Phosphoric acid dibenzyl ester (1R,2S,3R,4R,5S,6S)-2,5-bis-benzyloxy-3,4,6-tris-(bis-benzyloxy-phosphoryloxy)-cyclohexyl ester | 115432-20-7

• 英文名称: Phosphoric acid dibenzyl ester (1R,2S,3R,4R,5S,6S)-2,5-bis-benzyloxy-3,4,6-tris-(bis-benzyloxy-phosphoryloxy)-cyclohexyl ester
• 英文别名: Phosphoric acid dibenzyl ester (1S,2S,3S,4R,5S,6S)-2,5-bis-benzyloxy-3,4,6-tris-(bis-benzyloxy-phosphoryloxy)-cyclohexyl ester；octabenzyl 1,3,4,6-(2,5-di-O-benzyl-myo-inosityl)tetrakisphosphate；octabenzyl (±)-2,3,5,6-(1,4-di-O-benzyl-myo-inosityl)tetrakisphosphate
• CAS: 115432-20-7；125412-35-3；141040-65-5
• 化学式: C₇₆H₇₆O₁₈P₄
• 分子量: 1401.32
• InChiKey: OECLLIRUVYGXIK-PTRODMPTSA-N

物化性质

• 密度：
  1.34±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  18.88
• 重原子数：
  98.0
• 可旋转键数：
  38.0
• 环数：
  11.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  197.5
• 氢给体数：
  0.0
• 氢受体数：
  18.0

反应信息

• 作为反应物：
  描述：

  Phosphoric acid dibenzyl ester (1R,2S,3R,4R,5S,6S)-2,5-bis-benzyloxy-3,4,6-tris-(bis-benzyloxy-phosphoryloxy)-cyclohexyl ester 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 反应 6.5h， 以97%的产率得到D-myo-inositol 1,2,4,5-tetrakisphosphate octasodium salt
  参考文献：
  名称：

  Asymmetric Total Synthesis of d-myo-Inositol 1,2,4,5-Tetrakisphosphate and Its P-2-(O-Aminopropyl) Derivative

  摘要：

  DOI：

  10.1021/jo951057k
• 作为产物：
  描述：

  1-O-acetyl-3-O-benzyl-4,5-di-O-(p-methoxybenzyl)-2-deoxy-2-oxo-myo-inositol 在 四氮唑 、 sodium hydroxide 、 (NH₄)2Ce(NO₃)2 、 三乙酰氧基硼氢化钠 、 sodium hydride 、 对甲苯磺酸 、 溶剂黄146 、 间氯过氧苯甲酸 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 、 丙酮 、 乙腈 为溶剂， 反应 130.75h， 生成 Phosphoric acid dibenzyl ester (1R,2S,3R,4R,5S,6S)-2,5-bis-benzyloxy-3,4,6-tris-(bis-benzyloxy-phosphoryloxy)-cyclohexyl ester
  参考文献：
  名称：

  Asymmetric Total Synthesis of d-myo-Inositol 1,2,4,5-Tetrakisphosphate and Its P-2-(O-Aminopropyl) Derivative

  摘要：

  DOI：

  10.1021/jo951057k

文献信息

• Tetrakisphosphates and Bispyrophosphates of myo-Inositol Derivatives as Allosteric Effectors of Human Hemoglobin: Synthesis, Molecular Recognition, and Oxygen Release
  作者：Alexandros E. Koumbis、Carolina D. Duarte、Claude Nicolau、Jean-Marie Lehn

  DOI：10.1002/cmdc.201000421

  日期：2011.1.3

  of these proved to be efficient allosteric effectors, with similar affinities for hemoglobin to that of myo‐inositol hexakisphosphate, which is one of the best known allosteric effectors of hemoglobin. The efficacy was found to be higher for free phosphates than pyrophosphates. As allosteric Hb effectors, these compounds enable enhanced oxygen release. These effects increase with the strength of Hb

