1-(2-hydroxy-3,5-di-O-benzyl-4-C-cyanomethyl-β-D-ribofuranosyl)thymine | 938193-16-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(2-hydroxy-3,5-di-O-benzyl-4-C-cyanomethyl-β-D-ribofuranosyl)thymine
• 英文别名: 2-((2R,3S,4R,5R)-3-(benzyloxy)-2-((benzyloxy)methyl)-4-hydroxy-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl)acetonitrile
• CAS: 938193-16-9
• 化学式: C₂₆H₂₇N₃O₆
• 分子量: 477.517
• InChiKey: WGXSFELWCMNCAW-MWXBQQNOSA-N

物化性质

• 密度：
  1.35±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.19
• 重原子数：
  35.0
• 可旋转键数：
  9.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  126.57
• 氢给体数：
  2.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  1-(2-hydroxy-3,5-di-O-benzyl-4-C-cyanomethyl-β-D-ribofuranosyl)thymine 在 sodium tetrahydroborate 、 二异丁基氢化铝 作用下， 以 甲醇 、 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.0h， 生成 2-cyanoethyl ((Z)-1-((2R,3S,4R,5R)-3-(benzyloxy)-2-((benzyloxy)methyl)-4-((tertbutyldimethylsilyl)oxy)-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl)-13-cyano-5,10-dioxo-11-oxa-3,4,6,7,9-pentaazatridecan-8-ylidene)carbamate
  参考文献：
  名称：

  4′-Guanidinium-modified siRNA: a molecular tool to control RNAi activity through RISC priming and selective antisense strand loading

  摘要：

  我们提出了对4′-guanidino修饰siRNA的合成、生化、生物物理和计算评估。

  DOI：

  10.1039/c9cc04141a
• 作为产物：
  描述：

  1-[2-O-acetyl-3,5-di-O-benzyl-4-C-cyanomethyl-β-D-ribofuranosyl]thymine 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以91%的产率得到1-(2-hydroxy-3,5-di-O-benzyl-4-C-cyanomethyl-β-D-ribofuranosyl)thymine
  参考文献：
  名称：

  4′-Guanidinium-modified siRNA: a molecular tool to control RNAi activity through RISC priming and selective antisense strand loading

  摘要：

  我们提出了对4′-guanidino修饰siRNA的合成、生化、生物物理和计算评估。

  DOI：

  10.1039/c9cc04141a

文献信息

• Conformationally Constrained 2‘-<i>N</i>,4‘-<i>C</i>-Ethylene-Bridged Thymidine (Aza-ENA-T):  Synthesis, Structure, Physical, and Biochemical Studies of Aza-ENA-T-Modified Oligonucleotides
  作者：Oommen P. Varghese、Jharna Barman、Wimal Pathmasiri、Oleksandr Plashkevych、Dmytro Honcharenko、Jyoti Chattopadhyaya

  DOI：10.1021/ja0634977

  日期：2006.11.1

  l-4'-cyanomethylene 11 to give a pair of 3',5'-bis-OBn-protected diastereomerically pure aza-ENA-Ts (12a and 12b) with the fused piperidino skeleton in the chair conformation, whereas the pentofuranosyl moiety is locked in the North-type conformation (7 degrees < P < 27 degrees, 44 degrees < phi m < 52 degrees). The origin of the chirality of two diastereomerically pure aza-ENA-Ts was found to be due

  2'-脱氧-2'-N,4'-C-亚乙基桥连胸苷 (aza-ENA-T) 已使用涉及 2'-ara-三氟甲基磺酰基-4'-氰基亚甲基 11 的关键环化步骤合成，得到一对 3',5'-bis-OBn 保护的非对映异构纯 aza-ENA-Ts（12a 和 12b），具有椅子构象中的稠合哌啶骨架，而呋喃戊糖基部分锁定在 North 型构象（7度 < P < 27 度，44 度 < phi m < 52 度）。发现两个非对映异构纯 aza-ENA-T 的手性起源是由于环内手性 2'-氮，其在 12b 中具有轴向 NH，在 12a 中具有赤道 NH。后者是热力学优选的，而前者是动力学优选的，Ea = 25.4 kcal mol-1，这是迄今为止在双环胺中在锥体 NH 处观察到的最高反转势垒。5'-O-DMTr-aza-ENA-T-3'-亚磷酰胺用于固相合成，得到四种不同的单修饰 15 聚体反义寡核苷酸
• Distal Two-Bond versus Three-Bond Electronegative Oxo-Substituent Effect Controls the Kinetics and Thermodynamics of the Conversion of a <i>C</i>-Nitroso Function to the Corresponding Oxime in the Conformationally Locked Pentofuranose (Bicyclo[2.2.1]heptane) System
  作者：Mansoureh Karimiahmadabadi、Sayeh Erfan、Andras Földesi、Jyoti Chattopadhyaya

  DOI：10.1021/jo500266k

  日期：2014.8.15

  We report the high-yielding and scalable diastereospecific synthesis of isomeric bicyclo[2.2.1]heptane-7- and -8-oximes and their corresponding C-nitroso derivatives, which are the key intermediates for the synthesis of carbanucleosides. Neither the (C7-R)-nitroso- nor (C8-S)-nitrosobicycloheptane system requires any external base in DMSO-d6 to afford the corresponding oxime, and no reverse isomerization

  我们报告了高产和可扩展非对映异构体合成的异构双环[2.2.1]庚烷-7-和-8-肟及其相应的C-亚硝基衍生物，它们是合成碳核苷的关键中间体。（C 7- R）-亚硝基-和（C 8 -S）-亚硝基双环庚烷体系都不需要DMSO- d 6中的任何外部碱来提供相应的肟，并且未观察到从肟到C-亚硝基化合物的反向异构化。的（C 8 -C转化小号）亚硝基化合物与È / Ž -oximes为〜8倍的速度（在40℃）比的（C7- ř）-亚硝基衍生物。该机制涉及用于（C7- R）-或（C8- S）-亚硝基衍生物转化为相应的E / Z-肟的一级反应动力学。与（C8- S）-亚硝基衍生物相比，（C7- R）-亚硝基化合物向相应肟的转化率较低，这是由于酸性H8电离中心距离OPMB两个键后者中C1上的C1 OMe基团与H1距离较远，而C7中的H7与C1 OMe基团相距三个键，使得后者中C1的吸电子基团的作用更强。
• WO2007/145593
  申请人：——

  公开号：——

  公开（公告）日：——
• 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
  作者：Jianfeng Xu、Yi Liu、Christelle Dupouy、Jyoti Chattopadhyaya

  DOI：10.1021/jo901009w

  日期：2009.9.4

  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.