8-chloro-N¹-[[[2-(phenylthio)phosphoryl]oxy-ethoxy]methyl]-5'-O-phosphoryl-2',3'-O-isopropylideneinosine | 444989-19-9

• 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: 8-chloro-N¹-[[[2-(phenylthio)phosphoryl]oxy-ethoxy]methyl]-5'-O-phosphoryl-2',3'-O-isopropylideneinosine
• 英文别名: 2-[[9-[(3aR,4R,6R,6aR)-2,2-dimethyl-6-(phosphonooxymethyl)-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-8-chloro-6-oxopurin-1-yl]methoxy]ethoxy-phenylsulfanylphosphinic acid
• CAS: 444989-19-9
• 化学式: C₂₂H₂₇ClN₄O₁₂P₂S
• 分子量: 668.942
• InChiKey: DODYINGUXHGZMO-WVSUBDOOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  42
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  226
• 氢给体数：
  3
• 氢受体数：
  15

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  ——	8-chloro-N1-[[[bis(phenylthio)phosphoryl]oxy-ethoxy]methyl]-5'-O-(dianilinophosphoryl)-2',3'-O-isopropylideneinosine	444989-18-8	C40H41ClN6O9P2S2	911.333
  ——	9-[(3aR,4R,6R,6aR)-6-(dianilinophosphoryloxymethyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-8-bromo-1-(2-hydroxyethoxymethyl)purin-6-one	444989-17-7	C28H32BrN6O8P	691.475
  ——	5'-O-TBDMS-2',3'-O-isopropylidene-8-bromoinosine	203249-43-8	C19H29BrN4O5Si	501.453

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	(1R,20R,21R,25R)-3-chloro-15,17-dihydroxy-23,23-dimethyl-15,17-dioxo-11,14,16,18,22,24,26-heptaoxa-2,4,7,9-tetraza-15lambda5,17lambda5-diphosphapentacyclo[18.5.1.15,9.02,6.021,25]heptacosa-3,5,7-trien-27-one	444989-20-2	C16H21ClN4O12P2	558.763

反应信息

• 作为反应物：
  描述：

  8-chloro-N¹-[[[2-(phenylthio)phosphoryl]oxy-ethoxy]methyl]-5'-O-phosphoryl-2',3'-O-isopropylideneinosine 在 吡啶 、 碘 作用下， 生成 (1R,20R,21R,25R)-3-chloro-15,17-dihydroxy-23,23-dimethyl-15,17-dioxo-11,14,16,18,22,24,26-heptaoxa-2,4,7,9-tetraza-15lambda5,17lambda5-diphosphapentacyclo[18.5.1.15,9.02,6.021,25]heptacosa-3,5,7-trien-27-one
  参考文献：
  名称：

  Chemical synthesis and calcium release activity of N 1 -ether strand substituted cADPR mimic

  摘要：

  8-Chloro cyclic inosine 5'-diphosphate ethoxymethyl ether 3 was synthesized by means of chemical method from protected inosine via phenylthio-type biphosphate substrate. The detection of Ca2+ release activity shows that 3 is a potent agonist of cADPR and has activity in intact Hela cells. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00033-1
• 作为产物：
  描述：

  8-bromo-N¹-[(2-acetoxyethoxy)-methyl]-2',3'-O-isopropylideneinosine 在 吡啶 、 四氮唑 、 甲醇 、 triisopropylbenzenesulfonyl chloride 、 sodium methylate 、 乙酸酐 、 溶剂黄146 、 亚硝酸异戊酯 作用下， 以 吡啶 为溶剂， 反应 91.0h， 生成 8-chloro-N¹-[[[2-(phenylthio)phosphoryl]oxy-ethoxy]methyl]-5'-O-phosphoryl-2',3'-O-isopropylideneinosine
  参考文献：
  名称：

  Syntheses and Calcium-Mobilizing Evaluations of N-Glycosyl-Substituted Stable Mimics of Cyclic ADP-Ribose

  摘要：

  Cyclic ADP-ribose (cADPR) is not only a potent endogenous calcium modulator but also a second messenger. However, studies on the mechanism of cADPR action were limited due to its instability and lack of available structural modifications in the N-1-glyosyl unit of cADPR. In the present work, a series of N-1-glycosyl mimics with different configurational glycosyls or an ether strand were designed and synthesized mimicking the furanose ring. S(N)2 substitutions were carried out between the protected inosine and glycosyl triflates to form the N-1-glycosylinosine derivatives, accompanied with some O-6-glyeosyl-substituted as side products. The intramolecular cyclization was followed the strategy described by Matsuda et al. It was found that the 8-unsubstituted substrate could also be used to construct the intramolecular cyclic pyrophosphate. The activities of NI-glycosyl-substituted cADPR mimics were evaluated by induced Ca2+ release in rat brain microsomes and HeLa cells. It was found that the configuration of the N-1-glycosyl moiety in cADPR is not a critical structural factor for retaining the activity of mobilizing Ca2+ release. More interestingly, the N-1-acyclic analogue 6 exhibited strong activity by inducing Ca2+ release in both rat brain microsomes and HeLa cells. It constitutes a useful tool for further studies.

  DOI：

  10.1021/jm010530l

文献信息

• Chemical synthesis and calcium release activity of N 1 -ether strand substituted cADPR mimic
  作者：Li-Jun Huang、Yong-Yuan Zhao、Lan Yuan、Ji-Mei Min、Li-He Zhang

  DOI：10.1016/s0960-894x(02)00033-1

  日期：2002.3

  8-Chloro cyclic inosine 5'-diphosphate ethoxymethyl ether 3 was synthesized by means of chemical method from protected inosine via phenylthio-type biphosphate substrate. The detection of Ca2+ release activity shows that 3 is a potent agonist of cADPR and has activity in intact Hela cells. (C) 2002 Elsevier Science Ltd. All rights reserved.
• Syntheses and Calcium-Mobilizing Evaluations of <i>N</i>-Glycosyl-Substituted Stable Mimics of Cyclic ADP-Ribose
  作者：Li-Jun Huang、Yong-Yuan Zhao、Lan Yuan、Ji-Mei Min、Li-He Zhang

  DOI：10.1021/jm010530l

  日期：2002.11.1

  Cyclic ADP-ribose (cADPR) is not only a potent endogenous calcium modulator but also a second messenger. However, studies on the mechanism of cADPR action were limited due to its instability and lack of available structural modifications in the N-1-glyosyl unit of cADPR. In the present work, a series of N-1-glycosyl mimics with different configurational glycosyls or an ether strand were designed and synthesized mimicking the furanose ring. S(N)2 substitutions were carried out between the protected inosine and glycosyl triflates to form the N-1-glycosylinosine derivatives, accompanied with some O-6-glyeosyl-substituted as side products. The intramolecular cyclization was followed the strategy described by Matsuda et al. It was found that the 8-unsubstituted substrate could also be used to construct the intramolecular cyclic pyrophosphate. The activities of NI-glycosyl-substituted cADPR mimics were evaluated by induced Ca2+ release in rat brain microsomes and HeLa cells. It was found that the configuration of the N-1-glycosyl moiety in cADPR is not a critical structural factor for retaining the activity of mobilizing Ca2+ release. More interestingly, the N-1-acyclic analogue 6 exhibited strong activity by inducing Ca2+ release in both rat brain microsomes and HeLa cells. It constitutes a useful tool for further studies.