  各种2,5-和1,4-取代的和未取代的肌醇肌醇tetrakisphosphates和制备bispyrophosphates进行以下的一般合成途径。测试了所有最终化合物诱导氧气从人血红蛋白释放的能力。其中大多数被证明是有效的变构效应子，对血红蛋白的亲和力与对肌红蛋白的亲和力相似肌醇六磷酸酯，是最著名的血红蛋白变构效应物之一。发现游离磷酸盐的功效比焦磷酸盐更高。作为变构Hb效应物，这些化合物可增强氧气释放。这些效应随着Hb结合强度的增加而增加，并且主要对应于静电相互作用。立体化学和位阻因素在分子识别中也起着重要但次要的作用。鉴于缺氧在多种类型的疾病发挥了中心作用，勘探肌肌醇磷酸衍生物的代表在寻求作用于组织的氧合状态，并可能在发现和开发潜力显著物质的重要途径新型药物候选者。
• Syntheses of d- and l-myo-Inositol 1,2,4,5-tetrakisphosphate and stereoselectivity of the I(1,4,5)P3 receptor binding
  作者：Sung-Kee Chung、Boo-Gyo Shin、Young-Tae Chang、Byung-Chang Suh、Kyong-Tai Kim

  DOI：10.1016/s0960-894x(98)00081-x

  日期：1998.3

  D- and L-myo-Inositol 1,2,4,5-tetrakisphosphate [D- & L-I(1,2,4,5)P4], which are analogues of D-myo-Inositol 1,4,5-trisphosphate [D-I(1,4,5)P3], a calcium mobilizing second messenger, were synthesized via resolution of the camphanate ester of a myo-inositol derivative, and the binding affinities to I(1,4,5)P3 receptor were measured.

  D-和L-肌醇1,2,4,5-四磷酸[D-和LI（1,2,4,5）P4]，它们是D-肌醇1,4,5-三磷酸酯的类似物通过分解肌醇衍生物的樟脑酸酯合成了一种动员钙的第二信使[DI（1,4,5）P3]，并测定了与I（1,4,5）P3受体的结合亲和力。
• Total synthesis of myo-inositol polyphosphates from benzene via conduritol B derivatives
  作者：Howard A.J. Carless、Kofi Busia

  DOI：10.1016/s0040-4039(00)97419-7

  日期：1990.1

  The four (±)--inositol phosphates 1,4,5-IP3 (1), 2,4,5-IP3 (15), 1,2,4,5-IP4 (17) and 4,5-IP2 (19) have been synthesised from benzene, using the protected conduritol B (10) as the key intermediate.

  四种（±）--肌醇磷酸酯1,4,5-IP 3（1），2,4,5-IP 3（15），1,2,4,5-IP 4（17）和4,5 -IP 2（19）已经由苯合成，使用被保护的赤豆糖醇B（10）作为关键中间体。
• Synthesis of the enantiomers of myo-inositol 1,2,4,5-tetrakisphosphate, a regioisomer of myo-inositol 1,3,4,5-tetrakisphosphate
  作者：Stephen J. Mills、Barry V. L. Potter

