3'-de(oxyphosphinico)-3'-[methylene(methylimino)]-5'-O-(4,4'-dimethoxytriphenylmethyl)-2'-O-methyl-5-methyluridylyl-(3'->5')-2'-O-methyl-5-methyluridine | 183737-17-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 3'-de(oxyphosphinico)-3'-[methylene(methylimino)]-5'-O-(4,4'-dimethoxytriphenylmethyl)-2'-O-methyl-5-methyluridylyl-(3'->5')-2'-O-methyl-5-methyluridine
• 英文别名: 1-[(2R,3R,4R,5S)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-[[[(2R,3R,4R,5R)-3-hydroxy-4-methoxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-methylamino]methyl]-3-methoxyoxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 183737-17-9
• 化学式: C₄₅H₅₃N₅O₁₃
• 分子量: 871.942
• InChiKey: SHDNZLHLEPOQKA-KQDZNZBISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  63
• 可旋转键数：
  17
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  196
• 氢给体数：
  3
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  双(二异丙基氨基)(2-氰基乙氧基)膦 、 3'-de(oxyphosphinico)-3'-[methylene(methylimino)]-5'-O-(4,4'-dimethoxytriphenylmethyl)-2'-O-methyl-5-methyluridylyl-(3'->5')-2'-O-methyl-5-methyluridine 在 二异丙基铵盐四氮唑 作用下， 以 二氯甲烷 为溶剂， 以83%的产率得到3-[[(2R,3R,4R,5R)-2-[[[(2S,3R,4R,5R)-2-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-methoxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]methyl-methylamino]oxymethyl]-4-methoxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxy-[di(propan-2-yl)amino]phosphanyl]oxypropanenitrile
  参考文献：
  名称：

  Synthesis of 2′‐Substituted MMI Linked Nucleosidic Dimers: An Optimization Study in Search of High Affinity Oligonucleotides for Use in Antisense Constructs

  摘要：

  The synthesis of a series of methylene(methylimino) (MMI) linked oligodeoxyribonucleotide dimers modified at the 2'-position with fluoro and/or methoxy groups and their incorporation into different sequences has been accomplished. From these dimers, his 2'-OMe MMI dimer was selected for further studies based on its synthetic accessibility and the increased thermodynamic stability conferred upon oligonucleotides incorporating this modification.

  DOI：

  10.1081/ncn-120028337
• 作为产物：
  描述：

  3'-de(oxyphosphinico)-3'-[methylene(methylimino)]-5'-O-(tert-butyldiphenylsilyl)-2'-O-methyl-5-methyluridylyl-(3'->5')-3'-O-(tert-butyldiphenylsilyl)-2'-O-methyl-5-methyluridine 在 吡啶 、 triethylamine tris(hydrogen fluoride) 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 生成 3'-de(oxyphosphinico)-3'-[methylene(methylimino)]-5'-O-(4,4'-dimethoxytriphenylmethyl)-2'-O-methyl-5-methyluridylyl-(3'->5')-2'-O-methyl-5-methyluridine
  参考文献：
  名称：

  通过3'-碘代核苷和甲甲醛肟的立体选择性分子间自由基偶联合成新型核酸模拟物（1）。

  摘要：

  由双（三甲基锡烷基）苯并频哪酸酯（8）介导的烷基碘和肟的高度收敛性自由基偶联已被用于制备一系列二聚核苷，以模拟天然核酸。反应条件的系统优化允许将适当的碘化物和肟单步转化为中等至极好的收率的2'-脱氧二聚体9。例如，3'-脱氧-3'-碘-5'-（三苯基甲基）胸苷（6a）与3'-O-（叔丁基二苯基甲硅烷基）-5'-O-（亚甲基亚氨基）胸苷（7a）的反应在8存在下，在脱气的苯中得到81％的3'-脱（氧膦）-3'-（亚甲基亚氨基）-5'-O-（三苯甲基）胸苷基-（3'-> 5'）-3 -O-（叔丁基二苯基甲硅烷基）胸苷（9a）。同样制备的是含有嘧啶（胸腺嘧啶，5-甲基胞嘧啶）和嘌呤（腺嘌呤，鸟嘌呤）碱基的二聚体。该反应是高度立体选择性的，仅给出具有新引入的C-3'-支链亚甲基部分的核糖构型的单个二聚体物质。还制备了二聚体16，在二聚体的两半中都掺入了2'-O-甲基核糖核苷。这需要合成3'-脱氧-3

