5'-O-TBDMS-2',3'-O-isopropylideneinosine

• 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: 5'-O-TBDMS-2',3'-O-isopropylideneinosine
• 英文别名: 9-[(3aR,4R,6R,6aR)-6-[[tert-butyl(dimethyl)silyl]oxymethyl]-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-1H-purin-6-one
• 化学式: C₁₉H₃₀N₄O₅Si
• 分子量: 422.556
• InChiKey: IEXSGFQHEUKMCI-LSCFUAHRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.56
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  96.2
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  5'-O-TBDMS-2',3'-O-isopropylideneinosine 在 吡啶 、 四氮唑 、 甲醇 、 triisopropylbenzenesulfonyl chloride 、 四丁基氟化铵 、 sodium methylate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 64.5h， 生成 N¹-[[[bis-5''-(phenylthio)phosphoryl]oxyethoxy]methyl]-5'-O-dianilinophosphoryl-2',3'-O-isopropylideneinosine
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Novel Membrane-Permeant Cyclic ADP-Ribose Mimics:  N-[(5‘ ‘-O-Phosphorylethoxy)methyl]-5‘-O-phosphorylinosine 5‘,5‘ ‘-Cyclicpyrophosphate (cIDPRE) and 8-Substituted Derivatives

  摘要：

  N-1- [(5"-O-Phosphorylethoxy)methyl] -5'-O-phosphorylinosine 5',5"-cyclicpyrophosphate (cIDPRE 2a) and the 8-substituted derivatives 8-bromo-, 8-azido-, 8-amino-, and 8-Cl-cIDPRE (2b-e) were synthesized from N1- [(5"-acetoxyethoxy)methyl] -2',3'-O-isopropylideneinosine (5) in good yields. The pharmacological activities of cIDPRE and the 8-substituted derivatives (2a-e) were analyzed in intact and permeabilized. human Jurkat T-lymphocytes. The results indicate that cIDPRE permeates the plasma membrane, releases Ca2+ from an intracellular, cADPR-sensitive Ca2+ store, and subsequently initiates Ca2+ release-activated Ca2+ entry. The Ca2+-releasing activity of cIDPRE was confirmed directly in permeabilized. cells. Using time-resolved confocal Ca2+ imaging at the single cell level, the development of global Ca2+ signals starting from local small Ca2+ signals evoked by cIDPRE was observed. 8-N-3-cIDPRE 2c and 8-NH2-cIDPRE 2d were similarly effective in their agonistic activity as compared to cIDPRE 2a, showing almost indistinguishable concentration-response curves for 2a, 2c, and 2d and very similar kinetics of Ca2+ signaling. In contrast, the halogenated derivatives 8-Br- and 8-Cl-cIDPRE (2b and 2e) did not significantly elevate [Ca2+](i). Therefore, cIDPRE 2a, 8-N-3-cIDPRE 2c, and 8-NH2-cIDPRE 2d are novel membrane permeant cADPR mimic and may provide important novel tools to study cADPR-mediated Ca2+ signaling in intact cells.

  DOI：

  10.1021/jm040092t
• 作为产物：
  描述：

  肌苷 在 对甲苯磺酰氯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 5'-O-TBDMS-2',3'-O-isopropylideneinosine
  参考文献：
  名称：

  一种新的合成cADPR类似物的硫取代的环焦磷酸盐的方法

  摘要：

  开发了一种简便高效的合成cIDPRE的硫取代的环焦磷酸盐（PS1-cIDPRE ）的方案。关键步骤是环化过程，该过程由硫取代的环化前体1b通过一锅亚磷酰胺策略完成。

  DOI：

  10.1016/j.cclet.2014.07.010

文献信息

• Nucleophile-Catalyzed Additions to Activated Triple Bonds. Protection of Lactams, Imides, and Nucleosides with MocVinyl and Related Groups
  作者：Laura Mola、Joan Font、Lluís Bosch、Joaquim Caner、Anna M. Costa、Gorka Etxebarría-Jardí、Oriol Pineda、David de Vicente、Jaume Vilarrasa

