1,2-di-O-acetyl-5-O-(tert-butyldiphenylsilyl)-4-C-(1-methanesulfonyloxy-2-methoxyethyl)-3-O-(2-naphthylmethyl)-D-ribofuranose | 945628-68-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1,2-di-O-acetyl-5-O-(tert-butyldiphenylsilyl)-4-C-(1-methanesulfonyloxy-2-methoxyethyl)-3-O-(2-naphthylmethyl)-D-ribofuranose
• 英文别名: [(3R,4S,5R)-2-acetyloxy-5-[[tert-butyl(diphenyl)silyl]oxymethyl]-5-(2-methoxy-1-methylsulfonyloxyethyl)-4-(naphthalen-2-ylmethoxy)oxolan-3-yl] acetate
• CAS: 945628-68-2
• 化学式: C₄₀H₄₈O₁₁SSi
• 分子量: 764.966
• InChiKey: MILRBFHIKFOIKB-DIQGIVCJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.88
• 重原子数：
  53
• 可旋转键数：
  18
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  141
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  1,2-di-O-acetyl-5-O-(tert-butyldiphenylsilyl)-4-C-(1-methanesulfonyloxy-2-methoxyethyl)-3-O-(2-naphthylmethyl)-D-ribofuranose 、 尿嘧啶 在 N,O-双三甲硅基乙酰胺 、 三氟甲磺酸三甲基硅酯 作用下， 以 乙腈 为溶剂， 反应 0.25h， 生成 (2R,3R,4S,5R)-5-(((tert-butyldiphenylsilyl)oxy)methyl)-2-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-5-(2-methoxy-1-((methylsulfonyl)oxy)ethyl)-4-(naphthalen-2-ylmethoxy)tetrahydrofuran-3-yl acetate
  参考文献：
  名称：

  Synthesis and Biophysical Evaluation of 2′,4′-Constrained 2′O-Methoxyethyl and 2′,4′-Constrained 2′O-Ethyl Nucleic Acid Analogues

  摘要：

  We have recently shown that combining the structural elements of 2'O-methoxyethyl (MOE) and locked nuclecic acid (LNA) nucleosides yielded a series of nucleoside modification (cMOE, 2',4'-constrained MOE; cEt, 2',4'-constrained ethyl) that display improved potency over MOE and an improved therapeutic index relative to that of LNA antisense oligonucleotides. In this report we present details regarding the synthesis of the cMOE and cEt nucleoside phosphoramidites and the biophysical evaluation of oligonucleotides containing these nucleoside modification. The synthesis of the cMOE and eEt nucleoside phosphoramidites was efficiently accomplished starting from inexpensive commercially available diacetone allofuranose. The synthesis features the use of a seldom used 2-naphthylmethyl protecting group that provides crystalline intermediates during the synthesis and can be cleanly deprotected under mild conditions. The synthesis was greatly facilitated by the crystallinity of a key mono-TBDPS-protected diol intermediate. In the case of the cEt nucleosides, the introduction of the methyl group in either configuration was accomplished in a stereoselective manner. Ring closure of the 2'-hydroxyl group onto a secondary mesylate leaving group with clean inversion of stereochemistry was achieved under suprisingly mild conditions. For the S-cEt modification, the synthesis of all four (thymine, 5-methylcytosine, adenine, and guanine) nucleobase-modified phosphoramidites was accomplished on a multigram scale. Biophysical evaluation of the cMOE- and cEt-containing oligonucletides revealed that they possess hybridization and mismatch discrimination attributes similar to those of LNA but greatly improved resistance to exonuclease digestion.

  DOI：

  10.1021/jo902560f
• 作为产物：
  描述：

  1-((3aR,5R,6S,6aR)-5-(((tert-butyldiphenylsilyl)oxy)methyl)-2,2-dimethyl-6-(naphthalen-2-ylmethoxy)tetrahydrofuro[2,3-d][1,3]dioxol-5-yl)-2-methoxyethyl methanesulfonate 、 乙酸酐 在 硫酸 、 溶剂黄146 作用下， 反应 3.0h， 以10 g的产率得到1,2-di-O-acetyl-5-O-(tert-butyldiphenylsilyl)-4-C-(1-methanesulfonyloxy-2-methoxyethyl)-3-O-(2-naphthylmethyl)-D-ribofuranose
  参考文献：
  名称：

  Synthesis and Biophysical Evaluation of 2′,4′-Constrained 2′O-Methoxyethyl and 2′,4′-Constrained 2′O-Ethyl Nucleic Acid Analogues

  摘要：

  We have recently shown that combining the structural elements of 2'O-methoxyethyl (MOE) and locked nuclecic acid (LNA) nucleosides yielded a series of nucleoside modification (cMOE, 2',4'-constrained MOE; cEt, 2',4'-constrained ethyl) that display improved potency over MOE and an improved therapeutic index relative to that of LNA antisense oligonucleotides. In this report we present details regarding the synthesis of the cMOE and cEt nucleoside phosphoramidites and the biophysical evaluation of oligonucleotides containing these nucleoside modification. The synthesis of the cMOE and eEt nucleoside phosphoramidites was efficiently accomplished starting from inexpensive commercially available diacetone allofuranose. The synthesis features the use of a seldom used 2-naphthylmethyl protecting group that provides crystalline intermediates during the synthesis and can be cleanly deprotected under mild conditions. The synthesis was greatly facilitated by the crystallinity of a key mono-TBDPS-protected diol intermediate. In the case of the cEt nucleosides, the introduction of the methyl group in either configuration was accomplished in a stereoselective manner. Ring closure of the 2'-hydroxyl group onto a secondary mesylate leaving group with clean inversion of stereochemistry was achieved under suprisingly mild conditions. For the S-cEt modification, the synthesis of all four (thymine, 5-methylcytosine, adenine, and guanine) nucleobase-modified phosphoramidites was accomplished on a multigram scale. Biophysical evaluation of the cMOE- and cEt-containing oligonucletides revealed that they possess hybridization and mismatch discrimination attributes similar to those of LNA but greatly improved resistance to exonuclease digestion.

  DOI：

  10.1021/jo902560f

文献信息

• 6-MODIFIED BICYCLIC NUCLEIC ACID ANALOGS
  申请人：Swayze E. Eric

  公开号：US20070249049A1

  公开（公告）日：2007-10-25

  The present invention provides 6-modified bicyclic nucleoside analogs and oligomeric compounds comprising these nucleoside analogs. In preferred embodiments the nucleoside analogs have either (R) or (S)-chirality at the 6-position. These bicyclicnucleoside analogs are useful for enhancing properties of oligomeric compounds including nuclease resistance.

  本发明提供了6-修饰的双环核苷类似物和包含这些核苷类似物的寡聚化合物。在优选实施例中，核苷类似物在6位点具有(R)或(S)-手性。这些双环核苷类似物对提高包括核酸酶抗性在内的寡聚化合物的性能是有用的。