5-O-<(1,1-dimethylethyl)dimethylsilyl>-2,3-O-(1-methylethylidene)-β-D-ribofuranosyl chloride | 102690-95-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-O-<(1,1-dimethylethyl)dimethylsilyl>-2,3-O-(1-methylethylidene)-β-D-ribofuranosyl chloride
• 英文别名: [(3aR,4S,6R,6aR)-4-chloro-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methoxy-tert-butyl-dimethylsilane
• CAS: 102690-95-9
• 化学式: C₁₄H₂₇ClO₄Si
• 分子量: 322.904
• InChiKey: NRPBYXLEHPXGMA-DDHJBXDOSA-N

物化性质

• 沸点：
  356.6±42.0 °C(Predicted)
• 密度：
  1.08±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.49
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  36.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-O-<(1,1-dimethylethyl)dimethylsilyl>-2,3-O-(1-methylethylidene)-β-D-ribofuranosyl chloride 在 氢氧化钾 、 三(3,6-二氧杂庚基)胺 、 三氟乙酸 作用下， 反应 21.17h， 生成 2-amino-4-chloro-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine
  参考文献：
  名称：

  与7-去氮鸟苷相关的2,4-二取代的吡咯并[2,3- d ]嘧啶α-D-和β-D-呋喃核糖苷

  摘要：

  吡咯并[2,3- d ]嘧啶4a - d与5- O -[（1， 1-二甲基乙基）二甲基甲硅烷基] -2,3 - O-（1-甲基亚乙基）-α-D-核呋喃呋喃糖酰氯（5）立体选择得到保护的β-D-核苷6a - d（方案1）。相反，除少量的β-D-异头物外，β-D-卤代糖8产生相应的α-D-核苷（9a和9b）。去保护的核苷10a和11a被转化为4-取代的2-氨基吡咯并[2,3- d ]-嘧啶β-D-呋喃呋喃糖苷1。图10C，12，14，和16和到他们的α-d端基异构体，分别为（方案2）。从4b与5的反应中，分离出包含两个核碱基部分的糖基化产物7。

  DOI：

  10.1002/hlca.19900730710
• 作为产物：
  描述：

  2,3-O-isopropylidene-5-O-dimethyl-t-butylsiloxy-β-D-ribofuranose 在 四氯化碳 、 三(二甲胺基)膦 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 生成 5-O-<(1,1-dimethylethyl)dimethylsilyl>-2,3-O-(1-methylethylidene)-β-D-ribofuranosyl chloride
  参考文献：
  名称：

  立体异构合成纯D-呋喃呋喃糖基氯化物制备吡咯并[2,3- d ]嘧啶α-和β-D-核糖核苷：固液相转移糖基化和15 N-NMR光谱

  摘要：

  固-液相转移的糖基化（KOH，三[2-（2-甲氧基乙氧基）ethye]胺（TDA =-1），MeCN中）吡咯并[2,3的d ]嘧啶类，例如图3a和3b中与等摩尔量5- O -[（1，1-二甲基乙基）二甲基甲硅烷基] -2,3 - O-（1-甲基亚乙基）-α-D-呋喃呋喃糖基氯（1）的制备[6]得到了保护的β-D-核苷4a和图4b分别是立体选择性地（方案）。β-D-异头物2 [6]得到相应的带有痕量β-D-化合物的α-D-核苷5a和5b。6-取代的7-脱氮嘌呤核苷6a，7a和8被转化为结核菌素（10）或其α-D-异头物（11）。异头核糖核苷自旋-晶格弛豫测量表明Ť 1个在α-d系列HC的值（8）的增加相比，HC（8）在β-d系列显著而相对的对为真Ť 1的HC（1'）。分配了6个取代的7-脱氮嘌呤D-核呋喃糖苷的15 N-NMR数据，并将其与2'-脱氧化合物的15 N-NMR数据进行了比较。此

  DOI：

  10.1002/hlca.19880710623

文献信息

• [EN] OLIGONUCLEOTIDES HAVING MODIFIED NUCLEOSIDE UNITS<br/>[FR] OLIGONUCLEOTIDES A UNITES NUCLEOSIDIQUES MODIFIEES
  申请人：ISIS PHARMACEUTICALS INC

  公开号：WO2003099840A1

  公开（公告）日：2003-12-04

  Disclosed are oligonucleotides and oligonucleosides that include one or more modified nucleoside units. The oligonucleotides and oligonucleosides are particularly useful as antisense agents, ribozymes, aptamer, siRNA agents, probes and primers or, when hybridized to an RNA, as a substrate for RNA cleaving enzymes including RNase H and dsRNase.