  DOI：10.1021/jo4006409

  日期：2013.6.21

  Additions of lactams, imides, (S)-4-benzyl-1,3-oxazolidin-2-one, 2-pyridone, pyrimidine-2,4-diones (AZT derivatives), or inosines to the electron-deficient triple bonds of methyl propynoate, tert-butyl propynoate, 3-butyn-2-one, N-propynoylmorpholine, or N-methoxy-N-methylpropynamide in the presence of many potential catalysts were examined. DABCO and, second, DMAP appeared to be the best (highest

  将内酰胺，酰亚胺，（S）-4-苄基-1,3-恶唑烷-2-酮，2-吡啶酮，嘧啶-2,4-二酮（AZT衍生物）或肌苷添加到在许多潜在催化剂的存在下，检查了丙酸甲酯，丙酸叔丁酯，3-丁炔-2-酮，N-丙酰基吗啉或N-甲氧基-N-甲基丙炔酰胺。DABCO和其次是DMAP似乎是最好的（最高的反应速率和E / Z比），而RuCl 3，RuClCp *（PPh 3）2，AuCl，AuCl（PPh 3），CuI和Cu 2（OTf）2个不能催化这种添加。并入的基团（例如，我们称为MocVinyl的2-（甲氧基羰基）乙烯基）用作上述杂环CONH或CONHCO部分的保护基。脱保护是通过与良好的亲核试剂进行交换来实现的：1-十二烷硫醇根阴离子被证明是最通用，最有效的试剂，但在某些特定情况下，其他亲核试剂也起作用（例如，MocVinyl-肌苷可被琥珀酰亚胺阴离子裂解）。DFT和MP2计算帮助解决了一些结构和机械细节。
• Concise synthesis of novel acyclic analogues of cADPR with an ether chain as the northern moiety
  作者：Huimin Wu、Zhenjun Yang、Liangren Zhang、Lihe Zhang

  DOI：10.1039/b9nj00595a

  日期：——

  To study the properties of hydrolysates of cyclic adenosine diphosphate ribose (cADPR), a series of novel acyclic analogues of cADPR with an ether chain as the northern moiety and 8-substituted adenine or hypoxanthine as the base moiety were synthesized via an N1 substitution construction, followed by bisphosphorylation, phosphoramidition or pyrophosphorylation. These compounds also provide various precursors for synthesizing cADPR analogues.

  为了研究环腺苷二磷酸核糖（cADPR）水解产物的性质，合成了一系列以醚链作为北基团，8取代腺嘌呤或次黄嘌呤作为碱基团的新型无环类cADPR类似物，合成过程包括N1取代反应，随后进行双磷酸化、磷酰胺化或焦磷酸化。这些化合物还提供了合成cADPR类似物的多种前体。
• Synthesis and Biological Evaluation of a New Structural Simplified Analogue of cADPR, a Calcium-Mobilizing Secondary Messenger Firstly Isolated from Sea Urchin Eggs
  作者：Stefano D’Errico、Nicola Borbone、Bruno Catalanotti、Agnese Secondo、Tiziana Petrozziello、Ilaria Piccialli、Anna Pannaccione、Valeria Costantino、Luciano Mayol、Gennaro Piccialli、Giorgia Oliviero

  DOI：10.3390/md16030089

  日期：——

  Herein, we reported on the synthesis of cpIPP, which is a new structurally-reduced analogue of cyclic ADP-ribose (cADPR), a potent Ca2+-releasing secondary messenger that was firstly isolated from sea urchin eggs extracts. To obtain cpIPP the “northern” ribose of cADPR was replaced by a pentyl chain and the pyrophosphate moiety by a phophono-phosphate anhydride. The effect of the presence of the new phosphono-phosphate bridge on the intracellular Ca2+ release induced by cpIPP was assessed in PC12 neuronal cells in comparison with the effect of the pyrophosphate bridge of the structurally related cyclic N1-butylinosine diphosphate analogue (cbIDP), which was previously synthesized in our laboratories, and with that of the linear precursor of cpIPP, which, unexpectedly, revealed to be the only one provided with Ca2+ release properties.

