((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl methanesulfonate | 68179-90-8

• 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: ((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl methanesulfonate
• 英文别名: (3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-ylmethyl methanesulfonate；2'-O,3'-O-isopropylidene-5'-O-mesyladenosine；2',3'-O-isopropylidene-4'-O-mesyladenosine；5'-O-mesyl-2',3'-isopropylideneadenosine；O^{2'_,O3'_{-isopropylidene-O}5'}-methanesulfonyl-adenosine；[(3aR,4R,6R,6aR)-4-(6-aminopurin-9-yl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methyl methanesulfonate
• CAS: 68179-90-8
• 化学式: C₁₄H₁₉N₅O₆S
• 分子量: 385.401
• InChiKey: FRFKWAXFMQFSLP-QYVSTXNMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  149
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  ((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl methanesulfonate 在 硫酸 、 四丁基氟化铵 作用下， 以 乙腈 为溶剂， 反应 28.0h， 生成 5'-fluoro-5'-deoxyadenosine
  参考文献：
  名称：

  Cell-Free Biosynthesis of Fluoroacetate and 4-Fluorothreonine in Streptomyces cattleya

  摘要：

  DOI：

  10.1002/1521-3773(20021018)41:20<3913::aid-anie3913>3.0.co;2-e
• 作为产物：
  描述：

  腺苷 在 高氯酸 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 22.0h， 生成 ((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl methanesulfonate
  参考文献：
  名称：

  DOT1L抑制剂衍生的基于小分子亲和力的探针的原位蛋白质组分析和生物成像应用

  摘要：

  DOT1L是使赖氨酸79（H3K79）上的组蛋白H3甲基化的唯一蛋白质甲基转移酶，并且是一种有前途的抗癌药物。DOT1L的小分子抑制剂（例如FED1）是潜在的抗癌药，是研究DOT1L在人类疾病中的生物学作用的有用工具。FED1对DOT1L表现出优异的体外抑制活性，但其细胞作用相对较差。在这项研究中，我们设计并合成了具有光反应性和“可点击”亲和力的探针（AfBPs）P1和P2，它们是FED1的细胞渗透性和结构类似物。在体外和活的哺乳动物细胞（原位）中广泛研究了这两种探针对DOT1L蛋白的结合和抑制作用。随后在活细胞成像实验中研究了探针的细胞摄取和亚细胞定位特性，我们的结果表明，尽管P1和P2都容易进入哺乳动物细胞，但大多数不能到达细胞核，功能DOT1L驻留。这为FED1的细胞活性差提供了一个合理的解释。最后，使用P1 / P2进行大规模基于细胞的蛋白质组分析，然后进行定量LC-MS / MS

  DOI：

  10.1002/chem.201600259

文献信息

• Synthesis of asymmetrically substituted cyclen-based ligands for the controlled sensitisation of lanthanides
  作者：K. Eszter Borbas、James I. Bruce

  DOI：10.1039/b705757a

  日期：——

  A series of unsymmetrical cyclen-based ligands incorporating an antenna and a quencher have been prepared for the complexation of the visible- (Eu, Tb) and near IR-emitting (Nd, Yb) lanthanides. Eu and Tb were sensitised with coumarin 2, and Nd and Yb with rhodamine. Both antennae were paired with nucleoside (uridine and adenosine) quenchers. The interaction between the quencher and the antenna can be regulated by the addition of the complementary base or DNA to the complexes, resulting in changes in the lanthanide luminescence intensity and lifetime.

