(-)-1D-2,3,4-tri-O-benzyl-myo-inositol 4,5-bis(dibenzylphosphate) | 162879-82-5

• 英文名称: (-)-1D-2,3,4-tri-O-benzyl-myo-inositol 4,5-bis(dibenzylphosphate)
• 英文别名: 1D-2,3,6-tri-O-benzyl-myo-inositol 4,5-bis(dibenzyl phosphate)；1D-2,3,6-tri-O-benzyl-myo-inositol 4,5-bis-O-(dibenzylphosphate)；D-2,3,6-tri-O-benzyl-myo-inositol 4,5-bis-O-(dibenzylphosphate)
• CAS: 162879-82-5
• 化学式: C₅₅H₅₆O₁₂P₂
• 分子量: 970.99
• InChiKey: GLTJFFHBRVQAMA-XVMBTMSWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  11.97
• 重原子数：
  69.0
• 可旋转键数：
  25.0
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  137.44
• 氢给体数：
  1.0
• 氢受体数：
  12.0

反应信息

• 作为反应物：
  描述：

  (-)-1D-2,3,4-tri-O-benzyl-myo-inositol 4,5-bis(dibenzylphosphate) 在 20% palladium hydroxide on charcoal 、 氢气 、 三乙基碳酸氢铵缓冲液 作用下， 以 甲醇 、 水 为溶剂， 以76%的产率得到Inositol 4,5-bisphosphate triethylammonium
  参考文献：
  名称：

  Contribution of Phosphates and Adenine to the Potency of Adenophostins at the IP₃ Receptor: Synthesis of All Possible Bisphosphates of Adenophostin A

  摘要：

  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.

  DOI：

  10.1021/jm201571p
• 作为产物：
  描述：

  (1R,2R,3R,4R,5S,6S)-2,3,5-Tris-benzyloxy-4-(4-methoxy-benzyloxy)-6-[((E)-propenyl)oxy]-cyclohexanol 在 四氮唑 、 ammonium cerium(IV) nitrate 、 乙酰氯 、 间氯过氧苯甲酸 作用下， 以 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 8.5h， 生成 (-)-1D-2,3,4-tri-O-benzyl-myo-inositol 4,5-bis(dibenzylphosphate)
  参考文献：
  名称：

  Synthesis and biological evaluation of a PtdIns(4,5)P2 and a phosphatidic acid affinity matrixDedicated to the memory of the late Professor Roy Gigg.

  摘要：

  研究人员合成了二棕榈酰基磷脂酸（PA）的类似物、二月桂酰基 PA 和磷脂酰肌醇 4,5-二磷酸 [PtdIns(4,5)P2]，并将其固定在固体支持物 Affi-Gel 10 上。使用它们作为亲和基质，发现一些已知蛋白质和一组新型蛋白质能与 PA 特异性结合。

  DOI：

  10.1039/b200585a

文献信息

• Synthesis and biological evaluation of phosphatidylinositol phosphate affinity probes
  作者：Stuart J. Conway、James Gardiner、Simon J. A. Grove、Melloney K. Johns、Ze-Yi Lim、Gavin F. Painter、Diane E. J. E. Robinson、Christine Schieber、Jan W. Thuring、Leon S.-M. Wong、Meng-Xin Yin、Antony W. Burgess、Bruno Catimel、Phillip T. Hawkins、Nicholas T. Ktistakis、Leonard R. Stephens、Andrew B. Holmes

  DOI：10.1039/b913399b

  日期：——

  The synthesis of the complete family of phosphatidylinositol phosphate analogues (PIPs) from five key core intermediates A–E is described. These core compounds were obtained from myo-inositol orthoformate 1via regioselective DIBAL-H and trimethylaluminium-mediated cleavages and a resolution–protection process using camphor acetals 10. Coupling of cores A–E with phosphoramidites 34 and 38, derived from the requisite protected lipid side chains, afforded the fully-protected PIPs. Removal of the remaining protecting groups was achieved via hydrogenolysis using palladium black or palladium hydroxide on carbon in the presence of sodium bicarbonate to afford the complete family of dipalmitoyl- and amino-PIP analogues 42, 45, 50, 51, 58, 59, 67, 68, 76, 77, 82, 83, 92, 93, 99 and 100. Investigations using affinity probes incorporating these compounds have identified novel proteins involved in the PI3K intracellular signalling network and have allowed a comprehensive proteomic analysis of phosphoinositide interacting proteins.

