(1R,3R,4R,5S,6S,7S)-7-benzyloxy-1-benzyloxymethyl-6-hydroxy-5-trifluoroacetylamino-3-(thymin-1-yl)-2-oxa-bicyclo[2.2.1]heptane | 1186023-90-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (1R,3R,4R,5S,6S,7S)-7-benzyloxy-1-benzyloxymethyl-6-hydroxy-5-trifluoroacetylamino-3-(thymin-1-yl)-2-oxa-bicyclo[2.2.1]heptane
• CAS: 1186023-90-4
• 化学式: C₂₈H₂₈F₃N₃O₇
• 分子量: 575.541
• InChiKey: ULCAGXARQHBALJ-FEJAVCOZSA-N

反应信息

• 作为反应物：
  描述：

  (1R,3R,4R,5S,6S,7S)-7-benzyloxy-1-benzyloxymethyl-6-hydroxy-5-trifluoroacetylamino-3-(thymin-1-yl)-2-oxa-bicyclo[2.2.1]heptane 、 乙酸酐 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 以91.1%的产率得到(1R,3R,4R,5S,6S,7S)-7-benzyloxy-1-benzyloxymethyl-6-acetoxy-5-trifluoroacetylamino-3-(thymin-1-yl)-2-oxa-bicyclo[2.2.1]heptane
  参考文献：
  名称：

  Synthesis of Conformationally Locked Carba-LNAs through Intramolecular Free-Radical Addition to C═N. Electrostatic and Steric Implication of the Carba-LNA Substituents in the Modified Oligos for Nuclease and Thermodynamic Stabilities

  摘要：

  The syntheses of the hitherto unavailable parentfully unsubstituted carba-LNA and its C7'-amino and/or C6'-hydroxyl substituted derivatives, have been accomplished by the intramolecular 5-exo free-radical addition to a C4'-tethered C=N to give carba-LNAs with variable hydrophilic substituents at C6'/C7' (amino and/or hydroxyl). They have been introduced into isosequential antisense oligonucleotides (AONs) to examine how their relative electrostatic and steric effects in the minor groove of a putative AON-RNA duplex affect the target affinity, nuclease resistance, and RNase H elicitation. We show that 2'-oxygen in LNA is important in stabilizing the DNA/DNA and DNA/RNA duplexes vis-a-vis the unsubstituted carba-LNA and its other derivatives and that hydrophobic groups at C6'/C7' in both carba-LNA and carba-ENA relatively destabilize the AON/DNA duplex more profoundly than those in the AON/RNA duplexes. Two main factors affect the relative stabilities of AON/DNA versus AON/RNA duplexes: (i) hydration in the minor groove depending upon hydrophilicity vis-a-vis hydrophobicity of the substituents, and (ii) the relative size of the minor groove in the AON/DNA versus AON/RNA duplexes dictates the steric clash with the substituents depending upon their relative chiralities. We also show how the chirality and chemical nature of the C6'/C7' substituents affect the nuclease stability as well as the thermal stability and the RNase recruitment by AON/RNA duplexes.

  DOI：

  10.1021/jo901009w
• 作为产物：
  描述：

  三氟乙酸乙酯 、 1-[(1S,3R,4R,5S,6S,7S)-5-amino-6-hydroxy-7-phenylmethoxy-1-(phenylmethoxymethyl)-2-oxabicyclo[2.2.1]heptan-3-yl]-5-methylpyrimidine-2,4-dione 在 4-二甲氨基吡啶 作用下， 以 甲醇 为溶剂， 以77 mg的产率得到(1R,3R,4R,5S,6S,7S)-7-benzyloxy-1-benzyloxymethyl-6-hydroxy-5-trifluoroacetylamino-3-(thymin-1-yl)-2-oxa-bicyclo[2.2.1]heptane
  参考文献：
  名称：

  Synthesis of Conformationally Locked Carba-LNAs through Intramolecular Free-Radical Addition to C═N. Electrostatic and Steric Implication of the Carba-LNA Substituents in the Modified Oligos for Nuclease and Thermodynamic Stabilities

  摘要：

  The syntheses of the hitherto unavailable parentfully unsubstituted carba-LNA and its C7'-amino and/or C6'-hydroxyl substituted derivatives, have been accomplished by the intramolecular 5-exo free-radical addition to a C4'-tethered C=N to give carba-LNAs with variable hydrophilic substituents at C6'/C7' (amino and/or hydroxyl). They have been introduced into isosequential antisense oligonucleotides (AONs) to examine how their relative electrostatic and steric effects in the minor groove of a putative AON-RNA duplex affect the target affinity, nuclease resistance, and RNase H elicitation. We show that 2'-oxygen in LNA is important in stabilizing the DNA/DNA and DNA/RNA duplexes vis-a-vis the unsubstituted carba-LNA and its other derivatives and that hydrophobic groups at C6'/C7' in both carba-LNA and carba-ENA relatively destabilize the AON/DNA duplex more profoundly than those in the AON/RNA duplexes. Two main factors affect the relative stabilities of AON/DNA versus AON/RNA duplexes: (i) hydration in the minor groove depending upon hydrophilicity vis-a-vis hydrophobicity of the substituents, and (ii) the relative size of the minor groove in the AON/DNA versus AON/RNA duplexes dictates the steric clash with the substituents depending upon their relative chiralities. We also show how the chirality and chemical nature of the C6'/C7' substituents affect the nuclease stability as well as the thermal stability and the RNase recruitment by AON/RNA duplexes.

  DOI：

  10.1021/jo901009w