  在此，我们报告了 cpIPP 的合成，它是环状 ADP-核糖（cADPR）的一种新的结构还原类似物，cADPR 是一种强效的 Ca2+ 释放次级信使，最早从海胆卵提取物中分离出来。为了获得 cpIPP，cADPR 的 "北 "核糖被戊基链取代，焦磷酸分子被磷酸酐取代。我们在 PC12 神经细胞中评估了新的膦酰基磷酸桥对 cpIPP 诱导的细胞内 Ca2+ 释放的影响，并将其与我们实验室以前合成的结构相关的环 N1-丁基肌苷二磷酸类似物（cbIDP）的焦磷酸桥的影响以及 cpIPP 线性前体的焦磷酸桥的影响进行了比较。
• Probing the Ca2+ mobilizing properties on primary cortical neurons of a new stable cADPR mimic
  作者：Stefano D'Errico、Francesca Greco、Andrea Patrizia Falanga、Valentina Tedeschi、Ilaria Piccialli、Maria Marzano、Monica Terracciano、Agnese Secondo、Giovanni Nicola Roviello、Giorgia Oliviero、Nicola Borbone

  DOI：10.1016/j.bioorg.2021.105401

  日期：2021.12

  focuses on the synthesis of N1 substituted inosines, in the last few years we have produced new flexible cIDPR analogues, where the northern ribose has been replaced by alkyl chains. Interestingly, some of them mobilized Ca2+ ions in PC12 cells. To extend our SAR studies, herein we report on the synthesis of a new stable cIDPR derivative which contains the 2″S,3″R dihydroxypentyl chain instead of the

  环状二磷酸腺苷核糖 (cADPR) 是参与 Ca 2+稳态的第二信使。它的化学不稳定性促使研究人员逐点调整其结构，获得具有有趣生物学特性的稳定类似物。最具挑战性的衍生物之一是环状肌苷二磷酸核糖 (cIDPR)，其中次黄嘌呤等排取代腺嘌呤。由于我们的研究侧重于 N1 取代肌苷的合成，因此在过去几年中，我们生产了新的灵活 cIDPR 类似物，其中北部核糖已被烷基链取代。有趣的是，它们中的一些动员了 PC12 细胞中的 Ca 2+离子。为了扩展我们的 SAR 研究，我们在此报告了一种新的稳定 cIDPR 衍生物的合成，该衍生物包含 2"S ,3″ R二羟基戊基链而不是北核糖。有趣的是，新的环状衍生物及其开放前体诱导了细胞内钙浓度 ([Ca 2+ ] i ) 的增加，其功效与大鼠原代皮层神经元中的内源性 cADPR 相同。
• Mild and Efficient Functionalization at C6 of Purine 2‘-Deoxynucleosides and Ribonucleosides¹
  作者：Xiaoyu Lin、Morris J. Robins

  DOI：10.1021/ol000255h

  日期：2000.11.1

  [reaction: see text] Treatment of sugar-protected inosine and 2'-deoxyinosine derivatives with a cyclic secondary amine or imidazole and I(2)/Ph(3)P/EtN(i-Pr)(2)/(CH(2)Cl(2) or toluene) gave quantitative conversions into 6-N-(substituted)purine nucleosides. S(N)Ar reactions with 6-(imidazol-1-yl) derivatives gave 6-(N, O, or S)-substituted products. The 6-(benzylsulfonyl) group underwent S(N)Ar displacement

  [反应：请参见文本]用环状仲胺或咪唑和I（2）/ Ph（3）P / EtN（i-Pr）（2）/（CH（ 2）Cl（2）或甲苯）定量转化为6-N-（取代）嘌呤核苷。与6-（咪唑-1-基）衍生物的S（N）Ar反应得到6-（N，O或S）-取代的产物。在环境温度下用芳基胺对6-（苄基磺酰基）进行S（N）Ar取代。