(3R,4S,5R)-4-(benzyloxy)-5-((benzyloxy)methyl)-5-(2-(tosyloxy)ethyl)tetrahydrofuran-2,3-diyl diacetate | 452949-21-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (3R,4S,5R)-4-(benzyloxy)-5-((benzyloxy)methyl)-5-(2-(tosyloxy)ethyl)tetrahydrofuran-2,3-diyl diacetate
• 英文别名: 3,5-di-O-benzyl-4-C-(p-toluenesulfonyloxyethyl)-1,2-di-O-acetyl-D-erythropentofuranose；[(3R,4S,5R)-2-acetyloxy-5-[2-(4-methylphenyl)sulfonyloxyethyl]-4-phenylmethoxy-5-(phenylmethoxymethyl)oxolan-3-yl] acetate
• CAS: 452949-21-2
• 化学式: C₃₂H₃₆O₁₀S
• 分子量: 612.698
• InChiKey: QDYKNEJLTHEUOI-NJRPBVBHSA-N

物化性质

• 沸点：
  702.1±60.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  43
• 可旋转键数：
  16
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  132
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  (3R,4S,5R)-4-(benzyloxy)-5-((benzyloxy)methyl)-5-(2-(tosyloxy)ethyl)tetrahydrofuran-2,3-diyl diacetate 在 palladium dihydroxide 吡啶 、 sodium hydroxide 、 三氟甲磺酸三甲基硅酯 、 氢气 作用下， 以 甲醇 、 水 、 1,2-二氯乙烷 为溶剂， 反应 6.5h， 生成 2'-O,4'-C-ethyleneuridine
  参考文献：
  名称：

  作为有效的反义寡核苷酸的2'-O，4'-C-亚乙基桥核酸（ENA）的合成和性质。

  摘要：

  合成了新型双环核苷，2'-O，4'-C-乙烯核苷和2'-O，4'-C-丙烯核苷，作为反义寡核苷酸的构建基块，以进一步优化2'-O，4'-桥连核酸（2'，4'-BNA）或锁定核酸（LNA）的C-亚甲基键。这些核苷中的2'-O，4'-C-乙烯-和丙烯键都将糖的褶皱限制为RNA的N-构象，就像2'，4'-BNA / LNA一样。此外，具有2'-O，4'-C-乙烯核苷的乙烯桥连核酸（ENA）大大提高了对互补RNA的亲和力，并且与2'，4'-BNA / LNA（DeltaT （m）＝ + 3，每次修改约5摄氏度。另一方面，添加2'-O，4' 寡核苷酸中的-C-丙烯修饰导致与互补RNA的亲和力降低。至于对核酸酶的稳定性，在寡核苷酸中掺入一个2'-O，4'-C-乙烯或一个2'-O，4'-C-丙烯核苷可显着提高其对核酸外切酶的抗性至大于2'的程度。 ，4'-BNA / LNA。这些结果表明ENA比2'，4'-BNA

  DOI：

  10.1016/s0968-0896(03)00115-9
• 作为产物：
  描述：

  (3aR,5R,6S,6aR)-6-(benzyloxy)-5-((benzyloxy)methyl)-2,2-dimethyl-5-vinyltetrahydrofuro[2,3-d][1,3]dioxole 在 9-borabicyclo[3.3.1]nonane dimer 、 硫酸 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 溶剂黄146 为溶剂， 生成 (3R,4S,5R)-4-(benzyloxy)-5-((benzyloxy)methyl)-5-(2-(tosyloxy)ethyl)tetrahydrofuran-2,3-diyl diacetate
  参考文献：
  名称：

  2′-O,4′-C-ethylene-bridged nucleic acids (ENA): highly nuclease-resistant and thermodynamically stable oligonucleotides for antisense drug

  摘要：

  To develop antisense oligonucleotides, novel nucleosides, 2'-O-4'-C-ethylene nucleosides and their corresponding phosphoramidites, were synthesized as building blocks. The H-1 NMR analysis showed that the 2'-O,4'-C-ethylene linkage of these nucleosides restricts the sugar puckering to the N-conformation as well as the linkage of 2'-O,4'-C-methylene nucleosides which are known as bridged nucleic acids (BNA) or locked nucleic acids (LNA). The ethylene-bridged nucleic acids (ENA) showed a high binding affinity for the complementary RNA strand (DeltaT(m) = +5.2 degreesC/modification) and were more nuclease-resistant than natural DNA and BNA/LNA. These results indicate that ENA have better properties as antisense oligonucleotides than BNA/LNA. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00683-7

文献信息

• Synthesis of 2′-O,4′-C-alkylene-bridged ribonucleosides and their evaluation as inhibitors of HCV NS5B polymerase
  作者：Christopher Chapron、Rebecca Glen、Massimiliano La Colla、Benjamin A. Mayes、Joseph F. McCarville、Stephen Moore、Adel Moussa、Ruhul Sarkar、Maria Seifer、Ilaria Serra、Alistair Stewart

  DOI：10.1016/j.bmcl.2014.04.050

  日期：2014.6

  The synthesis of 2'-O,4'-C-methylene-bridged bicyclic guanine ribonucleosides bearing 2'-C-methyl or 5'C-methyl modifications is described. Key to the successful installation of the methyl functionality in both cases was the use of a one-pot oxidation-Grignard procedure to avoid formation of the respective unreactive hydrates prior to alkylation. The 2'-C-methyl- and 5'-C-methyl-modified bicyclic guanosines were evaluated, along with the known uracil-, cytosine-, adenine-, guanine-LNA and guanine-ENA nucleosides, as potential antiviral agents and found to be inactive in the hepatitis C virus (HCV) cell-based replicon assay. Examination of the corresponding nucleoside triphosphates, however, against the purified HCV NS5B polymerase indicated that LNA-G and 2'-C-methyl-LNA-G are potent inhibitors of both 1b wild type and S282T mutant enzymes in vitro. Activity was further demonstrated for the LNA-G-triphosphate against HCV NS5B polymerase genotypes 1a, 2a, 3a and 4a. A phosphorylation by-pass prodrug strategy may be required to promote anti-HCV activity in the replicon assay. (C) 2014 Elsevier Ltd. All rights reserved.