exo/endo-2',3'-O-p-methoxybenzylideneadenosine | 47578-96-1

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: exo/endo-2',3'-O-p-methoxybenzylideneadenosine
• 英文别名: 2',3'-O-p-Anisylidene adenosine；O^2'_,O3'-(4-methoxy-benzylidene)-adenosine；2',3'-O-(p-Methoxy-benzyliden)-adenosin；2',3'-O-(p-Anisyliden)adenosin；2',3'-O-p-Anisyliden-adenosin；2'.3'-O-p-Anisyliden-adenosin；[(3aR,4R,6R,6aR)-4-(6-aminopurin-9-yl)-2-(4-methoxyphenyl)-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methanol
• CAS: 47578-96-1
• 化学式: C₁₈H₁₉N₅O₅
• 分子量: 385.379
• InChiKey: BVSFPDDCDGRBLQ-WAOLGMKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  127
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  exo/endo-2',3'-O-p-methoxybenzylideneadenosine 在 吡啶 作用下， 反应 18.0h， 生成 [Bis-(4-methoxy-phenyl)-phenyl-methyl]-{9-[(3aR,4R,6R,6aR)-2-(4-methoxy-phenyl)-6-trimethylsilanyloxymethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-yl]-9H-purin-6-yl}-amine
  参考文献：
  名称：

  Synthesis of adenophostin A and congeners modified at glucose

  摘要：

  描述了超强效 1D-肌醇 1,4,5-三磷酸受体激动剂腺磷蛋白 A (2) 以及类似物 5 和 7 的收敛途径，其中葡萄糖二磷酸单元被相应的木糖二磷酸和甘露糖二磷酸取代分别为单位。腺苷转化为其2',3'-O-对甲氧基亚苯亚甲基衍生物8ab，并通过瞬时保护方法选择性地N6-二甲氧基三苯甲基化。 5'-O-苄基化，然后还原缩醛裂解，在与 3'-O-对甲氧基苄基异构体分离后，得到多功能糖基受体 5'-O-苄基-N6-二甲氧基三苯甲基-2'-O-对甲氧基苄基腺苷 13。 13 具有选择性保护的吡喃葡萄糖基、吡喃木糖基或吡喃甘露糖基亚磷酸二甲酯得到所需的3'-O-α-吡喃糖基腺苷衍生物。酸性水解得到相应的N6-未保护的三醇，将其使用双(苄氧基)(二异丙氨基)膦和三氟甲磺酸咪唑鎓进行亚磷酸化，无需进一步的N6-保护。脱保护得到目标三磷酸2、5和7。合成的腺苷磷汀A (2)在所有方面与天然材料样品相同。类似物 5 和 7 可用于腺苷磷酸酯的结构-活性研究。

  DOI：

  10.1039/b001386m
• 作为产物：
  描述：

  4-甲氧基苯甲醛 、 腺苷 在 zinc(II) chloride 作用下， 以 四氢呋喃 为溶剂， 反应 48.0h， 以94%的产率得到exo/endo-2',3'-O-p-methoxybenzylideneadenosine
  参考文献：
  名称：

  Selective Nucleoside Triphosphate Diphosphohydrolase-2 (NTPDase2) Inhibitors: Nucleotide Mimetics Derived from Uridine-5′-carboxamide

  摘要：

  Ecto-nucleoside triphosphate diphosphohydrolases (E-NTPDases, subtypes 1, 2, 3, 8 of NTPDases) dephosphorylate nucleoside tri- and diphosphates to the corresponding di- and monophosphates. In the present study we synthesized adenine and uracil nucleotide mimetics, in which the phosphate residues were replaced by phosphonic acid esters attached to the nucleoside at the 5'-position by amide linkers. Among the synthesized uridine derivatives, we identified the first potent and selective inhibitors of human NTP`Dase2. The most potent compound was 19a (PSB-6426), which was a competitive inhibitor of NTPDase2 exhibiting a Ki value of 8.2,uM and selectivity versus other NTPDases. It was inactive toward uracil nuc leotide- activated P2Y2, P2Y4, and P2Y6 receptor subtypes. Compound 19a was chemically and metabolically highly stable. In contrast to the few known (unselective) NTPDase inhibitors, 19a is an uncharged molecule and may be perorally bioavailable. NTPDase2 inhibitors have potential as novel cardioprotective drugs for the treatment of stroke and for cancer therapy.

  DOI：

  10.1021/jm800175e

文献信息

• Synthesis of adenophostin A
  作者：Rachel D Marwood、Vanessa Correa、Colin W Taylor、Barry V L. Potter

  DOI：10.1016/s0957-4166(99)00491-7

  日期：2000.2

  The natural product and potent agonist of the D-myo-inositol 1,4,5-trisphosphate receptor, adenophostin A, was synthesised from adenosine and D-glucose using efficient methodology. The synthetic material was equipotent with naturally occurring adenophostin A in evoking Ca(2+) release from the intracellular stores of permeabilised cells. (C) 2000 Elsevier Science Ltd. All rights reserved.
• KROXALEV, V. M.;MAKAROV, A. M.;RODYGIN, A. S.
  作者：KROXALEV, V. M.、MAKAROV, A. M.、RODYGIN, A. S.

