3-O-[2,6-di-O-benzyl-3,4-O-[(2S,3S)-2,3-dimethoxybutan-2,3-yl]-α-D-glucopyranosyl]-1,2-O-isopropylidene-α-D-ribofuranose | 295320-98-8

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: 3-O-[2,6-di-O-benzyl-3,4-O-[(2S,3S)-2,3-dimethoxybutan-2,3-yl]-α-D-glucopyranosyl]-1,2-O-isopropylidene-α-D-ribofuranose
• 英文别名: [(3aR,5R,6R,6aR)-6-[[(2S,3S,4aR,5R,7R,8R,8aS)-2,3-dimethoxy-2,3-dimethyl-8-phenylmethoxy-5-(phenylmethoxymethyl)-5,7,8,8a-tetrahydro-4aH-pyrano[3,4-b][1,4]dioxin-7-yl]oxy]-2,2-dimethyl-3a,5,6,6a-tetrahydrofuro[2,3-d][1,3]dioxol-5-yl]methanol
• CAS: 295320-98-8
• 化学式: C₃₄H₄₆O₁₂
• 分子量: 646.732
• InChiKey: ZVWDARAZZXKMSN-HYHGBJAFSA-N

物化性质

• 沸点：
  703.6±60.0 °C(Predicted)
• 密度：
  1.28±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.28
• 重原子数：
  46.0
• 可旋转键数：
  12.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  121.76
• 氢给体数：
  1.0
• 氢受体数：
  12.0

反应信息

• 作为反应物：
  描述：

  3-O-[2,6-di-O-benzyl-3,4-O-[(2S,3S)-2,3-dimethoxybutan-2,3-yl]-α-D-glucopyranosyl]-1,2-O-isopropylidene-α-D-ribofuranose 在 咪唑 、 碘 、 三苯基膦 作用下， 以 甲苯 为溶剂， 反应 0.25h， 以93%的产率得到3-O-[2,6-di-O-benzyl-3,4-O-[(2S,3S)-2,3-dimethoxybutan-2,3-diyl]-α-D-glucopyranosyl]-5-deoxy-5-iodo-1,2-O-isopropylidene-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
• 作为产物：
  描述：

  ethyl 2,3,4,6-tetra-O-acetyl-1-thio-β-D-glucopyranoside 在 甲醇 、 N-碘代丁二酰亚胺 、 三氟甲磺酸 、 4 A molecular sieve 、 camphor-10-sulfonic acid 、 四丁基氟化铵 、 sodium methylate 、 sodium hydride 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 3-O-[2,6-di-O-benzyl-3,4-O-[(2S,3S)-2,3-dimethoxybutan-2,3-yl]-α-D-glucopyranosyl]-1,2-O-isopropylidene-α-D-ribofuranose
  参考文献：
  名称：

  Synthesis of Potent Agonists of the d-myo-Inositol 1,4,5-Trisphosphate Receptor Based on Clustered Disaccharide Polyphosphate Analogues of Adenophostin A

  摘要：

  Clustered disaccharide analogues of adenophostin A (2), i.e. mono-, di-, and tetravalent derivatives 6-8, respectively, were synthesized and evaluated as novel ligands for the tetrameric D-myo-inositol 1,4,5-trisphosphate receptor (IP3R). The synthesis was accomplished via Sonogashira coupling of propargyl 2-O-acetyl-5-O-benzyl-3-O-(3,4-di-O-acetyl-2,6-di-O-benzyl-alpha-D-glucopyranosyl)-beta-D-ribofuranoside (16) with iodobenzene 18, 22, or 25, followed by deacetylation, phosphorylation, and deprotection. The abilities of the target compounds 6-8, as well as ribophostin 4, propylphostin 5, and IP3 (1), to evoke Ca2+ release from permeabilized hepatocytes or displacement of [H-3]IP3 from its receptor in hepatic membranes were compared. Although the binding affinities of 4-8 were similar, there were modest though significant differences in their potencies in Ca2+ release assays: tetraphostin 8 > IP3 similar to diphostin 7 > phenylphostin 6 > ribophostin 4 similar to propylphostin 5.

  DOI：

  10.1021/jm000957c

文献信息

• Synthesis of Clustered Disaccharide Polyphosphate Analogues of Adenophostin A
  作者：Martin de Kort、A.Rob P.M. Valentijn、Gijs A. van der Marel、Jacques H. van Boom

  DOI：10.1016/s0040-4039(97)01811-x

  日期：1997.10

  Three new potential ligands for the IP3 receptor (i.e. compounds 5–7) were prepared by Sonogashira coupling of propargyl 2-O-acetyl-5-O-benzyl-3-O-(3,4-di-O-acetyl-2,6-di-O-benzyl-α-d- glycopyranosyl)-β-d-ribofuranoside (15) with iodobenzene, 1,2-diiodobenzene and 1,2,4,5-tetraiodobenzene, followed by deacetylation, phosphorylation and deprotection. © 1997 Elsevier Science Ltd.

  通过炔丙基2 - O-乙酰基-5- O-苄基-3- O-（3,4-二-O-乙酰基- ）的Sonogashira偶联，制备了IP 3受体的三个新的潜在配体（即化合物5-7）。2,6-二-O-苄基-α-d-吡喃葡萄糖基）-β-d-呋喃核糖苷（15）与碘苯，1,2-二碘苯和1,2,4,5-四碘苯，然后进行脱乙酰基化，磷酸化和脱保护。©1997爱思唯尔科学有限公司。
• Synthesis of Photoaffinity Derivatives of Adenophostin A
  作者：Martin de Kort、Jaco Luijendijk、Gijs A. van der Marel、Jacques H. van Boom

  DOI：10.1002/1099-0690(200009)2000:17<3085::aid-ejoc3085>3.0.co;2-a

  日期：2000.9
• 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.
• Design and synthesis of indole derivatives of adenophostin A. A entry into subtype-selective IP3 receptor ligands
  作者：Tetsuya Mochizuki、Akihiko Tanimura、Akihiro Nezu、Mika Ito、Hiroshi Abe、Yoshihiro Ito、Mitsuhiro Arisawa、Satoshi Shuto

  DOI：10.1016/j.tetlet.2009.12.045

  日期：2010.2

  Indole derivatives 3a and 3b of adenophostin A (2) in which the adenine of 2 was replaced with indole or 4-fluoroindole was designed as potential inositol trisphosphate receptor ligands. These target compounds were successfully synthesized from the key disaccharide unit 6. Biological evaluation showed that 3b selectively activates IP(3)R1, a subtype of IP3 receptors. (C) 2009 Elsevier Ltd. All rights reserved.