9-[(2R,3R,4R,5R)-5-benzyl-4-[(2R,3R,4R,5R,6R)-4,5-bis[(3-oxido-1,5-dihydro-2,4,3-benzodioxaphosphepin-3-ium-3-yl)oxy]-3-phenylmethoxy-6-(phenylmethoxymethyl)oxan-2-yl]oxy-3-[(3-oxido-1,5-dihydro-2,4,3-benzodioxaphosphepin-3-ium-3-yl)oxy]oxolan-2-yl]purin-6-amine | 885671-73-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 5'-脱氧核糖核苷
• 英文名称: 9-[(2R,3R,4R,5R)-5-benzyl-4-[(2R,3R,4R,5R,6R)-4,5-bis[(3-oxido-1,5-dihydro-2,4,3-benzodioxaphosphepin-3-ium-3-yl)oxy]-3-phenylmethoxy-6-(phenylmethoxymethyl)oxan-2-yl]oxy-3-[(3-oxido-1,5-dihydro-2,4,3-benzodioxaphosphepin-3-ium-3-yl)oxy]oxolan-2-yl]purin-6-amine
• CAS: 885671-73-8
• 化学式: C₆₀H₆₀N₅O₁₇P₃
• 分子量: 1216.08
• InChiKey: GQBSIUCAOWDKER-JOWWZRHVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  85
• 可旋转键数：
  18
• 环数：
  13.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  268
• 氢给体数：
  1
• 氢受体数：
  21

反应信息

• 作为反应物：
  描述：

  9-[(2R,3R,4R,5R)-5-benzyl-4-[(2R,3R,4R,5R,6R)-4,5-bis[(3-oxido-1,5-dihydro-2,4,3-benzodioxaphosphepin-3-ium-3-yl)oxy]-3-phenylmethoxy-6-(phenylmethoxymethyl)oxan-2-yl]oxy-3-[(3-oxido-1,5-dihydro-2,4,3-benzodioxaphosphepin-3-ium-3-yl)oxy]oxolan-2-yl]purin-6-amine 在 钯 氢气 作用下， 以 甲醇 、 氯仿 为溶剂， 20.0 ℃ 、413.68 kPa 条件下， 以99%的产率得到5'-deoxy-5'-phenyladenophostin A
  参考文献：
  名称：

  Synthesis of Adenophostin A Analogues Conjugating an Aromatic Group at the 5‘-Position as Potent IP₃ Receptor Ligands

  摘要：

  Previous structure-activity relationship studies of adenophostin A, a potent IP3 receptor agonist, led us to design the novel adenophostin A analogues 5a-c, conjugating an aromatic group at the 5'-position to develop useful IP3 receptor ligands. The common key intermediate, a D-ribosyl alpha-D-glucoside 10 alpha, was stereoselectively synthesized by a glycosidation with the 1-sulfinylglucoside donor 11, which was conformationally restricted by a 3,4-O-cyclic diketal protecting group. After introduction of an aromatic group at the 5-position of the ribose moiety, an adenine base was stereoselectively introduced at the anomeric beta-position to form 7a-c, where the tetra-O-i-butyryl donors 9a-c were significantly more effective than the corresponding O-acetyl donor. Thus, the target compounds 5a-c were synthesized via phosphorylation of the 2', 3", and 4"-hydroxyls. The potencies of compounds 5a-c for Ca2+ release were shown to be indistinguishable from that of adenophostin A, indicating that bulky substitutions at the 5'-position of adenophostin A are well-tolerated in the receptor binding. This biological activity of 5a-c can be rationalized by molecular modeling using the ligand binding domain of the IP3 receptor.

  DOI：

  10.1021/jm060310d
• 作为产物：
  描述：

  1,2-O-isopropylidene-5-O-(tert-butyl)dimethylsilyl-α-D-ribofuranoside 在 吡啶 、 4-二甲氨基吡啶 、 2,6-二叔丁基-4-甲基吡啶 、 四丁基氟化铵 、 sodium methylate 、 咪唑 三氟甲磺酸盐 、 三乙胺 、 六甲基二硅氮烷 、 三氟乙酸 、 硫代氯甲酸苯酯 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 2.0h， 生成 9-[(2R,3R,4R,5R)-5-benzyl-4-[(2R,3R,4R,5R,6R)-4,5-bis[(3-oxido-1,5-dihydro-2,4,3-benzodioxaphosphepin-3-ium-3-yl)oxy]-3-phenylmethoxy-6-(phenylmethoxymethyl)oxan-2-yl]oxy-3-[(3-oxido-1,5-dihydro-2,4,3-benzodioxaphosphepin-3-ium-3-yl)oxy]oxolan-2-yl]purin-6-amine
  参考文献：
  名称：

  Synthesis of Adenophostin A Analogues Conjugating an Aromatic Group at the 5‘-Position as Potent IP₃ Receptor Ligands

  摘要：

  Previous structure-activity relationship studies of adenophostin A, a potent IP3 receptor agonist, led us to design the novel adenophostin A analogues 5a-c, conjugating an aromatic group at the 5'-position to develop useful IP3 receptor ligands. The common key intermediate, a D-ribosyl alpha-D-glucoside 10 alpha, was stereoselectively synthesized by a glycosidation with the 1-sulfinylglucoside donor 11, which was conformationally restricted by a 3,4-O-cyclic diketal protecting group. After introduction of an aromatic group at the 5-position of the ribose moiety, an adenine base was stereoselectively introduced at the anomeric beta-position to form 7a-c, where the tetra-O-i-butyryl donors 9a-c were significantly more effective than the corresponding O-acetyl donor. Thus, the target compounds 5a-c were synthesized via phosphorylation of the 2', 3", and 4"-hydroxyls. The potencies of compounds 5a-c for Ca2+ release were shown to be indistinguishable from that of adenophostin A, indicating that bulky substitutions at the 5'-position of adenophostin A are well-tolerated in the receptor binding. This biological activity of 5a-c can be rationalized by molecular modeling using the ligand binding domain of the IP3 receptor.

  DOI：

  10.1021/jm060310d

文献信息

• Design and Synthesis of 5‘-Deoxy-5‘-Phenyladenophostin A, a Highly Potent IP₃ Receptor Ligand¹
  作者：Tetsuya Mochizuki、Yoshihiko Kondo、Hiroshi Abe、Colin W. Taylor、Barry V. L. Potter、Akira Matsuda、Satoshi Shuto

  DOI：10.1021/ol0602710

  日期：2006.3.1

  5'-Deoxy-5'-phenyladenophostin A (5), designed as a useful IP3 receptor ligand based on the previous structure-activity relationship studies, was successfully synthesized via two key stereoselective glycosidation steps. This compound proved to be a highly potent IP3 receptor agonist.