  DOI：

  10.1021/jo961549c

文献信息

• The Synthesis of the Sixteen Possible 2′-<i>O</i>-Methyl MMI Dimer Phosphoramidites: Building Blocks for the Synthesis of Novel Antisense Oligonucleotides
  作者：Eric E. Swayze、Balkrishen Bhat、Didier Peoc'h、Yogesh S. Sanghvi

  DOI：10.1080/07328319708006118

  日期：1997.7
• Synthesis of 2′‐Substituted MMI Linked Nucleosidic Dimers: An Optimization Study in Search of High Affinity Oligonucleotides for Use in Antisense Constructs
  作者：Didier Peoc'h、Eric E. Swayze、Balkrishen Bhat、Yogesh S. Sanghvi

  DOI：10.1081/ncn-120028337

  日期：2004.1.1

  The synthesis of a series of methylene(methylimino) (MMI) linked oligodeoxyribonucleotide dimers modified at the 2'-position with fluoro and/or methoxy groups and their incorporation into different sequences has been accomplished. From these dimers, his 2'-OMe MMI dimer was selected for further studies based on its synthetic accessibility and the increased thermodynamic stability conferred upon oligonucleotides incorporating this modification.
• Synthesis of Novel Nucleic Acid Mimics <i>via</i> the Stereoselective Intermolecular Radical Coupling of 3‘-Iodo Nucleosides and Formaldoximes¹
  作者：Balkrishen Bhat、Eric E. Swayze、Patrick Wheeler、Stuart Dimock、Michel Perbost、Yogesh S. Sanghvi

  DOI：10.1021/jo961549c

  日期：1996.11.15

  5-methylcytosine) and purine (adenine, guanine) bases. The reaction was highly stereoselective, giving only a single dimeric species having the ribo-configuration of the newly introduced C-3'-branched methylene moiety. Also prepared were dimers 16, incorporating 2'-O-methyl ribonucleosides in both halves of the dimer. This required the synthesis of 3'-deoxy-3'-iodo-2'-O-methyl nucleosides 12 as well as 2'-O-me

  由双（三甲基锡烷基）苯并频哪酸酯（8）介导的烷基碘和肟的高度收敛性自由基偶联已被用于制备一系列二聚核苷，以模拟天然核酸。反应条件的系统优化允许将适当的碘化物和肟单步转化为中等至极好的收率的2'-脱氧二聚体9。例如，3'-脱氧-3'-碘-5'-（三苯基甲基）胸苷（6a）与3'-O-（叔丁基二苯基甲硅烷基）-5'-O-（亚甲基亚氨基）胸苷（7a）的反应在8存在下，在脱气的苯中得到81％的3'-脱（氧膦）-3'-（亚甲基亚氨基）-5'-O-（三苯甲基）胸苷基-（3'-> 5'）-3 -O-（叔丁基二苯基甲硅烷基）胸苷（9a）。同样制备的是含有嘧啶（胸腺嘧啶，5-甲基胞嘧啶）和嘌呤（腺嘌呤，鸟嘌呤）碱基的二聚体。该反应是高度立体选择性的，仅给出具有新引入的C-3'-支链亚甲基部分的核糖构型的单个二聚体物质。还制备了二聚体16，在二聚体的两半中都掺入了2'-O-甲基核糖核苷。这需要合成3'-脱氧-3