  一系列不对称的基于环的配体被制备，以结合可见光（Eu，Tb）和近红外发射（Nd，Yb）的锕系元素。这些配体中，Eu和Tb与香豆素2进行敏化，而Nd和Yb则与罗丹明结合。两个天线都与核苷（尿苷和腺苷）熄灭剂配对。通过向复合物中添加互补碱基或DNA，可以调节熄灭剂与天线之间的相互作用，从而导致锕系元素的发光强度和寿命发生变化。
• Efficient Synthesis of Methylenebis(phosphonate) Analogues of P¹,P²-Disubstituted Pyrophosphates of Biological Interest. A Novel Plausible Mechanism
  作者：Krzysztof W. Pankiewicz、Krystyna Lesiak、Kyoichi A. Watanabe

  DOI：10.1021/ja964058i

  日期：1997.4.1

  Synthesis of novel nucleoside bicyclic trisanhydrides 7 in the reaction of nucleoside-5'-methylenebis-(phosphonate)s (4) with DCC is described. They were obtained by P-1,P-3- and P-2,P-3-dehydration of initially formed P-1,P-2,P-3,P-4-bismethylenetetraphosphonate 6. Reaction of 7 (N = 2',3'-O-isopropylideneadenosin-5'-yl) with 2',3'-O-isopropylidenetiazofurin gave, after hydrolysis and deisopropylidenation, beta-methylene-TAD (10a), the known potent inhibitor of inosine monophosphate dehydrogenase (IMPDH). Similar reaction of 7 with benzyl 2,3-O-isopropylidene-beta-D-riboside followed by hydrolysis and deprotection afforded a new methylenebis(phosphonate) analogue of ADP-ribose 10b. Upon reaction of 7 with riboflavin, the corresponding beta-methylene-FAD (10c) was obtained. Bicyclic trisanhydride 7 prepared from (2',3'-O-isopropylidene-N-4-acetylcytidin-5'yl)methylenebis(phosphonate) was used in the synthesis of the methylenebis(phosphonate) analogues of CDP-ethanolamine 10d and CDP-dipalmitoylglycerol 10e.
• New Insights into the Design of Inhibitors of Human <i>S</i>-Adenosylmethionine Decarboxylase: Studies of Adenine C⁸ Substitution in Structural Analogues of <i>S</i>-Adenosylmethionine
  作者：Diane E. McCloskey、Shridhar Bale、John A. Secrist、Anita Tiwari、Thomas H. Moss、Jacob Valiyaveettil、Wesley H. Brooks、Wayne C. Guida、Anthony E. Pegg、Steven E. Ealick

  DOI：10.1021/jm801126a

  日期：2009.3.12

  S-adenosylmethionine decarboxylase (AdoMetDC) is a critical enzyme in the polyamine biosynthetic pathway and depends on a pyruvoyl group for the decarboxylation process. The crystal structures of the enzyme with various inhibitors at the active site have shown that the adenine base of the ligands adopts an unusual syn conformation when bound to the enzyme. To determine whether compounds that favor the syn conformation in solution would be more potent AdoMetDC inhibitors, several series of AdoMet substrate analogues with a variety of substituents at the 8-position of adenine were synthesized and analyzed for their ability to inhibit hAdoMetDC. The biochemical analysis indicated that an 8-methyl substituent resulted in more potent inhibitors, yet most other 8-substitutions provided no benefit over the parent compound. To understand these results, we used computational modeling and X-ray crystallography to study C(8)-substituted adenine analogues bound in the active site.
• [EN] 5'-SUBSTITUTED ADENOSYNES, PREPARATION THEREOF AND USE AS INHIBITORS OF S-ADENOSYLMETHIONINE DECARBOXYLASE<br/>[FR] ADÉNOSYNES SUBSTITUÉES EN 5', PRÉPARATION DE CELLES-CI ET UTILISATION COMME INHIBITEUR DE LA S-ADÉNOSYLMÉTHIONINE DÉCARBOXYLASE
  申请人：SOUTHERN RES INST

  公开号：WO2009018541A8

  公开（公告）日：2010-03-04
• Gani, David; Johnson, Alan W., Journal of the Chemical Society. Perkin transactions I, 1982, p. 1197 - 1204
  作者：Gani, David、Johnson, Alan W.

  DOI：——

  日期：——