(1R,3R,4R,7S)-1-(4,4'-dimethoxytrityloxymethyl)-7-hydroxy-3-(thymin-1-yl)-2-oxa-bicyclo[2.2.1]heptane | 1186024-10-1

• 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: (1R,3R,4R,7S)-1-(4,4'-dimethoxytrityloxymethyl)-7-hydroxy-3-(thymin-1-yl)-2-oxa-bicyclo[2.2.1]heptane
• 英文别名: 1-[(1R,3R,4R,7S)-1-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-7-hydroxy-2-oxabicyclo[2.2.1]heptan-3-yl]-5-methylpyrimidine-2,4-dione
• CAS: 1186024-10-1
• 化学式: C₃₃H₃₄N₂O₇
• 分子量: 570.642
• InChiKey: SSVCUSBEHCHCTH-NDYSUJMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  42
• 可旋转键数：
  9
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  107
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (1R,3R,4R,7S)-1-(4,4'-dimethoxytrityloxymethyl)-7-hydroxy-3-(thymin-1-yl)-2-oxa-bicyclo[2.2.1]heptane 、 2-氰乙基N,N-二异丙基氯亚磷酰胺 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 以84%的产率得到(1R,3R,4R,7S)-7-(2-cyanoethoxy(diisopropylamino)phosphinoxy)-1-(4,4'-dimethoxytrityloxymethyl)-3-(thymin-1-yl)-2-oxabicyclo[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：

  (1R,3R,4R,5R,7S)-7-hydroxy-1-hydroxymethyl-3-(thymin-1-yl)-2-oxabicyclo[2.2.1]heptane 、 4,4'-双甲氧基三苯甲基氯 在 吡啶 作用下， 以56 mg的产率得到(1R,3R,4R,7S)-1-(4,4'-dimethoxytrityloxymethyl)-7-hydroxy-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

文献信息

• FIVE- AND SIX-MEMBERED CONFORMATIONALLY LOCKED 2',4'-CARBOCYCLIC RIBO-THYMIDINES FOR THE TREATMENT OF INFECTIONS AND CANCER
  申请人：Chattopadhyaya Jyoti

  公开号：US20100087387A1

  公开（公告）日：2010-04-08

  Compounds (1, 2, 3, 4) according to the formulae shown below: (Formula 1, 2, 3, 4). For General Formula1-4:N=1-Thyminyl,9-Adeninyl,9-Guaninyl,1-Cytosinyl, 5-methyl-1-cytosinyl, 5-trifluoromethyl-1-cytosinyl, 5-fluoro-1-cytosinyl, 5-fluoro-1-cytosinyl, 5-trifluoromethyl-1-Uracilyl or Formula (A) (12a/12b) wherein for 12a: n=1, Q=CH 3 (R) [5-membered carbocyclic with C7′ in R configuration], 12b: n=1, Q=CH 3 (S) [5-membered carbocyclic with C7′ in S configuration].

  根据下面所示的公式，化合物（1、2、3、4）：（公式1、2、3、4）。对于一般的公式1-4：N = 1-胸腺嘧啶基，9-腺嘌呤基，9-鸟嘌呤基，1-胞嘧啶基，5-甲基-1-胞嘧啶基，5-三氟甲基-1-胞嘧啶基，5-氟-1-胞嘧啶基，5-氟-1-胞嘧啶基，5-三氟甲基-1-尿嘧啶基或公式（A）（12a / 12b），其中对于12a：n = 1，Q = CH3（R）[C7'以R构型的5元环碳环]，12b：n = 1，Q = （S）[C7'以S构型的5元环碳环]。
• US8461124B2
  申请人：——

  公开号：US8461124B2

  公开（公告）日：2013-06-11