6-amino-5',2",6"-tri-O-benzyl-3",4"-bis-O-(dibenzyloxyphosphoryl)-3'-O-(α-D-glucopyranosyl)-9-β-D-ribofuranosylpurine | 1146899-09-3

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷酸
• 英文名称: 6-amino-5',2",6"-tri-O-benzyl-3",4"-bis-O-(dibenzyloxyphosphoryl)-3'-O-(α-D-glucopyranosyl)-9-β-D-ribofuranosylpurine
• CAS: 1146899-09-3
• 化学式: C₆₅H₆₇N₅O₁₅P₂
• 分子量: 1220.22
• InChiKey: SGUSZRFKGSCNBL-SGCKVWAUSA-N

物化性质

• 密度：
  1.36±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  11.65
• 重原子数：
  87.0
• 可旋转键数：
  30.0
• 环数：
  11.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  234.75
• 氢给体数：
  2.0
• 氢受体数：
  20.0

反应信息

• 作为反应物：
  描述：

  6-amino-5',2",6"-tri-O-benzyl-3",4"-bis-O-(dibenzyloxyphosphoryl)-3'-O-(α-D-glucopyranosyl)-9-β-D-ribofuranosylpurine 在 palladium hydroxide on carbon 作用下， 以 甲醇 、 水 、 环己烯 为溶剂， 以92%的产率得到2'-Dephospho-adenophostin A
  参考文献：
  名称：

  Activation of IP3 receptors by synthetic bisphosphate ligands

  摘要：

  人们普遍认为，D-肌醇1,4,5-三磷酸受体（IP3R）释放的Ca2+需要IP3的邻位4,5-双磷酸基团，其中P-5和P-4与结合位点的α和β域结合；我们通过合成和突变发现，合成糖核苷酸的腺嘌呤通过与Arg504相互作用，可以取代P-1或P-5与α域的相互作用，分别产生迄今为止合成的最有效的双磷酸激动剂和第一个没有邻位双磷酸基团的IP3R激动剂；这将刺激IP3R配体设计的新方法。

  DOI：

  10.1039/b819328b
• 作为产物：
  描述：

  2'',5',6''-tri-O-benzyl-2',3'',4''-tris(dibenzyloxyphosphoryl)-3'-O-α-D-glucopyranosyl adenosine 在 potassium carbonate 、 苯甲醇 作用下， 以93%的产率得到6-amino-5',2",6"-tri-O-benzyl-3",4"-bis-O-(dibenzyloxyphosphoryl)-3'-O-(α-D-glucopyranosyl)-9-β-D-ribofuranosylpurine
  参考文献：
  名称：

  Activation of IP3 receptors by synthetic bisphosphate ligands

  摘要：

  人们普遍认为，D-肌醇1,4,5-三磷酸受体（IP3R）释放的Ca2+需要IP3的邻位4,5-双磷酸基团，其中P-5和P-4与结合位点的α和β域结合；我们通过合成和突变发现，合成糖核苷酸的腺嘌呤通过与Arg504相互作用，可以取代P-1或P-5与α域的相互作用，分别产生迄今为止合成的最有效的双磷酸激动剂和第一个没有邻位双磷酸基团的IP3R激动剂；这将刺激IP3R配体设计的新方法。

  DOI：

  10.1039/b819328b

文献信息

• Contribution of Phosphates and Adenine to the Potency of Adenophostins at the IP₃ Receptor: Synthesis of All Possible Bisphosphates of Adenophostin A
  作者：Kana M. Sureshan、Andrew M. Riley、Mark P. Thomas、Stephen C. Tovey、Colin W. Taylor、Barry V. L. Potter

  DOI：10.1021/jm201571p

  日期：2012.2.23

  Although adenophostin A (AdA), the most potent agonist of D-myoinositol 1,4,5-trisphosphate receptors (IP3R), is thought to mimic IP3, the relative roles of the different phosphate groups and the adenosine motif have not been established. We synthesized all three possible bisphosphate analogues of AdA and glucose 3,4-bisphosphate (7, AdA lacking the 2'-AMP). 2'-Dephospho-AdA (6) was prepared via a novel regioselective dephosphorylation strategy. Assessment of the abilities of these bisphosphates to stimulate intracellular Ca2+ release using recombinant rat type 1 IP3R (IP(3)R1) revealed that 6, a mimic of Ins(4,5)P-2, is only 4-fold less potent than IP3, while 7 is some 400-fold weaker and even 3 ''-dephospho-AdA (5) is measurably active, despite missing one of the vicinal bisphosphate groups normally thought to be crucial for IP3-like activity. Compound 6 is the most potent bisphosphate yet discovered with activity at IP3R. Thus, adenosine has a direct role independent of the 2'-phosphate group in contributing toward the potency of adenophostins, the vicinal bisphosphate motif is not essential for activity at the IP3R, as always thought, and it is possible to design potent agonists with just two of the three phosphates. A model with a possible adenine-R504 interaction supports the activity of 5 and 6 and also allows a reappraisal of the unexpected activity previously reported for the AdA regioisomer 2 ''-phospho-3 ''-dephospho-AdA 40.