5-deoxy-3-O-[2,6-di-O-benzyl-3,4-O-[(2S,3S)-2,3-dimethoxybutan-2,3-diyl]-α-D-glucopyranosyl]-1,2-O-isopropylidene-5-phenethyl-α-D-ribofuranose | 912567-46-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-deoxy-3-O-[2,6-di-O-benzyl-3,4-O-[(2S,3S)-2,3-dimethoxybutan-2,3-diyl]-α-D-glucopyranosyl]-1,2-O-isopropylidene-5-phenethyl-α-D-ribofuranose
• 英文别名: (2S,3S,4aR,5R,7R,8R,8aS)-7-[[(3aR,5R,6R,6aR)-2,2-dimethyl-5-(3-phenylpropyl)-3a,5,6,6a-tetrahydrofuro[2,3-d][1,3]dioxol-6-yl]oxy]-2,3-dimethoxy-2,3-dimethyl-8-phenylmethoxy-5-(phenylmethoxymethyl)-5,7,8,8a-tetrahydro-4aH-pyrano[3,4-b][1,4]dioxine
• CAS: 912567-46-5
• 化学式: C₄₂H₅₄O₁₁
• 分子量: 734.884
• InChiKey: ZMNDPNOQAHUMHH-VSCZCPERSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  53
• 可旋转键数：
  15
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  102
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  5-deoxy-3-O-[2,6-di-O-benzyl-3,4-O-[(2S,3S)-2,3-dimethoxybutan-2,3-diyl]-α-D-glucopyranosyl]-1,2-O-isopropylidene-5-phenethyl-α-D-ribofuranose 在 吡啶 、 4-二甲氨基吡啶 、 sodium methylate 、 咪唑 三氟甲磺酸盐 、 三乙胺 、 六甲基二硅氮烷 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 生成 9-[(2R,3R,4R,5R)-4-[(2R,3R,4R,5R,6R)-4,5-bis[(3-oxo-1,5-dihydro-2,4,3lambda5-benzodioxaphosphepin-3-yl)oxy]-3-phenylmethoxy-6-(phenylmethoxymethyl)oxan-2-yl]oxy-3-[(3-oxo-1,5-dihydro-2,4,3lambda5-benzodioxaphosphepin-3-yl)oxy]-5-(3-phenylpropyl)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
• 作为产物：
  描述：

  1,2-O-isopropylidene-5-O-(tert-butyl)dimethylsilyl-α-D-ribofuranoside 在 4-二甲氨基吡啶 、 2,6-二叔丁基-4-甲基吡啶 、 四丁基氟化铵 、 硫代氯甲酸苯酯 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 反应 2.0h， 生成 5-deoxy-3-O-[2,6-di-O-benzyl-3,4-O-[(2S,3S)-2,3-dimethoxybutan-2,3-diyl]-α-D-glucopyranosyl]-1,2-O-isopropylidene-5-phenethyl-α-D-ribofuranose
  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

• Synthesis of Adenophostin A Analogues Conjugating an Aromatic Group at the 5‘-Position as Potent IP₃ Receptor Ligands
  作者：Tetsuya Mochizuki、Yoshihiko Kondo、Hiroshi Abe、Stephen C. Tovey、Skarlatos G. Dedos、Colin W. Taylor、Michael Paul、Barry V. L. Potter、Akira Matsuda、Satoshi Shuto

  DOI：10.1021/jm060310d

  日期：2006.9.1

  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.