1-[(3aS,4R,6R,6aR)-6-(hydroxymethyl)spiro[4,5,6,6a-tetrahydro-3aH-cyclopenta[d][1,3]dioxole-2,1'-cyclohexane]-4-yl]pyrimidin-2-one | 210699-86-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-[(3aS,4R,6R,6aR)-6-(hydroxymethyl)spiro[4,5,6,6a-tetrahydro-3aH-cyclopenta[d][1,3]dioxole-2,1'-cyclohexane]-4-yl]pyrimidin-2-one
• CAS: 210699-86-8
• 化学式: C₁₆H₂₂N₂O₄
• 分子量: 306.362
• InChiKey: GLZYQGCUNKGQRK-SYQHCUMBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  71.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-[(3aS,4R,6R,6aR)-6-(hydroxymethyl)spiro[4,5,6,6a-tetrahydro-3aH-cyclopenta[d][1,3]dioxole-2,1'-cyclohexane]-4-yl]pyrimidin-2-one 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 20.0h， 生成 zebularine
  参考文献：
  名称：

  Carbocyclic Analogues of the Potent Cytidine Deaminase Inhibitor 1-(β-d-Ribofuranosyl)-1,2-dihydropyrimidin-2-one (Zebularine)

  摘要：

  Three carbocylic analogues of the potent cytidine deaminase inhibitor (CDA) zebularine [1-(beta-D-ribofuranosyl)-1,2-dihydropyrimidin-2- one-, 1a] were synthesized. The selected pseudosugar templates correspond, respectively, to the cyclopentenyl moiety of neplanocin A (compound 4), the cyclopentyl moiety of aristeromycin (compound 5), and a newly designed, rigid bicyclo[3.1,0]hexane moiety (compound 6). These three carba-nucleoside versions of zebularine were fashioned to overcome the inherent instability of the parent drug. Each target compound was approached differently using either convergent or linear approaches. The immediate precursor to the cyclopentenyl analogue 4 was obtained by a Mitsunobu coupling of pseudosugar 7 with 2-hydroxypyrimidine. The cyclopentyl analogue 5 was linearly constructed from carbocyclic amine 17, and the final target 6 was similarly constructed from the carbobicyclic amine 27. Of the three target compounds, only 5 showed a significant level of inhibition against human CDA, but it was 16 times less potent than zebularine (K-i = 38 mu M vs K-i(apparent) = 2.3 mu M). Although these carbocyclic analogues appeared to be more stable than zebularine, replacement of the electronegative CO4' oxygen for the less electronegative carbon in 4-6 presumably reduces the capacity of the pyrimidin-2(1H)-one ring to form a covalent hydrate, a step considered crucial for the compound to function as a transition-state inhibitor of the enzyme.

  DOI：

  10.1021/jm980111x
• 作为产物：
  描述：

  [(3aS,4R,6R,6aR)-4-[2-oxo-4-[2,4,6-tri(propan-2-yl)phenyl]sulfonyloxypyrimidin-1-yl]spiro[4,5,6,6a-tetrahydro-3aH-cyclopenta[d][1,3]dioxole-2,1'-cyclohexane]-6-yl]methyl benzoate 在 水 、 sodium methylate 、 三乙胺 、 silver(l) oxide 、 肼 作用下， 以 1,4-二氧六环 、 吡啶 、 甲醇 为溶剂， 反应 25.0h， 生成 1-[(3aS,4R,6R,6aR)-6-(hydroxymethyl)spiro[4,5,6,6a-tetrahydro-3aH-cyclopenta[d][1,3]dioxole-2,1'-cyclohexane]-4-yl]pyrimidin-2-one
  参考文献：
  名称：

  Carbocyclic Analogues of the Potent Cytidine Deaminase Inhibitor 1-(β-d-Ribofuranosyl)-1,2-dihydropyrimidin-2-one (Zebularine)

  摘要：

  Three carbocylic analogues of the potent cytidine deaminase inhibitor (CDA) zebularine [1-(beta-D-ribofuranosyl)-1,2-dihydropyrimidin-2- one-, 1a] were synthesized. The selected pseudosugar templates correspond, respectively, to the cyclopentenyl moiety of neplanocin A (compound 4), the cyclopentyl moiety of aristeromycin (compound 5), and a newly designed, rigid bicyclo[3.1,0]hexane moiety (compound 6). These three carba-nucleoside versions of zebularine were fashioned to overcome the inherent instability of the parent drug. Each target compound was approached differently using either convergent or linear approaches. The immediate precursor to the cyclopentenyl analogue 4 was obtained by a Mitsunobu coupling of pseudosugar 7 with 2-hydroxypyrimidine. The cyclopentyl analogue 5 was linearly constructed from carbocyclic amine 17, and the final target 6 was similarly constructed from the carbobicyclic amine 27. Of the three target compounds, only 5 showed a significant level of inhibition against human CDA, but it was 16 times less potent than zebularine (K-i = 38 mu M vs K-i(apparent) = 2.3 mu M). Although these carbocyclic analogues appeared to be more stable than zebularine, replacement of the electronegative CO4' oxygen for the less electronegative carbon in 4-6 presumably reduces the capacity of the pyrimidin-2(1H)-one ring to form a covalent hydrate, a step considered crucial for the compound to function as a transition-state inhibitor of the enzyme.

  DOI：

  10.1021/jm980111x