  揭示了包含一个或多个修饰核苷酸单元的寡核苷酸和寡核苷苷。这些寡核苷酸和寡核苷苷特别适用作为反义物质、核酶、适配体、siRNA物质、探针和引物，或者在与RNA杂交时，作为RNA裂解酶（包括RNase H和dsRNase）的底物。
• 一种α核苷合成方法
  申请人：上海兆维科技发展有限公司

  公开号：CN108424433B

  公开（公告）日：2021-04-23

  本发明公开了一种α核苷合成方法。所述方法包括步骤：(1)使结构如式Ⅳ所示的5‑O‑叔丁基二甲基硅烷‑2,3‑O‑异亚丙基‑D‑呋喃核糖上的羟基氯化得到含有结构如式Ⅱ所示化合物的反应液；(2)将含有结构如式Ⅱ所示化合物的反应液与碱基进行偶联得到结构如式Ⅲ所示的化合物；和(3)使结构如式Ⅲ所示的化合物脱保护得到结构如式Ⅰ所示的α核苷。
• Adenosine Kinase Inhibitors. 2. Synthesis, Enzyme Inhibition, and Antiseizure Activity of Diaryltubercidin Analogues
  作者：Bheemarao G. Ugarkar、Angelo J. Castellino、Jay M. DaRe、Joseph J. Kopcho、James B. Wiesner、Juergen M. Schanzer、Mark D. Erion

  DOI：10.1021/jm0000259

  日期：2000.7.1

  In the preceding article (Ugarkar et al. J. Med. Chem. 2000, 43) we reported that analogues of tubercidin are potent adenosine kinase (AK) inhibitors with antiseizure activity in the rat maximum electroshock (MES) model. Despite the discovery of several highly potent AK inhibitors (AKIs), e.g., 5'-amino-5'-deoxy-5-iodotubercidin (1c) (IC50 = 0.0006 mu M), no compounds were identified that exhibited a safety, efficacy, and side effect profile suitable for further development. In this article, we demonstrate that substitution of the tubercidin molecule with aromatic rings at the N4- and the C5-positions not only retains AKI potency but also improves in vivo activity. Synthesis of such compounds entailed transformation of 4-arylanlino-5-iodotubercidin analogues to their corresponding 5-aryl derivatives via the Suzuki reaction. Alternatively, 4-N-suylamino-5-arylpyrrolo[2,3-d]pyrimdine bases were constructed and then glycosylated with appropriately protected alpha-ribofuranosyl chlorides using a phase-transfer catalyst. Several compounds exhibited potent activity in the rat MES seizure assay with ED(50)s less than or equal to 2.0 mg/kg, ip, and showed relatively mild side effects.
• Selective Targeting of Distinct Active Site Nucleophiles by Irreversible Src-Family Kinase Inhibitors
  作者：Nathan N. Gushwa、Sumin Kang、Jing Chen、Jack Taunton

  DOI：10.1021/ja310659j

  日期：2012.12.19

  Src-family tyrosine kinases play pivotal roles in human physiology and disease, and several drugs that target members of this family are in clinical use. None of these drugs appear to discriminate among closely related kinases. However, assessing their selectivity toward endogenous kinases in living cells remains a significant challenge. Here, we report the design of two Src-directed chemical probes, each consisting of a nucleoside scaffold with a 5'-electrophile. A 5'-fluorosulfonylbenzoate (1) reacts with the conserved catalytic lysine (Lys295) and shows little discrimination among related kinases. By contrast, a 5'-vinylsulfonate (2) reacts with a poorly conserved, proximal cysteine (Cys277) found in three Src-family and six unrelated kinases. Both 1 and 2 bear an alkyne tag and efficiently label their respective endogenous kinase targets in intact cells. Using 1 as a competitive probe, we determined the extent to which ponatinib, a clinical Bcr-Abl inhibitor, targets Src-family kinases. Remarkably, while ponatinib had little effect on endogenous Fyn or Src, it potently blocked the critical T-cell kinase, Lck. Probes 1 and 2 thus enable competitive profiling versus distinct kinase subsets in living cells.
• Stereoselective preparations of ribofuranosyl chlorides and ribofuranosyl acetates.Solvent effects and stereoselectivity in the reaction of ribofuranosyl acetates with trimethylallylsilane
  作者：Craig S. Wilcox、Renee M. Otoski

  DOI：10.1016/s0040-4039(86)80035-1

  日期：1986.1