1-[(3'S,5'R,6'S)-5'-O-[(4,4'-dimethoxytriphenyl)methyl]-6'-[(ethoxycarbonyl)methyl]-3'-O-[(2-cyanoethoxy)-diisopropylaminophosphanyl]-2'-deoxy-3',5'-ethano-5',6'-methano-β-D-ribofuranosyl]thymine | 1374576-30-3

• 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: 1-[(3'S,5'R,6'S)-5'-O-[(4,4'-dimethoxytriphenyl)methyl]-6'-[(ethoxycarbonyl)methyl]-3'-O-[(2-cyanoethoxy)-diisopropylaminophosphanyl]-2'-deoxy-3',5'-ethano-5',6'-methano-β-D-ribofuranosyl]thymine
• CAS: 1374576-30-3
• 化学式: C₄₇H₅₇N₄O₁₀P
• 分子量: 868.964
• InChiKey: QQRJZBSSXOFWPQ-OKHVULSPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.68
• 重原子数：
  62.0
• 可旋转键数：
  19.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.49
• 拓扑面积：
  163.57
• 氢给体数：
  1.0
• 氢受体数：
  13.0

反应信息

• 作为反应物：
  描述：

  5’-(4,4’-二甲氧基三苯基)-3’-脱氧胸苷 2’-(2-氰乙基-N,N-二异丙基)亚磷酰胺 、 5'-O-(4,4'-dimethoxytrityl)-N-dimethyl-formamidine-2'-deoxyguanosine 3'-[(2-cyanoethyl)-(N,N-diisopropyl)]phosphoramidite 、 5’-O-(4,4’-二甲氧基三苯基)-N4-苯甲酰基-2’-脱氧胞苷-3’-(2-氰乙基-N,N-二异丙基)亚磷酰胺 、 5'-O-(4,4'-二甲氧基三苯基)-N6-苯甲酰基-2'-脱氧腺苷-3'-(2-氰乙基-N,N-二异丙基)亚磷酰胺 、 1-[(3'S,5'R,6'S)-5'-O-[(4,4'-dimethoxytriphenyl)methyl]-6'-[(ethoxycarbonyl)methyl]-3'-O-[(2-cyanoethoxy)-diisopropylaminophosphanyl]-2'-deoxy-3',5'-ethano-5',6'-methano-β-D-ribofuranosyl]thymine 、 1-[(3'S,5'R,6'S)-3'-O-trimethylsilyl-5'-O-(tert-butyldimethylsilyl)-6'-[(ethoxycarbonyl)methyl]-2'-deoxy-3',5'-ethano-5',6'-methano-β-D-ribofuranosyl]thymine 在 二氯乙酸 、 5-(乙硫基)-1H-四唑 作用下， 以 1,2-二氯乙烷 、 乙腈 为溶剂， 反应 0.03h， 生成
  参考文献：
  名称：

  Synthesis, Pairing, and Cellular Uptake Properties of C(6′)-Functionalized Tricyclo-DNA

  摘要：

  Tricyclo-DNA (tc-DNA) is a promising candidate for oligonucleotide-based therapeutic applications exhibiting increased affinity to RNA and increased resistance to nucleases. However, as many other oligonucleotide analogs, tc-DNA does not readily cross cell membranes. We wished to address this issue by preparing a prodrug of tc-DNA containing a metabolically labile group at C(6) that promotes cellular uptake. Two monomeric nucleoside building blocks bearing an ester function at C(6') (tc(ee)-T and tc(hd)-T) were synthesized starting from a known C(6') functionalized bicyclic sugar unit to which the cyclopropane ring was introduced via carbene addition. NIS-mediated nucleosidation of the corresponding glycal with in situ persilylated thymine afforded the beta-iodonucleoside exclusively that was dehalogenated via radical reduction. Diversity in the ester function was obtained by hydrolysis and reesterification. The two nucleosides were subsequently incorporated into DNA or tc-DNA by standard phosphoramidite chemistry. The reactivity of the ester function during oligonudeotide deprotection was explored and the corresponding C(6') amide, carboxylic acid, or unchanged ester functions were obtained, depending on the deprotection conditions. Compared to unmodified DNA, these tc-DNA derivatives increased the stability of duplexes investigated with Delta T-m/mod of +0.4 to +2.0 degrees C. The only destabilizing residue was tc(hd)-T, most likely due to self aggregation of the lipophilic side chains in the single stranded oligonucleotide. A decamer containing five tc(hd)-T residues was readily taken up by HeLa and HEK 293T cells without the use of a transfection agent.

  DOI：

  10.1021/jo300648u
• 作为产物：
  描述：

  (1S,3RS,5S)-5-hydroxy-3-methoxy-2-oxabicyclo[3.3.0]octan-8-one 在 吡啶 、 2,6-二甲基吡啶 、 N-碘代丁二酰亚胺 、 偶氮二异丁腈 、 Et₂Nipr₂ 、 氢氟酸 、 diethylzinc 、 三正丁基氢锡 、 N,O-双(三甲基硅烷基)三氟乙酰胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 为溶剂， 生成 1-[(3'S,5'R,6'S)-5'-O-[(4,4'-dimethoxytriphenyl)methyl]-6'-[(ethoxycarbonyl)methyl]-3'-O-[(2-cyanoethoxy)-diisopropylaminophosphanyl]-2'-deoxy-3',5'-ethano-5',6'-methano-β-D-ribofuranosyl]thymine
  参考文献：
  名称：

  Tricyclic nucleosides and oligomeric compounds prepared therefrom

  摘要：

  本发明提供了新颖的三环核苷和由此制备的寡聚合物化合物。将一种或多种三环核苷并入寡聚合物化合物中，预计会增强寡聚合物化合物的一种或多种性质。这种寡聚合物化合物也可以包含在双链组合物中。在某些实施方式中，本文提供的寡聚合物化合物预计会与靶RNA的部分杂交，导致靶RNA的正常功能丧失。

  公开号：

  EP2639238A1

文献信息

• [EN] TRICYCLIC NUCLEOSIDES AND OLIGOMERIC COMPOUNDS PREPARED THEREFROM<br/>[FR] NUCLÉOSIDES TRICYCLIQUES ET COMPOSÉS OLIGOMÈRES PRÉPARÉS À PARTIR DE CEUX-CI
  申请人：UNIV BERN VERWALTUNGSDIREKTION

  公开号：WO2013135900A1

  公开（公告）日：2013-09-19

  The present invention provides novel tricyclic nucleosides and oligomeric compounds prepared therefrom. Incorporation of one or more of the tricyclic nucleosides into an oligomeric compound is expected to enhance one or more properties of the oligomeric compound. Such oligomeric compounds can also be included in double stranded compositions. In certain embodiments, the oligomeric compounds provided herein are expected to hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA.

  本发明提供了新颖的三环核苷和由其制备的寡聚合物化合物。将一个或多个三环核苷并入寡聚合物化合物中预计会增强寡聚合物化合物的一个或多个性质。这种寡聚合物化合物也可以包含在双链组合物中。在某些实施例中，本文提供的寡聚合物化合物预计会与靶RNA的部分杂交，导致靶RNA的正常功能丧失。