  DOI：——

  日期：——
• Selective Nucleoside Triphosphate Diphosphohydrolase-2 (NTPDase2) Inhibitors: Nucleotide Mimetics Derived from Uridine-5′-carboxamide
  作者：Andreas Brunschweiger、Jamshed Iqbal、Frank Umbach、Anja B. Scheiff、Mercedes N. Munkonda、Jean Sévigny、Aileen F. Knowles、Christa E Müller

  DOI：10.1021/jm800175e

  日期：2008.8.1

  Ecto-nucleoside triphosphate diphosphohydrolases (E-NTPDases, subtypes 1, 2, 3, 8 of NTPDases) dephosphorylate nucleoside tri- and diphosphates to the corresponding di- and monophosphates. In the present study we synthesized adenine and uracil nucleotide mimetics, in which the phosphate residues were replaced by phosphonic acid esters attached to the nucleoside at the 5'-position by amide linkers. Among the synthesized uridine derivatives, we identified the first potent and selective inhibitors of human NTP`Dase2. The most potent compound was 19a (PSB-6426), which was a competitive inhibitor of NTPDase2 exhibiting a Ki value of 8.2,uM and selectivity versus other NTPDases. It was inactive toward uracil nuc leotide- activated P2Y2, P2Y4, and P2Y6 receptor subtypes. Compound 19a was chemically and metabolically highly stable. In contrast to the few known (unselective) NTPDase inhibitors, 19a is an uncharged molecule and may be perorally bioavailable. NTPDase2 inhibitors have potential as novel cardioprotective drugs for the treatment of stroke and for cancer therapy.
• Synthesis of adenophostin A and congeners modified at glucose
  作者：Rachel D. Marwood、Andrew M. Riley、David J. Jenkins、Barry V. L. Potter

  DOI：10.1039/b001386m

  日期：——

  A convergent route is described to the super-potent 1D-myo-inositol 1,4,5-trisphosphate receptor agonist adenophostin A (2) and analogues 5 and 7, in which the glucose bisphosphate unit is replaced by corresponding xylose bisphosphate and mannose bisphosphate units respectively. Adenosine was converted into its 2′,3′-O-p-methoxybenzylidene derivative 8ab, which was selectively N6-dimethoxytritylated by a transient protection method. 5′-O-Benzylation followed by reductive acetal cleavage gave, after separation from its 3′-O-p-methoxybenzyl isomer, the versatile glycosyl acceptor 5′-O-benzyl-N6-dimethoxytrityl-2′-O-p-methoxybenzyladenosine 13. Coupling of 13 with selectively protected glucopyranosyl, xylopyranosyl or mannopyranosyl dimethyl phosphites gave the required 3′-O-α-pyranosyl adenosine derivatives. Acidic hydrolysis gave corresponding N6-unprotected triols which were phosphitylated using bis(benzyloxy)(diisopropylamino)phosphine and imidazolium triflate without further N6-protection. Deprotection gave the target trisphosphates 2, 5 and 7. Synthetic adenophostin A (2) was identical with a sample of natural material in all respects. Analogues 5 and 7 will be useful for structure–activity studies on the adenophostins.

  描述了超强效 1D-肌醇 1,4,5-三磷酸受体激动剂腺磷蛋白 A (2) 以及类似物 5 和 7 的收敛途径，其中葡萄糖二磷酸单元被相应的木糖二磷酸和甘露糖二磷酸取代分别为单位。腺苷转化为其2',3'-O-对甲氧基亚苯亚甲基衍生物8ab，并通过瞬时保护方法选择性地N6-二甲氧基三苯甲基化。 5'-O-苄基化，然后还原缩醛裂解，在与 3'-O-对甲氧基苄基异构体分离后，得到多功能糖基受体 5'-O-苄基-N6-二甲氧基三苯甲基-2'-O-对甲氧基苄基腺苷 13。 13 具有选择性保护的吡喃葡萄糖基、吡喃木糖基或吡喃甘露糖基亚磷酸二甲酯得到所需的3'-O-α-吡喃糖基腺苷衍生物。酸性水解得到相应的N6-未保护的三醇，将其使用双(苄氧基)(二异丙氨基)膦和三氟甲磺酸咪唑鎓进行亚磷酸化，无需进一步的N6-保护。脱保护得到目标三磷酸2、5和7。合成的腺苷磷汀A (2)在所有方面与天然材料样品相同。类似物 5 和 7 可用于腺苷磷酸酯的结构-活性研究。

表征谱图