2',3'',4''-tri-O-acetyl-2'',5',6''-tri-O-benzyl-3'-O-α-D-glucopyranosyl-6-chloro-9-β-D-ribofuranosidopurine | 628316-74-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2',3'',4''-tri-O-acetyl-2'',5',6''-tri-O-benzyl-3'-O-α-D-glucopyranosyl-6-chloro-9-β-D-ribofuranosidopurine
• 英文别名: 2',3'',4''-tri-O-acetyl-2'',5',6''-tri-O-benzyl-3'O-α-D-glucopyranosyl-6-chloro-9-β-D-ribofuranosylpurine；[(2R,3R,4S,5R,6R)-4-acetyloxy-6-[(2R,3R,4R,5R)-4-acetyloxy-5-(6-chloropurin-9-yl)-2-(phenylmethoxymethyl)oxolan-3-yl]oxy-5-phenylmethoxy-2-(phenylmethoxymethyl)oxan-3-yl] acetate
• CAS: 628316-74-5
• 化学式: C₄₃H₄₅ClN₄O₁₂
• 分子量: 845.303
• InChiKey: PMCWLXJOOGRAEM-GKLCPUMKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  60
• 可旋转键数：
  20
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  178
• 氢给体数：
  0
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  2',3'',4''-tri-O-acetyl-2'',5',6''-tri-O-benzyl-3'-O-α-D-glucopyranosyl-6-chloro-9-β-D-ribofuranosidopurine 在 氨 作用下， 以 乙醇 为溶剂， 反应 72.0h， 以92%的产率得到2'',5',6''-tri-O-benzyl-3'-O-α-D-glucopyranosyl adenosine
  参考文献：
  名称：

  Adenophostin A and analogues modified at the adenine moiety: synthesis, conformational analysis and biological activity

  摘要：

  报告了腺苷 A（2）和两种在腺嘌呤分子上进行了修饰的类似物[乙烯腺苷（4）和 8-溴腺苷（5）]的合成过程。通过核磁共振分析和分子建模相结合的方法来比较它们在溶液中的结构，结果表明它们都采用了非常相似的构象。对这些类似物从表达重组 1 型大鼠 Ins(1,4,5)P3R 的 DT40 细胞中调动 Ca2+ 的能力进行了测试，结果显示乙烯腺苷是 Ins(1,4,5)P3R 的高亲和力荧光探针。8-Bromo adenophostin 的效力略低。生物学结果支持了我们目前关于腺苷 A 与 Ins(1,4,5)P3R 结合模式的假设，即碱基分子与受体 Arg 504 之间的阳离子-π 相互作用与 H 键结合可能是腺苷 A 相对于 Ins(1,4,5)P3 具有高效力的原因。

  DOI：

  10.1039/b415229h
• 作为产物：
  描述：

  6-氯嘌呤 、 1,2,3',4'-Tetra-O-acetyl-2',5,6'-tri-O-benzyl-3-O-α-D-glucopyranosyl-D-ribofuranose 在 三氟甲磺酸三甲基硅酯 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 乙腈 为溶剂， 反应 1.0h， 以89%的产率得到2',3'',4''-tri-O-acetyl-2'',5',6''-tri-O-benzyl-3'-O-α-D-glucopyranosyl-6-chloro-9-β-D-ribofuranosidopurine
  参考文献：
  名称：

  Synthesis and Ca²⁺-Mobilizing Activity of Purine-Modified Mimics of Adenophostin A:  A Model for the Adenophostin−Ins(1,4,5)P₃ Receptor Interaction

  摘要：

  The synthesis of a series of adenophostin A analogues modified at C-6 and C-2 of adenine is described. The target compounds were synthesized by a convergent route involving a modified Vorbruggen condensation of either 6-chloropurine or 2,6-dichloropurine with a protected disaccharide, yielding two versatile intermediates capable of undergoing substitution with a range of nucleophiles. The new analogues showed a range of abilities to mobilize Ca2+ from the intracellular stores of permeabilized hepatocytes and are among the first totally synthetic compounds to approach the activity of adenophostin A. In agreement with the biological results, docking studies of adenophostin A using the recently reported X-ray crystal structure of the type 1 Ins(1,4,5)P-3 receptor binding core suggested that, in likely binding modes of adenophostin A, the area around N-6 may be relatively open, identifying this region of the adenophostin A molecule as a promising target for further elaboration. The docking results also point to specific interactions involving residues within the binding domain of the Ins(1,4,5)P-3 receptor that may be involved in the molecular recognition of the adenophostins.

  DOI：

  10.1021/jm030883f

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.