  报道了从五个关键的核心中间体A-E合成完整的磷脂酰肌醇磷酸类似物（PIPs）家族的方法。这些核心化合物通过选择性DIBAL-H和三甲基铝介导的裂解以及使用樟脑乙缩醛的解析保护过程，从肌醇原甲酸1中获得。将核心A-E与从所需保护的脂质侧链衍生的磷酰胺34和38偶联，得到了完全保护的PIPs。通过使用钯黑或碳上的钯氢氧化物在碳酸氢钠存在下的氢解，去除了剩余的保护基团，得到了完整的二棕榈酰和氨基PIP类似物42、45、50、51、58、59、67、68、76、77、82、83、92、93、99和100。利用包含这些化合物的亲和探针进行的研究，鉴定了参与PI3K细胞内信号网络的新蛋白，并允许对磷脂酰肌醇相互作用蛋白进行全面的蛋白质组学分析。
• The preparation of intermediates for the synthesis of 1d-myo-inositol 1,4,5- and 2,4,5-trisphosphates, 1,4-bisphosphate 5-phosphorothioate, and 4,5-bisphosphate 1-phosphorothioate from 1d-3,6-di-O-benzyl-1,2-O-isopropylidene-myo-inositol
  作者：Trupti Desai、Jill Gigg、Roy Gigg、Eloísa Martín-Zamora

  DOI：10.1016/0008-6215(94)84005-9

  日期：1994.9

  3,6-tri-O-benzyl-myo-inositol (an intermediate for the synthesis of 1D-myo-inositol 1,4,5-trisphosphate) and 1D-2,3,6-tri-O-benzyl-1-O-p-methoxybenzyl-myo-inositol (an intermediate for the synthesis of the 1-phosphorothioate analogue of 1D-myo-inositol 1,4,5-trisphosphate). 1D-3,6-Di-O-benzyl-1,2-O-isopropylidene-myo-inositol was also converted into 1D-2,3,6-tri-O-benzyl-5-O-p-methoxybenzyl[and -5

  描述了1D-1,6-二-O-苄基-2,5-二-Op-甲氧基苄基-肌醇的制备。该化合物和1D-3,6-二-O-苄基-1,2-O-异亚丙基-肌醇被转化为1D-1,3,6-三-O-苄基-肌醇被磷酸化为得到用于合成1D-肌醇2,4,5-三磷酸的中间体。1D-3,6-二-O-苄基-1,2-O-异亚丙基-肌醇被转化为1D-2,3,6-三-O-苄基-肌醇1D-肌醇1,4,5-三磷酸酯）和1D-2,3,6-三-O-苄基-1-Op-甲氧基苄基-肌醇（一种中间体的合成的1-磷酸硫代磷酸酯类似物） 1D-肌醇1,4,5-三磷酸）。1D-3,6-二-O-苄基-1,2-O-异亚丙基-肌醇也被转化为1D-2,3，6-三-O-苄基-5-Op-甲氧基苄基[和-5-O（顺-丙-1-烯基）]-肌醇-它们都是合成1D-的5-硫代磷酸酯类似物的中间体肌醇1,4,5-三磷酸。由1D-2,3,6-三-O-苄基-合成1D-2,3,6-三-O-苄基-肌醇1
• A synthetic diphosphoinositol phosphate analogue of inositol trisphosphate
  作者：Andrew M. Riley、Judith E. Unterlass、Vera Konieczny、Colin W. Taylor、Thomas Helleday、Barry V. L. Potter

  DOI：10.1039/c8md00149a

  日期：——

  (diphosphate) groups. Converting a phosphate group in an InsP into a diphosphate has been reported to enhance affinity for some binding proteins. We synthesised 1-PP-Ins(4,5)P2, the first diphosphate analogue of the intracellular signalling molecule InsP3, and examined its effects on InsP3 receptors, which are intracellular Ca2+ channels. 1-PP-Ins(4,5)P2 was indistinguishable from InsP3 in its ability

  二磷酸肌醇磷酸盐 (PP-InsPs) 是含有 PP（二磷酸盐）基团的肌醇磷酸盐 (InsPs)。据报道，将 InsP 中的磷酸基团转化为二磷酸基团可以增强对某些结合蛋白的亲和力。我们合成了 1-PP-Ins(4,5)P 2 ，这是细胞内信号分子 InsP 3的第一个二磷酸类似物，并检查了其对 InsP 3受体（细胞内 Ca 2+通道）的影响。1-PP-Ins(4,5)P 2在结合和激活 1 型 InsP 3 受体的能力方面与InsP 3没有区别，这表明 InsP 3的二磷酸修饰既不影响亲和力也不影响功效。尽管如此，1-PP-Ins(4,5)P 2是迄今为止已确定的最有效的 InsP 3 1-磷酸修饰类似物。PP-InsP 通常被二磷酸肌醇多磷酸磷酸水解酶 (DIPP) 水解，但 1-PP-Ins(4,5)P 2不易被人 DIPP 代谢。差示扫描荧光测定显示1-PP-Ins(4,5)P 2