  DOI：10.1039/a608337d

  日期：——

  Routes for the synthesis of racemic myo-inositol 1,2,4,5-tetrakisphosphate DL-Ins(1,2,4,5)P4 5ab and the chiral antipodes D- and L-myo-inositol 1,2,4,5-tetrakisphosphate 5a and 5b, respectively, are described. For the synthesis of racemate 5ab, 3,6-di-O-benzoyl-1,2:4,5-di-O -isopropylidene-myo-inositol 7ab is prepared in two steps from myo-inositol. The ketals are hydrolysed under acidic conditions to give DL-1,4-di-O-benzoyl- myo-inositol 8ab. Phosphitylation of compounds 8ab using chloro(diethoxy)phosphine in the presence of base, followed by oxidation and a three-step deprotection strategy, gives DL-Ins(1,2,4,5)P4 5ab.The chiral tetrakisphosphates 5a and 5b are synthesized using a different route. The 4,5-isopropylidene group of DL-3,6-di-O -benzyl-1,2:4,5-di-O-isopropylidene-myo -inositol 13ab are selectively removed under mild acidic conditions to give diol 14ab. p-Methoxybenzylation at the 4,5-positions followed by acid hydrolysis of the cis-isopropylidene ketal affords cis-diol 16ab. Selective coupling of (S)-(+)-O -acetylmandelic acid with diol 16ab at the equatorial hydroxy group provides two diastereoisomers 18 and 19, which are separated by chromatography. Basic hydrolysis of the individual diastereoisomers provides the enantiomers 16a and 16b. Acidic hydrolysis gives D- and L-3,6-di-O-benzyl- myo-inositol 20a and 20b, respectively. Phosphitylation and oxidation of tetraols 20a and 20b gives the fully blocked derivatives, which are deprotected to give tetrakisphosphates 5a and 5b, respectively. The absolute configuration of compound 20a is established by a chemical method. DL-1,2:4,5-Di-O -isopropylidene-myo-inositol 12ab is coupled to (S)-(+)-O -acetylmandelic acid to give a mixture of bis-esters 26 and 27 and crystallisation of the mixture of diastereoisomers affords pure isomer 27. Basic hydrolysis gives the pure enantiomer 12a (for which the absolute configuration is known) and benzylation followed by acid hydrolysis gives tetraol 20a with the same physical properties as compound 20a prepared by a different route described previously. D-Ins(1,2,4,5)P4 5a is a potent mobiliser of intracellular Ca2+ ions in permeabilised platelets, while L-Ins(1,2,4,5)P4 5b is inactive.

  本文描述了合成外消旋肌醇1,2,4,5-四磷酸DL-Ins(1,2,4,5)P₄ 5ab及其对映体D-和L-肌醇1,2,4,5-四磷酸5a和5b的路线。对于合成外消旋体5ab，3,6-二-O-苯甲酰基-1,2:4,5-二-O-异亚丙基-肌醇7ab通过两步反应从肌醇制备得到。在酸性条件下水解缩酮得到DL-1,4-二-O-苯甲酰基-肌醇8ab。然后使用氯(二乙氧基)膦在碱存在下对化合物8ab进行膦酸化，随后进行氧化和三步去保护策略，得到DL-Ins(1,2,4,5)P₄ 5ab。手性四磷酸盐5a和5b则通过不同的路线合成。在温和酸性条件下选择性地除去DL-3,6-二-O-苄基-1,2:4,5-二-O-异亚丙基-肌醇13ab的4,5-异亚丙基保护基，得到二醇14ab。在4,5-位进行对甲氧基苄基化，然后酸水解顺式异亚丙基缩酮，得到顺式二醇16ab。在赤道羟基上选择性地与(S)-(+)-O-乙酰基扁桃酸偶联合成，得到两个非对映异构体18和19，通过色谱法分离。单一非对映异构体在碱性条件下水解得到对映体16a和16b。酸性水解得到D-和L-3,6-二-O-苄基-肌醇20a和20b。四醇20a和20b进行膦酸化和氧化得到完全保护的衍生物，然后去保护得到四磷酸盐5a和5b。化合物20a的绝对构型通过化学方法确定。DL-1,2:4,5-二-O-异亚丙基-肌醇12ab与(S)-(+)-O-乙酰基扁桃酸偶联得到双酯混合物26和27，通过非对映异构体混合物的结晶得到纯异构体27。碱性水解得到纯对映体12a（其绝对构型已知），苄基化后酸水解得到四醇20a，其物理性质与先前通过不同路线合成的化合物20a相同。D-Ins(1,2,4,5)P₄ 5a是一种有效的细胞内Ca²⁺离子动员剂，而L-Ins(1,2,4,5)P₄ 5b则无效。
• An efficient method for polyphosphorylation of inositol derivatives
  作者：Yutaka Watanabe、Hiroyuki Nakahira、Motonobu Bunya、Shoichiro Ozaki

  DOI：10.1016/s0040-4039(00)95572-2

  日期：——