzoyloxyoxolan-2-yl]methyl benzoate
• CAS: 864155-80-6
• 化学式: C₃₂H₂₆N₄O₈
• 分子量: 594.58
• InChiKey: NNNPTEVDRPDFMT-CYRJMILMSA-N

物化性质

• 沸点：
  796.5±70.0 °C(Predicted)
• 密度：
  1.48±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  44
• 可旋转键数：
  11
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  171
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2-amino-7-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-5H-pyrrolo<3,2-d>pyrimidin-4(3H)-one 在 高氯酸 、 sodium methylate 作用下， 以 甲醇 、 丙酮 为溶剂， 反应 0.5h， 生成 2-amino-7-(2,3-O-isopropylidene-β-D-ribofuranosyl)pyrrolo<3,2-d>pyrimidin-4(3H)-one
  参考文献：
  名称：

  Direct C-glycosylation of guanine analogs: the synthesis and antiviral activity of certain 7- and 9-deazaguanine C-nucleosides

  摘要：

  C-Glycosylation of two guanine analogues, 9-deaza- and 7-deazaguanine, has been achieved under Friedel-Crafts conditions, providing a direct synthetic route to 9-deazaguanosine (4; 2-amino-7-beta-D-ribofuranosyl-5H-pyrrolo[3,2-d]pyrimidin-4(3H)-one) and 8-beta-D-ribofuranosyl-7-deazaguanine (16), respectively. This electrophilic C-glycosylation was applied successfully to six guanine and substituted-guanine analogues resulting in yields of approximately 50%. This represents the first reported C-ribosylation of preformed nitrogen heterocycles isosteric with guanine. These C-nucleosides were evaluated for their ability to provide protection against a lethal Semliki Forest virus infection in mice, relative to 7-thia-8-oxoguanosine which was used as a positive control. Two of the C-nucleosides, 2-amino-6-chloro-5-methyl-7-beta-D-ribofuranosyl-5H-pyrrolo [3,2-d]pyrimidin-4(3H)-one (12) and the corresponding 6-bromo derivative (13), showed good prophylactic activity in this virus model system.

  DOI：

  10.1021/jm00172a011
• 作为产物：
  描述：

  1-乙酰基-三-苄氧基-罗伯糖 在 palladium dihydroxide 四氯化锡 、 环己烯 作用下， 以 硝基甲烷 、 乙醇 为溶剂， 反应 3.0h， 生成 2-amino-7-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-5H-pyrrolo<3,2-d>pyrimidin-4(3H)-one
  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',3'-Didehydro-2',3'-Dideoxy-9-Deazaguanosine, a Monophosphate Prodrug and Two Analogues, 2',3'-Dideoxy-9-Deazaguanosine and 2',3'-Didehydro-2',3'-Dideoxy-9-Deazainosine
  作者：Mao-Chin Liu、Mei-Zhen Luo、Diane Mozdziesz、Ginger Dutschman、Elizabeth Gullen、Yung-Chi Cheng、Alan Sartorelli

  DOI：10.1081/ncn-200051898

  日期：2005.2.1

  2',3'-Didehydro-2',3'-dideoxy-9-deazaguanosine (1), its monaphosphate prodrug (2), and two analogues, 2',3'-dideoxy-9-deazaguanosine (3) and 2',3'-didehydro-2',3'-dideoxy-9-deazainosine (4), have been synthesized from benzoylated 9-deazaguanosine (5). Basic hydrolysis of 5, selective protection of the 2-amino and 5'-hydroxy functions with isobulyryl and silyl groups, respectively, followed by reaction with thiocarbonyldiimidazole gave the cyclic thiocarbonate, which, upon reaction with triethyl phosphite, followed 4 deprotection, afforded 1. Treatment of 1 with phenyl methoxyalaninyl phosphochloridate and N-methylimidazole gave 2. Catalytic hydrogenation of 1 gave 3. Hydrodediazoniation of 1 with tert-butyl nitrite and tris(trimethylsilyl)silane gave 4. Compounds 1-4 were found to be inactive against the human immunodeficiency virus and exhibited minimal to no cytotoxic activity against the L1210 leukemia, CCRF-CEM lymphoblastic leukemia, and B16F10 melanoma in vitro.