(1S,4R,5S)-1-(6-aminopurine-9-yl)-2-fluoro-4,5-(O-isopropylidenedioxy)-3-(trityloxymethyl)-2-cyclopentene | 805245-44-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: (1S,4R,5S)-1-(6-aminopurine-9-yl)-2-fluoro-4,5-(O-isopropylidenedioxy)-3-(trityloxymethyl)-2-cyclopentene
• 英文别名: 9-((3As,4s,6ar)-5-fluoro-2,2-dimethyl-6-(trityloxymethyl)-4,6a-dihydro-3ah-cyclopenta[d][1,3]dioxol-4-yl)-9h-purin-6-amine；9-[(3aR,6S,6aS)-5-fluoro-2,2-dimethyl-4-(trityloxymethyl)-6,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-6-yl]purin-6-amine
• CAS: 805245-44-7
• 化学式: C₃₃H₃₀FN₅O₃
• 分子量: 563.631
• InChiKey: PNAHJAOPXHNQPV-NLDZOOGBSA-N

物化性质

• 沸点：
  714.8±70.0 °C(Predicted)
• 密度：
  1.35±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  42
• 可旋转键数：
  7
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  97.3
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (1S,4R,5S)-1-(6-aminopurine-9-yl)-2-fluoro-4,5-(O-isopropylidenedioxy)-3-(trityloxymethyl)-2-cyclopentene 在 盐酸 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 15.0h， 以88%的产率得到(1S,2R,5S)-5-(6-amino-9H-purin-9-yl)-4-fluoro-3-(hydroxymethyl)cyclopent-3-ene-1,2-diol
  参考文献：
  名称：

  Structure–Activity Relationships of Neplanocin A Analogues as S-Adenosylhomocysteine Hydrolase Inhibitors and Their Antiviral and Antitumor Activities

  摘要：

  On the basis of the potent inhibitory activity of neplanocin A (1) against S-adenosylhomocysteine (AdoHcy) hydrolase, we analyzed the comprehensive structure-activity relationships by modifying the adenine and carbasugar moiety of 1 to find the pharmacophore in the active site of the enzyme. The introduction of 7-deazaadenine instead of adenine eliminated the inhibitory activity against the AdoHcy hydrolase, while 3-deazaadenine maintained the inhibitory activity of the enzyme, indicating that N-7 is essential for its role as a hydrogen bonding acceptor. The substitution of hydrogen at the 6'-position with fluorine increased the inhibitory activity Of the enzyme. The one-carbon homologation at the 5'-position generally decreased the inhibitory activity of the enzyme, indicating that steric repulsion exists. A molecular docking study also supported these experimental data. In this study, 6'-fluoroneplanocin A (2) was the most potent inhibitor of AdoHcy hydrolase (IC50 = 0.24 mu M). It showed a potent anti-VSV activity (EC50 = 0.43 mu M) and potent anticancer activity in all the human tumor cell lines tested.

  DOI：

  10.1021/acs.jmedchem.5b00553
• 作为产物：
  描述：

  tert-butyl(((3aR,4R,6aR)-5-iodo-2,2-dimethyl-6-((trityloxy)methyl)-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)oxy)diphenylsilane 在 正丁基锂 、 18-冠醚-6 、 四丁基氟化铵 、 potassium carbonate 、 N-氟代双苯磺酰胺 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.5h， 生成 (1S,4R,5S)-1-(6-aminopurine-9-yl)-2-fluoro-4,5-(O-isopropylidenedioxy)-3-(trityloxymethyl)-2-cyclopentene
  参考文献：
  名称：

  Synthesis of 5′-substituted fluoro-neplanocin A analogues: importance of a hydrogen bonding donor at 5′-position for the inhibitory activity of S-adenosylhomocysteine hydrolase

  摘要：

  Four 5'-substituted fluoro-neplanocin A analogues 1a-d were designed and synthesized, using cyclopentenone derivative 2 as a key intermediate. The inhibitory activity against SAH was in the following order: NH2 > SH > F, N-3, indicating a hydrogen bonding donor such as OH or NH2 was essential for inhibitory activity. All the final compounds showed much less decreased cytotoxicity in two cancer cell lines (Col2 and A549), implying that phosphorylation of the 5'-hydroxyl group of fluoro-neplanocin A is closely related to its high cytotoxicity. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.08.047

文献信息

• STRUCTURE-ACTIVITY RELATIONSHIP OF 5′-SUBSTITUTED FLUORO-NEPLANOCIN A ANALOGUES AS POTENT INHIBITORS OF <i>S</i>-ADENOSYLHOMOCYSTEINE HYDROLASE
  作者：Hyung Ryong Moon、Kang Man Lee、Hyun Joo Lee、Sang Kook Lee、Seung Bin Park、Moon Woo Chun、Lak Shin Jeong

  DOI：10.1081/ncn-200060286

  日期：2005.4.1

  Four 5-substitutedfluoro-neplanocin A analogues 1a-d were designed and synthesized, and the inhibitory activity against SAH was in the following order: NH2 > SH > F, N-3, indicating a hydrogen bonding donor is essential for inhibitory activity.